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ObjectiveCombination treatment regimens consisting of both immune checkpoint inhibitors (ICI) and chemotherapeutic agents have emerged as the standard of care for a range of cancers. This network meta-analysis (NMA) examined the toxicity profiles and safety rankings of these different ICI-based combination regimens.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all randomized controlled trials (RCTs) published as of March 1, 2022 comparing two or more treatment regimens in which at least one arm was comprised of an ICI + platinum-based chemotherapeutic regimen. Treatment-related adverse events (AEs) of any grade and AEs of grade 3 or higher were the primary endpoints for this analysis, while specific AE types were secondary endpoints. This NMA combined both direct and indirect comparisons when analyzing odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) for different ICI-based treatment regimens.ResultsIn total, 33 RCTs enrolling 19,012 cancer patients were included in this NMA. Of the analyzed regimens, avelumab + chemotherapy and camrelizumab + chemotherapy were associated with a significantly greater risk of AEs of any grade relative to ipilimumab + chemotherapy, durvalumab + chemotherapy, or pembrolizumab + chemotherapy. No significant differences in the risk of AEs of grade 3 or higher were observed when comparing different ICI regimens. Hepatotoxicity and pyrexia were the most common AEs associated with atezolizumab + chemotherapy treatment. Ipilimumab + chemotherapy was associated with a relatively higher risk of gastrointestinal and skin toxicity. Skin toxicity and hypothyroidism were the major AEs associated with nivolumab + chemotherapy. Fatigue and pneumonia were the most common AEs respectively associated with sugemalimab + chemotherapy and pembrolizumab + chemotherapy regimens.ConclusionsOf the evaluated regimens, camrelizumab + chemotherapy and avelumab + chemotherapy were associated with significantly higher rates of AEs of any grade, whereas durvalumab and sintilimab were relatively safe PD-L1 and PD-1 inhibitors, respectively, when administered in combination with platinum-based chemotherapy. However, none of the evaluated ICI + chemotherapy regimens exhibited any differences with respect to the incidence of grade 3 or higher AEs, offering guidance that may be of value in routine clinical practice.

BackgroundThe immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA‐EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis.Methods and MaterialsWe identified 190 LA‐EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte‐related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally.ResultsMedian follow‐up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30) was linked to worse survival (HR: 1.013, 95% CI: 1.001–1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335–3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage‐IVA (p = 0.017), platelet‐to‐lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843.ConclusionHigher doses of pericardial radiation might affect LA‐EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune‐checkpoint inhibitor treatment.

Purpose: The study evaluated whether antibiotic treatment before chemoradiotherapy in uenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods: The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017 at xxx were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The in uence of antibiotics on progressionfree survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression.Results: Of 522 patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4 mo, p<0.001) and OS (20.4 vs. 25.3 mo, p=0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients that received chemoradiotherapy (HR, 1.234; 95% CI, 1.019-1.494; p=0.031). Prognosis was also in uenced by the antibiotic type, length of treatment, and interval between discontinuation and start of chemoradiotherapy initiation. β-lactamase inhibitors were found to be the most harmful (median OS for β-lactamase inhibitors /Fluoroquinolones / Cephalosporins:16.5/19.9/25.9 mo, p=0.045). Cutoff values for interval and duration calculated by the Xtile procedure showed that intervals of 7-16 days or durations ≤6 days did not signi cantly affect OS relative to untreated patients (intervals: p=0.9, duration: p=0.93).Conclusions: Antibiotic treatment for longer than six days, especially with β-lactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16 days after antibiotic discontinuation may reduce these negative effects.

Patrick Hwu, MD, president and chief executive offi cer of Moffi tt Cancer Center, along with fellow physicians is part of a band called the ReMissions. In this special episode, Hwu details being a guitarist and pianist, the teamwork that goes into performing, and the diverse selection of genres he enjoys playing.

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Purpose: The study evaluated whether antibiotic treatment before chemoradiotherapy influenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods: The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017 at xxx were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The influence of antibiotics on progression-free survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression.Results: Of 522 patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4 mo, p<0.001) and OS (20.4 vs. 25.3 mo, p=0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients that received chemoradiotherapy (HR, 1.234; 95% CI, 1.019-1.494; p=0.031). Prognosis was also influenced by the antibiotic type, length of treatment, and interval between discontinuation and start of chemoradiotherapy initiation. β-lactamase inhibitors were found to be the most harmful (median OS for β-lactamase inhibitors /Fluoroquinolones / Cephalosporins:16.5/19.9/25.9 mo, p=0.045). Cutoff values for interval and duration calculated by the X-tile procedure showed that intervals of 7-16 days or durations ≤6 days did not significantly affect OS relative to untreated patients (intervals: p=0.9, duration: p=0.93). Conclusions: Antibiotic treatment for longer than six days, especially with β-lactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16 days after antibiotic discontinuation may reduce these negative effects.