Houston Lee Moffitt Cancer Center & Research Institute is a nonprofit cancer treatment and research center located in Tampa, Florida. Established in 1981 by the Florida Legislature, the hospital opened in October 1986 on the University of South Florida's campus. Moffitt is one of two National Cancer Institute-designated Comprehensive Cancer Centers based in Florida. In 2021, U.S. News & World Report ranked Moffitt Cancer Center as a top 30 cancer hospital in the United States.S.S.
Endoscopic management offers acceptable oncologic control in select patients with upper tract urothelial carcinoma (UTUC) while preserving renal function. Adjuvant intracavitary treatment with chemotherapy or Bacillus Calmette-Guérin (BCG) has been proposed to reduce recurrence risk. We aimed to evaluate the impact of adjuvant intracavitary treatment on ipsilateral UTUC recurrence following endoscopic management. We queried a multi-institutional cohort of patients who underwent endoscopic management for UTUC. Treatment groups were defined as no instillation, single post-operative instillation, or multiple instillations. Ipsilateral UTUC recurrence-free survival (RFS) was estimated using Kaplan-Meier curves and Cox proportional hazards models evaluated factors associated with recurrence. A total of 599 renal units, of which 43 received single instillation and 86 multiple instillations, in 334 patients treated endoscopically for UTUC were analyzed. The median follow-up time for patients without recurrence was 12 months (IQR 4–33). Multiple adjuvant instillations of any intracavitary treatment were associated with a significantly improved RFS (HR 0.52, 95
Complete thyroid ultrasound reporting allows appropriate risk stratification and management of patients with thyroid nodules. Our objective was to assess the completeness of thyroid ultrasound reports based on documentation of key nodule features recommended by clinical guidelines. We conducted a retrospective review of patients who underwent thyroid ultrasound between 2013 and 2020, including those with at least one nodule larger than 1 cm. Using a rule-based natural language processing (NLP) pipeline, key thyroid nodule features were extracted from the reports. At the nodule level reports were classified as complete if all guideline-recommended characteristics were documented. Out of 8,855 thyroid ultrasound reports reviewed, 5,792 (65
PURPOSE:The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. METHODS:We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS:PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION:PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.
The onset of acquired resistance limits the efficacy of KRASG12C inhibitors in patients with lung cancer. Experiments in preclinical model systems and retrospective analyses of patients treated with these inhibitors have both suggested that the activation of DNA repair pathways and G2/M kinases is common in lung cancers with acquired resistance to KRASG12C inhibitors. In this study, we identified a shared vulnerability to the CDK12/13-selective inhibitor SR-4835 in several KRASG12C-mutant cell lines with acquired resistance to sotorasib. In pairs of KRASG12C-mutant parental and sotorasib-resistant cell lines, CDK12/13 inhibition suppressed DNA repair gene expression and induced mitotic arrest, which was exacerbated in sotorasib-resistant cells by failure to activate the G2/M checkpoint and suppression of an oncogenic isoform of TP73. Combined treatment with both sotorasib and SR-4835 yielded an additive response and suppressed the development of acquired resistance to either inhibitor. The inhibitor combination caused additive G1 and G2/M arrest, and the increased sensitivity of emerging drug-resistant cell populations to SR-4835 extended the duration of response over single-agent treatment in cell culture and mouse models. These results support combining KRAS and CDK12/13 inhibitors to extend the duration of response in KRAS-mutant lung cancer. Patients with acquired resistance to sotorasib may benefit from follow-up monotherapy with CDK12/13 inhibitors, the first of which, recently entered clinical trials. Targeting CDK12/13 thus offers a promising strategy to overcome or prevent resistance to KRAS inhibitors. SIGNIFICANCE:CDK12/13 is an effective target to prevent the development of acquired resistance to KRASG12C inhibitors and to treat cancers that have developed resistance, providing a combinatorial approach for optimizing KRAS-mutant tumor treatment. See related article by Solanki et al., p. 467.
Cryoablation is emerging as a minimally invasive alternative to lumpectomy for select women with early-stage breast cancer. The FROST trial (NCT01992250) was a prospective, phase 2 multicenter study evaluating the outcome of cryoablation in the management of stage I, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative invasive ductal carcinoma. Women 50 years old or older with unifocal, ultrasound-visible tumors were stratified by age: stratum 1 (age ≥70 years, endocrine therapy only) and stratum 2 (age 50–69 years, endocrine therapy + radiotherapy + optional sentinel node biopsy). Cryoablation was performed using a single cryoprobe under ultrasound guidance. Core biopsy 6 months after ablation was performed to confirm complete ablation. Patients were followed with clinical exams and imaging. The study included 83 completed cryoablations and follow-up evaluations. The median tumor size was 9 mm. More than 85
