OBJECTIVE The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty.INTERVENTIONS There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m 2 on day 1, capecitabine 625 mg/m 2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. MAIN OUTCOMES AND MEASURESFirst, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival.RESULTS A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes.CONCLUSIONS AND RELEVANCE This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment.

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ObjectivesStereotactic Ablative Radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I non-small cell lung cancer (NSCLC). Previous non-randomised evidence supports SABR as an alternative to surgery, but high quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible.Design and MethodsSABRTooth was a UK multi-centre, randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher-risk of surgical complications. Fifty-four patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates.ResultsBetween July 2015 and January 2017, 318 patients were considered for the study and 205(64.5%) were deemed ineligible. Of 106 assessed as eligible (33.3%), 24 patients (22.6%) were randomised to SABR (n=14) or surgery (n=10). A key theme for non-participation was treatment preference with 43 (41%) preferring non-surgical treatment and 19(18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of 3. Fifteen patients underwent their allocated treatment, 12 SABR, 3 surgery.ConclusionsWe conclude that a phase III RCT randomising higher-risk patients between SABR and surgery is not feasible in the National Health Service (NHS). Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a non-surgical approach.

2021): Sources of emotional challenge for practitioners delivering family centred care after the death of child: an inductive thematic analysis, Mortality,

patients treated with linear accelerator-based SABR between 2009 and 2016 were retrospectively studied. Impact of patient, tumor, and treatment parameters on LC, OS and toxicity-free survival (TFS) were evaluated by multivariate analyses. Result: Forty-eight PL and 22 OM lesions were analyzed, including 20 (28%) re-irradiation (Re-RT) cases. Median total, fractionated, and biological equivalent doses in BED10 and BED3 were 55 (30-60), 9.75 (4-18), 110 (41-151), and 228 (90-378) Gy, respectively. Doses given as Re-RT were lower (median Re-RT BED10 dose 94 vs. 110 Gy, P¼0.009). Complete response (CR) was obtained in 43 (61%) lesions. None of the analyzed factors correlated to CR. After a median follow-up of 57 (48-65, 95%CI) months, 10 (14%) lesions had relapsed and 37 (57%) patients had died (2 and 5year LC and OS rates were 84/70% and 52/28%, respectively). In univariate analysis, 2-year LC was lower for lesions with no CR and for colorectal cancer lesions. Only "no CR" was significant (100 vs. 51%; HR¼18.2, CI 2.3-146, P¼0.006) in final multivariate analyses. Median OS was significantly lower in patients with grade 3+ toxicity (5 months after grade 3+ toxicity, vs. 39 months in others [HR 4.7,P<0.0001]). OS was marginally lower in patients with primary lung cancer compared to patients with OM tumors (19 vs. 49 months, HR 2.3, CI 1-5.6, P¼0.06). Among 17 toxicities, 5 reached grade 5. For patients with grade 3+ toxicities, TFS was lower after Re-RT (2-year TFS 63% vs. 96%, HR 5.1, CI 1.3-20.3, P¼0.022) but did not differ significantly for lesions abutting TBT (2-year TFS 69% vs. 93.4%, HR 3.5, CI 0.9-13.9, P¼0.08). Conclusion: SABR is an effective treatment modality in centrally located lung tumors. SABR to re-irradiated lesions and possibly lesions abutting TBT may have the higher risks for serious toxicities. Further studies are indicated.