European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer.

BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. DESIGN: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. CONCLUSION: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.

Twelve ESMO Congress 2022 breakthroughs: practicing oncologists' perceptions and potential application on presented data.

BACKGROUND: During the European Society for Medical Oncology (ESMO) Congress 2022, outcome data of a great number of clinical trials were presented. For the attending medical oncologist, it is important to structure these data in a way that facilitates a trade-off between treatment burden and benefit. MATERIALS AND METHODS: To illustrate this, we carried out a narrative non-systematic review of 12 selected oral presentations with potential impact on future daily practice, focusing on trial methodology, possible study flaws, reported clinical benefit and implementability. RESULTS: The selected presentations encompassed 10 phase III trials, 1 randomized phase II trial and 1 phase II trial. In 7 out of 12 trials, quality of life and/or patient-reported outcomes had been evaluated. None of the trials, which reported progression-free survival (PFS) data, provided information, which could exclude informative censoring bias. In none of the trials reporting overall survival (OS) data, potential flaws due to undesirable crossover and imbalance between study groups regarding post-progression treatments were addressed. For the 11 reviewed randomized trials, the ESMO-Magnitude of Clinical Benefit Scale (MCBS) grade achieved with the new intervention was calculated based on the presented data. The MCBS grade varied from 1 to 5. CONCLUSIONS: Our review confirms the high-quality standard of current cancer research and the clinical relevance of the research questions answered. However, during presentation of PFS and/or OS data, factors known to affect PFS and OS analysis should be structurally addressed. In order to keep cancer care affordable and sustainable, it could be considered to include an ESMO-MCBS threshold in the drug appraisal process of regulatory authorities.

11 ESMO 2021 breakthroughs: practicing oncologist's perceptions on data presentation.

BACKGROUND: The European Society for Medical Oncology (ESMO) 2021 conference provided a high number of randomized phase III trial reports, many of which were claimed to be practice changing. Given the short time available for conference presentations, results and conclusions tend to have greatest priority with less time remaining for study background and study methodology. PURPOSE: On behalf of the ESMO Practicing Oncologists Working Group, 11 potentially practice-changing reports were selected and screened for three main questions: (i) Did the investigators provide sufficient details with regard to Patients and Methods to make the results comprehensible? (ii) Were there any reasons to consider bias? (iii) To which extent did the results presented translate to clinical benefit? RESULTS: In 2 out of 11 trials, the study design presented differed considerably from the study design described at ClinicalTrials.gov. Allocation concealment was not carried out in 6 out of 11 trials. In none of the trials reporting progression-free survival was informative censoring considered an issue. In none of the trials reporting overall survival was desirable crossover considered an issue. Defined trial outcome measures depicted at ClinicalTrials.gov, which could boost or weaken the ESMO-Magnitude of Clinical Benefit Scale score, were often lacking in the presentation. Study success was claimed in a heterogeneous manner, which was often not clearly linked to overall clinical benefit. CONCLUSION: ESMO conference presentations can inform the scientific community and catalyze further research but cannot replace the full papers in peer-reviewed journals, which are needed to estimate the thoroughness of the results, the overall impact on clinical benefit and the consequences for future treatment guidelines.

Effect of different treatment methods on survival in patients with pancreatic cancer.

PURPOSE: To assess the benefit of treatment modalities on the survival in patients with pancreatic cancer. MATERIAL AND METHODS: Eighty-five patients with pancreatic cancer were treated by surgery, radiotherapy, chemotherapy and combined therapy. The data was reviewed retrospectively and the benefit of various treatment methods to the median survival time of the patients was assessed. RESULTS: Median survival time of the patients diagnosed with local disease treated by radical resection and adjuvant treatment was 21.5 months; with radical resection only--12.6 months (p = 0.6). In patients with locally advanced disease and treated by radical resection and adjuvant therapies the median survival time was 12.1 months and by radical resection only 7.7 months (p = 0.6). For patients treated by palliative surgery, chemotherapy and radiotherapy median survival was 8.8 months and by palliative surgery alone 1.8 month (p = 0.015). 1-year actual survival of patients treated with radical resection and adjuvant therapies was 11.7%. For patients with radical resection only--10.5%. 3-year actual survival for the same groups of patients was 3.5% and 2.3%, respectively. 1-year actual survival of patients treated by palliative methods was 2.3%. CONCLUSIONS: Surgery with adjuvant treatment seems to be beneficial for pancreatic adenocarcinoma patients. In locally advanced and metastatic pancreatic cancer palliative chemotherapy or radiotherapy statistically significantly improved survival.