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Introduction: Computed tomography (CT) is used for restaging of gastric cancer patients during neoadjuvant chemotherapy (NAC). The treatment strategy could be altered after detection of distant interval metastases, possibly leading to a reduction in unnecessary chemotherapy cycles, its related toxicity, and surgical procedures. The aim of this study was to evaluate the additive value of restaging-CT during NAC in guiding clinical decision making in gastric cancer., Materials and Methods: This retrospective, multicenter cohort study identified all patients with surgically resectable gastric adenocarcinoma (cT1-4a-x, N0-3-x, M0-x), who started NAC with curative intent. Restaging-CT was performed after 2 out of 3 cycles of NAC. The primary outcome was treatment alterations made based on restaging-CT by a multidisciplinary tumor board. Confirmation of metastases was obtained by surgery or biopsy., Results: Between 2007 and 2015, CT-restaging was performed in 122 out of 152 included patients and timed after 2 cycles (n = 76) or after 3 cycles (n = 46) of NAC. Restaging-CT revealed a metastasis in 1 out of 122 restaged patients (1%) after which surgical resection was omitted, whereas 4 patients (3%) with distant interval metastases were not identified by restaging-CT and underwent a futile laparotomy. In 5 out of 76 patients (7%) disease progression was detected while undergoing NAC, leading to omission of the 3rd cycle of chemotherapy., Conclusion: The additive value of restaging-CT during NAC in gastric cancer is limited in guiding clinical decision making and therefore not recommended. Further studies may identify subgroups that may benefit of alternative diagnostic modalities., Competing Interests: Declaration of competing interest ECG, CdJ, HJFB, ACM, IAMJB, ML, DB, DtBH, LvL, FJW, RvH and JPR declare that they have no declarations of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in patients with cancer. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand the preferences of patients with cancer concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS)., Methods: In a quantitative multicentre study, adult patients with cancer (any stage and origin of disease) were surveyed through a digital questionnaire based on previous semi-structured interviews. Background knowledge was provided by showing two videos, introducing basic concepts of genetics and general information about different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance)., Results: In total 1072 patients were included of whom 701 participants completed the whole questionnaire. Overall, 686 (85.1%) participants wanted to be informed about UFs in general. After introduction of four UFs categories, 113 participants (14.8%) changed their answer: 718 (94.2%) participants opted for actionable variants, 537 (72.4%) for non-actionable variants, 635 (87.0%) participants for UFs of reproductive significance and 521 (71.8%) for UFs of unknown significance. Men were more interested in receiving certain UFs than women: non-actionable: OR 3.32; 95% CI 2.05 to 5.37, reproductive significance: OR 1.97; 95% CI 1.05 to 3.67 and unknown significance: OR 2.00; 95% CI 1.25 to 3.21. In total, 244 (33%) participants conceded family members to have access to their UFs while still alive. 603 (82%) participants agreed to information being shared with relatives, after they would pass away., Conclusion: Our study showed that the vast majority of patients with cancer desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Incorporation of categories in informed consent procedures supports patients in making informed decisions on UFs., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Cabazitaxel has been shown to improve overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel in the TROPIC trial. However, trial populations may not reflect the real-world population. We compared patient characteristics and outcomes of cabazitaxel within and outside trials (standard of care, SOC)., Patients and Methods: mCRPC patients treated with cabazitaxel directly after docetaxel therapy before 2017 were retrospectively identified and followed to 2018. Patients were grouped on the basis of treatment within a trial or SOC. Outcomes included OS and prostate-specific antigen (PSA) response., Results: From 3616 patients in the CAPRI registry, we identified 356 patients treated with cabazitaxel, with 173 patients treated in the second line. Trial patients had favorable prognostic factors: fewer symptoms, less visceral disease, lower lactate dehydrogenase, higher hemoglobin, more docetaxel cycles, and longer treatment-free interval since docetaxel therapy. PSA response (≥ 50% decline) was 28 versus 12%, respectively (P = .209). Median OS was 13.6 versus 9.6 months for trial and SOC subgroups, respectively (hazard ratio = 0.73, P = .067). After correction for prognostic factors, there was no difference in survival (hazard ratio = 1.00, P = .999). Longer duration of androgen deprivation therapy treatment, lower lactate dehydrogenase, and lower PSA were associated with longer OS; visceral disease had a trend for shorter OS., Conclusion: Patients treated with cabazitaxel in trials were fitter and showed outcomes comparable to registration trials. Conversely, those treated in daily practice showed features of more aggressive disease and worse outcome. This underlines the importance of adequate estimation of trial eligibility and health status of mCRPC patients in daily practice to ensure optimal outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Older patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery., Methods: Included were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders., Results: Response rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL., Conclusion: Colorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: In studies of colorectal cancer, the elderly have been frequently underrepresented because comorbid conditions and functional status often lead to study exclusion. For elderly patients with an indication for neoadjuvant chemoradiotherapy (nCRT), physicians usually decide using clinical factors whether nCRT should be offered. The aim of the present retrospective study was to assess the tolerability of nCRT with capecitabine and the surgical outcomes in patients aged ≥ 70 years with locally advanced rectal cancer., Patients and Methods: Data from 1372 rectal cancer patients diagnosed from 2002 to 2012 at 4 Dutch hospitals were used. Patients aged ≥ 70 years were included if they had received nCRT, and their data were analyzed for treatment deviations, postoperative complications, mortality, disease-free survival (DFS), and overall survival (OS). The data were stratified into 3 age groups (ie, 70-74, 75-79, and ≥ 80 years)., Results: We identified 447 patients aged ≥ 70 years. Of these patients, 42 had received nCRT, and 37 (88%) had completed nCRT. Radiation dermatitis, fatigue, and diarrhea were reported in 62%, 57%, and 43% of the 42 patients, respectively. Of the 42 patients, 40 (95%) underwent surgery, 1 patient refused resection, and 1 patient died during nCRT of severe mucositis due to dihydropyrimidine dehydrogenase deficiency. The postoperative complication rate was 30%, and the 30-day mortality rate was 0%. A pathologic complete response was found in 7.5%. The 2- and 5-year DFS and OS rates were 58.5% and 40.7% and 81.0% and 58.2%, respectively., Conclusion: The results of the present multicenter study have shown that if selected on clinical factors, nCRT with capecitabine is safe and well tolerated in elderly patients. No negative effect on surgical outcome was measured, and the beneficial effect (pathologic complete response, DFS, and OS) seemed comparable to that for younger age groups. We believe that elderly patients should not be excluded from nCRT on the basis of age only., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: With the ageing of society, optimising decision-making for older patients with cancer becomes increasingly important. A first step is awareness of current clinical practice. We analysed how treatment decisions regarding chemotherapy for older and younger patients with colorectal cancer are currently being made by the multidisciplinary team, the oncologist and the patient., Methods: A total of 316 patients with colorectal cancer (median age 68.3 years), discussed at the multidisciplinary gastrointestinal oncology team meetings between 2010 and 2013, were reviewed to select patients for whom guidelines recommended chemotherapy. Multidisciplinary decision-making and subsequent clinical course were extracted from medical files., Results: The multidisciplinary team recommended chemotherapy in 97% of younger patients treated with curative intent, compared to 65% of older patients; 86% of younger patients and 42% of older patients subsequently received chemotherapy. In a palliative setting, the multidisciplinary team recommended chemotherapy in 98% of younger and 69% of older patients and 81% and 45%, respectively, subsequently received this treatment. In addition to comorbidity and the patient's physical condition, chronological age was an important reason for withholding chemotherapy. When older patients did receive chemotherapy, reduced intensity regimens were often effectuated., Conclusion: Multidisciplinary decision-making regarding chemotherapy for older patients with colorectal cancer is still frequently based on clinical impressions, preconceptions or chronological age alone. Rather, treatment decisions should be made after thorough evaluation of the patient's health status across multiple domains, either by a geriatrician or within the oncology team itself. Given the preference-sensitive nature of chemotherapy decisions in the elderly, shared decision-making should be strived for whenever possible., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: A phase I trial of raltitrexed in combination with cisplatin in patients with locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN)., Patients and Methods: Eligible patients had locally advanced or metastatic SCCHN. Cohorts of patients were treated with escalating doses of raltitrexed (2.0 mg/m2 to 3.5 mg/m2) as a 15-minute intravenous infusion immediately followed by cisplatin (80 mg/m2) administered over four hours every three weeks to determine the maximum tolerated dose (MTD)., Results: A total of 17 patients was administered 60 courses of an escalating dose of raltitrexed. Starting dose of cisplatin was initially 100 mg/m2 in the first three patients treated at the first dose level. Due to cisplatin-induced nephrotoxicity expressed as a creatinine clearance decrease by more than 50%, the cisplatin dose was reduced to 80 mg/m2 for all subsequent treatment cycles. Dose-limiting toxicity was observed at raltitrexed dose of 3.5 mg/m2 in two out of five patients. Dose-limiting grade 4 (CTC) neutropenia, grade 4 diarrhoea, grade 3 lethargy and elevation of transaminases and bilirubine was seen in these two patients. One patient treated at the level of the MTD, died 23 days after the first cycle with unresolved gastro-intestinal toxicity. In all other dose levels toxicity was very limited. The recommended dose for further study was raltitrexed 3.0 mg/m2 in combination with cisplatin 80 mg/m2. In 15 evaluable patients, we observed 9 WHO objective responses (1 complete and 8 partial). At the recommended dose level 3 partial responses were observed in five evaluable patients., Conclusion: The regimen of raltitrexed 3.0 mg/m2 followed by cisplatin 80 mg/m2 on day 1, every three weeks has manageable toxicity and these doses are recommended for phase II evaluation. Results indicate that this combination is active for the treatment of patients with locally advanced or metastatic SCCHN. Recently, a phase II study has been started.