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North East and Cumbria

Cancer Organisations and Resources
Cancer News from the North East
Latest Research Publications from the North East

Cancer Organisations and Resources (17 links)


Cancer News from the North East (2 links)

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    Latest Research Publications from the North East

    Rice TW, Chen LQ, Hofstetter WL, et al.
    Worldwide Esophageal Cancer Collaboration: pathologic staging data.
    Dis Esophagus. 2016; 29(7):724-733 [PubMed] Related Publications
    We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

    Ravaud A, Motzer RJ, Pandha HS, et al.
    Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.
    N Engl J Med. 2016; 375(23):2246-2254 [PubMed] Related Publications
    Background Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. Methods In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. Results The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Conclusions Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).

    Donovan JL, Hamdy FC, Lane JA, et al.
    Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.
    N Engl J Med. 2016; 375(15):1425-1437 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
    Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

    Churg A, Attanoos R, Borczuk AC, et al.
    Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum: Recommendations From the International Collaboration on Cancer Reporting (ICCR).
    Arch Pathol Lab Med. 2016; 140(10):1104-10 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
    CONTEXT: -The International Collaboration on Cancer Reporting is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom; the College of American Pathologists; the Canadian Association of Pathologists-Association Canadienne des Pathologists, in association with the Canadian Partnership Against Cancer; and the European Society of Pathology. Its goal is to produce common, internationally agreed upon, evidence-based datasets for use throughout the world.
    OBJECTIVE: -To describe a dataset developed by the Expert Panel of the International Collaboration on Cancer Reporting for reporting malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of "required" (mandatory) and "recommended" (nonmandatory) elements.
    DESIGN: -Based on a review of the most recent evidence and supported by explanatory commentary.
    RESULTS: -Eight required elements and 7 recommended elements were agreed upon by the Expert Panel to represent the essential information for reporting malignant mesothelioma of the pleura and peritoneum.
    CONCLUSIONS: -In time, the widespread use of an internationally agreed upon, structured, pathology dataset for mesothelioma will lead not only to improved patient management but also provide valuable data for research and international benchmarks.

    Mehanna H, Wong WL, McConkey CC, et al.
    PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer.
    N Engl J Med. 2016; 374(15):1444-54 [PubMed] Related Publications
    BACKGROUND: The role of image-guided surveillance as compared with planned neck dissection in the treatment of patients with squamous-cell carcinoma of the head and neck who have advanced nodal disease (stage N2 or N3) and who have received chemoradiotherapy for primary treatment is a matter of debate.
    METHODS: In this prospective, randomized, controlled trial, we assessed the noninferiority of positron-emission tomography-computed tomography (PET-CT)-guided surveillance (performed 12 weeks after the end of chemoradiotherapy, with neck dissection performed only if PET-CT showed an incomplete or equivocal response) to planned neck dissection in patients with stage N2 or N3 disease. The primary end point was overall survival.
    RESULTS: From 2007 through 2012, we recruited 564 patients (282 patients in the planned-surgery group and 282 patients in the surveillance group) from 37 centers in the United Kingdom. Among these patients, 17% had nodal stage N2a disease and 61% had stage N2b disease. A total of 84% of the patients had oropharyngeal cancer, and 75% had tumor specimens that stained positive for the p16 protein, an indicator that human papillomavirus had a role in the causation of the cancer. The median follow-up was 36 months. PET-CT-guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 vs. 221); rates of surgical complications were similar in the two groups (42% and 38%, respectively). The 2-year overall survival rate was 84.9% (95% confidence interval [CI], 80.7 to 89.1) in the surveillance group and 81.5% (95% CI, 76.9 to 86.3) in the planned-surgery group. The hazard ratio for death slightly favored PET-CT-guided surveillance and indicated noninferiority (upper boundary of the 95% CI for the hazard ratio, <1.50; P=0.004). There was no significant difference between the groups with respect to p16 expression. Quality of life was similar in the two groups. PET-CT-guided surveillance, as compared with neck dissection, resulted in savings of £1,492 (approximately $2,190 in U.S. dollars) per person over the duration of the trial.
    CONCLUSIONS: Survival was similar among patients who underwent PET-CT-guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective. (Funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK; PET-NECK Current Controlled Trials number, ISRCTN13735240.).

    Golabek T, Bukowczan J, Szopinski T, et al.
    Obesity and renal cancer incidence and mortality--a systematic review of prospective cohort studies.
    Ann Agric Environ Med. 2016; 23(1):37-43 [PubMed] Related Publications
    INTRODUCTION AND OBJECTIVE: There have been many studies published recently on obesity and the risk of renal cancer; however, the epidemiological evidence for such an association has not been consistent. Therefore, a systematic review was conducted of the prospective cohort studies to assess the association between obesity and the risk of renal cancer incidence and death.
    MATERIALS AND METHODS: A search was conducted of the PubMed database and references to published studies from inception until May 2013. Guidelines for Assessing Quality in Prognostic Studies on the Basis of Framework for Potential Biases were followed for quality assessment of studies included in the systematic review.
    RESULTS: Twenty eligible studies were identified and included in the systematic review. Among the 20 selected studies, overall study quality was high. Although the evidence from the prospective cohort studies, linking obesity with renal cancer incidence, has not been entirely consistent, there is a convincing body of data for a positive relationship. Moreover, cumulative data is compelling for a strong positive association between obesity and fatal renal cancer.
    CONCLUSIONS: There is a relatively consistent amount of evidence that obesity increases the risk of renal cancer and fatal renal cancer. Further research is needed as better understanding of mechanisms by which obesity may influence renal cancer development and progression will aid the fostering of strategies for prevention and treatment of one of the most lethal human malignancies.

    Molloy S, Sewell MD, Platinum J, et al.
    Is balloon kyphoplasty safe and effective for cancer-related vertebral compression fractures with posterior vertebral body wall defects?
    J Surg Oncol. 2016; 113(7):835-42 [PubMed] Related Publications
    BACKGROUND AND OBJECTIVES: Balloon kyphoplasty (BKP) is a percutaneous treatment for cancer-related vertebral compression fractures (VCF). Posterior vertebral body wall (PVBW) involvement is considered a contraindication for BKP. This study assesses whether BKP is safe and effective for cancer-related VCFs involving the PVBW.
    METHODS: This study analyzed data on 158 patients with 228 cancer-related VCFs who underwent BKP. One hundred and twelve patients had VCFs with PVBW defects, and 46 had VCFs with no PVBW defect. Outcomes were assessed preoperatively and at 3 months.
    RESULTS: In the PVBW defect group, mean pain score decreased from 7.5 to 3.6 (P < 0.001), EQ5D increased from 0.39 to 0.48 and Oswestry Disability Index (ODI) decreased from 50 to 42. Cement leaks occurred in 31%. In the PVBW intact group, mean pain decreased from 7.3 to 3.3 (P < 0.001), EQ5D increased from 0.35 to 0.48 (P < 0.001), and ODI decreased from 53 to 50. Cement leaks occurred in 20%. No significant difference was observed in functional improvements between groups. Radiographically kyphotic angle and anterior and middle vertebral body heights were significantly worse in the PVBW defect group (P < 0.05).
    CONCLUSIONS: BKP can alleviate pain and improve QoL and function in patients with cancer-related VCFs with PVBW defects with no appreciable increase in risk. J. Surg. Oncol. 2016;113:835-842. © 2016 Wiley Periodicals, Inc.

    Usset JL, Raghavan R, Tyrer JP, et al.
    Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors.
    Cancer Epidemiol Biomarkers Prev. 2016; 25(5):780-90 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
    BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women.
    METHODS: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed.
    RESULTS: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10(-6)).
    CONCLUSIONS: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2 Future work is needed to develop powerful statistical methods able to detect these complex interactions.
    IMPACT: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780-90. ©2016 AACR.

    Amirian ES, Zhou R, Wrensch MR, et al.
    Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.
    Cancer Epidemiol Biomarkers Prev. 2016; 25(2):282-90 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
    BACKGROUND: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk.
    METHODS: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema.
    RESULTS: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma.
    CONCLUSION: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental.
    IMPACT: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention.

    Kotsopoulos IC, Kucukmetin A, Mukhopadhyay A, et al.
    Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors.
    Int J Gynecol Cancer. 2016; 26(4):763-9 [PubMed] Related Publications
    Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited-largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas.

    Chaddad A, Desrosiers C, Bouridane A, et al.
    Multi Texture Analysis of Colorectal Cancer Continuum Using Multispectral Imagery.
    PLoS One. 2016; 11(2):e0149893 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
    PURPOSE: This paper proposes to characterize the continuum of colorectal cancer (CRC) using multiple texture features extracted from multispectral optical microscopy images. Three types of pathological tissues (PT) are considered: benign hyperplasia, intraepithelial neoplasia and carcinoma.
    MATERIALS AND METHODS: In the proposed approach, the region of interest containing PT is first extracted from multispectral images using active contour segmentation. This region is then encoded using texture features based on the Laplacian-of-Gaussian (LoG) filter, discrete wavelets (DW) and gray level co-occurrence matrices (GLCM). To assess the significance of textural differences between PT types, a statistical analysis based on the Kruskal-Wallis test is performed. The usefulness of texture features is then evaluated quantitatively in terms of their ability to predict PT types using various classifier models.
    RESULTS: Preliminary results show significant texture differences between PT types, for all texture features (p-value < 0.01). Individually, GLCM texture features outperform LoG and DW features in terms of PT type prediction. However, a higher performance can be achieved by combining all texture features, resulting in a mean classification accuracy of 98.92%, sensitivity of 98.12%, and specificity of 99.67%.
    CONCLUSIONS: These results demonstrate the efficiency and effectiveness of combining multiple texture features for characterizing the continuum of CRC and discriminating between pathological tissues in multispectral images.

    Williams MT, Yousafzai YM, Elder A, et al.
    The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukemia blasts.
    Blood. 2016; 127(16):1998-2006 [PubMed] Related Publications
    Prevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.Cg- ITALIC! Prkdc (ITALIC! scid) ITALIC! Il2rg (ITALIC! tm1Wjl)/SzJ mice. CNS engraftment was seen in 23 of 29 diagnostic samples (79%): 2 of 2 from patients with overt CNS disease and 21 of 27 from patients thought to be CNS negative by diagnostic lumbar puncture. Histologic findings mimic human pathology and demonstrate that leukemic cells transit the blood-cerebrospinal fluid barrier situated close to the dural sinuses, the site of recently discovered CNS lymphatics. Retrieval of blasts from the CNS showed no evidence for chemokine receptor-mediated selective trafficking. The high frequency of infiltration and lack of selective trafficking led us to postulate that CNS tropism is a generic property of leukemic cells. To test this, we performed serial dilution experiments which showed CNS engraftment in 5 of 6 mice after transplant of as few as 10 leukemic cells. Clonal tracking techniques confirmed the polyclonal nature of CNS-infiltrating cells, with multiple clones engrafting in both the CNS and periphery. Overall, these findings suggest that subclinical seeding of the CNS is likely to be present in most BCP-ALL patients at original diagnosis, and efforts to prevent CNS relapse should concentrate on effective eradication of disease from this site rather than targeting entry mechanisms.

    Præstegaard C, Kjaer SK, Nielsen TS, et al.
    The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies.
    Cancer Epidemiol. 2016; 41:71-9 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated.
    METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model.
    RESULTS: Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking.
    CONCLUSION: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.

    Ghanouni A, Plumb A, Hewitson P, et al.
    Patients' experience of colonoscopy in the English Bowel Cancer Screening Programme.
    Endoscopy. 2016; 48(3):232-40 [PubMed] Related Publications
    BACKGROUND AND STUDY AIMS: Understanding patients' experience of screening programs is crucial for service improvement. The English Bowel Cancer Screening Programme (BCSP) aims to achieve this by sending out questionnaires to all patients who undergo a colonoscopy following an abnormal fecal occult blood test result. This study used the questionnaire data to report the experiences of these patients.
    PATIENTS AND METHODS: Data on patients who underwent colonoscopy between 2011 and 2012 were extracted from the BCSP database. Descriptive statistics were used to summarize key questionnaire items relating to informed choice, psychological wellbeing, physical experience, and after-effects. Multilevel logistic regression was used to test for associations with variables of interest: sex, age, socioeconomic status, colonoscopy results, and screening center performance (adenoma detection rate, cecal intubation rate, proportion of colonoscopies involving sedation).
    RESULTS: Data from 50,858 patients (79.3 % of those eligible) were analyzed. A majority reported a positive experience on items relating to informed choice (e. g. 95.7 % felt they understood the risks) and psychological wellbeing (e. g. 98.3 % felt they were treated with respect). However, an appreciable proportion experienced unexpected test discomfort (21.0 %) or pain at home (14.8 %). There were few notable demographic differences, although women were more likely than men to experience unexpected discomfort (25.1 % vs. 18.0 %; P < 0.01) and pain at home (18.2 % vs. 12.3 %; P < 0.01). No associations with center-level variables were apparent.
    CONCLUSIONS: Colonoscopy experience was generally positive, suggesting high satisfaction with the BCSP. Reported pain and unexpected discomfort were more negative than most other outcomes (particularly for women); measures to improve this should be considered.

    Cosway B, Lovat P
    The role of autophagy in squamous cell carcinoma of the head and neck.
    Oral Oncol. 2016; 54:1-6 [PubMed] Related Publications
    Half a million new head and neck cancers are diagnosed each year worldwide. Although traditionally thought to be triggered by alcohol and smoking abuse, there is a growing subset of oropharyngeal cancers driven by the oncogenic human papilloma virus (HPV). Despite advances in both surgical and non-surgical treatment strategies, survival rates have remained relatively static emphasising the need for novel therapeutic approaches. Autophagy, the principal catabolic process for the lysosomal--mediated breakdown of cellular products is a hot topic in cancer medicine. Increasing evidence points towards the prognostic significance of autophagy biomarkers in solid tumours as well as strategies through which to harness autophagy modulation to promote tumour cell death. However, the role of autophagy in head and neck cancers is less well defined. In the present review, we summarise the current understanding of autophagy in head and neck cancers, revealing key areas for future translational research.

    Veal GJ, Cole M, Chinnaswamy G, et al.
    Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma.
    Eur J Cancer. 2016; 55:56-64 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    INTRODUCTION: Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology.
    METHODS: A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤ 18 years receiving cyclophosphamide (250 mg/m(2)), were used to characterise a population pharmacokinetic model. Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed.
    RESULTS: A two-compartment model provided the best fit of the population analysis. The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 (1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m(2), respectively; mean ± standard deviation from empirical Bayes estimates; P < 0.001). The presence of at least one CYP2B6*6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 (1.54 ± 0.11 L/h/m(2) versus 2.20 ± 0.31 L/h/m(2), P = 0.033) and dose 5 (3.12 ± 0.17 L/h/m(2) versus 4.35 ± 0.37 L/h/m(2), P = 0.0028), as compared to homozygous wild-type patients. No pharmacokinetic parameters investigated were shown to have a significant influence on progression free survival.
    CONCLUSION: The results do not support previous findings of a link between cyclophosphamide pharmacokinetics or metabolism and disease recurrence in childhood B-cell NHL. While CYP2B6 genotype was shown to influence pharmacokinetics, there was no clear impact on clinical outcome.

    Winham SJ, Pirie A, Chen YA, et al.
    Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer.
    Cancer Epidemiol Biomarkers Prev. 2016; 25(3):446-54 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    BACKGROUND: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).
    METHODS: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped).
    RESULTS: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E-6; Pcorrected = 0.01).
    CONCLUSIONS: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.
    IMPACT: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446-54. ©2016 AACR.

    Mulder RL, van der Pal HJ, Levitt GA, et al.
    Transition guidelines: An important step in the future care for childhood cancer survivors. A comprehensive definition as groundwork.
    Eur J Cancer. 2016; 54:64-8 [PubMed] Related Publications
    Evidence-based clinical practice guidelines are essential to ensure that childhood cancer survivors at risk of chronic health conditions receive effective long-term follow-up care. However, adult survivors of childhood cancer are not always engaged in recommended health promotion and follow-up practices, as many centres do not have a formal transition programme that prepares survivors and their families for successful transfer from child-centred to adult-oriented healthcare. The need for a specific pan-European guideline for the transition of care for childhood cancer survivors has been recognised. The first step is to define the concept of transition of care for survivors of childhood cancer based on existing evidence.

    Baltatzis M, Chan AK, Jegatheeswaran S, et al.
    Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches.
    Eur J Surg Oncol. 2016; 42(2):159-65 [PubMed] Related Publications
    BACKGROUND: The management of colorectal cancer with synchronous liver-limited metastases currently lacks randomised trial evidence to inform case selection for any of the bowel-first, liver-first or synchronous surgery routes. We examine the literature to report outcome data from reports utilising all three approaches.
    METHODS: A systematic review was conducted using OvidSP (including Embase, EBM Reviews and MEDLINE databases) to find articles reporting discrete peri-operative and long-term outcomes for patients undergoing sequential bowel-first, liver-first surgery or synchronous liver and bowel surgery.
    RESULTS: Of 223 unique citations, 3 cohort studies were identified comprising a pooled population of 1203 patients who completed treatment protocols between 1982 and 2011. Patients were allocated to bowel-first surgery (748 patients, 62.2%), liver-first surgery (75, 6.2%) or synchronous liver/bowel surgery (380, 31.6%). Minor complications were similar between procedures. Major complications were consistent with a pooled fixed estimate of 9.1% (95%CI: 7.6%-10.8%, I(2) = 48%). Post-operative death was rare and consistent with a pooled fixed effect estimate of 3.1% (95%CI: 2.2%-4.3%, I(2) = 0%). Median follow-up ranged from 25.1 to 40.0 months, with a pooled underlying 5-year survival fixed effect estimate of 44% (I(2) = 39%).
    CONCLUSION: This review assesses outcomes of patients with colorectal cancer with synchronous liver metastases managed by either synchronous, sequential liver-first or bowel-first surgery. Overall treatment-related mortality is low and survival is similar among the three groups. These findings provide support for the continued use of all three pathways until better evidence to guide selection of an individual treatment option is available.

    Hatton MQ, Hill R, Fenwick JD, et al.
    Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase I study.
    Radiother Oncol. 2016; 118(3):471-7 [PubMed] Related Publications
    INTRODUCTION: Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009.
    METHODS: Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6G y (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3).
    RESULTS: Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed.
    CONCLUSIONS: CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies.

    Decock A, Ongenaert M, Cannoodt R, et al.
    Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma.
    Oncotarget. 2016; 7(2):1960-72 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature.

    Scarbrough PM, Weber RP, Iversen ES, et al.
    A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.
    Cancer Epidemiol Biomarkers Prev. 2016; 25(1):193-200 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    BACKGROUND: DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility.
    METHODS: We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling.
    RESULTS: We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10(-6)), MSH5 (P < 5.09 × 10(-6)), and BRCA2 (P = 5.70 × 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways.
    CONCLUSIONS: Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways.
    IMPACT: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria.

    Spagnolo F, Sestak I, Howell A, et al.
    Anastrozole-Induced Carpal Tunnel Syndrome: Results From the International Breast Cancer Intervention Study II Prevention Trial.
    J Clin Oncol. 2016; 34(2):139-43 [PubMed] Related Publications
    PURPOSE: Carpal tunnel syndrome (CTS) occurs when the median nerve is compressed at the wrist in the carpal tunnel. It has been suggested that hormonal risk factors may be involved in the pathogenesis of CTS, and a higher incidence of CTS has been reported in randomized clinical trials with aromatase inhibitors (AIs) compared with tamoxifen.
    PATIENTS AND METHODS: This was an exploratory analysis of the International Breast Cancer Intervention Study II, a double-blind randomized clinical trial in which women at increased risk of breast cancer were randomly assigned to receive anastrozole or placebo. This is the first report of risk factors for and characteristics of CTS in women taking an AI in a placebo-controlled trial.
    RESULTS: Overall, 96 participants with CTS were observed: 65 (3.4%) in the anastrozole arm and 31 (1.6%) in the placebo arm (odds ratio, 2.16 [1.40 to 3.33]; P < .001). Ten participants were reported as having severe CTS, of which eight were taking anastrozole (P = .08). Eighteen women (0.9%) in the anastrozole arm and six women (0.3%) in the placebo arm reported surgical intervention, which was significantly different (odds ratio, 3.06 [1.21 to 7.72], P = .018). Six women discontinued with the allocated treatment because of the onset of CTS. Apart from treatment allocation, a high body mass index and an a prior report of musculoskeletal symptoms after trial entry were the only other risk factors for CTS identified in these postmenopausal women.
    CONCLUSIONS: The use of anastrozole was associated with a higher incidence of CTS but few participants required surgery. Further investigations are warranted into the risk factors and treatment of AI-induced CTS.

    Block KI, Gyllenhaal C, Lowe L, et al.
    Designing a broad-spectrum integrative approach for cancer prevention and treatment.
    Semin Cancer Biol. 2015; 35 Suppl:S276-304 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.

    Klein K, Kaspers G, Harrison CJ, et al.
    Clinical Impact of Additional Cytogenetic Aberrations, cKIT and RAS Mutations, and Treatment Elements in Pediatric t(8;21)-AML: Results From an International Retrospective Study by the International Berlin-Frankfurt-Münster Study Group.
    J Clin Oncol. 2015; 33(36):4247-58 [PubMed] Related Publications
    PURPOSE: This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML).
    PATIENTS AND METHODS: Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival.
    RESULTS: Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m(2) and etoposide doses greater than 500 mg/m(2) in the first induction course and high-dose cytarabine 3 g/m(2) during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m(2) and etoposide greater than 1,500 mg/m(2) were associated with lower CIR rates and better probability of event-free survival.
    CONCLUSION: Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide.

    Barash O, Zhang W, Halpern JM, et al.
    Differentiation between genetic mutations of breast cancer by breath volatolomics.
    Oncotarget. 2015; 6(42):44864-76 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.

    Carey LA, Berry DA, Cirrincione CT, et al.
    Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib.
    J Clin Oncol. 2016; 34(6):542-9 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    PURPOSE: Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features.
    PATIENTS AND METHODS: Patients with stage II to III HER2-positive breast cancer underwent tumor biopsy followed by random assignment to paclitaxel plus trastuzumab alone (TH) or with the addition of lapatinib (THL) for 16 weeks before surgery. An investigational arm of paclitaxel plus lapatinib (TL) was closed early. The primary end point was pCR in the breast; correlative end points focused on molecular features identified by gene expression-based assays.
    RESULTS: Among 305 randomly assigned patients (THL, n = 118; TH, n = 120; TL, n = 67), the pCR rate was 56% (95% CI, 47% to 65%) with THL and 46% (95% CI, 37% to 55%) with TH (P = .13), with no effect of dual therapy in the hormone receptor-positive subset but a significant increase in pCR with dual therapy in those with hormone receptor-negative disease (P = .01). The tumors were molecularly heterogeneous by gene expression analysis using mRNA sequencing (mRNAseq). pCR rates significantly differed by intrinsic subtype (HER2 enriched, 70%; luminal A, 34%; luminal B, 36%; P < .001). In multivariable analysis treatment arm, intrinsic subtype, HER2 amplicon gene expression, p53 mutation signature, and immune cell signatures were independently associated with pCR. Post-treatment residual disease was largely luminal A (69%).
    CONCLUSION: pCR to dual HER2-targeted therapy was not significantly higher than single HER2 targeting. Tissue analysis demonstrated a high degree of intertumoral heterogeneity with respect to both tumor genomics and tumor microenvironment that significantly affected pCR rates. These factors should be considered when interpreting and designing trials in HER2-positive disease.

    Naik R, Bayne L, Founta C, et al.
    Patient Support Groups Identifying Clinical Equipoise in UK Gynaecological Oncology Surgeons as the Basis for Trials in Ultraradical Surgery for Advanced Ovarian Cancer.
    Int J Gynecol Cancer. 2016; 26(1):91-4 [PubMed] Related Publications
    "Clinical equipoise" is defined as the genuine uncertainty by the expert medical community of the most beneficial treatment. A survey performed in 2013 by a patient support group, Ovacome, of gynaecological oncologists in the UK on ultra-radical surgery in advanced ovarian cancer has shown that there is a wide variation in surgical practice across the country. In addition, there were mixed views on the quality of published evidence justifying it's performance, signifying a state of clinical equipoise. The survey also identified widespread insufficient infra-structural resources and lack of surgical training and skills. The majority of respondents would be prepared to undertake additional training to acquire the surgical skills and/or refer to other centres/surgeons already performing the surgery and/or recruit to surgical trials investigating ultra-radical surgery in advanced ovarian cancer.

    Renfro LA, Loupakis F, Adams RA, et al.
    Body Mass Index Is Prognostic in Metastatic Colorectal Cancer: Pooled Analysis of Patients From First-Line Clinical Trials in the ARCAD Database.
    J Clin Oncol. 2016; 34(2):144-50 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    PURPOSE: In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear.
    PATIENTS AND METHODS: Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted).
    RESULTS: BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m(2), and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m(2) had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43% to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect.
    CONCLUSION: Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways.

    Pashankar F, Hale JP, Dang H, et al.
    Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative.
    Cancer. 2016; 122(2):230-7 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
    BACKGROUND: There is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted.
    METHODS: Data from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS).
    RESULTS: One hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort.
    CONCLUSIONS: The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved. Cancer 2016;122:230-237. © 2015 American Cancer Society.

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