Current negativity definition in esophageal cancer screening overlooks the risk heterogeneity between individuals with non-dysplastic Lugol's unstained lesions (ND-LULs) and normal-stained epithelium. We aimed to define the screening negativity by the incidence risk of severe dysplasia and above lesions (SDAs) after chromoendoscopy and ascertain their re-screening interval.

Treatment of high-risk soft-tissue sarcoma (STS) of extremity or trunk wall involves neoadjuvant chemotherapy (NACT) followed by surgery. Histopathological response could estimate patient outcomes.

Neoadjuvant chemoimmunotherapy does not benefit all non-small cell lung cancer (NSCLC) patients, and reliable biomarkers are urgently needed. We conducted this prospective phase II trial of neoadjuvant chemoimmunotherapy to explore the role of cell-free DNA (cfDNA) features in pathological response assessment.

In the DREAMM-8 trial, belantamab mafodotin, pomalidomide, and dexamethasone demonstrated a statistically significant reduction in the risk of progression or death compared with bortezomib, pomalidomide, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory multiple myeloma. We present patient-reported outcomes from this trial.

The role of postmastectomy chest-wall irradiation in patients with breast cancer classified as pN1 (with involvement of one to three axillary nodes) or pN0 (pathologically node negative) with additional risk factors is uncertain.

With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress are essential in patient clinical care. Mindfulness meditation is a mind-body therapy that is being investigated as a non-pharmacological strategy to alleviate cancer symptoms and improve QoL. Given the potential of this intervention, we hypothesized that mindfulness meditation is feasible and may benefit patients with brain tumors on active therapy by decreasing stress and anxiety.

Molecular glioblastoma (molGBM) is a variant lacking the full histopathological profile of glioblastoma. We report a trial aimed at addressing the optimal management of this newly recognized rarer form of glioma.

Considerable variability exists among liver surgeons in assessing resectability and local treatment planning of initially unresectable colorectal cancer liver-only metastases (CRLM). This study analysed short-term and survival outcomes of one-stage versus two-stage surgery for CRLM.

A phase II trial (MO-Ped; NCT03442985) assessed palovarotene in pediatric patients with multiple hereditary exostosis (MHE). Patients aged ≤ 14 years with MHE were randomized 1:1:1 to placebo, palovarotene 2.5 mg, or palovarotene 5.0 mg daily. Due to concerns of premature physeal closure (PPC), a partial clinical hold was instituted, followed by trial termination. The primary efficacy endpoint was the annualized rate of new osteochondromas (OCs). Safety was assessed. Overall, 193 patients received ≥ 1 dose of palovarotene or placebo. Due to trial termination, no patients completed planned treatment. Prior to 06 December 2019 (patients notified of clinical hold and treatment stopped), 30 patients completed Month 12 efficacy imaging. No significant differences in the annualized rate of new OCs, or change from baseline in volume of OCs or OC cartilage, were observed between treatment groups. The adverse event profile was consistent with systemic retinoids. There was no evidence of an effect of palovarotene on linear growth and no cases of PPC. Overall, palovarotene showed no clear efficacy signal in MHE, resulting in a non-favorable benefit-risk profile. Interpretation of results was limited by the reduced treatment duration and smaller than expected cohort. The trial yielded important data on the natural history of MHE.Trial registration: NCT03442985 (first posted 22 February 2018).

Older adults with HER2-positive early breast cancer are underrepresented in clinical trials, and the benefit of chemotherapy in this population remains uncertain. We evaluated the HER2DX genomic assay within the randomized RESPECT trial (NCT01104935), which compared adjuvant trastuzumab with or without chemotherapy in patients aged 70-80 years. In this prespecified translational analysis (Trans-RESPECT), HER2DX scores were available for 154 patients. The HER2DX risk score classified 74.0% as low risk and 26.0% as high risk. Ten-year relapse-free and overall survival were higher in the low-risk group. HER2DX remained independently associated with overall survival in multivariable analysis. The HER2DX immune, luminal, and proliferation signatures that compose the risk score were also prognostic. While the HER2DX pCR score was not prognostic overall, exploratory subgroup analyses suggested a potential survival benefit from chemotherapy in the pCR-high group. HER2DX offers prognostic value and may guide chemotherapy use in older patients with HER2-positive early breast cancer. Clinical Trial Information NCT01104935.

Actinic keratoses (AKs) are precancerous lesions that may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is an established treatment, often preceded by mechanical curettage to enhance photosensitizer penetration. However, curettage is associated with pain and discomfort, necessitating alternative pretreatment strategies, also applicable in daylight PDT.

Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are generally resistant to targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib, and there are no standard therapeutic options for advanced SDH-deficient GISTs. The precise oncogenic mechanisms of SDH mutations in GIST have not been elucidated. Olverembatinib, a novel multikinase inhibitor, has shown promising activity in treating imatinib-resistant GIST. We conducted a phase 1 study (NCT03594422) to evaluate the safety and antitumor activity of olverembatinib in 66 patients with unresectable/metastatic GIST/other solid tumors, including 26 with TKI-failed SDH-deficient GISTs. To our knowledge, this is the largest prospective clinical trial for this rare GIST subtype. The median follow-up was 14.5 (0.9-57.5) months. Olverembatinib was well tolerated; treatment-emergent adverse events (≥20%) included increases in hepatic transaminases, increases in leukocytes and neutrophils, anemia, and pyrexia. For SDH-deficient GISTs, confirmed partial responses were observed in 6 of the 26 evaluable patients (objective response rate, 23.1%; 95% CI, 9-43.7); an additional 16 (61.5%) did not progress during the first 6 months of treatment. This resulted in a clinical benefit rate of 84.6% (95% CI, 65.1-95.6), and the median progression-free survival was 25.7 months (95% CI, 12.9-NR). As a putative mechanism of action, translational research revealed significant lipid enrichment with the overexpression of lipid uptake-related genes and proteins, including CD36, fatty acid binding proteins, fatty acid transport proteins, and lipid metabolites, in SDH-deficient GIST patients, and olverembatinib suppressed lipid uptake and CD36 expression in GIST cells. Olverembatinib also exerts antitumor effects by inhibiting tumorigenic signaling pathways associated with hypoxia, angiogenesis, proliferation, and survival.

Several studies have evaluated PD-1 inhibitors plus chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), but comparative data with chemoradiotherapy (CRT) remain limited. This multicenter, randomized, open-label, phase 2 non-inferiority trial (REVO, NCT05007145) assessed the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy (ICT) versus CRT in patients with resectable, locally advanced ESCC. A total of 104 patients were randomized to ICT (camrelizumab, nab-paclitaxel, cisplatin) or CRT (nab-paclitaxel, cisplatin, radiotherapy). The primary endpoint was pathologic complete response (pCR). ICT achieved a pCR rate of 32.7% versus 34.6% with CRT (rate ratio 0.94, 90% CI 0.6-1.49), demonstrating non-inferiority and meeting the pre-specified primary endpoint. Major pathologic response was observed in 42.3% of ICT patients and 57.7% of CRT patients, with R0 resection achieved in 100% of both groups. 1-year disease-free survival was 89.1% versus 78.2%, and 1-year overall survival was 100% versus 92.3% for ICT and CRT, respectively. Grade ≥3 treatment-related adverse events occurred in 19.2% of ICT patients and 33.3% of CRT patients, and surgical complications were reported in 31.1% and 35.9%, respectively. These findings indicate that ICT is a safe and effective neoadjuvant strategy for resectable ESCC with a more favorable safety profile.

The incidence of multiple primary lung cancer (MPLC) continues to increase, with synchronous multifocal ground-glass nodules (GGNs) representing a characteristic manifestation. In this study evaluated the efficacy and safety of tislelizumab in patients with MPLC who presented with synchronous multifocal GGNs were evaluated.

The phase II REPLACEMENT study showed promising clinical benefit from atezolizumab plus bevacizumab in transcatheter arterial chemoembolization (TACE)-naïve patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-7 criteria, meeting its primary endpoint of progression-free survival (PFS). Here, we report the final overall survival (OS) analysis.

A recently published phase 2 neoadjuvant trial in patients with early-stage non-small cell lung cancer (NSCLC) (NCT02818920) evaluated the potential efficacy of pembrolizumab administration in the absence of chemotherapy. This communication reports on conventional and distribution-based immune profiling efforts in efforts to identify novel biomarkers predictive of benefit.

IntroductionPatients with cancer may overestimate their ability to adhere to oral anticancer treatments (OAT) which may significantly reduce adherence rates. However, only few studies have investigated the specific role of personality traits and cognitive distortions in the definition of the adherence trajectory in the cancer field.MethodsThis study is nested in the Pfizer project (65080791), and it is a secondary, observational analysis of prospectively collected data from a randomized controlled trial (RCT). To avoid potential bias from comparing measurements across different time points, we limited the evaluation of associations among variables to the baseline data. 94 metastatic breast cancer (MBC) patients (mean age 56.8) receiving OAT for MBC have been enrolled. Each participant filled a set of measures assessing personality (Big Five), adherence (AAI-28 and MMAS-8) (© 2006 Donald E Morisky), and optimistic bias (VAS), and Quality of Life (EORTC QLQ-C30 and EORTC QLQ-BR23).ResultsA discrepancy between self-oriented and other-oriented evaluation of the capacity to take the therapy in the doses, frequencies, and times prescribed was observed (P < 0.001). A negative association between adherence rate and the self-perception of treatment adherence was identified (P < 0.001). Further, conscientiousness correlated positively with the perception of risk to their own health (P = 0.034), and negative association between extraversion and self-perception of treatment adherence (P = 0.05) and between agreeableness and self-perception of treatment adherence have been observed (P = 0.029).ConclusionsOur findings suggest that optimistic bias and personality may contribute to shaping adherence in MBC patients. Personality traits influence adherence both directly, by increasing the perception of health risks, and indirectly, by influencing coping strategies and emotion regulation. MBC patients having an OB may underestimate the important side effects and physical comorbidities, as well as difficulties in the daily management and adjustment of therapy due to disease progression.

Gastric cancer (GC) patients often have nutritional risks or malnutrition, and neoadjuvant chemotherapy (NAC) tends to exacerbate malnutrition. Body composition parameters are associated with the prognosis of GC patients. Little is known about body composition changes during NAC and its role in clinical outcomes.

Cadonilimab, a bispecific antibody simultaneously targeting programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4, may further boost antitumor activity compared with PD-1 or programmed cell death ligand 1 (PD-L1) inhibitors. Here, we evaluated the safety and efficacy of cadonilimab combined with chemotherapy as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC).

In several countries, whole-body imaging has been introduced in the routine follow-up of individuals with high-risk cutaneous malignant melanoma after surgery. However, there is scarce evidence that earlier detection of recurrent disease by regular scanning improves survival. In this interim analysis, we investigated whether imaging in the follow-up programme for high-risk cutaneous malignant melanoma improves survival and assessed whether the study should continue to include participants.