This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)-associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.6% (90% CI, 87.2% to 93.1%) and 95.3% (93.0% to 96.9%), respectively. The 54-month PFS by arm was A 93.2% (79.6% to 97.8%; all four recurrences among N1 patients), B 94.9% (89.7% to 97.5%), C 90.2% (82.7% to 94.6%), and D 85.5% (77.5% to 90.8%). The 54-month OS by arm was A 97.1% (85.7% to 99.4%), B 97.9% (93.5% to 99.3%), C 95.1% (90.1% to 97.6%), and D 92.5% (86.9% to 95.7%). PFS or OS did not differ by primary site or smoking history. TOS and neck dissection with deintensified postoperative management results in outstanding 54-month PFS and OS. Among patients with favorable pathologic characteristics, those with N1 disease are at risk of late recurrence without radiation.

There is limited clinical evidence of docosahexaenoic acid (DHA) efficacy during breast cancer neoadjuvant chemotherapy (NAC). This randomized, double-blind, placebo-controlled trial aimed to investigate the safety and efficacy of DHA supplementation in breast cancer patients undergoing NAC. Participants (n = 49) were assigned to receive either DHA 4.4 g/day orally (algae triacylglycerol) or a placebo (corn/soy oil) over six cycles (18 weeks) of NAC. The primary outcome was the evaluation of changes in the percentage of Ki-67 expression, assessed by immunohistochemistry analysis from pre- to post-treatment. Secondary outcomes included pathological complete response, incidence of adverse effects, and 3-year survival analysis. Compliance was evaluated by fatty acid analysis of plasma phospholipids and erythrocyte total lipids quantified by gas-liquid chromatography. The expression of Ki-67 significantly decreased in both groups, with no significant effects of the DHA intervention (p = 0.38). When stratified by breast cancer subtype, there was a trend of greater reduction in Ki-67 expression in the human epidermal growth receptor 2 (HER2+++) subtype in the DHA group compared to placebo (p = 0.1). The % of DHA in erythrocytes and plasma phospholipids was increased by two-fold at 9 and 15 weeks of therapy in the DHA group, while it remained unchanged in the placebo group (p-interaction <0.001). There was no reported incidence of adverse effects related to the intervention, and no significant effects were found in the other secondary outcomes. NAC significantly decreased the expression of Ki-67, with no additional beneficial effects observed by DHA supplementation. Further research is necessary to confirm these findings.

The TGF-β pathway can influence breast cancer progression and therapy efficacy, exhibiting both pro- and anti-tumoral effects. This study examined the impact of active TGF-β signaling on recurrence and radiotherapy (RT) benefit in early-stage breast cancer, using nuclear phosphorylated Smad2 (pSMAD2) as a marker for pathway activation.

To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG.

Most HER2-positive breast cancers co-express estrogen receptor (ER). Given crosstalk between HER2 and ER signaling pathways, dual blockade may be beneficial.

The randomized phase 3 THOR study showed significantly longer survival with erdafitinib (pan-fibroblast growth factor receptor [FGFR] inhibitor) over chemotherapy in adults with FGFR-altered locally advanced or metastatic urothelial cancer (la/mUC) who had progressed during or after anti-programmed death-(ligand) 1 (anti-PD-[L]1) therapy (Cohort 1). This exploratory post-hoc analysis was conducted to evaluate the efficacy and safety of erdafitinib in the Asian subpopulation within THOR Cohort 1.

To assess the technical success of radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC), an artificial intelligence (AI) model was developed to estimate the tumor coverage without the need for segmentation or registration tools.

To explore the benefits and safety of supervised and unsupervised exercise among localized and metastatic prostate cancer patients (PCa) during long-term androgen deprivation therapy (ADT). A total of 44 PCa patients were enrolled in this randomized controlled trial (RCT). Participants were randomized in a 1:1 ratio into the supervised exercise sessions group or the unsupervised home-based exercise group for three months. The primary outcomes assessed included quality of life (QoL), body composition, and metabolic markers, which were measured at baseline, after 3 months, and at 6 months. Muscle strength was evaluated exclusively in the supervised exercise group. The main statistical models used were the Mann-Whitney U-test for between-group comparisons and the Wilcoxon rank-sum test for within-group changes. No adverse events were reported during the exercise period. There were no significant differences in QoL, body composition, or metabolic profiles between the intervention and control groups. The supervised exercise group demonstrated significant improvement in emotional functioning (Z = -2.102, p = 0.036) and all exercise performance metrics (p < 0.001), with the most pronounced gains observed in the leg press (Z = -4.17, p < 0.001). Furthermore, a significant association was identified between strength improvements and enhanced self-evaluated physical function (p < 0.001). Supervised exercise is safe for patients with localized and metastatic PCa undergoing ADT and leads to significant improvements in emotional well-being and muscle strength, which translate to better self-reported physical function. Findings underscore the need for RCTs with longer intervention and follow-up periods on supervised exercise, especially in metastatic PCa patients. Trial Registration: ClinicalTrials.gov identifier: #NCT04050397.

Peritoneal metastasis (PM) after radical surgery is an important cause of treatment failure in colorectal cancer (CRC). Intraoperative intraperitoneal perfusion chemotherapy may be an effective method for preventing postoperative PM in patients with CRC. This study aimed to explore the safety and feasibility of intraoperatively preventive intraperitoneal perfusion chemotherapy using lobaplatin for CRC.

Proteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer. This trial is registered at clinicaltrials.gov (NCT00770809).

Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR).

The aim of this study was to describe the impact of surgical resections on tumour-infiltrating lymphocyte (TIL) therapy, based on results from a randomized phase III trial comparing TIL therapy with standard ipilimumab in patients with metastatic melanoma (NCT02278887).

This paper reports the feasibility testing of the Younger Women's Wellness after Cancer Program in Aotearoa New Zealand (the 'Kōwhai Study') by examining (a) intervention uptake, adherence, and sustainability over time and (b) the feasibility of the proposed trial methods.

Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide.

To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

The PALLAS phase III, randomized trial investigated whether the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) improved invasive disease-free survival (iDFS) over adjuvant ET alone. This study reports the patient-reported outcomes (PROs) by treatment arm.

The efficacy of immune checkpoint inhibitors is limited in patients with high-grade serous ovarian cancer (HGSC). The predictive and prognostic value of tumor-stroma proportion (TSP) was assessed in patients with HGSC treated with platinum-based chemotherapy and pembrolizumab in the NeoPembrOV trial.

The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure.

Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years' follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (n = 165) or preoperative placebo (n = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47-1.21; disease-free survival HR, 0.76; 95% CI, 0.44-1.30; overall survival HR, 0.56; 95% CI, 0.30-1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935 .

Effective prognostication improves selection of patients with prostate cancer for treatment combinations. We aimed to evaluate whether a previously developed multimodal artificial intelligence (MMAI) algorithm was prognostic in very advanced prostate cancer using data from four phase 3 trials of the STAMPEDE platform protocol.