Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy

BackgroundIn patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life. However, the study was conducted prior to the current era of adjuvant systemic therapies and when CLND was the standard approach for microscopic nodal disease. As such, there is currently no data on the role of adjuvant RT in patients with melanoma who recur during or after adjuvant immunotherapy, including those that may or may not have undergone prior CLND. In this study, we aimed to answer this question.MethodsPatients with resected stage III melanoma who received adjuvant anti-programmed cell death protein-1 (PD-1) (±ipilimumab) immunotherapy with a subsequent locoregional (lymph node and/or in-transit metastases) recurrence were retrospectively identified. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was rate of subsequent locoregional recurrence; secondary outcomes were locoregional recurrence-free survival (lr-RFS2) and overall RFS (RFS2) to second recurrence.ResultsIn total, 71 patients were identified: 42 (59%) men, 30 (42%) BRAF V600E mutant, 43 (61%) stage IIIC at diagnosis. Median time to first recurrence was 7 months (1–44), 24 (34%) received adjuvant RT and 47 (66%) did not. Thirty-three patients (46%) developed a second recurrence at a median of 5 months (1–22). The rate of locoregional relapse at second recurrence was lower in those who received adjuvant RT (8%, 2/24) compared with those who did not (36%, 17/47, p=0.01). Adjuvant RT at first recurrence was associated with an improved lr-RFS2 (HR 0.16, p=0.015), with a trend towards an improved RFS2 (HR 0.54, p=0.072) and no effect on risk of distant recurrence or overall survival.ConclusionThis is the first study to investigate the role of adjuvant RT in patients with melanoma with locoregional disease recurrence during or after adjuvant anti-PD-1-based immunotherapy. Adjuvant RT was associated with improved lr-RFS2, but not risk of distant recurrence, demonstrating a likely benefit in locoregional disease control in the modern era. Further prospective studies are required to validate these results

A Study on the Effects of the Use of Propofol in Experimental Model Inferior Epigastric Island Flap on Ischemia-Reperfusion Injury

Problems concerning vascular blood flow are the most frequently encountered ones after flap applications. The flap tissue starts to develop ischemia in patients with a vascular blood flow insufficiency. And reperfusion starts in those patients in whom the ischemia is temporary, triggering an ischemia-reperfusion injury depending on the duration of the ischemia. The aim of this study was to evaluate the effect of propofol, which is an anesthetic agent known to have an antioxidant effect and a free radical scavenging feature on the ischemia-reperfusion injury created on an experimental epigastric island flap

The correlates of benefit from neoadjuvant chemotherapy before surgery in non-small-cell lung cancer: a metaregression analysis

Background: Although neoadjuvant chemotherapy (NCT) is widely used, it is not clear which subgroup of locally advanced non-small-cell lung cancer (NSCLC) patients should be treated with this approach, and if a particular benefit associated with NCT exists. In this study, we aimed to investigate the potential correlates of benefit from NCT in patients with NSCLC.Methods: All randomized clinical trials (RCTs) utilizing a NCT arm (without radiotherapy) versus a control arm before surgery were included for metaregression analysis. All regression analyses were weighed for trial size. Separate analyses were conducted for trials recruiting patients with different stages of disease. Previously published measures of treatment efficacy were used for the purpose of this study, regardless of being published in full text or abstract form.Results: A total of 14 RCTs, consisting of 3,615 patients, were selected. Histology, stage, various characteristics of the NCT protocol, and different trial features including trial quality score were not associated with the benefit of NCT. However, in trials of stage 3 disease only, there was a greater benefit in terms of reduction in mortality from NCT, if protocols with three chemotherapeutics were used (B = -0.18, t = -5.25, P = 0.006).Conclusions: We think that patients with stage 3 NSCLC are served better with NCT before surgery if protocols with three chemotherapy agents or equally effective combinations are used. In addition, the effect of neoadjuvant chemotherapy is consistent with regard to disease and patient characteristics. This finding should be tested in future RCTs or individual patient data meta-analyses. © 2012 Bozcuk et al.; licensee BioMed Central Ltd

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

Context The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. Methods This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. Results Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. Conclusion Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism