Chemoradiotherapy with cisplatin in a triweekly regimen of 100 mg/m2 body surface area, is used to treat locally advanced head and neck squamous cell carcinoma (HNSCC) with curative intent. Cisplatin dose limiting toxicity (CDLT) occurs often and impedes obtaining the planned cumulative cisplatin dose. A cumulative cisplatin dose of 200 mg/m2 or more is warranted for better survival and locoregional control. Patients with a low skeletal muscle mass (SMM) have a three-fold higher risk of developing CDLT than patients with a normal SMM. SMM can be assessed through measurements on routinely performed diagnostic head and neck CT- or MRI-scans. A weekly regimen of 40 mg/m2 body surface area cisplatin is proposed as a less toxic schedule, which possibly decreases the risk of developing CDLT and enables reaching a higher cumulative cisplatin dose. The aim of this multicenter randomized clinical trial (NL76533.041.21, registered in the Netherlands Trial Register) is to identify whether a regimen of weekly cisplatin increases compliance to the planned chemotherapy scheme in HNSCC patients with low SMM. The primary outcome is the difference in compliance rate, defined as absence of CDLT, between low SMM patients receiving either the weekly or triweekly regimen. Secondary outcomes consist of toxicities, the cumulative cisplatin dose, time to recurrence, incidence of recurrence at two years of follow-up, location of recurrence, 2-year overall, disease free and disease specific survival, quality of life, patient’s experiences, and cost-effectiveness.

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.

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: 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.