Background: Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates. Methods: Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas' Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells. Results: Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50-0.94) and disease-free survival (HR = 0.75, 95% CI 0.58-0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy associated adverse events and completion were similarly distributed between treatment groups. Conclusions: Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable. 2022 Elsevier Ltd. All rights reserved.

Efficacy of afatinib in EGFR mutant patients with comorbidities or those with suspected EGFR mutations unfit for chemotherapy is poorly explored. We evaluated afatinib in this population, with serial plasma ctDNA to investigate the role of molecular EGFR genotyping and monitoring. Phase-II trial enrolled NSCLC patients with comorbidities precluding chemotherapy, and either (i) EGFR-mutation, PS 0-3, or (ii) suspected EGFR-mutation (tissue unavailable/failed genotyping), never/former-light smoker, adenocarcinoma, and PS 0-2. Afatinib (40mg daily) given until progression/toxicity. Blood samples obtained at baseline and 12-weekly until discontinuation; plasma ctDNA performed using InVisionSeq™ (amplicon-based NGS). 39 patients recruited (14 UK centres). Median age 72 years; 27 PS 0-1/12 PS 2-3. 21 patients (54%) had known tissue EGFR-mutations. Additional 8 patients with unknown tissue status (8/17;47%), were ctDNA EGFR-mutant, making 74% EGFR-mutant in total (29/39). Combined tissue and ctDNA data identified 21 patients with common mutations (exon 19/L858R), 8 with rare mutations (exon 18/20), and 10 suspected only. Corresponding median PFS of these cohorts were 10.2/3.9/5.3 months, with 6-month PFS of 71/38/50% all exceeding the 30% target; median OS were 24.8/5.7/11.4 months (p<0.001). Therefore, all patient groups benefitted; known EGFR-mutants having best outcomes. In April 2018, 5/39 patients survived >36 months, including 4/39 progression-free (median follow-up 33 months, maximum 55). Patients with ctDNA mutation clearance during afatinib treatment had substantially improved outcomes compared to those without clearance (Figure). 40% (4/10) of mutant cases who discontinued after 3 cycles because of progressive disease developed an exon 20 EGFR-mutation. Patients unsuitable for chemotherapy with confirmed/suspected EGFR-mutations by tissue or ctDNA benefit from afatinib. Serial ctDNA is a potentially useful stratification and monitoring tool; amplicon-based ctDNA analysis can identify EGFR mutations when tissue is unavailable. Exon 20 mutations were observed at acquired resistance. ctDNA clearance during afatinib treatment is strongly associated with better PFS/OS.

Introduction: NICE approved CisPem for first-line treatment of advanced large cell or adenocarcinoma NSCLC patients in September 2009. We reviewed outcomes for this regimen within KMCN, a large cancer network of 1.8 million population. Therapy was given at 7 sites within a nurse led model incorporating close clinical oversight. Methods: A retrospective analysis of patients receiving CisPem as first-line treatment for NSCLC (September 2009 August 2010) was undertaken. Results: 39 chemotherapy-naive patients with locally advanced or metastatic non-squamous NSCLC were identified; 37 were treated with CisPem. Baseline demographics are shown below: 59% male; median age 63 years; smoking status 27% current, 32% previous, 38% unknown, 2.7% never-smokers; stage at presentation III = 22%, IV = 70%; performance status PS = 0 8%, PS = 1 84%, PS = 2 5%. Five patients did not receive treatment due to rapid progression. A median of 4 cycles of chemotherapy was delivered: 67% completed 4 cycles, 5.4% received 6 cycles, 13% only completed 1 2 cycles. Of 109 cycles of chemotherapy, just 0.9% of cycles were delayed. Cisplatin dose was reduced or omitted in 7% and 5% of cycles respectively. Pemetrexed doses were reduced or omitted in 4% and 5% of cycles respectively. 25% of patients were admitted at some point during their chemotherapy. The reasons for admission were non-neutropenic sepsis (12%), thromboembolic phenomena (24%) and progressive disease (64%). There were no deaths within 30 days of CisPem administration. Partial responses were documented in 62.5% of cases. Stable disease was seen in 12.5% and progressive disease in 25%. As of August 2010, 12 patients had died (median overall survival of 6.5 months and median progression-free survival 6.0 months). Conclusions: First line CisPem delivered within a community/nurseled setting provides similar efficacy outcomes to published trial data. The high rate of hospital admission and thromboembolic complications warrants further investigation.

Laparoscopic approaches for colorectal surgery have been improved recently; however, it is often difficult to achieve total mesorectal excision (TME) for lower rectal cancer laparoscopically because of a narrow pelvis and a thickened mesentery.TME was successfully performed in 6 patients (4 men, 2 women) with dissection of the rectum transanally from the anal side of the tumor. The preoperative stage was T3N1M0 in 1 patient and T3N0M0 in 5 patients. The mean body mass index was 29.8 kg/m2 (range, 28.7–31.2 kg/m2), and the mean tumor size was 46.5 mm (range, 30–60 mm).The mean duration of the anal portion of the operation was 64 minutes (56 minutes in women, 79 minutes in men). No complications occurred during surgery or postoperatively.This technique is a simple and effective procedure for successfully performing laparoscopic TME of lower rectal cancer in patients with bulky tumors, narrow pelvises, and thickened mesenteries.