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PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Renovascular hypertension is the most common cause of secondary hypertension, and radiologist awareness of the various imaging appearances and various causes is crucial for accurate diagnosis and guiding treatment.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented. Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair. Study Design: Prospective cohort study; Level of evidence, 2. Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 were selected. Six-year follow-up was obtained to determine whether any subsequent surgery had occurred since their initial revision ACLR. If so, operative reports were obtained, whenever possible, to verify pathological condition and treatment. Results: In total, 221 patients from 1234 revision ACLRs underwent concurrent primary meniscal repairs (18% of the cohort). There were 238 repairs performed: 173 medial and 65 lateral. The majority of these repairs (n = 181; 76%) were performed with an all-inside technique. Six-year surgical follow-up was obtained in 77% (171/221) of the cohort, or 189 of 238 (79%) of the repairs (136 medial, 53 lateral). The meniscal repair failure rate, defined as reoperation, was 16% (31/189) at 6 years. Of the 31 failures, 28 were medial (24 all-inside, 4 inside-out; 28/136 = 20.6% failure rate) and 3 were lateral (2 all-inside, 1 inside-out; 3/53 = 5.7% failure rate). Three medial failures were treated in conjunction with a subsequent repeat revision ACLR. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears (20.6% vs 5.7%; P = .01) and had a significantly shorter survival time compared with lateral tears ( P = .02). No difference was found between the failure and nonfailure groups when it came to tear type, tear length, repair technique utilized, suture/implant type, or number of sutures used between the 2 groups. Conclusion: Meniscal repair in the revision ACLR setting has a 16% failure rate at 6 years. Failure rates for medial tears (20.6%) were found to be higher than that for lateral tears (5.7%), which aligns with previous studies in both the revision and primary ACLR setting.

Abstract While immunotherapy has transformed treatment in multiple solid tumors, its efficacy in high-grade glioma (HGG) remains limited. Understanding the molecular and clinical factors that influence HGG’s response to immunotherapy is essential to improving outcomes. We identified patients with grade 4 gliomas who had been treated with checkpoint inhibitor (CPI), virus therapy, or CMV-specific T- cell therapy and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes. We identified 66 patients, 57 glioblastoma and 9 astrocytoma, IDH-mutant grade 4; 38 were treated with CPI, 22 with virus therapy, and 6 with CMV-specific T- cell therapy. PIK3CA mutation was associated with shorter PFS and OS (p=0.022, 0.073, respectively) among all patients and a shorter OS among CPI-treated patients (p=0.004). PIK3CA wild-type tumors had less PD-1 expression in CD3+/CD8+ T cells. In CPI-treated patients, IDH1/2 mutation was associated with a shorter OS (p=0.002), and mutations in RB1 and TERT promoter were associated with a shorter PFS (p-value=0.00056, 0.022, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p=0.048, 0.062, respectively), while steroid use at baseline was associated with a shorter OS (p=0.00023). Multifocal disease was associated with shorter PFS and OS durations (p=0.0017, 0.0013, respectively) among all patients. In HGG, PIK3CA, IDH1/2, RB1, and TERT promoter mutations may be associated with a poor response to immunotherapy. These results need to be validated in larger studies. Our results may provide the rationale for clinical trials combining PI3K and IDH inhibitors with CPI in HGG.

Stiff Person Syndrome (SPS) is a rare, progressive autoimmune neurological disorder characterized by painful spasms, muscle rigidity, and heightened sensitivity to external stimuli. Management often relies on therapies that fall outside standard hospice formularies, creating challenges in end-of-life care for affected individuals. We present the case of a 57-year-old woman with metastatic colorectal cancer and SPS whose primary concern in transitioning to hospice was the risk of symptom destabilization if standard neurological treatments, including intravenous immunoglobulin and intrathecal baclofen, were discontinued. Through close interdisciplinary collaboration among palliative care, neurology, and the hospice team, an individualized plan of care was developed that preserved access to symptom-modifying treatments while aligning with the hospice philosophy. Environmental and pharmacologic strategies—including diazepam, levetiracetam, and anticipatory planning—were employed to address evolving symptoms, resulting in effective symptom control and avoidance of hospital readmission. This case highlights the need for flexible, patient-centered approaches in hospice care for rare neurological conditions like SPS. Continuation of disease-specific therapies for symptom palliation can be ethically and clinically appropriate when integrated with clear goals of care. Adaptable interdisciplinary models are essential to attend to quality of life and support care that is in alignment with patient values at the end of life.

Patient-derived organoids (PDOs) have emerged as powerful tools in personalized medicine applicable to both non-malignant conditions and to cancer, where they are increasingly used for personalized drug screening and precision treatment strategies in part due to their ability to replicate tumor heterogeneity. They also serve as study model systems to understand disease mechanisms, pathways, and the impact of ex vivo exposures. We present a detailed step-by-step protocol for generating organoids from normal crypts, polyps, and tumors, including methods for tissue processing, crypt isolation, culture establishment, and the transition from basolateral to apical-out polarity for co-culture and exposure-based studies. The protocol also includes immunofluorescence staining procedures for cellular characterization and quality control measures. Our standardized approach successfully generates organoids from diverse colorectal tissues with high efficiency and reproducibility. This comprehensive guide addresses common technical challenges and provides troubleshooting strategies to improve success rates across different sample types. We believe that this resource will enhance reproducibility in organoid research and expand their utility in translational applications, particularly for personalized medicine approaches in colorectal cancer.

Airway obstruction is a distressing and potentially life-threatening complication in patients with advanced head and neck cancers, particularly squamous cell carcinoma (SCC) of the pharynx. This case highlights the clinical, ethical, and interdisciplinary complexities involved in managing airway compromise in the context of progressive disease and limited treatment options. A 75-year-old man with recurrent SCC of the soft palate, nasopharynx, oropharynx, and hypopharynx, recently initiated on pembrolizumab and radiation therapy, presented with dysphagia, stridor, and intermittent tumor bleeding. Imaging revealed a large pharyngeal mass causing critical airway narrowing. Plans for tracheostomy to manage anticipated radiation-induced edema were aborted following the patient’s acute neurological deterioration, with imaging confirming bilateral carotid artery occlusions and a new stroke. With poor prognosis and elevated risk of carotid blowout syndrome (CBS), further disease-directed treatments were deemed inappropriate. A multidisciplinary team, including palliative care, oncology, and ENT, facilitated a transition to comfort-focused care, emphasizing symptom control, airway management, and emotional support. The patient was transferred to inpatient hospice for end-of-life care. This case underscores the multifactorial nature of airway obstruction in advanced pharyngeal SCC, including tumor burden, treatment-related edema, and vascular complications. It highlights the importance of risk stratification for tracheostomy, especially in the setting of stroke, bleeding risk, and impending CBS. Symptom management was pivotal in maintaining comfort. Nonpharmacologic strategies and psychosocial-spiritual support further contributed to comprehensive end-of-life care. Individualized, multidisciplinary, and patient-centered approaches are essential when curative therapies are no longer appropriate in advanced head and neck cancer. Prioritizing comfort, clear communication, and integrative symptom management can optimize quality of life and support dignity at the end of life.

ImportancePatients with metastatic castration–resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.ObjectiveTo investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.Design, Setting, and ParticipantsThis retrospective cohort study used the deidentified Flatiron-Health electronic health record–derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.ExposuresAge, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.Main Outcomes and MeasuresThe receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.ResultsOf 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).Conclusions and RelevanceThis retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of NSCLC. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines, with a focus on systemic therapy options for the treatment of patients with nonmetastatic NSCLC and the corresponding molecular testing considerations.