Clinical trials demonstrate that screening can reduce lung cancer mortality by over 20%. However, lung cancer screening effectiveness (reduction in lung cancer specific mortality) may vary by personal risk-factors. Here we evaluate heterogeneity in lung cancer screening effectiveness through traditional sub-group analyses, predictive modelling approaches and machine-learning in individual-level data from the Dutch-Belgian lung cancer screening trial (NELSON; 14,808 participants, 12,429 men, 2377 women, 2 persons with an unknown sex) and the National Lung Screening Trial (NLST; 53,405 participants, 31,501 men, 21,904 women). We find that screening effectiveness varies by pack-years (screening effectiveness ranges across trials: lowest groups = 26.8-50.9%, highest groups = 5.5-9.5%), smoking status (screening effectiveness ranges across trials: former smokers = 37.8-39.1%, current smokers = 16.1-22.7%) and sex (screening effectiveness ranges across trials: women = 24.6-25.3%; men = 8.3-24.9%). Furthermore, screening effectiveness varies by histology (screening effectiveness ranges across trials: adenocarcinoma = 17.8-23.0%, other lung cancers = 24.5-35.5%, small-cell carcinoma = 9.7%-11.3%). Screening is ineffective for squamous-cell carcinoma in NLST (screening effectiveness = 27.9% (95% confidence interval: 69.8% increase to 4.5% decrease) mortality increase) but effective in NELSON (screening effectiveness = 52.2% (95% confidence interval: 25.7-69.1% decrease) mortality reduction). We find that variations in screening effectiveness across pack-years, smoking status, and sex are primarily explained by a greater prevalence of histologies with favourable screening effectiveness in these groups. Our study shows that heterogeneity in lung screening effectiveness is primarily driven by histology and that relaxing smoking-related screening eligibility criteria may enhance screening effectiveness.

Brain metastases are common in patients with lung and breast cancer and are associated with poor outcomes. While there is some intracranial activity with systemic therapies, most chemotherapies are minimally effective. Etirinotecan pegol (EP) is a PEGylated chemotherapy with favorable pharmacokinetics over irinotecan.

This study aimed to evaluate the efficacy and safety of pemetrexed/oxaliplatin (PemOx) in patients with advanced or metastatic biliary tract cancer (aBTC) after failure of gemcitabine/cisplatin (GP)-based chemotherapy.

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC) were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial (GASTO1002, NCT01996098), patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months, or to undergo observation. The primary endpoint was disease-free survival (DFS). This trial was terminated early. A total of 251 patients were randomized. Adjuvant icotinib for 12 months significantly improved DFS (hazard ratio [HR]: 0.40, 95% confidence interval [CI], 0.27-0.61; P < 0.001) and overall survival (OS; HR: 0.55, 95% CI, 0.32-0.96; P = 0.032) compared with observation. Adjuvant icotinib of 6 months also significantly improved DFS (HR: 0.41, 95% CI, 0.27-0.62; P < 0.001) and OS (HR: 0.56, 95% CI, 0.32-0.98; P = 0.038) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P = 0.89) or OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 6.0% and 2.4% for the 12-month icotinib, 6-month icotinib, and observation groups, respectively. Adjuvant icotinib for 12 months or 6 months following adjuvant chemotherapy improved DFS and OS compared with observation in patients with resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile, supporting it as a potential treatment option.

This study investigated prognostic biomarkers in oropharyngeal squamous cell carcinoma (OPSCC), with a focus on tumors related to human papillomavirus (HPV) infection and potential molecular effects of tobacco smoking, as smokers with HPV+ OPSCC often have poorer outcomes.

The clinical use of indocyanine green (ICG) in laparoscopic radical gastrectomy for gastric cancer remains at an exploratory stage.

Single-agent maintenance poly(ADP-ribose) polymerase (PARP) inhibition may represent an effective strategy in patients with advanced/metastatic endometrial cancer responding to platinum-based chemotherapy, including for molecular subtypes with suboptimal options. To explore this approach, we initiated the randomized phase IIb UTOLA trial (NCT03745950). Female patients without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer were randomized 2:1 to twice-daily maintenance oral olaparib 300 mg or placebo until progression or intolerance, stratified by p53 status, mismatch repair status, and response to initial chemotherapy. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints were PFS in subgroups, time to second progression or death, time to first and second subsequent therapy, objective response rate, overall survival, patient-reported outcomes, and safety. In the intention-to-treat population (n = 145), there was no PFS difference between olaparib and placebo (median 5.6 vs. 4.0 months, respectively; hazard ratio 0.94, 95% confidence interval 0.65-1.35; p = 0.74). However, intriguing numerical PFS effects were observed in exploratory analyses of pre-specified subgroups (p53-abnormal, complete response to initial chemotherapy, chromosomal instability). There was no overall survival difference between treatments. Grade 3/4 adverse events occurred in 36% versus 10% of olaparib- versus placebo-treated patients and were consistent with the olaparib safety profile in other cancers. Maintenance olaparib did not improve PFS, but promising numerical effects in subsets of patients warrant prospective evaluation.

Anti-programmed cell death-1 (PD-1) immunotherapy and platinum-based chemotherapy are key components of first-line treatment for advanced Gastric or Gastroesophageal Junction (G/GEJ) cancer. However, the role of immune cells infiltrating the tumor microenvironment (TME) in predicting both therapy responses is still unclear.

This post-hoc analysis of the LASRE trial aims to evaluate the impact of body mass index (BMI) on surgical difficulty and oncological outcomes in patients undergoing laparoscopic or open resection for low rectal cancer.

Lung cancer is a leading cause of cancer-related deaths. Perioperative therapies, including neoadjuvant chemo-immunotherapy, have improved outcomes, but combining them with antiangiogenic drugs may offer further benefits. This study evaluated the 3-year efficacy and safety of neoadjuvant sintilimab, anlotinib, and chemotherapy in resectable NSCLC patients from the TD-NeoFOUR trial.

Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a high recurrence rate after first-line immunotherapy or chemoimmunotherapy. The presence of a high density of tumor-infiltrating lymphocytes (TILs) in HNSCC tumors was shown to be associated with improved clinical outcomes. One-time autologous TIL cell therapy was evaluated in patients with recurrent and/or metastatic HNSCC.

Goal-concordant care is achieved when treatment is aligned with goals. This study describes patient-reported concordance between care goals and treatment intent in advanced cancer compared to other serious illnesses.

An increasing number of early-stage breast cancer (EBC) survivors and limited health care resources have raised interest in developing digital methods for communication between patients and health care personnel. In 2015, Helsinki University Hospital (HUS) Comprehensive Cancer Center (CCC) launched a digital solution called Noona (Helsinki University Hospital; Noona Healthcare) for patients with cancer, which allows patients to report their symptoms or side effects and ask questions with a computer or smart mobile device.

Geriatric assessment (GA)-guided supportive care (GAIN-S) may improve decision-making in older adults with cancer, but its effects on prognostic awareness remain unclear. The authors evaluated whether GAIN-S enhances prognostic awareness among older adults with metastatic cancer in Brazil.

Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin (GemCis) has shown survival benefits in advanced biliary tract cancer (BTC). Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically, and further enhance antitumor effects. ZSAB-TOP was a single-arm, multicenter, phase 2 study (NCT05023109) evaluating efficacy and safety of first-line tislelizumab (a PD-1 inhibitor) plus ociperlimab (a TIGIT inhibitor) and GemCis in advanced BTC. Eligible patients received tislelizumab (200 mg) and ociperlimab (900 mg) on day 1 until unacceptable toxicity or disease progression, in combination with cisplatin (25 mg/m²) and gemcitabine (1000 mg/m²) on days 1 and 8 of a 21-day cycle for a maximum eight cycles. The primary endpoint was confirmed objective response rate (ORR) evaluated by the investigator, which was compared with a historical ORR of 25% with GemCis, with a statistical superiority setting at p ≤ 0.05. From March 8, 2022, to January 18, 2023, 45 patients were enrolled. Among the 41 patients in the efficacy analysis set, the confirmed ORR was 51.2% (95% CI 35.1-67.1), achieving the statistical superiority criteria (p = 0.0003). Patients who had TIGIT+/PD-L1+ (n = 16) tended to have a numerically greater confirmed ORR (75.0% [95% CI 47.6-92.7]). After a median follow-up of 14.6 months, median progression-free survival was 7.7 months (95% CI 6.0-9.4), with a median overall survival of 17.4 months (95% CI 11.7-not reached). Treatment-related adverse events of grade ≥3 occurred in 60.0% of patients; immune-mediated adverse events of any grade was observed in 42.2%, with the majority being grade 1 or 2. In conclusion, first-line tislelizumab and ociperlimab plus GemCis yielded clinically promising tumor response and survival outcomes in advanced BTC and were generally well tolerated without new safety signals.

Docetaxel and capecitabine combination have not previously been studied in advanced head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the combination's safety and efficacy in this population.

Enfortumab vedotin (EV), a novel antibody-drug conjugate directed against Nectin-4, was explored in patients with non-small cell lung cancer (NSCLC) in cohorts 3 and 4 of the open-label, multicohort, Phase 2 EV-202 study (NCT04225117).

Although allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo-HCT remains a major limitation. Post-transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo-HCT is limited due to concerns regarding graft-versus-host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo-HCT for multiple myeloma. This was a prospective, multicenter, phase I/II clinical trial conducted from 2014 to 2019. Lenalidomide maintenance therapy was initiated 100-365 days post-allo-HCT. Eligible patients received lenalidomide on days 1-21 of a 28-day cycle for at least four cycles, beginning at 5 mg/day. A standard 3 + 3 dose-escalation design (Fibonacci method) was used to determine DLT and MTD. The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo-HCT to initiation of lenalidomide was 244 days (range, 169-330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day. No acute GVHD was observed. Two additional patients developed mild chronic GVHD, which resolved spontaneously without treatment. The 2-year progression-free survival (PFS) and overall survival (OS) rates from the start of maintenance therapy were 53% and 78%, respectively. Late initiation of lenalidomide maintenance therapy after allo-HCT for multiple myeloma was feasible at a dose of 10 mg/day and was associated with a low incidence of GVHD-related complications. However, further studies are required to confirm treatment efficacy.

This trial evaluated the efficacy and safety of anti-programmed cell death 1 antibody (SCT-I10A) and anti-epidermal growth factor receptor (EGFR) antibody (SCT200) in patients with previously treated advanced esophageal squamous cell carcinoma (ESCC) (trial registration number: NCT04229537).

The efficacy and safety of conventional first-line chemotherapeutic regimens for the treatment of advanced biliary tract carcinomas (ABTCs) have been unsatisfactory.