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Head and Neck Oncology
Head and Neck Oncology Organisations Specialist Journals Recent PublicationsHead and Neck Oncology Organisations (6 links)
| Title Link to Website | Info Mouseover | Acr. | Country Link to Directory |
| American Head and Neck Society |  | AHNS |  USA |
| Australia and New Zealand Head and Neck Cancer Society |  Australia | ||
| British Association of Head & Neck Oncologists | | BAHNO |  UK |
| British Association of Head and Neck Oncology Nurses | | UK | |
| International Federation of Head and Neck Oncologic Societies | |  International | |
| South African Head and Neck Oncology Society | | SAHNOS |  South Africa |
Specialist Journals (2 links)
Oncology JournalsRecent Publications
Lapthanasupkul P, Juengsomjit R, Klanrit P, et al.
Oral and maxillofacial lesions in a Thai pediatric population: a retrospective review from two dental schools.
J Med Assoc Thai. 2015; 98(3):291-7 [PubMed] Related Publications
Oral and maxillofacial lesions in a Thai pediatric population: a retrospective review from two dental schools.
J Med Assoc Thai. 2015; 98(3):291-7 [PubMed] Related Publications
OBJECTIVE: To determine the prevalence of oral and maxillofacial lesions in a Thai pediatric population.
MATERIAL AND METHOD: Oral biopsy records from pediatric patients between the ages of 0 and 15 years in the files ofFaculty of Dentistry, Mahidol University, and the files of Faculty of Dentistry, Khon Kaen University were reviewed. The patients were divided into three age groups, including 0 to 5, 6 to 10, and 11 to 15 years. Excluding the diagnosis of normal tissues, the oral and maxillofacial lesions were classified into nine categories.
RESULTS: Of 13,050 biopsied oral and maxillofacial lesions, 1,389 cases (10.6%) came from pediatric patients. The largest number of lesions was odontogenic cysts and tumors, followed by inflammatory and reactive lesions, and salivary gland pathology The top ten most prevalent lesions contributed 73% of all oral biopsies. The most common lesion was dentigerous cyst, followed by mucocele and pyogenic granuloma.
CONCLUSION: The vast majority of oral diseases in children were benign and related to either developmental or tissue reaction, while malignant lesions were found in a very small proportion of all oral biopsies.
MATERIAL AND METHOD: Oral biopsy records from pediatric patients between the ages of 0 and 15 years in the files ofFaculty of Dentistry, Mahidol University, and the files of Faculty of Dentistry, Khon Kaen University were reviewed. The patients were divided into three age groups, including 0 to 5, 6 to 10, and 11 to 15 years. Excluding the diagnosis of normal tissues, the oral and maxillofacial lesions were classified into nine categories.
RESULTS: Of 13,050 biopsied oral and maxillofacial lesions, 1,389 cases (10.6%) came from pediatric patients. The largest number of lesions was odontogenic cysts and tumors, followed by inflammatory and reactive lesions, and salivary gland pathology The top ten most prevalent lesions contributed 73% of all oral biopsies. The most common lesion was dentigerous cyst, followed by mucocele and pyogenic granuloma.
CONCLUSION: The vast majority of oral diseases in children were benign and related to either developmental or tissue reaction, while malignant lesions were found in a very small proportion of all oral biopsies.
Related: 
Oral Cancer Thailand
Oral Cancer Thailand
Machiels JP, Haddad RI, Fayette J, et al.
Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.
Lancet Oncol. 2015; 16(5):583-94 [PubMed] Related Publications
Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.
Lancet Oncol. 2015; 16(5):583-94 [PubMed] Related Publications
BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy.
METHODS: In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682.
FINDINGS: Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1-9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months [95% CI 2·0-2·7] for the afatinib group vs 1·7 months [1·5-2·4] for the methotrexate group; hazard ratio [HR] 0·80 [95% CI 0·65-0·98], p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients.
INTERPRETATION: Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC.
FUNDING: Boehringer Ingelheim.
METHODS: In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682.
FINDINGS: Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1-9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months [95% CI 2·0-2·7] for the afatinib group vs 1·7 months [1·5-2·4] for the methotrexate group; hazard ratio [HR] 0·80 [95% CI 0·65-0·98], p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients.
INTERPRETATION: Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC.
FUNDING: Boehringer Ingelheim.
Williams L, Thompson LD, Seethala RR, et al.
Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression.
Am J Surg Pathol. 2015; 39(5):705-13 [PubMed] Related Publications
Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression.
Am J Surg Pathol. 2015; 39(5):705-13 [PubMed] Related Publications
Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC.
Glogovšek M, Gaberšček S, Zorman M
A simple graphical quantitative analysis of ultrasonography images to decide when to perform fine needle aspiration biopsy in diagnosing malignancy in solid thyroid nodules? A two centres prospective study.
Hell J Nucl Med. 2015 Jan-Apr; 18(1):25-30 [PubMed] Related Publications
A simple graphical quantitative analysis of ultrasonography images to decide when to perform fine needle aspiration biopsy in diagnosing malignancy in solid thyroid nodules? A two centres prospective study.
Hell J Nucl Med. 2015 Jan-Apr; 18(1):25-30 [PubMed] Related Publications
OBJECTIVE: Since the prevalence of thyroid nodules is high and ultrasonography (USG)-guided fine-needle aspiration biopsy (FNAB) as a diagnostic means cannot be performed in all cases, we aimed to evaluate the feasibility and applicability of simple graphical analysis of USG two-dimensional images, to identify patients with suspicious thyroid nodules who would benefit from FNAB.
SUBJECTS AND METHODS: We studied prospectively 211 consecutive patients with thyroid nodules: 122 from the University Clinical Centre (UCC) of Maribor and 89 from the University Medical Centre (UMC) of Ljubljana who underwent USGguided FNAB from January 2011 to October 2013. The cytology report was categorized as benign or suspicious/malignant. Blind to cytology reports, we later performed graphical analysis of USG images using ImageJ (version 1.48r) which is a public domain Java image processing and analysis programme. We compared the average gray value and standard deviation (SD) of the gray values used to generate the mean gray within the selection, with cytology reports.
RESULTS: According to cytology reports, 24 thyroid nodules were suspicious/malignant (14/10) and 187 benign. Graphical analysis of USG images performed with ImageJ demonstrated significantly higher values of SD of the gray values used to generate the mean gray value in suspicious/malignant thyroid nodules as compared to unsuspicious nodules in both UCC Maribor and in UMC Ljubljana (P<0.001 and P=0.002, respectively). A higher value of the SD of gray value used to generate the mean gray value meant variation or dispersion from the average value and was correlated by the presence of micro-calcifications. By applying a cut-off level of the quotient between the SD value of an examined thyroid nodule and the SD value of normal/reference thyroid tissue of 1.20, we found that 21/24 nodules were classified as true positive and 114/187 as true negative.
CONCLUSION: Our results showed that our graphical quantitative analysis of USG images had a negative predictive value of more than 90% and was able to suggest which thyroid nodules were potentially malignant and needed further investigation.
SUBJECTS AND METHODS: We studied prospectively 211 consecutive patients with thyroid nodules: 122 from the University Clinical Centre (UCC) of Maribor and 89 from the University Medical Centre (UMC) of Ljubljana who underwent USGguided FNAB from January 2011 to October 2013. The cytology report was categorized as benign or suspicious/malignant. Blind to cytology reports, we later performed graphical analysis of USG images using ImageJ (version 1.48r) which is a public domain Java image processing and analysis programme. We compared the average gray value and standard deviation (SD) of the gray values used to generate the mean gray within the selection, with cytology reports.
RESULTS: According to cytology reports, 24 thyroid nodules were suspicious/malignant (14/10) and 187 benign. Graphical analysis of USG images performed with ImageJ demonstrated significantly higher values of SD of the gray values used to generate the mean gray value in suspicious/malignant thyroid nodules as compared to unsuspicious nodules in both UCC Maribor and in UMC Ljubljana (P<0.001 and P=0.002, respectively). A higher value of the SD of gray value used to generate the mean gray value meant variation or dispersion from the average value and was correlated by the presence of micro-calcifications. By applying a cut-off level of the quotient between the SD value of an examined thyroid nodule and the SD value of normal/reference thyroid tissue of 1.20, we found that 21/24 nodules were classified as true positive and 114/187 as true negative.
CONCLUSION: Our results showed that our graphical quantitative analysis of USG images had a negative predictive value of more than 90% and was able to suggest which thyroid nodules were potentially malignant and needed further investigation.
Related: Thyroid Cancer
Thyroid Cancer
Tan T, Lim WT, Fong KW, et al.
Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma.
Int J Radiat Oncol Biol Phys. 2015; 91(5):952-60 [PubMed] Related Publications
Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma.
Int J Radiat Oncol Biol Phys. 2015; 91(5):952-60 [PubMed] Related Publications
PURPOSE: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone.
PATIENTS AND METHODS: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m(2), carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m(2) given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m(2)), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power.
RESULTS: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases-free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms.
CONCLUSION: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.
PATIENTS AND METHODS: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m(2), carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m(2) given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m(2)), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power.
RESULTS: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases-free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms.
CONCLUSION: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.
Inohara H, Takenaka Y, Yoshii T, et al.
Phase 2 study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III-IV squamous cell carcinoma of the head and neck.
Int J Radiat Oncol Biol Phys. 2015; 91(5):934-41 [PubMed] Related Publications
Phase 2 study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III-IV squamous cell carcinoma of the head and neck.
Int J Radiat Oncol Biol Phys. 2015; 91(5):934-41 [PubMed] Related Publications
PURPOSE: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck.
METHODS AND MATERIALS: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m(2), followed by cisplatin, 20 mg/m(2), administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR.
RESULTS: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure.
CONCLUSIONS: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.
METHODS AND MATERIALS: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m(2), followed by cisplatin, 20 mg/m(2), administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR.
RESULTS: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure.
CONCLUSIONS: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.
Ozawa H, Imanishi Y, Ito F, et al.
PiCO2 monitoring of transferred jejunum perfusion using an air tonometry technique after hypopharyngeal cancer surgery.
Medicine (Baltimore). 2015; 94(11):e632 [PubMed] Related Publications
PiCO2 monitoring of transferred jejunum perfusion using an air tonometry technique after hypopharyngeal cancer surgery.
Medicine (Baltimore). 2015; 94(11):e632 [PubMed] Related Publications
This study aimed to investigate the usefulness of intraluminal PCO2 (PiCO2) monitoring by air tonometry for the assessment of the vascular condition of the transferred jejunum after surgery for hypopharyngeal cancer.PiCO2 in the transplanted jejunum of 24 patients was monitored using air tonometry after radical surgery for hypopharyngeal cancer from 2003 to 2010.All but 1 patient, who removed the catheter before monitoring began, were monitored safely. PiCO2 in the transferred jejunum correlated with arterial PCO2 (PaCO2) that was measured concurrently, and dissociation of PiCO2 from PaCO2 was observed in cases with vascular complication. In those cases without postoperative vascular complication, the PiCO2 value gradually increased for 3 hours but then decreased by 12 hours after surgery. Three patients experienced major vascular complication. All 3 patients had continuous elevation of PiCO2 >100 mm Hg, although vascular flow in 1 patient recovered by removal of a venous thrombosis and reanastomosis of the vein 7.5 hours after surgery. Four other patients who experienced elevation of PiCO2 had their skin suture released for decompression of their neck wound, resulting in a decrease in PiCO2 after treatment.The current results demonstrated that continuous monitoring of PiCO2 by air tonometry accurately reflects the vascular condition of the transferred jejunum, and this method is one of the best options for postoperative monitoring of jejunum blood perfusion.
Related: Hypopharyngeal Cancer
Hypopharyngeal Cancer
Talsma AK, Damhuis RA, Steyerberg EW, et al.
Determinants of improved survival after oesophagectomy for cancer.
Br J Surg. 2015; 102(6):668-75 [PubMed] Related Publications
Determinants of improved survival after oesophagectomy for cancer.
Br J Surg. 2015; 102(6):668-75 [PubMed] Related Publications
BACKGROUND: Survival after oesophagectomy for cancer seems to be improving. This study aimed to identify the most important contributors to this change.
METHODS: Patients who underwent oesophagectomy from 1999 to 2010 were extracted from the Netherlands Cancer Registry. Four time periods were compared: 1999-2001 (period 1), 2002-2004 (period 2), 2005-2007 (period 3) and 2008-2010 (period 4). Hospital type, tumour location, tumour type, tumour differentiation, neoadjuvant therapy, operation type, (y)pT category, involvement of surgical resection margins, number of removed lymph nodes and number of involved lymph nodes were investigated in relation to trends in survival using multivariable analysis.
RESULTS: A total of 4382 patients were identified. Two-year overall survival rates improved from 49·3 per cent in period 1 to 58·4, 56·2 and 61·0 per cent in periods 2, 3 and 4 respectively (P < 0·001). Multivariable survival analysis revealed that the improvement in survival between periods 3 and 4 was related to the introduction of neoadjuvant therapy. The improvement in survival between periods 1 and 2 could not be explained completely by the factors studied. The number of examined lymph nodes increased, especially between periods 2 and 3, but this increase was not associated with the improvement in survival.
CONCLUSION: The observed increase in long-term survival after surgery for oesophageal cancer between 1999 and 2010 in the Netherlands is difficult to explain fully, although the recent increase seems to be partly attributable to the introduction of neoadjuvant therapy.
METHODS: Patients who underwent oesophagectomy from 1999 to 2010 were extracted from the Netherlands Cancer Registry. Four time periods were compared: 1999-2001 (period 1), 2002-2004 (period 2), 2005-2007 (period 3) and 2008-2010 (period 4). Hospital type, tumour location, tumour type, tumour differentiation, neoadjuvant therapy, operation type, (y)pT category, involvement of surgical resection margins, number of removed lymph nodes and number of involved lymph nodes were investigated in relation to trends in survival using multivariable analysis.
RESULTS: A total of 4382 patients were identified. Two-year overall survival rates improved from 49·3 per cent in period 1 to 58·4, 56·2 and 61·0 per cent in periods 2, 3 and 4 respectively (P < 0·001). Multivariable survival analysis revealed that the improvement in survival between periods 3 and 4 was related to the introduction of neoadjuvant therapy. The improvement in survival between periods 1 and 2 could not be explained completely by the factors studied. The number of examined lymph nodes increased, especially between periods 2 and 3, but this increase was not associated with the improvement in survival.
CONCLUSION: The observed increase in long-term survival after surgery for oesophageal cancer between 1999 and 2010 in the Netherlands is difficult to explain fully, although the recent increase seems to be partly attributable to the introduction of neoadjuvant therapy.
Related: Cancer of the Esophagus Esophageal Cancer
Cancer of the Esophagus Esophageal Cancer
Slaby O, Srovnal J, Radova L, et al.
Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.
Carcinogenesis. 2015; 36(5):521-7 [PubMed] Related Publications
Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.
Carcinogenesis. 2015; 36(5):521-7 [PubMed] Related Publications
Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC.
Kong F, Cai B, Lin S, et al.
Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma: a prospective study.
J BUON. 2015 Jan-Feb; 20(1):206-11 [PubMed] Related Publications
Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma: a prospective study.
J BUON. 2015 Jan-Feb; 20(1):206-11 [PubMed] Related Publications
PURPOSE: To explore the clinical efficacy of radiotherapy combined with concurrent combination chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma (NPC).
METHODS: Two hundred patients with stage III/IV NPC were randomly allocated into the treatment group (N=100) and the control group (N=100). Patients in the control group received conventional fractionated radiotherapy, while patients in the treatment group received conventional fractionated radiotherapy combined with concurrent combination chemotherapy with cisplatin and 5-fluorouracil (5-FU). Short-term efficacy, radiotherapy toxicity, shortand long-term survival were compared.
RESULTS: The short-term response rate of the treatment group was 96%, which was significantly higher than that of the control group (87%, p<0.05). The local radiation toxicity of the treatment group was similar to that of the control group p>0.05), but the hematological and gastrointestinal toxicities were significantly higher in the treatment group p<0.05). The 1-, 3- and 5-year overall survival rates were 87, 80, and 76%, respectively, in the treatment group and 74, 64, and 51%, respectively, in the control group, significantly favoring the treatment group p<0.05).
CONCLUSION: Radiotherapy with concurrent combination chemotherapy can improve the prognosis of patients with advanced NPC but at the cost of significant toxicity.
METHODS: Two hundred patients with stage III/IV NPC were randomly allocated into the treatment group (N=100) and the control group (N=100). Patients in the control group received conventional fractionated radiotherapy, while patients in the treatment group received conventional fractionated radiotherapy combined with concurrent combination chemotherapy with cisplatin and 5-fluorouracil (5-FU). Short-term efficacy, radiotherapy toxicity, shortand long-term survival were compared.
RESULTS: The short-term response rate of the treatment group was 96%, which was significantly higher than that of the control group (87%, p<0.05). The local radiation toxicity of the treatment group was similar to that of the control group p>0.05), but the hematological and gastrointestinal toxicities were significantly higher in the treatment group p<0.05). The 1-, 3- and 5-year overall survival rates were 87, 80, and 76%, respectively, in the treatment group and 74, 64, and 51%, respectively, in the control group, significantly favoring the treatment group p<0.05).
CONCLUSION: Radiotherapy with concurrent combination chemotherapy can improve the prognosis of patients with advanced NPC but at the cost of significant toxicity.
Schwartz DL, Harris J, Yao M, et al.
Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522.
Int J Radiat Oncol Biol Phys. 2015; 91(4):721-9 [PubMed] Related Publications
Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522.
Int J Radiat Oncol Biol Phys. 2015; 91(4):721-9 [PubMed] Related Publications
PURPOSE: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting.
METHODS AND MATERIALS: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes.
RESULTS: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited.
CONCLUSION: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.
METHODS AND MATERIALS: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes.
RESULTS: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited.
CONCLUSION: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.
Soularue É, Cohen R, Tournigand C, et al.
Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: a retrospective study.
Bull Cancer. 2015; 102(4):324-31 [PubMed] Related Publications
Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: a retrospective study.
Bull Cancer. 2015; 102(4):324-31 [PubMed] Related Publications
BACKGROUND: Trastuzumab with 5-fluorouracil (5-FU) and cisplatin offers prolonged survival in patients with HER2-overexpressing advanced gastric cancer (AGC) and advanced gastro-oesophageal junction cancer (AGOJ). Oxaliplatin in combination with intravenous 5-FU plus leucovorin (LV; modified [m]FOLFOX6) or capecitabine (XELOX) improves tolerability compared with 5-FU/cisplatin regimen. There are few data available on the efficacy and safety of trastuzumab-oxaliplatin-based chemotherapy in previously untreated HER2-positive AGC and AGOJ patients.
METHODS: Clinical data were retrospectively analysed in patients receiving trastuzumab plus mFOLFOX6 or XELOX as first-line therapy between July 2009 and December 2012. Eligible patients had histologically proven AGC or AGOJ, HER2 overexpression, and no prior chemotherapy for metastatic disease.
RESULTS: Thirty-four patients met the eligibility criteria. Median age was 63 years, 79% of patients had ECOG PS score of 0-1, and all had metastatic disease. Median duration of treatment was 7.5 months. Overall response rate was 41% (95% CI: 25-56). Median progression-free survival and overall survival were 9.0 months (95% CI: 5.6-12) and 17.3 months (95% CI: 13.5-32.3), respectively. Tolerability was acceptable. The most frequent grade 3-4 toxicities were neutropenia (8.8%) and neuropathy (17.6%).
CONCLUSION: mFOLFOX6-trastuzumab combination is an efficient regimen with an acceptable safety profile for AGC and AGOJ patients. These results warrant further prospective study.
METHODS: Clinical data were retrospectively analysed in patients receiving trastuzumab plus mFOLFOX6 or XELOX as first-line therapy between July 2009 and December 2012. Eligible patients had histologically proven AGC or AGOJ, HER2 overexpression, and no prior chemotherapy for metastatic disease.
RESULTS: Thirty-four patients met the eligibility criteria. Median age was 63 years, 79% of patients had ECOG PS score of 0-1, and all had metastatic disease. Median duration of treatment was 7.5 months. Overall response rate was 41% (95% CI: 25-56). Median progression-free survival and overall survival were 9.0 months (95% CI: 5.6-12) and 17.3 months (95% CI: 13.5-32.3), respectively. Tolerability was acceptable. The most frequent grade 3-4 toxicities were neutropenia (8.8%) and neuropathy (17.6%).
CONCLUSION: mFOLFOX6-trastuzumab combination is an efficient regimen with an acceptable safety profile for AGC and AGOJ patients. These results warrant further prospective study.
Durante C, Costante G, Lucisano G, et al.
The natural history of benign thyroid nodules.
JAMA. 2015; 313(9):926-35 [PubMed] Related Publications
The natural history of benign thyroid nodules.
JAMA. 2015; 313(9):926-35 [PubMed] Related Publications
IMPORTANCE: Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious nodules. Current guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed.
OBJECTIVE: To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed.
MAIN OUTCOMES AND MEASURES: Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up.
RESULTS: Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes ≥1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer.
CONCLUSIONS AND RELEVANCE: Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.
OBJECTIVE: To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed.
MAIN OUTCOMES AND MEASURES: Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up.
RESULTS: Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes ≥1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer.
CONCLUSIONS AND RELEVANCE: Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.
Related: Thyroid Cancer
Thyroid Cancer
Melichar B, Adenis A, Lockhart AC, et al.
Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study.
Lancet Oncol. 2015; 16(4):395-405 [PubMed] Related Publications
Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study.
Lancet Oncol. 2015; 16(4):395-405 [PubMed] Related Publications
BACKGROUND: Alisertib is an investigational, oral, selective inhibitor of aurora kinase A. We aimed to investigate the safety and activity of single-agent alisertib in patients with predefined types of advanced solid tumours.
METHODS: We did a multicentre phase 1/2 study at 40 centres in four countries (Czech Republic, France, Poland, and the USA). Here, we report results from phase 2; enrolment for the study began on Feb 16, 2010, and ended on May 3, 2013. Adult patients were eligible for the study if they had either breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, or gastro-oesophageal adenocarcinoma that had relapsed or was refractory to chemotherapy. Patients had to have undergone two or fewer previous cytotoxic regimens (four or fewer for breast cancer patients), not including adjuvant or neoadjuvant treatments. Enrolment followed a two-stage design: to proceed to the second stage, two or more objective responses were needed in the first 20 response-assessable patients in each of the five tumour cohorts. Alisertib was administered orally in 21-day cycles at the recommended phase 2 dose of 50 mg twice daily for 7 days followed by a break of 14 days. The protocol-specified primary endpoint was the proportion of patients with an objective response, assessed by Response Evaluation Criteria In Solid Tumors version 1.1 in the response-assessable population (ie, patients with measurable disease who received at least one dose of alisertib and had undergone at least one post-baseline tumour assessment). This completed trial is registered with ClinicalTrials.gov, NCT01045421.
FINDINGS: By May 31, 2013, 249 patients had been treated, 53 with breast cancer, 60 with small-cell lung cancer, 26 with non-small-cell lung cancer, 55 with head and neck squamous-cell carcinoma, and 55 with gastro-oesophageal adenocarcinoma. Among response-assessable patients, an objective response was noted in nine (18%, 95% CI 9-32) of 49 women with breast cancer, ten (21%, 10-35) of 48 participants with small-cell lung cancer, one (4%, 0-22) of 23 patients with non-small-cell lung cancer, four (9%, 2-21) of 45 people with head and neck squamous-cell carcinoma, and four (9%, 2-20) of 47 individuals with gastro-oesophageal adenocarcinoma; all were partial responses. Adverse events were similar across tumour types. The most frequent drug-related grade 3-4 adverse events included neutropenia (n=107 [43%]), leukopenia (53 [21%]), and anaemia (26 [10%]). Serious drug-related adverse events were reported in 108 (43%) patients.
INTERPRETATION: These data support further clinical assessment of alisertib in patients with solid tumours, particularly those with breast cancer and small-cell lung cancer.
FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
METHODS: We did a multicentre phase 1/2 study at 40 centres in four countries (Czech Republic, France, Poland, and the USA). Here, we report results from phase 2; enrolment for the study began on Feb 16, 2010, and ended on May 3, 2013. Adult patients were eligible for the study if they had either breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, or gastro-oesophageal adenocarcinoma that had relapsed or was refractory to chemotherapy. Patients had to have undergone two or fewer previous cytotoxic regimens (four or fewer for breast cancer patients), not including adjuvant or neoadjuvant treatments. Enrolment followed a two-stage design: to proceed to the second stage, two or more objective responses were needed in the first 20 response-assessable patients in each of the five tumour cohorts. Alisertib was administered orally in 21-day cycles at the recommended phase 2 dose of 50 mg twice daily for 7 days followed by a break of 14 days. The protocol-specified primary endpoint was the proportion of patients with an objective response, assessed by Response Evaluation Criteria In Solid Tumors version 1.1 in the response-assessable population (ie, patients with measurable disease who received at least one dose of alisertib and had undergone at least one post-baseline tumour assessment). This completed trial is registered with ClinicalTrials.gov, NCT01045421.
FINDINGS: By May 31, 2013, 249 patients had been treated, 53 with breast cancer, 60 with small-cell lung cancer, 26 with non-small-cell lung cancer, 55 with head and neck squamous-cell carcinoma, and 55 with gastro-oesophageal adenocarcinoma. Among response-assessable patients, an objective response was noted in nine (18%, 95% CI 9-32) of 49 women with breast cancer, ten (21%, 10-35) of 48 participants with small-cell lung cancer, one (4%, 0-22) of 23 patients with non-small-cell lung cancer, four (9%, 2-21) of 45 people with head and neck squamous-cell carcinoma, and four (9%, 2-20) of 47 individuals with gastro-oesophageal adenocarcinoma; all were partial responses. Adverse events were similar across tumour types. The most frequent drug-related grade 3-4 adverse events included neutropenia (n=107 [43%]), leukopenia (53 [21%]), and anaemia (26 [10%]). Serious drug-related adverse events were reported in 108 (43%) patients.
INTERPRETATION: These data support further clinical assessment of alisertib in patients with solid tumours, particularly those with breast cancer and small-cell lung cancer.
FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Chao YK, Yeh CJ, Lee MH, et al.
Factors associated with false-negative endoscopic biopsy results after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.
Medicine (Baltimore). 2015; 94(8):e588 [PubMed] Related Publications
Factors associated with false-negative endoscopic biopsy results after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.
Medicine (Baltimore). 2015; 94(8):e588 [PubMed] Related Publications
The usefulness of endoscopic biopsy following neoadjuvant chemoradiotherapy (nCRT) is limited because of its high false-negative (FN) rates. However, data on the factors associated with FN biopsy results remain scarce. The purpose of this study was to investigate factors associated with FN results on endoscopic biopsies in patients with esophageal squamous cell carcinoma (ESCC) following nCRT. We retrospectively reviewed the records of ESCC patients who were treated at the Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1999 and 2013. Inclusion criteria were receiving nCRT as first-line treatment before esophagectomy and having been preoperatively submitted to an endoscopic biopsy. Endoscopic findings at the lesion site were classified into 6 distinct categories: stricture, tumor, ulcer, scar, other findings, or normal. Univariate and multivariate analyses were used to identify factors associated with FN biopsy findings. A total of 227 patients were selected, of which 92 (41.9%) had positive biopsy results. Among patients with negative biopsy findings (n = 135), 85 were found to have residual cancer on the resected esophagus. Multivariate analysis identified endoscopic findings as the only independent predictor of FN biopsy results. The negative predictive values were 77.8%, 61.9%, 52.6%, 30.3%, 23.1%, and 20.0% for the normal, scar, other findings, ulcer, stricture, and tumor categories, respectively (P < 0.001). In ESCC patients, the FN rate of endoscopic biopsy after nCRT is associated with the type of residual lesion.
Related: Cancer of the Esophagus Esophageal Cancer
Cancer of the Esophagus Esophageal Cancer
Lorenzen S, Riera Knorrenschild J, Haag GM, et al.
Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie.
Eur J Cancer. 2015; 51(5):569-76 [PubMed] Related Publications
Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie.
Eur J Cancer. 2015; 51(5):569-76 [PubMed] Related Publications
INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) amplification is present in a subgroup of gastroo-esophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-epidermal growth factor receptor (EGFR) and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC.
MATERIALS AND METHODS: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250mg per day 1-21 plus capecitabine (CAP) 2000mg/m(2) on days 1-14 of a 21-day cycle or LAP 1500mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary end-point was the objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). We aimed to include 38 pts per arm to show an interesting response rate of ⩾20% in either of the two arms.
RESULTS: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% confidence interval (CI): 1.37-34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38-61) days in the LAP group and 83 (95% CI: 42-86) days in the LAP+CAP group. Other secondary efficacy end-points (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhoea were higher with LAP+CAP (61%; 95% CI: 35-83) compared to 26% (95% CI 9-51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] versus 17 [90%]).
DISCUSSION: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier, NCT01145404).
MATERIALS AND METHODS: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250mg per day 1-21 plus capecitabine (CAP) 2000mg/m(2) on days 1-14 of a 21-day cycle or LAP 1500mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary end-point was the objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). We aimed to include 38 pts per arm to show an interesting response rate of ⩾20% in either of the two arms.
RESULTS: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% confidence interval (CI): 1.37-34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38-61) days in the LAP group and 83 (95% CI: 42-86) days in the LAP+CAP group. Other secondary efficacy end-points (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhoea were higher with LAP+CAP (61%; 95% CI: 35-83) compared to 26% (95% CI 9-51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] versus 17 [90%]).
DISCUSSION: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier, NCT01145404).
Arantes LM, de Carvalho AC, Melendez ME, et al.
Validation of methylation markers for diagnosis of oral cavity cancer.
Eur J Cancer. 2015; 51(5):632-41 [PubMed] Related Publications
Validation of methylation markers for diagnosis of oral cavity cancer.
Eur J Cancer. 2015; 51(5):632-41 [PubMed] Related Publications
PURPOSE: Activation of proto-oncogenes and inactivation of tumour suppressor genes are the major genetic alterations involved in carcinogenesis. The increase in methylation at the promoter region of a tumour suppressor gene can lead to gene inactivation, selecting cells with proliferative advantage. Thus, promoter hypermethylation is considered a marker in a variety of malignant tumours, including oral cavity.
EXPERIMENTAL DESIGN: The methylation pattern of eight genes was evaluated in 40 oral cavity squamous cell carcinomas (OSCCs) and 40 saliva samples from healthy individuals by Q-MSP. Different combinations of genes were also assessed in order to identify gene panels that could better distinguish between OSCC and saliva samples.
RESULTS: CCNA1, DAPK, DCC and TIMP3 methylation were highly specific for being found in the OSCC samples. Moreover, the combination of these genes improved detection when compared with single markers, reaching values of 92.5% for sensitivity and specificity (when using the panel CCNA1, DCC, TIMP3). Moreover, DAPK, DCC and TIMP3 were hypermethylated in nearly 90% of clinically T1 and T2 cases.
CONCLUSION: The pursuing of this panel of hypermethylated genes is an important tool for the detection of individuals with OSCC. Moreover, the identification of these markers in early stages of OSCC shows the feasibility of using the panel on saliva as possible biomarkers for early diagnosis. The lack of association between the methylation status of these genes and clinical characteristics shows that they are able to distinguish OSCC cases irrespective of social and clinical factors (gender, age, human papillomavirus (HPV) status, clinical stage, vascular embolisation and perineural invasion).
EXPERIMENTAL DESIGN: The methylation pattern of eight genes was evaluated in 40 oral cavity squamous cell carcinomas (OSCCs) and 40 saliva samples from healthy individuals by Q-MSP. Different combinations of genes were also assessed in order to identify gene panels that could better distinguish between OSCC and saliva samples.
RESULTS: CCNA1, DAPK, DCC and TIMP3 methylation were highly specific for being found in the OSCC samples. Moreover, the combination of these genes improved detection when compared with single markers, reaching values of 92.5% for sensitivity and specificity (when using the panel CCNA1, DCC, TIMP3). Moreover, DAPK, DCC and TIMP3 were hypermethylated in nearly 90% of clinically T1 and T2 cases.
CONCLUSION: The pursuing of this panel of hypermethylated genes is an important tool for the detection of individuals with OSCC. Moreover, the identification of these markers in early stages of OSCC shows the feasibility of using the panel on saliva as possible biomarkers for early diagnosis. The lack of association between the methylation status of these genes and clinical characteristics shows that they are able to distinguish OSCC cases irrespective of social and clinical factors (gender, age, human papillomavirus (HPV) status, clinical stage, vascular embolisation and perineural invasion).
Yoon DH, Jang G, Kim JH, et al.
Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.
Int J Radiat Oncol Biol Phys. 2015; 91(3):489-96 [PubMed] Related Publications
Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.
Int J Radiat Oncol Biol Phys. 2015; 91(3):489-96 [PubMed] Related Publications
PURPOSE: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.
PATIENTS AND METHODS: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.
RESULTS: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.
CONCLUSIONS: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.
PATIENTS AND METHODS: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.
RESULTS: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.
CONCLUSIONS: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.
Laohawiriyakamol S, Sunpaweravong S, Leelamanit V, et al.
Evaluating synchronous esophageal cancer in head and neck cancer patients using Lugol dye chromoendoscopy.
J Med Assoc Thai. 2014; 97(11):1164-70 [PubMed] Related Publications
Evaluating synchronous esophageal cancer in head and neck cancer patients using Lugol dye chromoendoscopy.
J Med Assoc Thai. 2014; 97(11):1164-70 [PubMed] Related Publications
OBJECTIVE: Routine screening for esophageal cancer in head and neck cancer patients in Thailand is controversial, because of concerns regarding the screening methods and cost effectiveness. Since Lugol dye chromoendoscopy is an effective technique for early detection of squamous cell carcinoma of the esophagus, the objectives of the present study are to evaluate the synchronous esophageal cancer in head and neck cancer patients and the effectiveness of Lugol dye chromoendoscopy for routine screening.
MATERIAL AND METHOD: All diagnosed patients with head and neck cancer between September 1, 2009 and June 30, 2011 were enrolled into the study. Both conventional esophagoscopy and Lugol dye chromoendoscopy were done. The incidence of esophageal cancer was calculated. A diagnostic statistical analysis was done to compare the diagnostic properties between conventional esophagoscopy and Lugol dye chromoendoscopy. Univariate and multivariate logistic regression analyses were used to find significant factors associated with esophageal cancer in this study.
RESULTS: Eighty-nine head and neck cancer patients were enrolled in this study. The incidence of esophageal cancer in head and neck cancer patients was 12.4% (11/89). Conventional esophagoscopy found a highly suspicious malignant lesion in only six patients, while the Lugol dye chromoendoscopy detected all 11 esophageal cancers. The sensitivity and specificity for conventional esophagoscopy were 54.5% and 100%, respectively, andfor Lugol dye chromoendoscopy were 100% and 70.5%, respectively. The three significant factors that increased the likelihood of synchronous esophageal cancer from univariate analysis were age less than 50 years, presence of dysphagia, and an unstained Lugol dye area ≥10 mm. Howeve, these factors were not statistically significant by multivariate analysis.
CONCLUSION: Lugol dye chromoendoscopy is a promising tool to enhance the diagnosis of esophageal cancer among head and neck cancer patients.
MATERIAL AND METHOD: All diagnosed patients with head and neck cancer between September 1, 2009 and June 30, 2011 were enrolled into the study. Both conventional esophagoscopy and Lugol dye chromoendoscopy were done. The incidence of esophageal cancer was calculated. A diagnostic statistical analysis was done to compare the diagnostic properties between conventional esophagoscopy and Lugol dye chromoendoscopy. Univariate and multivariate logistic regression analyses were used to find significant factors associated with esophageal cancer in this study.
RESULTS: Eighty-nine head and neck cancer patients were enrolled in this study. The incidence of esophageal cancer in head and neck cancer patients was 12.4% (11/89). Conventional esophagoscopy found a highly suspicious malignant lesion in only six patients, while the Lugol dye chromoendoscopy detected all 11 esophageal cancers. The sensitivity and specificity for conventional esophagoscopy were 54.5% and 100%, respectively, andfor Lugol dye chromoendoscopy were 100% and 70.5%, respectively. The three significant factors that increased the likelihood of synchronous esophageal cancer from univariate analysis were age less than 50 years, presence of dysphagia, and an unstained Lugol dye area ≥10 mm. Howeve, these factors were not statistically significant by multivariate analysis.
CONCLUSION: Lugol dye chromoendoscopy is a promising tool to enhance the diagnosis of esophageal cancer among head and neck cancer patients.
Schlumberger M, Tahara M, Wirth LJ, et al.
Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.
N Engl J Med. 2015; 372(7):621-30 [PubMed] Related Publications
Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.
N Engl J Med. 2015; 372(7):621-30 [PubMed] Related Publications
BACKGROUND: Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).
METHODS: In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety.
RESULTS: The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related.
CONCLUSIONS: Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.).
METHODS: In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety.
RESULTS: The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related.
CONCLUSIONS: Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.).
Related: Thyroid Cancer
Thyroid Cancer
Shenouda G, Zhang Q, Ang KK, et al.
Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.
Int J Radiat Oncol Biol Phys. 2015; 91(5):907-15 [PubMed] Related Publications
Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.
Int J Radiat Oncol Biol Phys. 2015; 91(5):907-15 [PubMed] Related Publications
PURPOSE: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).
METHODS AND MATERIALS: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.
RESULTS: A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.
CONCLUSIONS: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.
METHODS AND MATERIALS: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.
RESULTS: A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.
CONCLUSIONS: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.
Budach V, Stromberger C, Poettgen C, et al.
Hyperfractionated accelerated radiation therapy (HART) of 70.6 Gy with concurrent 5-FU/Mitomycin C is superior to HART of 77.6 Gy alone in locally advanced head and neck cancer: long-term results of the ARO 95-06 randomized phase III trial.
Int J Radiat Oncol Biol Phys. 2015; 91(5):916-24 [PubMed] Related Publications
Hyperfractionated accelerated radiation therapy (HART) of 70.6 Gy with concurrent 5-FU/Mitomycin C is superior to HART of 77.6 Gy alone in locally advanced head and neck cancer: long-term results of the ARO 95-06 randomized phase III trial.
Int J Radiat Oncol Biol Phys. 2015; 91(5):916-24 [PubMed] Related Publications
PURPOSE: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer.
PATIENTS AND METHODS: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses.
RESULTS: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264).
CONCLUSIONS: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.
PATIENTS AND METHODS: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses.
RESULTS: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264).
CONCLUSIONS: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.
Petrick JL, Steck SE, Bradshaw PT, et al.
Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA).
Br J Cancer. 2015; 112(7):1291-300 [PubMed] Article available free on PMC after 31/03/2016 Related Publications
Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA).
Br J Cancer. 2015; 112(7):1291-300 [PubMed] Article available free on PMC after 31/03/2016 Related Publications
BACKGROUND: Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival.
METHODS: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively.
RESULTS: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide.
CONCLUSIONS: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.
METHODS: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively.
RESULTS: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide.
CONCLUSIONS: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.
Kiernan CM, Parikh AA, Parks LL, Solórzano CC
Use of radioiodine after thyroid lobectomy in patients with differentiated thyroid cancer: does it change outcomes?
J Am Coll Surg. 2015; 220(4):617-25 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
Use of radioiodine after thyroid lobectomy in patients with differentiated thyroid cancer: does it change outcomes?
J Am Coll Surg. 2015; 220(4):617-25 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
BACKGROUND: Radioiodine (RAI) lobe ablation in lieu of completion thyroidectomy is not recommended. This study describes RAI use patterns and outcomes in patients with well-differentiated thyroid cancer (DTC) after thyroid lobectomy (TL).
STUDY DESIGN: A total of 170,330 patients diagnosed with DTC between 1998 and 2011 were identified using the National Cancer Database. Demographic, tumor, and treatment variables were analyzed using both univariate and multivariate regression.
RESULTS: A total of 32,119 patients (20%) underwent TL as the definitive procedure. Mean age at diagnosis was 48 years, median tumor size was 1 cm, 4% had extrathyroidal extension, 4% had positive lymph nodes, and <1% distant metastases. Radioiodine was administered to 24% of patients in the TL cohort and represented 10% of the overall RAI use. In multivariate analysis, RAI use was associated with age younger than 45 years (odds ratio [OR] = 1.51), community facilities (OR = 1.26), ≥ 1 cm tumors (OR = 5.67), stage II (OR = 1.54) or III (OR = 2.05), positive lymph nodes (OR = 1.78), and extrathyroidal extension (OR = 1.36). On both univariate and multivariate analysis, RAI after TL was associated with improved survival at both 5 and 10 years follow-up (97% vs 95% and 91% vs 89%, respectively; hazard ratio = 0.53; 95% CI, 0.38-0.72; p < 0.001) CONCLUSIONS: Nearly one quarter of TL patients received RAI. The strongest predictors of RAI use were larger cancers and advanced stage. Use of RAI in these patients was associated with improved overall survival. Future studies and guidelines will need to more clearly address this practice and educate providers about the appropriate use of RAI in TL patients.
STUDY DESIGN: A total of 170,330 patients diagnosed with DTC between 1998 and 2011 were identified using the National Cancer Database. Demographic, tumor, and treatment variables were analyzed using both univariate and multivariate regression.
RESULTS: A total of 32,119 patients (20%) underwent TL as the definitive procedure. Mean age at diagnosis was 48 years, median tumor size was 1 cm, 4% had extrathyroidal extension, 4% had positive lymph nodes, and <1% distant metastases. Radioiodine was administered to 24% of patients in the TL cohort and represented 10% of the overall RAI use. In multivariate analysis, RAI use was associated with age younger than 45 years (odds ratio [OR] = 1.51), community facilities (OR = 1.26), ≥ 1 cm tumors (OR = 5.67), stage II (OR = 1.54) or III (OR = 2.05), positive lymph nodes (OR = 1.78), and extrathyroidal extension (OR = 1.36). On both univariate and multivariate analysis, RAI after TL was associated with improved survival at both 5 and 10 years follow-up (97% vs 95% and 91% vs 89%, respectively; hazard ratio = 0.53; 95% CI, 0.38-0.72; p < 0.001) CONCLUSIONS: Nearly one quarter of TL patients received RAI. The strongest predictors of RAI use were larger cancers and advanced stage. Use of RAI in these patients was associated with improved overall survival. Future studies and guidelines will need to more clearly address this practice and educate providers about the appropriate use of RAI in TL patients.
Related: Thyroid Cancer
Thyroid Cancer
Nyflot MJ, Kruser TJ, Traynor AM, et al.
Phase 1 trial of bevacizumab with concurrent chemoradiation therapy for squamous cell carcinoma of the head and neck with exploratory functional imaging of tumor hypoxia, proliferation, and perfusion.
Int J Radiat Oncol Biol Phys. 2015; 91(5):942-51 [PubMed] Related Publications
Phase 1 trial of bevacizumab with concurrent chemoradiation therapy for squamous cell carcinoma of the head and neck with exploratory functional imaging of tumor hypoxia, proliferation, and perfusion.
Int J Radiat Oncol Biol Phys. 2015; 91(5):942-51 [PubMed] Related Publications
PURPOSE: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies.
METHODS AND MATERIALS: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m(2) and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [(18)F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [(61)Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course.
RESULTS: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course.
CONCLUSIONS: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable changes in tumor proliferation, hypoxia, and perfusion after bevacizumab monotherapy and during chemoradiation therapy. These findings suggest opportunities to preview the clinical outcomes for individual patients and thereby design personalized therapy approaches in future trials.
METHODS AND MATERIALS: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m(2) and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [(18)F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [(61)Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course.
RESULTS: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course.
CONCLUSIONS: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable changes in tumor proliferation, hypoxia, and perfusion after bevacizumab monotherapy and during chemoradiation therapy. These findings suggest opportunities to preview the clinical outcomes for individual patients and thereby design personalized therapy approaches in future trials.
Ma G, Zhang X, Ma Q, et al.
A novel multivariate scoring system for determining the prognosis of lymph node-negative esophageal squamous cell carcinoma following surgical therapy: an observational study.
Eur J Surg Oncol. 2015; 41(4):541-7 [PubMed] Related Publications
A novel multivariate scoring system for determining the prognosis of lymph node-negative esophageal squamous cell carcinoma following surgical therapy: an observational study.
Eur J Surg Oncol. 2015; 41(4):541-7 [PubMed] Related Publications
BACKGROUND: Identifying patients with esophageal squamous cell carcinoma (ESCC) with negative prognostic factors, which have an extremely low survival rate, has been problematic.
METHODS: We retrospectively collected clinical data for 648 patients with lymph node-negative ESCC who were treated at the Sun Yat-Sen University Cancer Center from 1990 to 2005. Survival difference was compared using Kaplan-Meier analysis and multivariate Cox regression analysis.
RESULTS: We identified advancing age, smoking history, alcohol consumption history, decreased forced expiratory volume in 1 s (FEV1), surgical procedure, tumor location, number of resected lymph nodes, poor tumor differentiation, and surgical stage as independent prognostic risk factors. Furthermore, based on the results of multivariate analysis, we constructed a novel scoring system that included the factors of age, smoking history, alcohol consumption history, number of resected lymph nodes, tumor differentiation, and surgical stage. Risk score (RS) was computed with the scoring system, and patients were divided into Class A (RS: 0-5) and Class B (RS: 6-10). P < 0.001 indicated statistical significance. A significant difference (p < 0.001) demonstrated that Class B was strongly related to a low survival rate and poor prognosis.
CONCLUSION: We developed a new simple flexible scoring system of high prognostic significance, which has the potential to guide postoperative therapeutic strategies and follow-up frequency and to provide better prognostic information for patients and their families.
METHODS: We retrospectively collected clinical data for 648 patients with lymph node-negative ESCC who were treated at the Sun Yat-Sen University Cancer Center from 1990 to 2005. Survival difference was compared using Kaplan-Meier analysis and multivariate Cox regression analysis.
RESULTS: We identified advancing age, smoking history, alcohol consumption history, decreased forced expiratory volume in 1 s (FEV1), surgical procedure, tumor location, number of resected lymph nodes, poor tumor differentiation, and surgical stage as independent prognostic risk factors. Furthermore, based on the results of multivariate analysis, we constructed a novel scoring system that included the factors of age, smoking history, alcohol consumption history, number of resected lymph nodes, tumor differentiation, and surgical stage. Risk score (RS) was computed with the scoring system, and patients were divided into Class A (RS: 0-5) and Class B (RS: 6-10). P < 0.001 indicated statistical significance. A significant difference (p < 0.001) demonstrated that Class B was strongly related to a low survival rate and poor prognosis.
CONCLUSION: We developed a new simple flexible scoring system of high prognostic significance, which has the potential to guide postoperative therapeutic strategies and follow-up frequency and to provide better prognostic information for patients and their families.
Related: Cancer of the Esophagus Esophageal Cancer
Cancer of the Esophagus Esophageal Cancer
Wheeler SE, Egloff AM, Wang L, et al.
Challenges in EGFRvIII detection in head and neck squamous cell carcinoma.
PLoS One. 2015; 10(2):e0117781 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
Challenges in EGFRvIII detection in head and neck squamous cell carcinoma.
PLoS One. 2015; 10(2):e0117781 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) accounts for more than 5% of all cancers worldwide. The mortality rate of HNSCC has remained unchanged (approximately 50%) over the last few decades. Ubiquitous overexpression of wild type EGFR in many solid tumors has led to the development of EGFR targeted therapies. EGFR can be constitutively activated via several mechanisms including the truncated, EGFR variant III isoform (EGFRvIII). EGFRvIII lacks exons 2-7 and has been reported to be present in up to 20-40% of HNSCC. EGFRvIII has been shown to contribute to cetuximab resistance. The mechanisms leading to EGFRvIII expression in HNSCC are unknown. The present investigation was undertaken to determine the etiology of EGFRvIII in HNSCC.
MATERIALS AND METHODS: Fixed HNSCC and glioma tissues were analyzed by fluorescence in situ hybridization for EGFR amplification. DNA and RNA from fresh frozen specimens were used to determine the presence of EGFRvIII transcripts and the mechanisms of expression via PCR, RT-PCR and RNA sequencing.
RESULTS: Unlike glioma, EGFRvIII expression in HNSCC did not correlate with EGFR amplification. We found evidence of genomic deletion of the exon 2-7 in 6 of 7 HNSCC cases examined, however, the presence of genomic deletion did not always result in mRNA expression of EGFRvIII. RNA sequencing with automated alignment did not identify EGFRvIII due to microhomology between intron 1 and exon 8. RNA sequencing analyzed by manual alignment methods did not correlate well with RT-PCR and PCR findings.
CONCLUSION: These findings suggest that genomic deletion as well as additional regulatory mechanisms may contribute to EGFRvIII expression in HNSCC. Further, large scale automated alignment of sequencing are unlikely to identify EGFRvIII and an assay specifically designed to detect EGFRvIII may be necessary to detect this altered form of EGFR in HNSCC tumors.
MATERIALS AND METHODS: Fixed HNSCC and glioma tissues were analyzed by fluorescence in situ hybridization for EGFR amplification. DNA and RNA from fresh frozen specimens were used to determine the presence of EGFRvIII transcripts and the mechanisms of expression via PCR, RT-PCR and RNA sequencing.
RESULTS: Unlike glioma, EGFRvIII expression in HNSCC did not correlate with EGFR amplification. We found evidence of genomic deletion of the exon 2-7 in 6 of 7 HNSCC cases examined, however, the presence of genomic deletion did not always result in mRNA expression of EGFRvIII. RNA sequencing with automated alignment did not identify EGFRvIII due to microhomology between intron 1 and exon 8. RNA sequencing analyzed by manual alignment methods did not correlate well with RT-PCR and PCR findings.
CONCLUSION: These findings suggest that genomic deletion as well as additional regulatory mechanisms may contribute to EGFRvIII expression in HNSCC. Further, large scale automated alignment of sequencing are unlikely to identify EGFRvIII and an assay specifically designed to detect EGFRvIII may be necessary to detect this altered form of EGFR in HNSCC tumors.
Li B, Xiang J, Zhang Y, et al.
Comparison of Ivor-Lewis vs Sweet esophagectomy for esophageal squamous cell carcinoma: a randomized clinical trial.
JAMA Surg. 2015; 150(4):292-8 [PubMed] Related Publications
Comparison of Ivor-Lewis vs Sweet esophagectomy for esophageal squamous cell carcinoma: a randomized clinical trial.
JAMA Surg. 2015; 150(4):292-8 [PubMed] Related Publications
IMPORTANCE: Sweet esophagectomy is performed widely in China, while the Ivor-Lewis procedure, with potential benefit of an extended lymphadenectomy, is limitedly conducted owing to concern for a higher risk for morbidity. Thus, the role of the Ivor-Lewis procedure for thoracic esophageal cancer needs further investigation.
OBJECTIVE: To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower third of the thoracic esophagus. Intent-to-treat analysis was performed.
INTERVENTIONS: Patients were randomly assigned to receive either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy.
MAIN OUTCOMES AND MEASURES: The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge.
RESULTS: Resection without macroscopical residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no significant difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]) (P = .04). More patients in the Sweet group (8 of 150 [5.3%]) received reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) (P = .04). The median hospital stay was 18 days in the Sweet group vs 16 days in the Ivor-Lewis group (P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively (P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs 18, P < .001).
CONCLUSIONS AND RELEVANCE: Early results of this study demonstrate that the Ivor-Lewis procedure can be performed with lower rates of postoperative complications and more lymph node retrieval. Ivor-Lewis and Sweet esophagectomies are both safe procedures with low operative mortalities.
TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01047111.
OBJECTIVE: To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower third of the thoracic esophagus. Intent-to-treat analysis was performed.
INTERVENTIONS: Patients were randomly assigned to receive either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy.
MAIN OUTCOMES AND MEASURES: The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge.
RESULTS: Resection without macroscopical residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no significant difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]) (P = .04). More patients in the Sweet group (8 of 150 [5.3%]) received reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) (P = .04). The median hospital stay was 18 days in the Sweet group vs 16 days in the Ivor-Lewis group (P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively (P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs 18, P < .001).
CONCLUSIONS AND RELEVANCE: Early results of this study demonstrate that the Ivor-Lewis procedure can be performed with lower rates of postoperative complications and more lymph node retrieval. Ivor-Lewis and Sweet esophagectomies are both safe procedures with low operative mortalities.
TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01047111.
Related: Cancer of the Esophagus Esophageal Cancer
Cancer of the Esophagus Esophageal Cancer
Kataoka K, Tsushima T, Mizusawa J, et al.
A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).
Jpn J Clin Oncol. 2015; 45(5):494-8 [PubMed] Related Publications
A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).
Jpn J Clin Oncol. 2015; 45(5):494-8 [PubMed] Related Publications
Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm).
Deeken JF, Wang H, Subramaniam D, et al.
A phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies.
Cancer. 2015; 121(10):1645-53 [PubMed] Article available free on PMC after 15/05/2016 Related Publications
A phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies.
Cancer. 2015; 121(10):1645-53 [PubMed] Article available free on PMC after 15/05/2016 Related Publications
BACKGROUND: Acquired resistance to antiepidermal growth factor receptor (anti-EGFR) therapy may be caused by EGFR-v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ErbB2) heterodimerization and pathway reactivation. In preclinical studies, inhibiting ErbB2 blocked this resistance mechanism and resensitized cells to anti-EGFR therapy. Cetuximab targets EGFR, whereas lapatinib inhibits both EGFR and ErbB2. The objective of this phase 1 trial was to assess the safety, dose-limiting toxicities (DLTs), and maximum tolerated doses (MTDs) of cetuximab and lapatinib in patients with solid tumors.
METHODS: Patients received standard weekly cetuximab with escalating lapatinib doses of 750 mg, 1000 mg, or 1250 mg daily in 3-week cycles. DLTs were monitored through the end of cycle 2. Pretreatment and post-treatment tumor biopsies and germline DNA samples were obtained for correlative studies.
RESULTS: Twenty-two patients were enrolled, and 18 patients each were evaluable for toxicity and response. Fifty-nine percent of patients had received prior anti-EGFR therapy. Common toxicities included rash and diarrhea. No patient experienced a DLT at the highest dose level, and no grade 4 toxicity was observed. Response included no complete responses, 3 partial responses, 9 patients with stable disease, and 6 patients with disease progression, for an overall response rate of 17% and a clinical benefit rate of 67%. The clinical benefit rate in patients who had previously received anti-EGFR therapy was 70%. The mean treatment duration was 4.7 cycles (range, 1-14 cycles). Decreased expression of EGFR/ErbB2 pathway components after treatment was correlated with response, whereas increased expression in the PI3K, Jak/Stat, and MAPK pathways occurred in nonresponders.
CONCLUSIONS: The combination of cetuximab and lapatinib was well tolerated, had the expected toxicities, and exhibited notable clinical activity, including in patients who had received previous anti-EGFR therapy. Further clinical study of this combination is warranted.
METHODS: Patients received standard weekly cetuximab with escalating lapatinib doses of 750 mg, 1000 mg, or 1250 mg daily in 3-week cycles. DLTs were monitored through the end of cycle 2. Pretreatment and post-treatment tumor biopsies and germline DNA samples were obtained for correlative studies.
RESULTS: Twenty-two patients were enrolled, and 18 patients each were evaluable for toxicity and response. Fifty-nine percent of patients had received prior anti-EGFR therapy. Common toxicities included rash and diarrhea. No patient experienced a DLT at the highest dose level, and no grade 4 toxicity was observed. Response included no complete responses, 3 partial responses, 9 patients with stable disease, and 6 patients with disease progression, for an overall response rate of 17% and a clinical benefit rate of 67%. The clinical benefit rate in patients who had previously received anti-EGFR therapy was 70%. The mean treatment duration was 4.7 cycles (range, 1-14 cycles). Decreased expression of EGFR/ErbB2 pathway components after treatment was correlated with response, whereas increased expression in the PI3K, Jak/Stat, and MAPK pathways occurred in nonresponders.
CONCLUSIONS: The combination of cetuximab and lapatinib was well tolerated, had the expected toxicities, and exhibited notable clinical activity, including in patients who had received previous anti-EGFR therapy. Further clinical study of this combination is warranted.
