Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

Objectives: Despite optimal local control obtained with neoadjuvant chemoradiotherapy (CRT), data on overall survival (OS) and disease-free survival (DFS) of local advanced rectal cancer patients are still equivocal. This meta-analysis aimed to estimate the pathological complete response (pCR), regression rate, DFS, and OS probabilities of rectal cancer patients treated with a second chemotherapy drug added to fluoropyrimidine and long-term radiotherapy. Methods: Computerized bibliographic searches of MEDLINE, PUBMED, Web of Science and the Cochrane Central Register of Controlled Trials databases (1970–2023) were supplemented with hand searches of reference lists. Studies were included if they were randomised controlled trials (RCTs) comparing intensified chemotherapy with CRT to preoperative CRT and if they had patients with resectable, histologically proven rectal adenocarcinoma without metastases. Results: Eighteen RCTs (7695 patients) were analysed. Data on population, intervention, and outcomes were extracted from each RCT, following the intention-to-treat method, by three independent observers and combined using the DerSimonian and Laird methods. A chemotherapy with two drug and long-term radiotherapy CRT, compared to preoperative CRT (fluoropyrimidine and long-term radiotherapy), significantly increases the rate of pathological complete response (OR 1.37 (95% CI, 1.16–1.63) p = 0.0003) and the regression rate (OR 1.57 (95% CI, 1.16–2.14) p < 0.00001). Furthermore, it increases DFS (HR 0.87 (95% CI, 0.79 to 0.95) p = 0.002 and OS HR 0.84 (95% CI, 0.74 to 0.95) p = 0.007). The risk of severe adverse events (≥G3) is increased OR 1.96 (95% CI 1.35–2.85), p = 0.0005. Conclusions: In patients with resectable rectal cancer, intensified chemotherapy can reduce by 13% the risk of disease progression and by 16% the risk of death.

Objective: The SHARON (Short course RadiatiON therapy for palliative treatment) Bone trial is a phase III randomized non-inferiority multicentric study comparing symptom relief for complicated bone metastases (BMs) achieved through hypofractionated accelerated palliative radiotherapy (RT) to a standard RT regimen. Methods: Eligible participants were adults with ECOG PS ≤ 3 who were referred for palliative RT for painful BMs. Patients were assigned to receive either 30 Gy delivered in 10 daily fractions or 20 Gy in 4 fractions over two consecutive days. The primary outcome was pain relief one month post-treatment. Pain relief and adverse events were also evaluated at 2, 3, 6, and 12 months after RT. This trial was registered at clinicaltrials.gov (NCT03503682). Results: Between February 2018 and November 2021, 83 patients were enrolled (30 Gy: 41; 20 Gy: 42). In the standard RT group, five patients did not complete the prescribed RT, while none in the experimental arm discontinued treatment (p = 0.026). Due to early mortality, the primary endpoint was evaluable in 73 patients (35 and 38 in the standard and experimental arms, respectively). The rate of complete pain response at one month was 22.9% and 28.9% in the 30 Gy and 20 Gy arms, respectively (p: 0.571). The overall pain response rates, which included complete and partial responses, were 74.3% and 78.9% in the 30 Gy and 20 Gy arms, respectively (p = 0.638), when considering at least a 2-point reduction in the numerical rating scale. In both arms, 4.8% of patients experienced Grade >2 toxicity. Conclusions: Administering 20 Gy in four fractions twice a day is non-inferior to the standard 30 Gy delivered in 10 fractions for pain relief in the context of complicated BMs. Furthermore, this regimen demonstrated comparable safety in terms of acute toxicity, with a lower incidence of definitive interruptions of radiotherapy.

Background: Opioid-induced constipation (OIC) is a frequent and clinically relevant complication of long-term opioid therapy in both cancer and non-cancer populations, negatively affecting symptoms, treatment adherence, and health-related quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAs) represent a mechanism-based therapeutic approach targeting peripheral opioid effects while preserving analgesic activity. However, the overall value of PAMORAs, integrating clinical outcomes, patient-reported benefits, and health-economic implications, has not been comprehensively assessed. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PAMORAs versus placebo in adults with OIC was performed. PubMed, Embase, Cochrane CENTRAL, and Web of Science were searched up to June 2025. Studies were stratified according to clinical setting (cancer versus non-cancer populations). The primary outcome was the change in mean weekly spontaneous bowel movements (SBMs). Secondary outcomes included constipation-related quality of life assessed by the Patient Assessment of Constipation–Quality of Life (PAC-QOL) questionnaire and health utility estimation through EQ-5D mapping. A two-step exploratory framework linking SBM improvement to PAC-QOL and subsequently to EQ-5D utilities was applied to extend the economic evaluation across the available evidence base. Results: Nineteen RCTs including 5565 patients (2785 PAMORA-treated and 2780 placebo-treated patients) were included. PAMORAs significantly increased weekly SBMs compared with placebo (mean difference [MD] 1.49; 95% CI 1.04–1.95; p < 0.0001). The treatment effect was highly consistent in non-cancer populations (MD 1.28; 95% CI 1.10–1.46; I² = 0%) and larger but more heterogeneous in cancer populations (MD 2.67; 95% CI −0.001 to 5.35; I² = 93.7%). In five trials reporting quality-of-life outcomes, PAMORAs were associated with a statistically significant improvement in PAC-QOL scores compared with placebo (MD −0.25; 95% CI −0.41 to −0.10); however, only one study demonstrated an improvement approaching a clinically meaningful threshold, limiting the certainty regarding the clinical relevance of the pooled effect. Mapping analyses provided an exploratory estimate of the relationship between bowel function, patient-reported quality of life, and EQ-5D utilities, allowing estimation of illustrative value-based treatment thresholds. Estimated acceptable monthly treatment costs ranged from approximately €25 to €101 depending on population and trial characteristics. Conclusions: PAMORAs consistently improve bowel function in patients with opioid-induced constipation across cancer and non-cancer settings. Available evidence also suggests an improvement in constipation-related quality of life, although the clinical relevance of this effect remains uncertain because of the limited number of studies and the lack of consistently clinically meaningful changes. The exploratory integration of clinical outcomes, patient-reported measures, and health-economic parameters provides a potential framework for personalized treatment evaluation, but the estimated economic thresholds should be interpreted cautiously and should not be considered direct estimates of cross-country cost-effectiveness.