Surgery is the main treatment for many types of solid tumour, especially when the cancer has not spread to other parts of the body. This involves surgical removal of all or part of the cancer. Sometimes surgery may be used in conjunction with chemotherapy and/or radiotherapy. The type of operation will depend on the location of the main tumour, its size and other factors.
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Surgical Oncology (specialty)
Overviews - Cancer Surgery (5 links)These resources provide general overviews of surgery for cancer.
Latest Research Publications
Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.
Lancet. 2015; 386(9990):249-57 [PubMed] Related Publications
METHODS: In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2), or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1.18. This trial is registered, number ISRCTN74802813, and is closed to new participants.
FINDINGS: Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22.6 months in the primary-surgery group versus 24.1 months in primary chemotherapy. The HR for death was 0.87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0.98 (95% CI 0.72-1.05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0.0007, and 14 women [6%] vs 1 woman [<1%], p=0.001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0.0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group.
INTERPRETATION: In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.
FUNDING: Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.
Variability in surgical quality in a phase III clinical trial of radical cystectomy in patients with organ-confined, node-negative urothelial carcinoma of the bladder.
J Surg Oncol. 2015; 111(7):923-8 [PubMed] Related Publications
METHODS: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS).
RESULTS: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing.
CONCLUSIONS: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.
Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.
J Natl Cancer Inst. 2015; 107(6):djv064 [PubMed] Related Publications
METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided.
RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses.
CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.
Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.
Lancet Oncol. 2015; 16(3):266-73 [PubMed] Related Publications
METHODS: Between April 16, 2003, and Dec 22, 2009, 1326 women aged 65 years or older with early breast cancer judged low-risk (ie, hormone receptor-positive, axillary node-negative, T1-T2 up to 3 cm at the longest dimension, and clear margins; grade 3 tumour histology or lymphovascular invasion, but not both, were permitted), who had had breast-conserving surgery and were receiving adjuvant endocrine treatment, were recruited into a phase 3 randomised controlled trial at 76 centres in four countries. Eligible patients were randomly assigned to either whole-breast radiotherapy (40-50 Gy in 15-25 fractions) or no radiotherapy by computer-generated permuted block randomisation, stratified by centre, with a block size of four. The primary endpoint was ipsilateral breast tumour recurrence. Follow-up continues and will end at the 10-year anniversary of the last randomised patient. Analyses were done by intention to treat. The trial is registered on ISRCTN.com, number ISRCTN95889329.
FINDINGS: 658 women who had undergone breast-conserving surgery and who were receiving adjuvant endocrine treatment were randomly assigned to receive whole-breast irradiation and 668 were allocated to no further treatment. After median follow-up of 5 years (IQR 3·84-6·05), ipsilateral breast tumour recurrence was 1·3% (95% CI 0·2-2·3; n=5) in women assigned to whole-breast radiotherapy and 4·1% (2·4-5·7; n=26) in those assigned no radiotherapy (p=0·0002). Compared with women allocated to whole-breast radiotherapy, the univariate hazard ratio for ipsilateral breast tumour recurrence in women assigned to no radiotherapy was 5·19 (95% CI 1·99-13·52; p=0·0007). No differences in regional recurrence, distant metastases, contralateral breast cancers, or new breast cancers were noted between groups. 5-year overall survival was 93·9% (95% CI 91·8-96·0) in both groups (p=0·34). 89 women died; eight of 49 patients allocated to no radiotherapy and four of 40 assigned to radiotherapy died from breast cancer.
INTERPRETATION: Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment resulted in a significant but modest reduction in local recurrence for women aged 65 years or older with early breast cancer 5 years after randomisation. However, the 5-year rate of ipsilateral breast tumour recurrence is probably low enough for omission of radiotherapy to be considered for some patients.
FUNDING: Chief Scientist Office (Scottish Government), Breast Cancer Institute (Western General Hospital, Edinburgh).
Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial.
Lancet Oncol. 2015; 16(1):47-56 [PubMed] Related Publications
METHODS: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033.
FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001).
INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years.
FUNDING: Fonds Cancer, Belgium.
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.
Lancet Oncol. 2014; 15(12):1303-10 [PubMed] Free Access to Full Article Related Publications
METHODS: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612.
FINDINGS: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years.
INTERPRETATION: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity.
FUNDING: EORTC Charitable Trust.
Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer.
Ann Surg. 2014; 260(5):807-13; discussion 813-4 [PubMed] Related Publications
BACKGROUND: Standard treatment for potentially curable esophageal cancer is nCRT plus surgery after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged TTS is associated with a higher pCR rate and possibly with better survival.
METHODS: We identified patients treated with nCRT plus surgery for esophageal cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery) varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect of TTS on pCR rate, postoperative complications, and survival was determined with (ordinal) logistic, linear, and Cox regression, respectively.
RESULTS: In total, 325 patients were included. Median TTS was 48 days (p25-p75=40-60). After 45 days, TTS was associated with an increased probability of pCR [odds ratio (OR)=1.35 per additional week of TSS, P=0.0004] and a small increased risk of postoperative complications (OR=1.20, P<0.001). Prolonged TTS had no effect on disease-free and overall survivals (HR=1.00 and HR=1.06 per additional week of TSS, P=0.976 and P=0.139, respectively).
CONCLUSIONS: Prolonged TTS after nCRT increases the probability of pCR and is associated with a slightly increased probability of postoperative complications, without affecting disease-free and overall survivals. We conclude that TTS can be safely prolonged from the usual 4 to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait-and-see strategy after neoadjuvant chemoradiotherapy to be tested.
Impact of secondary cytoreductive surgery on survival in patients with platinum sensitive recurrent ovarian cancer: analysis of the CALYPSO trial.
Gynecol Oncol. 2015; 136(1):18-24 [PubMed] Related Publications
METHODS: Using data from the CALYPSO trial, OS of patients who had SCR was compared to those treated with chemotherapy alone. Multivariate analyses were performed to adjust for prognostic factors. We also tested for an interaction between baseline prognostic groupings and the benefit of surgery.
RESULTS: Of the 975 patients randomised in CALYPSO, 19% had SCR and 80% had chemotherapy alone. OS was longer for the SCR group than for chemotherapy alone (median, 49.9 vs. 29.7 months; adjusted hazard ratio (HR), 0.68; P = 0.004). For patients with SCR, the 3-year OS was 72% for those with no measurable disease, and 28% if residual tumour was larger than 5 cm. Patients with good prognostic features benefited the most from SCR (HR 0.43; P < 0.001). The benefit of SCR was less in patients with poorer prognostic features (test of trend P < 0.001).
CONCLUSION: SCR was associated with improved OS in platinum-sensitive ROC, particularly in patients with favourable prognostic characteristics. However, these findings may be due to selection bias, and hence randomised trials are still essential.
The CAIRO4 study: the role of surgery of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastases of colorectal cancer--a randomized phase III study of the Dutch Colorectal Cancer Group (DCCG).
BMC Cancer. 2014; 14:741 [PubMed] Free Access to Full Article Related Publications
METHODS/DESIGN: The CAIRO4 study is a multicentre, randomized, phase III study of the Dutch Colorectal Cancer Group (DCCG). Patients with synchronous unresectable metastases of CRC and few or absent symptoms of the primary tumour are randomized 1:1 between systemic therapy only, and resection of the primary tumour followed by systemic therapy. Systemic therapy will consist of fluoropyrimidine-based chemotherapy in combination with bevacizumab. The primary objective of this study is to determine the clinical benefit in terms of overall survival of initial resection of the primary tumour. Secondary endpoints include progression free survival, surgical morbidity, quality of life and the number of patients requiring resection of the primary tumour in the control arm.
DISCUSSION: The CAIRO4 study is a multicentre, randomized, phase III study that will assess the benefit of resection of the primary tumour in patients with synchronous metastatic CRC.
TRIAL REGISTRATION: The CAIRO4 study is registered at clinicaltrials.gov (NCT01606098).
A randomized controlled trial comparing laparoscopic surgery with open surgery in palliative resection of primary tumor in incurable Stage IV colorectal cancer: Japan Clinical Oncology Group Study JCOG 1107 (ENCORE trial).
Jpn J Clin Oncol. 2014; 44(11):1123-6 [PubMed] Related Publications
Impact of brachytherapy on local recurrence rates after sublobar resection: results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small-cell lung cancer.
J Clin Oncol. 2014; 32(23):2456-62 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
PATIENTS AND METHODS: High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm.
RESULTS: Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97).
CONCLUSION: Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.
Multicenter randomized controlled trial of conventional versus laparoscopic surgery for colorectal cancer within an enhanced recovery programme: EnROL.
J Clin Oncol. 2014; 32(17):1804-11 [PubMed] Related Publications
PATIENTS AND METHODS: Adults with colorectal cancer suitable for elective resection were randomly assigned at a ratio of 1:1 to laparoscopic or open surgery within an ERP, stratified by center, cancer site (colon v rectum), and age group (<66 v 66-75 v >75 years) using minimization. The primary outcome was physical fatigue at 1 month postsurgery. Secondary outcomes included hospital stay, complications, other patient-reported outcomes (PROs), and physical function. Patients and outcome assessors were blinded until 7 days postsurgery or discharge if earlier. Central independent and blinded pathologic assessment of surgical quality was undertaken.
RESULTS: A total of 204 patients (laparoscopy, n=103; open surgery, n=101) were recruited from 12 UK centers from July 2008 to April 2012. One-month physical fatigue scores were similar in both groups (mean: laparoscopy, 12.28; 95% CI, 11.37 to 13.19 v open surgery, 12.05; 95% CI, 11.14 to 12.96; adjusted mean difference, -0.23; 95% CI, -1.52 to 1.07). Median total hospital stay was significantly shorter after laparoscopic surgery (median: laparoscopy, 5; interquartile range [IQR], 4 to 9 v open surgery, 7; IQR, 5 to 11 days; P=.033). There were no differences in other secondary outcomes or in specimen quality after central pathologic review.
CONCLUSION: In patients treated by experienced surgeons within an ERP, physical fatigue and other PROs were similar in both groups, but laparoscopic surgery significantly reduced length of hospital stay.
Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumours responding to imatinib: a prospective randomised trial in China.
Eur J Cancer. 2014; 50(10):1772-8 [PubMed] Related Publications
METHODS: Between 3 and 12months after starting IM for recurrent/metastatic GISTs, eligible patients were randomised to two arms: Arm A (surgery for residual disease) and Arm B (IM treatment alone). In Arm A (19pts), surgery was performed to remove residual macroscopic lesions as completely as possible, and IM treatment continued after surgery. In Arm B (22pts), IM was given alone at a dose of 400mg per day until disease progression. The primary end-point was PFS measured from the date IM started. This study was registered in the ChiCTR registry with the ID number ChiCTR-TRC-00000244.
RESULTS: This randomised trial was closed early due to poor accrual. Only 41 patients were enrolled as opposed to 210 patients planned. 2-year PFS was 88.4% in the surgery arm and 57.7% in the IM-alone arm (P=0.089). Median overall survival (mOS) was not reached in the surgery arm and 49months in patients with IM-alone arm (P=0.024).
CONCLUSIONS: While no significant differences were observed in the two arms, this study suggests that surgical removal of the metastatic lesion may improve the outcome of advanced GIST patients and should stimulate additional research on this topic.
The impact of obesity on surgical staging, complications, and survival with uterine cancer: a Gynecologic Oncology Group LAP2 ancillary data study.
Gynecol Oncol. 2014; 133(1):23-7 [PubMed] Related Publications
METHODS: An ancillary data analysis of GOG LAP2 was performed. Categorical variables were compared using Pearson chi-square test and continuous variables using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests by BMI group. Survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate independent prognostic factors on survival. Statistical tests were two-tailed with α=0.05, except where noted. Statistical analyses utilized R programming language.
RESULTS: 2596 women were included. BMI (kg/m(2)) groups were <25 (29.5%), 25-30 (28.2%), 30-35 (21%), 35-40 (10.9%), and ≥40 (10.4%). Stage (p=0.021), grade (p<0.001), and histology (p=0.005) differed by BMI. Obese women were less likely to have high risk (HR) disease (+lymph nodes/ovaries/cytology) or tumor features that met GOG99 high intermediate risk (HIR) criteria (p<0.001). Adjuvant therapy (p=0.151) and recurrence (p=0.46) did not vary by BMI. Hospitalization >2days, antibiotic use, wound infection, and venous thrombophlebitis were higher with BMI ≥40. BMI (p=0.016), age (p<0.0001), race (p=0.033), and risk group (p<0.0001) predicted all-cause mortality. BMI was not predictive of disease-specific survival (p=0.79), but age (p=0.032) and risk group (p<0.0001) were significant factors.
CONCLUSION: Obese women have greater surgical risk and lower risk of metastatic disease. BMI is associated with all-cause but not disease-specific mortality, emphasizing the detrimental effect of obesity (independent of EC), which deserves particular attention.
Methylene blue-assisted technique for harvesting lymph nodes after radical surgery for gastric cancer: a prospective randomized phase III study.
BMC Cancer. 2014; 14:155 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
METHODS/DESIGN: Patients that undergo distal or total gastrectomy with radical nodal dissection will be randomly assigned to Group A: the standard group, the lymph nodes (LNs) will be harvested from the fresh specimen immediately after surgery, or Group B: the methylene blue-assisted group, where the LNs will be harvested from specimens fixed with 10% buffered formalin with methylene blue for 48 hours after surgery. The primary endpoint is the ratio of the number of the harvested LNs per time (minute). The secondary endpoint is the number of harvested LNs. A 25% reduction in the ratio of harvested lymph-node/time (minute) was determined to be necessary for this test treatment, considering the balance between the cost and benefit. Retrospective data was used to estimate the ratio of the number of the harvested LNs per time (minute) to be 40/30 minutes in Group A. A 25% risk reduction and a rate of 40/22.5 minutes is expected in Group B. Therefore, the sample size required ensuring a two-sided alpha error of 5% and statistical power of 80% is 52 patients, with 26 patients per arm. The number of patients to be accrued was set at 60 in total, due to the likelihood of enrolling ineligible patients.
TRIAL REGISTRATION: UMIN000008624.
Randomized comparison of surgical stress and the nutritional status between laparoscopy-assisted and open distal gastrectomy for gastric cancer.
Ann Surg Oncol. 2014; 21(6):1983-90 [PubMed] Related Publications
METHODS: This study was performed as an exploratory analysis of a phase III trial comparing LADG and ODG for stage I gastric cancer during the period between May and December of 2011. All patients received the same perioperative care via fast-track surgery. The level of surgical stress was evaluated based on the white blood cell count and the interleukin-6 (IL-6) level. The nutritional status was measured according to the total body weight, amount of lean body mass, lymphocyte count, and prealbumin level.
RESULTS: Twenty-six patients were randomized to receive ODG (13 patients) or LADG (13 patients). The baseline characteristics and surgical outcomes were similar between the two groups. The median IL-6 level increased from 0.8 to 36.3 pg/dl in the ODG group and from 1.5 to 53.3 pg/dl in the LADG group. The median amount of lean body mass decreased from 48.3 to 46.8 kg in the ODG group and from 46.6 to 46.0 kg in the LADG group. There are no significant differences between two groups.
CONCLUSIONS: The level of surgical stress and the nutritional status were found to be similar between the ODG and LADG groups in a randomized comparison using the same perioperative care of fast-track surgery.
Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study.
BMC Cancer. 2014; 14:22 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
METHODS/DESIGN: Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat.
DISCUSSION: Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.
Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.
J Clin Oncol. 2014; 32(6):504-12 [PubMed] Related Publications
PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy.
RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001).
CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.
A randomized controlled trial of the conventional technique versus the no-touch isolation technique for primary tumor resection in patients with colorectal cancer: Japan Clinical Oncology Group Study JCOG1006.
Jpn J Clin Oncol. 2014; 44(1):97-100 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial.
J Clin Oncol. 2013; 31(30):3831-7 [PubMed] Related Publications
PATIENTS AND METHODS: A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat.
RESULTS: After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity.
CONCLUSION: GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
Quality of life of advanced ovarian cancer patients in the randomized phase III study comparing primary debulking surgery versus neo-adjuvant chemotherapy.
Gynecol Oncol. 2013; 131(2):437-44 [PubMed] Related Publications
METHODS: Patients with stages IIIc or IV ovarian cancer completed the EORTC QLQ-C30 before treatment, at the third and sixth cycle of chemotherapy, and at 6- and 12-month follow-up.
RESULTS: Data of 404 patients (N=201 PDS arm; N=203 IDS arm) were included in the QOL analysis. Between treatment arms no statistically significant differences were found in any of the QOL functioning scales. Patients showed a clinically relevant improvement (>10 points) on the global health/QOL, role functioning, emotional functioning and social functioning scales during and after treatment independent of the type of treatment. Clinically relevant differences from baseline to the follow-up assessments were noted for fatigue, pain, insomnia, appetite loss, constipation, diarrhea indicating symptom control in both treatment arms. Institutions with good QOL compliance were associated with better outcomes. There was a statistical significant difference in the overall debulking status with 39.9% optimal debulking surgery in institutions with good QOL compliance compared to 19.9% in institutions with poor QOL compliance (p=0.0011). Overall survival (median 32.30 versus 23.29 months; p=0.0006) and progression free survival (median 12.35 versus 9.92 months; p=0.0002) were also significantly better.
CONCLUSIONS: Survival and QOL after NACT followed by surgery was similar to survival and QOL after PDS followed by chemotherapy. However, institutions with good QOL compliance had better survival outcomes.
Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer.
J Minim Invasive Gynecol. 2014 Jan-Feb; 21(1):3-8 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904.
Eur Urol. 2014; 65(2):372-7 [PubMed] Related Publications
OBJECTIVE: To examine the impact of NSS relative to RN on kidney function in EORTC 30904.
DESIGN, SETTING, AND PARTICIPANTS: This phase 3 international randomized trial was conducted in patients with a small (≤5 cm) renal mass and normal contralateral kidney who were enrolled from March 1992 to January 2003.
INTERVENTION: Patients were randomized to RN (n=273) or NSS (n=268).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up estimated glomerular filtration rates (eGFR; milliliters per minute per 1.73 m(2)) were recorded for 259 subjects in the RN arm and 255 subjects in the NSS arm. Percentages of subjects developing at least moderate renal dysfunction (eGFR <60), advanced kidney disease (eGFR <30), or kidney failure (eGFR <15) were calculated for each treatment arm based on the lowest recorded follow-up eGFR (intent-to-treat analysis).
RESULTS AND LIMITATIONS: With a median follow-up of 6.7 yr, eGFR <60 was reached by 85.7% with RN and 64.7% with NSS, with a difference of 21.0% (95% CI, 13.8-28.3); eGFR <30 was reached by 10.0% with RN and 6.3% with NSS, with a difference of 3.7% (95% CI, -1.0 to 8.5); and eGFR <15 was reached by 1.5% with RN and 1.6% with NSS, with a difference of -0.1% (95% CI, -2.2 to 2.1). Lack of longer follow-up for eGFR is a limitation of these analyses.
CONCLUSIONS: Compared with RN, NSS substantially reduced the incidence of at least moderate renal dysfunction (eGFR <60), although with available follow-up the incidence of advanced kidney disease (eGFR <30) was relatively similar in the two treatment arms, and the incidence of kidney failure (eGFR <15) was nearly identical. The beneficial impact of NSS on eGFR did not result in improved survival in this study population.
REGISTRATION: EORTC trial 30904; ClinicalTrials.gov identifier NCT00002473.
Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas - PRODIGE 19 - FFCD1103 - ADCI002.
BMC Cancer. 2013; 13:281 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
METHODS/DESIGN: PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner.
DISCUSSION: As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard perioperative chemotherapeutic strategy. This randomised phase II/III trial is the first dedicated to this histological subtype. Whilst the development of new biomarkers and targeted therapies are awaited, the results of this trial should further help in devising individualised protocols of patient care in a tumour group whose diversity increasingly demands assessment of alternative strategies.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT01717924.
Current use and surgical efficacy of laparoscopic colectomy in colon cancer.
J Am Coll Surg. 2013; 217(1):56-62; discussion 62-3 [PubMed] Related Publications
STUDY DESIGN: Surgical data were reviewed for all patients randomized into a national phase III clinical trial for adjuvant therapy in stage III CC (North Central Cancer Treatment Group trial N0147). Colon resections were grouped as open (traditional laparotomy) or laparoscopic, including laparoscopic; laparoscopic assisted; hand assisted; and laparoscopic converted to OC. Statistical methods included nonparametric methods, categorical analysis, and logistic regression modeling.
RESULTS: A total of 3,393 evaluable patients were accrued between 2004 and 2009; 53% were male, median age was 58 years, 86% were white, and 70% had a body mass index >25 kg/m(2). Two thousand one hundred thirteen (62%) underwent OC. One thousand two hundred eighty (38%) were initiated as laparoscopic procedures, 25% (n = 322) were laparoscopic, 32% (n = 410) were laparoscopic assisted, 26% (n = 339) were hand assisted, and 16% (n = 209) were LC converted to OC. Significant predictors of LC (vs OC) in multivariate models were T stage (T1 or T2 vs T3 or T4; p = 0.0286), and absence of perforation, bowel obstruction, or adherence to surrounding organs (p < 0.01 each). Increasing rates of LC were observed over time, with LC eclipsing OC in 2009 (p < 0.0001). Surgical efficacy, measured by lymph node retrieval, was similar, with the mean number of lymph nodes retrieved higher in the LC group (20.6 vs 19.5 nodes; p = 0.0006).
CONCLUSIONS: This study demonstrated a steadily increasing use of LC for the surgical treatment of CC between 2004 and 2009, with LC preferred by study completion. Surgical efficacy was similar in stage III CC patients.
Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial.
Ann Oncol. 2013; 24(8):1980-5 [PubMed] Related Publications
PATIENTS AND METHODS: In NeoALTTO, patients with HER2-positive breast cancer were randomly assigned to either trastuzumab, lapatinib or their combination with paclitaxel before surgery with pCR as the primary end point. We investigated the association between the surgery type and clinicopathological factors and response to treatment, adjusting for the treatment arm.
RESULTS: Four hundred and twenty-nine patients were subjected to breast surgery. Two hundred and forty-two (56%) and 187 (44%) patients underwent mastectomy and BCS, respectively. In a logistic regression model, negative estrogen receptor (ER), multicentricity and the presence of a palpable mass before surgery were significantly associated with a low chance of BCS. Conversely, patients with small tumors and those eligible for BCS at diagnosis were managed more with BCS, independent of the treatment arm. Radiological response was not associated with the surgical decision.
CONCLUSIONS: Tumor characteristics before neoadjuvant therapy play a main role in deciding the type of surgery calling for a clear consensus on the role of BCS in patients responding to neoadjuvant therapy.
Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial.
Lancet Oncol. 2013; 14(3):210-8 [PubMed] Related Publications
METHODS: A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries. Patients (aged ≥18 years) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, stratified by centre, location of tumour, and preoperative radiotherapy. The study was not masked. Secondary (short-term) outcomes-including operative findings, complications, mortality, and results at pathological examination-are reported here. Analysis was by modified intention to treat, excluding those patients with post-randomisation exclusion criteria and for whom data were not available. This study is registered with ClinicalTrials.gov, number NCT00297791.
FINDINGS: The study was undertaken between Jan 20, 2004, and May 4, 2010. 1103 patients were randomly assigned to the laparoscopic (n=739) and open surgery groups (n=364), and 1044 were eligible for analyses (699 and 345, respectively). Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group (median 200 mL [IQR 100-400] vs 400 mL [200-700], p<0·0001); however, laparoscopic procedures took longer (240 min [184-300] vs 188 min [150-240]; p<0·0001). In the laparoscopic surgery group, bowel function returned sooner (2·0 days [1·0-3·0] vs 3·0 days [2·0-4·0]; p<0·0001) and hospital stay was shorter (8·0 days [6·0-13·0] vs 9·0 days [7·0-14·0]; p=0·036). Macroscopically, completeness of the resection was not different between groups (589 [88%] of 666 vs 303 [92%] of 331; p=0·250). Positive circumferential resection margin (<2 mm) was noted in 56 (10%) of 588 patients in the laparoscopic surgery group and 30 (10%) of 300 in the open surgery group (p=0·850). Median tumour distance to distal resection margin did not differ significantly between the groups (3·0 cm [IQR 2·0-4·8] vs 3·0 cm [1·8-5·0], respectively; p=0·676). In the laparoscopic and open surgery groups, morbidity (278 [40%] of 697 vs 128 [37%] of 345, respectively; p=0·424) and mortality (eight [1%] of 699 vs six [2%] of 345, respectively; p=0·409) within 28 days after surgery were similar.
INTERPRETATION: In selected patients with rectal cancer treated by skilled surgeons, laparoscopic surgery resulted in similar safety, resection margins, and completeness of resection to that of open surgery, and recovery was improved after laparoscopic surgery. Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013.
FUNDING: Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region, Sahlgrenska University Hospital.
The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011).
Trials. 2012; 13:228 [PubMed] Article available free on PMC after 10/08/2015 Related Publications
METHODS: The qualitative study used a 'Framework Analysis' that included 'constant comparison' in which semi-structured interviews are transcribed, analyzed, compared and contrasted both between and within transcripts. Three researchers coded and interpreted data.
RESULTS: Twenty-four patients agreed to enter the interview study; 10 decliners of randomization and 14 accepters, of whom 2 subsequently declined their allocated treatment.The main theme applying to the majority of the sample was confusion and ambiguity. There was little indication that confusion directly impacted on decisions to enter the SPARE trial. However, confusion did appear to impact on ethical considerations surrounding 'informed consent', as well as cause a sense of alienation between patients and health personnel.Sub-optimal communication in many guises accounted for the confusion, together with the logistical elements of a trial that involved treatment options delivered in a number of geographical locations.
CONCLUSIONS: These data highlight the difficulty of providing balanced and clear trial information within the UK health system, despite best intentions. Involvement of multiple professionals can impact on communication processes with patients who are considering participation in RCTs. Our results led us to question the 'deficit' model of patient behavior. It is suggested that health professionals might consider facilitating a context in which patients feel fully included in the trial enterprise and potentially consider alternatives to randomization where complex interventions are being tested.
TRIAL REGISTRATION: ISRCTN61126465.
Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma.
J Clin Oncol. 2013; 31(6):744-51 [PubMed] Related Publications
PATIENTS AND METHODS: A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety.
RESULTS: Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control.
CONCLUSION: Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.
Accelerated partial breast irradiation: a review and description of an early North American surgical experience with the intrabeam delivery system.
Cancer Control. 2012; 19(4):295-308 [PubMed] Related Publications
METHODS: Prospectively gathered estrogen receptor-positive, clinically node-negative patients with invasive breast cancer < 3 cm receiving IORT using the Intrabeam system were reviewed. IORT-related effects and early postoperative outcome were assessed. A literature review was also performed.
RESULTS: Forty-two patients (median age 71 years) underwent lumpectomy, sentinel lymph node (SLN) biopsy, and concurrent IORT from January 2011 to July 2011. Ninety-one percent of patients had invasive ductal histology with a median tumor size of 1.0 cm. This review highlights the patient selection criteria, describes commercially available accelerated partial breast irradiation (APBI) treatment options, and discusses outcomes for the variety of APBI techniques currently utilized in clinical practice as well as an institutional review of our early surgical experience using the Intrabeam radiotherapy delivery system.
CONCLUSIONS: While a variety of APBI techniques are currently available for clinical use, our early North American operative experience with IORT shows it is well tolerated with low morbidity. Delivery of IORT adds moderate operative time and may require creating subcutaneous tissue fl aps. The addition of WBI may be necessary in situations for positive residual margins or microscopic nodal disease in patients who do not undergo additional surgery.