BACKGROUND:Recently, the CheckMate 067, KEYNOTE-006, and RELATIVITY-047 trials demonstrated the long-term efficacy and safety of 5 first-line therapies for advanced melanoma, including nivolumab + relatlimab, with >10 years of follow-up. However, the long-term economic outcomes are still unclear. This study aimed to assess the comparative cost-effectiveness of these strategies from a US health care perspective using more than a decade of clinical trial data. METHODS:Based on the data from clinical trial reports, we simulated a cohort of 1,662 patients with advanced melanoma across 5 treatment groups in which patients received ipilimumab, nivolumab, pembrolizumab, nivolumab + ipilimumab, or nivolumab + relatlimab as first-line therapy. A flexible parametric survival model was used, combined with background mortality rates, to estimate patients' lifetime overall survival and progression-free survival. A partitioned survival model was constructed to assess the total cost, quality-adjusted life-years (QALYs), total life-years, and incremental cost-effectiveness ratios (ICERs) for the 5 treatment strategies. Sensitivity analyses, including univariate, probabilistic, scenario, and subgroup analyses, were conducted to evaluate the robustness of the model and population differences. RESULTS:Nivolumab + ipilimumab provided the highest QALYs (7.30), followed by nivolumab + relatlimab (6.67 QALYs). Ipilimumab and nivolumab + relatlimab were associated with the lowest ($239,168) and highest ($471,610) costs, respectively. Compared with nivolumab, only nivolumab + ipilimumab resulted in ICERs below the willingness-to-pay threshold of $150,000/QALY. Drug costs and body weight were the most influential factors affecting ICERs. Nivolumab + ipilimumab demonstrated the highest probability of being the most cost-effective strategy. CONCLUSIONS:Among first-line immunotherapy strategies for advanced melanoma, nivolumab + ipilimumab and nivolumab + relatlimab provided the greatest survival benefits. After integrating treatment costs, safety, and health-related quality of life, nivolumab + ipilimumab was the most cost-effective strategy under base-case assumptions, followed by nivolumab monotherapy.
Castleman disease (CD) comprises a heterogeneous group of rare lymphoproliferative disorders unified by characteristic lymph node histopathology but with substantial clinical, biologic, and therapeutic diversity. Over the past decade, major advances in disease classification, pathophysiologic understanding, and targeted therapy have reshaped the management of CD, particularly idiopathic multicentric CD (iMCD). The introduction of IL-6-directed therapy has transformed the management of iMCD by shifting treatment from empirical immunosuppression or cytotoxic chemotherapy toward a biologic-based approach, achieving durable disease control in most patients. Progress has also been made over the past several years in the anatomic, etiologic, and clinical classification of CD, enabling more individualized, severity-adapted treatment approaches across the disease spectrum. Emerging paradigms in CD management include the recognition of oligocentric CD (OligoCD) as an intermediate anatomic entity with distinct therapeutic implications, as well as the validation of idiopathic plasmacytic lymphadenopathy (IPL) as a clinically distinct subtype of iMCD. These developments underscore the importance of integrating disease distribution, subtype, and severity into therapeutic decision-making. In addition, the recent paradigm of CD management emphasizes early identification of refractory disease and timely escalation beyond biologic therapy. This review provides an updated overview of CD management, drawing on recent advances to discuss practical considerations in treatment selection across disease subtypes, as well as ongoing challenges and future directions.
BACKGROUND:Medical debt is recognized as a social determinant of health. This study examines associations of county-level medical debt in collections with diagnosis stage and survival among individuals newly diagnosed with cancer in the United States. PATIENTS AND METHODS:A cohort of individuals aged ≥18 years newly diagnosed with cancer in 2011-2019 was identified from the National Cancer Database and followed through December 31, 2019. The county-level share of adults with medical debt in collections was combined with patient-level data. Hierarchical multivariable logistic and Cox proportional hazard models estimated associations of county-level medical debt with cancer diagnosis stage and overall survival, respectively, for all patients and by cancer type, clinical, and socioeconomic subgroups. RESULTS:A total of 7,558,658 individuals with cancer were identified, with median county-level medical debt of 18%, ranging from 0% to 56%. Patients in the highest medical debt quartile had the highest proportion with stage IV disease and lowest 5-year survival rate. After adjusting for other patient- and county-level characteristics, patients living in counties in the highest quartile of medical debt were more likely to be diagnosed with stage IV disease (odds ratio, 1.079; 95% CI, 1.064-1.094) and had poorer survival (hazard ratio, 1.072; 95% CI, 1.061-1.082) than those living in counties in the lowest quartile of medical debt, with a statistically significant dose-response relationship (P for trend <.001). Patterns were observed across major cancer types and were consistent across socioeconomic and clinical subgroups. CONCLUSIONS:County-level medical debt was associated with advanced-stage diagnosis and worse survival among individuals newly diagnosed with cancer. Future research is warranted to evaluate the recent and ongoing US policy changes on medical debt prevalence and their effects on cancer care and outcomes.
The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.
This review summarizes the current NCCN recommendations for the surgical management of pleural mesothelioma, highlighting the clinical trials and retrospective analyses that have shaped current practice and informed guideline recommendations. Advances in systemic therapy, surgical technique, and radiation therapy have shifted management toward multidisciplinary care. Contemporary treatment paradigms emphasize the importance of histology, stage, performance status, and institutional expertise when considering surgical intervention. Surgery can still be considered part of the multimodality treatment strategy in carefully selected patients, despite recent evidence suggesting its possible lack of benefit. Further investigation is required to improve patient stratification, refine multimodal regimens, and develop novel therapeutic approaches. This review aims to provide a contemporary framework for understanding the current role of surgery within the broader management of pleural mesothelioma.
Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.
BACKGROUND:Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases (BMs) in patients with limited-stage small cell lung cancer (LS-SCLC). However, predictive biomarkers that identify patients most likely to benefit from PCI have not been established. This study investigates the potential of 18F-fluoro-2-deoxyglucose (18F-FDG) PET as a predictor of PCI benefit in patients with LS-SCLC. PATIENTS AND METHODS:This multicenter study analyzed patients with LS-SCLC who underwent brain MRI and 18F-FDG PET/CT at baseline, followed by treatment with concurrent chemoradiotherapy. To evaluate whether the benefit of PCI varies according to BM risk, we compared outcomes between PCI-treated and untreated patients stratified by risk group. RESULTS:Of 261 patients overall, 171 received PCI and 90 did not. In patients not receiving PCI, high metabolic tumor volume (MTV; >45.201 cm3) was associated with inferior intracranial time to progression (iTTP; hazard ratio [HR], 5.62; 95% CI, 1.69-18.77; P=.005), progression-free survival (PFS; HR, 2.35; 95% CI, 1.38-4.02; P=.002), and overall survival (OS; HR, 2.23; 95% CI, 1.27-3.91; P=.005). Conversely, MTV demonstrated no significant association with survival outcomes among PCI recipients. Subgroup analysis revealed that PCI conferred no survival advantage in the low-MTV group, whereas in the high-MTV group, PCI was associated with improved iTTP (HR, 0.27; 95% CI, 0.15-0.51; P<.001), PFS (HR, 0.49; 95% CI, 0.35-0.69; P<.001), and OS (HR, 0.56; 95% CI, 0.40-0.80; P=.001). Interaction analysis confirmed a significant effect modification between MTV status and PCI benefit for iTTP, PFS, and OS, supporting MTV as an independent predictive biomarker for PCI benefit. CONCLUSIONS:Baseline PET-derived MTV serves as a clinically relevant predictor of PCI benefit in LS-SCLC, supporting a risk-adapted PCI strategy guided by metabolic imaging biomarkers. This approach may reduce unnecessary neurotoxicity and optimize treatment outcomes and should be prospectively validated.
BACKGROUND:Survivors of hematopoietic cell transplantation (HCT) have an increased risk of skin cancer, yet adherence to recommended skin self-examination (SSE) and annual physician skin examinations is low. Scalable strategies to improve screening in this high-risk population are needed. PATIENTS AND METHODS:We conducted a randomized controlled trial of 720 adult survivors of HCT enrolled between October 30, 2020, and December 13, 2023. Participants received remotely delivered print materials and 12 educational text messages over 9 months (patient activation and education [PAE]). In the PAE plus physician activation group (PAE + Phys), providers also received educational materials and guidance on performing skin examinations. Primary outcomes were participant-reported SSE within the prior 2 months and physician skin examination within the prior 12 months, assessed at baseline and 12 months. Secondary outcomes included the number of body regions examined and skin cancer knowledge. RESULTS:Median age at enrollment was 61 years (range, 18-81), and the median time from HCT until enrollment was 3.1 years (range, 1.7-5.3). The proportion of participants reporting both physician skin examination and SSE increased in both groups, from 15.8% to 47.5% in the PAE group (odds ratio [OR], 4.98; 95% CI, 3.54-7.02) and from 18.0% to 52.1% in the PAE + Phys group (OR, 5.49; 95% CI, 4.03-7.50), with no significant between-group difference. SSE increased significantly in both groups, from 34.7% to 81.5% in the PAE group and from 31.5% to 79.0% in the PAE + Phys group, without no significant between-group difference. Physician skin examinations increased from 32.1% to 55.3% in the PAE group and from 33.2% to 64.8% in the PAE + Phys group, with a significantly greater increase in the PAE + Phys group (P=.01). The mean number of body regions examined more than doubled in both groups, and skin cancer knowledge and self-efficacy improved significantly. CONCLUSIONS:Remotely delivered interventions improved skin cancer screening among HCT survivors. Patient activation substantially increased SSE, whereas physician activation provided additional benefit for physician-performed skin examinations. These findings suggest that physician activation enhances clinician-performed screening and supports scalable survivorship care models for high-risk populations. CLINICALTRIALS:gov identifier: NCT04358276.
Monitoring and detection of relapse are key components of the current treatment paradigm for relapsed or refractory (R/R) multiple myeloma. The degree of clinical disease and biochemical disease progression, as well as the drug classes patients have been exposed or are refractory to, guides the sequencing and timing of therapies for patients with R/R disease. Supportive care focusing on bone health, infection, and thrombosis remains important for these patients. The cornerstones of management of R/R multiple myeloma are a multidisciplinary approach and early referral to tertiary cancer centers.
BACKGROUND:The AJCC staging system has assigned variable prognostic weight to multifocal disease across versions for intrahepatic cholangiocarcinoma (iCCA). We aimed to better delineate how multifocality influences survival in patients with resectable iCCA to refine clinical staging and better inform treatment sequencing. PATIENTS AND METHODS:We retrospectively identified patients undergoing curative-intent hepatectomy for iCCA between 2000 and 2024 from 6 international, high-volume hepatobiliary centers. Patients were stratified by multifocality, T classification, and N classification. Overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses, and a novel modified system was proposed based on current AJCC groupings. RESULTS:A total of 731 patients met the study inclusion criteria. Multifocal disease was present in 36% of patients with T2-T4 tumors and was independently associated with worse OS (hazard ratio, 1.64; 95% CI, 1.21-2.22; P=.002) compared with solitary tumors on multivariable analysis. This survival disadvantage persisted across T2 classification (28.8 vs 44.8 months; P=.001) and T3 classification (21.2 vs 36.5 months; P=.003), and remained significant after adjustment for nodal status (P=.003 and P=.017, respectively). Compared with solitary disease, multifocality also conferred worse OS in patients with node-negative (36.0 vs 58.9 months; P=.003) and regionally node-positive disease (19.2 vs 23.8 months; P=.016). Current AJCC staging failed to distinguish prognostic differences between stage II and stage IIIA disease (48.3 vs 46.9 months; P=.190). However, our proposed modifications, which classify multifocal tumors as T3 and upstage multifocality from stage II to stage IIIA in node-negative disease and from stage IIIB to a newly defined stage IIIC in node-positive disease, better stratified overall risk (P<.001). CONCLUSIONS:Multifocality independently predicts poor prognosis in resectable iCCA. Refining the current staging system by reclassifying multifocal tumors as T3 may improve prognostic stratification and better inform treatment sequencing.
BACKGROUND:Combination amivantamab-lazertinib, osimertinib + chemotherapy, and osimertinib monotherapy are the current standard first-line therapies for treatment-naïve patients with EGFR-mutated advanced lung cancer. We aim to compare the cost-effectiveness of all 3 regimens. METHODS:This economic evaluation with a 20-year time horizon and annual 3% discount was conducted from the perspective of the health care sectors in Taiwan and the Unites States (US). Simulated patients were entered into partitioned survival models upon initiation of amivantamab-lazertinib, osimertinib + chemotherapy, and osimertinib monotherapy. Model inputs were derived from trials and network meta-analyses (progression-free/overall survival, adverse events, and subsequent therapies), insurance payments or retail prices (costs of drug administration, physician visits, monitoring, and end-of-life care), and hospital cohorts (health utility). Subgroup, one-way deterministic, and probabilistic analyses were performed. RESULTS:The incremental cost-effectiveness ratios (ICERs) of osimertinib + chemotherapy versus osimertinib monotherapy (Taiwan: $231,234 per quality-adjusted life-year [QALY]; US: $442,506/QALY) and amivantamab-lazertinib versus osimertinib + chemotherapy (Taiwan: $412,332/QALY; US: $2,623,132/QALY) exceeded willingness-to-pay (WTP) thresholds (Taiwan: $70,000/QALY; US: $150,000/QALY). Cost of drugs and adverse event management accounted for the main cost differences among the 3 strategies. ICERs remained higher than WTP thresholds across patient subgroups. The lowest ICER for amivantamab-lazertinib versus osimertinib + chemotherapy (Taiwan: $232,192/QALY; US: $1,319,408/QALY) was noted among patients aged ≥65 years. Osimertinib + chemotherapy had a 2.0% (Taiwan) and 0.4% (US) probability of being cost-effective at the respective WTP thresholds, with amivantamab-lazertinib showing an even lower probability. CONCLUSIONS:Our analysis suggests that despite the superior efficacy of amivantamab-lazertinib and osimertinib + chemotherapy, neither is cost-effective compared with osimertinib as first-line treatment for EGFR-mutated advanced lung cancer.
BACKGROUND:Among older adults with cancer, poverty is associated with end-of-life (EoL) care quality; however, its impact on care among adolescents and young adults (AYAs) is poorly understood. We examined the relationship between neighborhood poverty and EoL care among AYAs. METHODS:We identified AYAs with cancer who died between the ages of 12 and 39 years from 2003 to 2019 at Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California. Outcomes abstracted from medical records included care/treatment information, symptom evaluation, and psychosocial/spiritual care. Neighborhood poverty was derived by linking patient ZIP Code Tabulation Areas to the 2009 to 2013 American Community Survey. Multivariable logistic regression models assessed the relationship between neighborhood poverty and outcomes, adjusting for age at death, sex, race, ethnicity, cancer site, and care site. RESULTS:Included AYAs (n=1,905) had median age of 30 years at diagnosis and 32 years at death; 55% were female, 61% were White, 27% were Hispanic/Latino, and 19% were from a high-poverty neighborhood. In bivariate analyses, compared with AYAs from low-poverty neighborhoods, AYAs from high-poverty neighborhoods were more likely to be hospitalized ≥2 times in their last 30 days (29% vs 22%; P=.004) and had lower hospice use (57% vs 64%; P=.008). Pain was assessed among 98% and was assessed less often among AYAs from high-poverty neighborhoods (96% vs 99%; P=.008). In multivariable analyses, AYAs from high-poverty neighborhoods had higher odds of >1 emergency department visit (odds ratio [OR], 1.33; 95% CI, 1.00-1.76) and >1 hospitalization in the last 30 days of life (OR, 1.33; 95% CI, 1.02-1.75), and lower odds of hospice use (OR, 0.76; 95% CI, 0.58-0.98). CONCLUSIONS:Sustainable care delivery methods for patients who lack resources to address their EoL needs outside of the health care system are needed.
BACKGROUND:The Health Equity Report Card (HERC) was developed to establish best practice recommendations and promote accountability among health systems in addressing care inequities. Recognizing the growing importance of health equity, particularly in cancer care, this study aims to evaluate the feasibility of implementing the HERC within academic cancer centers and to gather insights on its benefits and challenges during implementation to improve its usability. METHODS:This quality improvement study used a mixed-methods approach, collecting both quantitative and qualitative data over an 18-month period from April 2022 to October 2024 from 5 NCCN Member Institutions. Participants completed self- and third-party scores, as well as survey evaluations providing feedback on the process of using the HERC. Feedback from stakeholders was systematically collected to assess usability and identify areas for improvement. RESULTS:All participating sites successfully achieved the feasibility objectives by completing the self- and third-party scoring processes using the HERC, with unanimous agreement among the sites regarding the feasibility of the HERC for implementation. Site feedback indicated areas for enhancement, particularly in improving question clarity and simplifying the scoring process. Continuous feedback loops facilitated iterative improvements to the HERC, ultimately enhancing user experience and the scoring process. CONCLUSIONS:The HERC demonstrates strong potential as a viable framework for prioritizing and assessing equity in care delivery within academic cancer centers. The successful implementation across multiple sites, along with positive stakeholder feedback, underscores its utility in enhancing accountability and promoting best practices in addressing health inequities. Future studies should explore the long-term impacts of HERC implementation on patient outcomes and equity in care delivery. A study testing the HERC for applicability in community oncology settings is ongoing.
BACKGROUND:Patients undergoing bone marrow transplantation (BMT) experience significant physical and psychological symptoms. Scalable psychosocial interventions to reduce distress and improve quality of life (QoL) are limited. Virtual reality (VR), with its 3-dimensional capabilities, offers a novel, scalable, patient-centered modality to address these needs. METHODS:We randomized adult patients with hematologic malignancies undergoing autologous or allogeneic BMT to receive either a VR supportive care intervention (BMT-VR) or usual care during hospitalization. BMT-VR consists of 6 modules focused on: (1) psychoeducation and managing expectations; (2) psychosocial skill-building to promote coping; and (3) strategies to facilitate acceptance while facing uncertainty. The primary endpoint was feasibility (≥60% enrollment and ≥60% completion of ≥4 of 6 modules). Secondary outcomes included QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant), depression and anxiety (Hospital Anxiety and Depression Scale), and posttraumatic stress disorder symptoms (Post-Traumatic Stress Disorder Checklist-Civilian Version) at baseline and at weeks 2, 4, 12, and 24 post-BMT. The System Usability Scale (≥80 indicates excellent usability) was administered at 4 weeks post-BMT. RESULTS:Of eligible patients, 62.5% (85/136) consented and 59.6% (81/136) enrolled in the study (mean [SD] age, 57.9 [14.7] years; 51.9% female; 70.4% underwent allogeneic BMT). Among those assigned to BMT-VR, 64.1% completed ≥4 of 6 modules, exceeding feasibility benchmarks, and 69.2% (27/39) rated usability as excellent. After 4 weeks, patients assigned to BMT-VR reported improved QoL (108.2 vs 96.8; P=.014) and anxiety symptoms (3.6 vs 5.3; P=.016) versus usual care. No differences in depression or PTSD symptoms emerged at 4 weeks. Longitudinally, BMT-VR participants showed greater improvements in QoL (β = 3.8; P=.002), depression (β = -0.8; P<.001), and PTSD (β = -1.7; P=.006), but not in anxiety, compared with usual care. CONCLUSIONS:A VR-delivered psychosocial intervention is feasible during hospitalization for autologous or allogeneic BMT and shows promising preliminary effects on QoL and psychological outcomes. A future multisite trial is needed to assess efficacy for improving QoL and psychological distress in BMT recipients.
Background: Although studies have reported on the impact of the COVID-19 pandemic on colorectal cancer (CRC) screening, data on long-term changes remain limited, particularly during the later phases of the pandemic (post 2021) and among racial and ethnic subgroups. Patients and Methods: We analyzed data from the 2019, 2021, and 2023 National Health Interview Survey to assess clinician recommendations for CRC screening, past 2-year screening rates, and screening modalities used. Trends were compared across racial/ethnic groups and social determinants of health, including insurance status and income. Results: Our sample represented 95 million individuals in 2019, 97 million in 2021, and 98 million in 2023. Compared with 2019, CRC screening recommendations dropped by 20% in 2021 ( P <.0001), with larger decreases among Hispanics (28%) and uninsured individuals (41%). Recommendations remained 11% lower in 2023 ( P =.03). In 2021, past 2-year colonoscopy use declined by 8% ( P =.001), whereas multitarget stool DNA testing (mt-sDNA) increased by 18% ( P =.03) and fecal immunochemical test/fecal occult blood test (FIT/FOBT) use increased by 55% ( P <.001). Colonoscopy declines were greatest among Asian individuals (32%), whereas increases in FIT/FOBT use were highest among Hispanic (78%) and Black (92%) individuals. By 2023, colonoscopy use had returned to prepandemic levels (28%), and mt-sDNA use increased by an additional 40%, resulting in an overall 8% increase in past 2-year screening compared with 2019 ( P <.001). Conclusions: Early in the pandemic, increased stool-based testing offset reduced colonoscopy uptake. Colonoscopy rates have since recovered, whereas stool-based testing continues to increase, with notable differences across ethnic groups. This sustained shift toward stool-based testing offers an opportunity to improve screening, especially where colonoscopy access is limited.
The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.
The NCCN Guidelines for Bladder Cancer provide strategies for the diagnosis, treatment, and follow-up of patients with bladder cancer, which is the sixth most common cancer in the United States. Bladder cancer can be divided into 3 categories along a clinical spectrum: (1) non-muscle-invasive bladder cancer; (2) muscle-invasive bladder cancer; and (3) metastatic bladder cancer, with most patients falling into the category of non-muscle-invasive disease. Thus, the selected content featured in this issue specifically covers the clinical presentation and workup of and subsequent management recommendations for non-muscle-invasive bladder cancer.
