Lot A. Devriese

Background: Monitoring skeletal muscle mass (SMM) during radiotherapy (RT) is important, as SMM loss is associated with poorer clinical outcomes. Cone-beam CT (CBCT), acquired before each RT fraction, offers the potential to track the lumbar skeletal muscle index (LSMI) over time. However, CBCT has lower image quality than conventional CT. This study assessed the agreement between CT and CBCT and evaluated the reliability of LSMI measurements in patients with head and neck squamous cell carcinoma. Methods: Patients who underwent both CT and CBCT on the same day during RT were included. The cross-sectional muscle area at C3 was measured, converted to L3, and used to calculate the LSMI. Two researchers analyzed all scans, with one repeating the measurements. Agreement and reliability were quantified using intraclass correlation coefficients (ICCs) and visualized with Bland–Altman plots. Results: LSMI measurements showed excellent agreement between CBCT and CT (ICC: 0.97–0.99; 95% CI: 0.95–0.99). The intrarater (ICC: 0.99; 95% CI 0.98–0.99) and interrater reliability (ICC: 0.97; 95% CI: 0.66–0.99) were high. Bland–Altman plots, however, revealed wide limits of agreement. Conclusion: CBCT provides reliable LSMI measurements and agrees well with CT, but the observed variability suggests cautious interpretation. When both modalities are available, CT remains the preferred standard for SMM assessment.

Background: Sarcopenia, defined as the presence of low skeletal muscle mass, is highly prevalent in cancer patients and associated with adverse events and lower survival. Given the chronic inflammation associated with sarcopenia, it is especially relevant in patients receiving immunotherapy. The current research is limited to small sample sizes and single cancer types leaving the overall effect of sarcopenia unclear. This review and meta-analysis examined the prognostic effect of sarcopenia in cancer patients treated with immunotherapy. Methods: A systematic review was conducted using EMBASE, MEDLINE, Cochrane, and Scopus. Studies were included if they investigated the association of baseline low skeletal muscle mass, as measured on CT or MRI and normalised for height, and survival in patients with solid tumours treated with immunotherapy. A meta-analysis of hazard ratios (HR) was performed using a random effects model for overall survival (OS) and progression-free survival (PFS). Results: In total, 48 studies were included in this review, of which 42 were included in the meta-analysis. The prevalence of sarcopenia ranged between 19.5% and 83.6%. The meta-analysis showed an overall prognostic effect of sarcopenia for OS and PFS (HR = 1.58; 95% CI 1.35–1.85; p < 0.0001 and HR = 1.50; 95% CI 1.30–1.72; p < 0.001, respectively). High heterogeneity was present between the included studies, which could possibly be explained by the differences in sarcopenia definition, cutoff values, and measurement techniques. Conclusions: Sarcopenia is a significant adverse prognostic factor for both OS and PFS in patients with solid tumours treated with immunotherapy across cancer types. Further research into the underlying mechanism of sarcopenia and its relation to the immune response and survival is needed. Prospective intervention studies are required to establish the care needed, such as nutrition and exercise, to improve the prognosis of sarcopenic patients.

Background/Objectives: Hematological toxicities (i.e., neutropenia, thrombocytopenia, and anemia), are common chemotherapy complications and may be exacerbated by renal or hepatic impairment due to altered drug exposure. This study assessed the association between renal and hepatic impairment and hematologic toxicities during chemotherapy in routine clinical practice. Methods: A single-center retrospective cohort study using the Utrecht Patient Oriented Database (UPOD) identified all chemotherapy administrations at the University Medical Centre Utrecht between 2011 and 2024. Regimens administered in ≥10 patients and ≥5 renally (GFR < 60 mL/min) or hepatically (bilirubin or AST > 1× ULN) impaired patients were included in descriptive analyses. Cox proportional hazards models estimated associations between organ impairment and grade ≥ 3 hematologic toxicities for regimens with ≥10 events per toxicity endpoint. Results: Overall, 4489 patients were included in renal analyses and 6218 in hepatic analyses, with smaller endpoint-specific subgroups for survival analyses. Renal impairment was associated with grade ≥ 3 neutropenia (HR: 1.43 [95% CI: 1.18–1.73]), thrombocytopenia (HR: 1.46 [95% CI: 1.15–1.86], and anemia (HR: 1.66 [1.27–2.16]). Hepatic impairment was similarly associated with neutropenia (HR: 1.25 [95% CI: 1.11–1.40]), thrombocytopenia (HR: 1.33 [95% CI: 1.13–1.57]), and anemia (HR: 1.62 [95% CI: 1.34–1.95]). Cyclophosphamide (pro-drug) regimens showed higher toxicity risk in renally impaired patients and reduced risk in hepatically impaired patients. Etoposide, melphalan and methotrexate were associated with increased toxicity in hepatically impaired patients. Conclusions: Renal and hepatic impairment significantly increase chemotherapy-induced hematologic toxicity. Several high-risk chemotherapy regimens were identified; however, larger multi-center datasets are needed to refine dosing guidance based on renal and hepatic function.

Aims: The aim of this study was to determine if head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin chemoradiotherapy and short hydration (SH) experience less dose‐limiting toxicity (DLT) and receive more cisplatin than those with medium hydration (MH) or long hydration (LH). Methods: Baseline characteristics, cumulative cisplatin dose and toxicities were collected. Differences between LH, MH and SH were tested, with separate analyses for triweekly 100 mg/m ² cisplatin and weekly 40 mg/m ² cisplatin. Mixed models assessed the hydration schedule's effect on cumulative dose. Results: A total of 389 patients were included. DLT occurrence was comparable between hydration groups ( P = .060), but DLT type differed ( P = .007). Nephrotoxicity was common with LH and MH (n = 11, 61% and n = 26, 45%, respectively), and ototoxicity with SH (n = 35, 36%). DLT occurrence in triweekly patients differed between LH and MH (n = 18, 64% vs n = 25, 32%, P = .004), but not between MH and SH ( P = .171) or LH and SH ( P = .055) patients. Cisplatin dose differed between LH and MH (median 200 vs 300, P = .008) as well as between LH and SH (median 200 vs 300, P = .024) but not between MH and SH ( P = .429) patients. Hydration had no effect on dose ( F = 2.09, P = .125). Conclusions: DLT cause differed between hydration groups, with less nephrotoxicity but more ototoxicity in HNSCC patients with SH. Triweekly cisplatin LH patients had more DLT and lower cumulative dose compared to MH and SH, but no hydration effect in general on dose was found.

Supplementary Table S8. Overview per patient included in biomarker analysis.

Supplementary Table S5. Baseline characteristics and clinical outcome data of melanoma cohort.

Supplementary Table S1. Representativeness of study participants.

Supplementary Table S4. Evaluated immune marker gene sets.