The Christie Hospital in Manchester, England, is one of the largest cancer treatment centres in Europe. It is managed by The Christie NHS Foundation Trust.
Purpose Midface reconstruction poses a complex set of challenges for reconstructive surgeons. The optimal midface reconstruction must possess a durable underlying bone construct capable of integrating dental implants. Facial contour is restored by the overlying microvascular soft tissue reconstruction with reestablishment of the oral cavity. A plethora of microvascular flaps used in clinical practice have been described including those harvested from the iliac crest, scapula, fibula, forearm and back (latissimus dorsi). The objective was to share our experiences with each of these treatment options that have continued to evolve over time for the benefit of patients. Methods Our institution has over three decades of experience in reconstructing complex midface defects and this article summarizes midface reconstruction from an evolutionary perspective (for type II, III and IV defect; Browns classification, Supplementary Table I). We broadly divide this into (i) flaps supplied by the subscapular system (ii) autologous reconstruction with titanium mesh and (iii) fibula microvascular flaps using 3D planning. Results The advantages and disadvantages for each approach are discussed (Supplementary Table II). Conclusion In the future, it is expected that 3D planning coupled with rapid prototyping, intraoperative navigation and CT imaging will become standard procedural practice.
OBJECTIVES:Real-world analyses of first-line maintenance (1LM) immuno-oncology (IO) treatment with or without pemetrexed for patients with non-squamous (NSQ) advanced/metastatic non-small cell cancer (a/mNSCLC), including the relative impact of 1LM pemetrexed, are lacking. This retrospective analysis describes 1LM treatment patterns and their outcomes in England. METHODS:Data from the National Disease Registration Service were collated to identify 2 cohorts of patients with NSQ a/mNSCLC completing ≥ 4 cycles of first-line (1L) platinum-based chemotherapy with IO plus pemetrexed, diagnosed from 1 March to 31 December 2019 (Cohort 1), or during a period where interim coronavirus disease 2019 (COVID-19) guidelines were in effect (1 March to 31 December 2020; Cohort 2). Baseline characteristics, 1LM treatment, overall survival (OS) and time to next treatment or death in both cohorts, and in a combined cohort of patients receiving 1LM stratified by the presence/absence of 1LM pemetrexed, were analyzed. RESULTS:Overall, 595 and 516 NSQ a/mNSCLC patients were included in Cohorts 1 and 2, respectively. Median OS (95% confidence interval [CI], months) from start of 1L was numerically longer in Cohort 1 (19.5 [17.6-22.2] months) versus Cohort 2 (15.7 [14.2-18.0] months). Combined (Cohort 1 and Cohort 2) median OS from 1L was broadly similar irrespective of pemetrexed presence (19.5 [17.5-21.6] months) or absence (18.6 [15.6-23.0] months) in 1LM. CONCLUSIONS:Survival was numerically shorter for patients diagnosed during the COVID-19 pandemic (Cohort 2; interim guidance) versus Cohort 1 (pre-COVID-19). In a combined cohort, survival was broadly similar regardless of 1LM pemetrexed use.
Adjuvant chemotherapy for colorectal cancer (CRC) with oxaliplatin and fluoropyrimidine was traditionally given for 6 months but is associated with cumulative peripheral neuropathy. The SCOT study (ISRCTN59757862) was an international, randomized, phase III, noninferiority trial investigating treatment reduction from 6 to 3 months. It originally reported noninferior disease-free survival with reduced toxicity and improved quality of life for 3 months of treatment in 6,088 patients. Here, we report overall survival (OS) with 38 months of additional follow-up. Patients with high-risk stage II and stage III CRC were assigned (1:1) to receive 3 or 6 months of either capecitabine and oxaliplatin (CAPOX) or infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX; bolus and infused fluorouracil with oxaliplatin) that were selected before random assignment. With a median of 113 months follow-up and 1,255 OS events, 5-year OS for 3 versus 6 months of treatment was 82.4% in both groups (hazard ratio, 0.96; 95% CI, 0.8 to 1.07), proving noninferiority of 3 months of treatment. Noninferiority of 3 months of treatment for OS was also shown in 1,087 patients with rectal cancer. The duration effect is regimen-dependent with noninferiority shown for CAPOX but not for FOLFOX. In summary, SCOT has shown noninferiority for OS with 3 months of adjuvant chemotherapy treatment, which should be recommended for most patients.
Following approval of axicabtagene ciloleucel (axi-cel) as second-line (2 L) treatment for large B-cell lymphoma (LBCL), results from real-world CAR T cohorts will be key to confirm safety and efficacy in standard practice. We present comprehensive clinical outcomes of LBCL patients intended to be treated with 2 L axi-cel through the UK National CAR T service. Of 345 patients approved for 2 L axi-cel, 302 (87.5%) were infused. The median age was 62 years (range 22-78); 21% were over 70 years. 75% of patients were approved for CAR T within 3 months from end of first-line (1 L) therapy. 42% of patients required pre-apheresis holding therapy, and 97% received bridging therapy. The best overall response rate was 86% (64% complete response). The 12-month OS was 73.9% (95% CI: 68.3-78.7) for infused patients and 1.5 months (0.9-3.0) for patients not proceeding to CAR T. The 12-month PFS was 52.4% (46.3-58.0). In multivariable analysis, advanced stage, male sex, no response to 1 L therapy, high LDH, and high CRP pre-infusion were independently associated with PFS. Grade ≥3 CRS and ICANS rates were 5% and 18%, respectively. Outcomes in patients aged ≥70 years were similar to the younger population. In this large UK real-world cohort of 2 L axi-cel in LBCL, we demonstrate efficacy and toxicity outcomes comparable to the pivotal ZUMA-7 trial, despite 42% patients requiring urgent holding therapy. Outcomes were favorable in patients aged ≥70 years, supporting the use of 2 L CAR T in older fit patients.
BACKGROUND:Retifanlimab has activity in programmed death ligand 1-positive advanced squamous cell anal carcinoma (SCAC) that has progressed on platinum chemotherapy. We aimed to prospectively assess the benefit of adding retifanlimab to initial carboplatin-paclitaxel for this disease. METHODS:This global, multicentre, double-blind, randomised, controlled, phase 3 trial was done at 70 centres in 12 countries across the EU, Australia, Japan, the UK, and the USA. Patients aged ≥18 years with inoperable locally recurrent or metastatic SCAC, an Eastern Cooperative Oncology Group performance status of 0 or 1, no previous systemic therapy, and well controlled HIV (ie, CD4+ count >200/μL and undetectable viral load) were eligible. Patients were randomly assigned (1:1) to retifanlimab (500 mg intravenous) or placebo every 4 weeks with standard carboplatin-paclitaxel for up to 1 year. Patients in the placebo group could cross over to retifanlimab monotherapy on confirmed disease progression. The primary endpoint was independently assessed progression-free survival (ie, time from date of randomisation to date of first documented progressive disease or death due to any cause) per Response Evaluation Criteria in Solid Tumours version 1.1. Efficacy was assessed by intention to treat. This trial is registered with ClinicalTrials.gov (NCT04472429) and EUDRA-CT (2020-000826-24) and is active but closed to enrolment. FINDINGS:Between Nov 12, 2020, and July 3, 2023, 376 patients were assessed for eligibility and 308 were randomly assigned to retifanlimab plus carboplatin-paclitaxel (n=154) or placebo plus carboplatin-paclitaxel (n=154). 222 (72%) of 308 patients were female and 86 (28%) were male. Median progression-free survival was 9·3 months (95% CI 7·5-11·3) in the retifanlimab group and 7·4 months (7·1-7·7) in the placebo group (hazard ratio 0·63 [95% CI 0·47-0·84]; one-sided p=0·0006). Serious and grade 3 or worse adverse events were more frequent in the retifanlimab plus carboplatin-paclitaxel group compared with the placebo plus carboplatin-paclitaxel group (47·4% vs 38·8% and 83·1% vs 75·0%, respectively). The most common grade ≥3 adverse events were neutropenia (35·1% for retifanlimab plus carboplatin-paclitaxel vs 29·6% for placebo plus carboplatin-paclitaxel) and anaemia (19·5% vs 20·4%). Four fatal adverse events occurred in the retifanlimab plus carboplatin-paclitaxel group, only one (pancytopenia) of which was treatment related. One fatal adverse event occurred in the placebo plus carboplatin-paclitaxel group and was not treatment related. INTERPRETATION:Retifanlimab provides clinical benefit, with a manageable safety profile, when added to first-line chemotherapy in advanced squamous cell carcinoma of the anal canal. These results suggest retifanlimab with carboplatin plus paclitaxel should be considered as the new standard of care for patients with advanced squamous cell anal carcinoma. FUNDING:Incyte.
