Journal of the National Comprehensive Cancer Network : JNCCN最新文献

Background: Multicancer early detection (MCED) tests are not currently covered by most payers but have begun to emerge in clinical practice. Little is known about whether payers would cover confirmatory diagnostics that are necessary after a positive MCED test. Understanding coverage for confirmatory testing is particularly important for oncology professionals who receive referrals for patients with positive MCED results ordered elsewhere, typically in primary care. Our objective was to examine the views of US private payers on coverage for confirmatory diagnostics after a positive, noncovered MCED test.

Methods: We conducted semistructured interviews with 16 private payers: 8 large national insurers, 5 regional insurers, and 3 organizations providing coverage decision support to insurers. Thematic analysis was complemented by simple frequencies of themes to further describe findings.

Results: Although no payers in our cohort covered MCED, most (63%; 10/16) would cover confirmatory testing after a positive MCED test, although 70% (7/10) would cover it only under specific clinical scenarios (high risk or symptoms). Only a minority (19%; 3/16) would cover repeat confirmatory testing if cancer was not diagnosed. No payer had a formal policy for post-MCED confirmatory testing and only 19% (3/16) planned to establish such a policy. Almost all payers expressed general concerns about patient barriers to confirmatory testing, and most (63%; 10/16) planned to address patient barriers to confirmatory testing if/when MCED is covered, but only 5 payers would consider reducing related patient cost-sharing.

Conclusions: Our findings inform oncology professionals caring for patients with positive MCED results, institutions implementing MCED programs, and payers, policymakers, and researchers addressing MCED challenges. Our study highlights the importance of developing explicit coverage policies for confirmatory diagnostics following a noncovered detection test, as this issue will likely extend beyond MCED for similar novel tests. Patient cost-sharing should be addressed as a national policy issue as MCED adoption grows.

Background: The role of adjuvant immunotherapy (IO) in the treatment of Merkel cell carcinoma (MCC) is currently being explored in clinical trials. Here we aim to evaluate the real-world impact of adjuvant IO on survival in patients with MCC.

Methods: A retrospective analysis of the National Cancer Database was performed to identify patients with stage I-III MCC. Our main predictor of interest was IO in an adjuvant setting, stratified by receipt of radiotherapy (RT). A multivariable Cox proportional hazards regression model with inverse probability treatment weighting was used to estimate overall survival.

Results: A total of 353 patients received adjuvant IO, while 5,340 underwent surgery without adjuvant therapy. Among patients who received adjuvant IO, 10.2% had stage I disease, 7.1% stage II, and 82.7% stage III. Overall, adjuvant IO was not associated with a difference in survival (hazard ratio [HR], 1.04; 95% CI, 0.86-1.26). Stratified analyses by stage demonstrated similar findings (stage I: HR, 1.4; 95% CI, 0.79-2.50; stage II: HR, 1.45; 95% CI, 0.67-3.13; stage III: HR, 0.98; 95% CI, 0.79-1.20). However, when an interaction term with RT was introduced with adjuvant IO, both treatments were associated with improved survival compared with surgery alone (HR, 0.53; 95% CI, 0.28-0.99), whereas adjuvant IO without RT was not associated with a significant survival difference (HR, 1.14; 95% CI, 0.83-1.60).

Conclusions: The association between adjuvant IO on survival may be modified by RT, which should be considered when interpreting current adjuvant IO trials in MCC.

Background: Although intermediate clinical endpoints (ICEs) may expedite completion of randomized controlled trials (RCTs) evaluating perioperative systemic treatments for localized muscle-invasive bladder cancer (MIBC), no validated surrogate for overall survival (OS) has been established. We aimed to assess the surrogacy of pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) for OS.

Patients and methods: We analyzed 4,828 patients with MIBC (cT2-T4N0M0) who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) across 29 European centers (2001-2024). The inverse probability of treatment weighting (IPTW) approach was used to adjust for confounding between NAC and RC-only groups. Surrogacy was evaluated using: (1) adapted Prentice criteria to test whether each ICE remained a significant predictor of OS while the treatment effect disappeared in IPTW-adjusted multivariable Cox models; (2) the proportion of treatment effect explained (PTE); and (3) an emulated 2-stage meta-analytic framework to estimate the pseudo-trial-level R2 between treatment effects on each ICE and OS across 1,000 replicates of 5 random clusters. The surrogate threshold effect (STE) was calculated for ICEs demonstrating strong surrogacy (R2≥0.7).

Results: Overall, 1,288 (26.7%) patients received NAC followed by RC and 3,540 (73.3%) underwent RC alone. In IPTW-adjusted Cox regression analyses including NAC and each ICE separately, pCR (hazard ratio [HR], 0.32; 95% CI, 0.24-0.41; P<.001), pOR (HR, 0.26; 95% CI, 0.21-0.31; P<.001), and DFS (HR, 5.17; 95% CI, 4.56-5.86; P<.001) were independent predictors of OS. The PTE was 0.42 (95% CI, 0.22-0.54), 0.48 (95% CI, 0.24-0.58), and 0.84 (95% CI, 0.66-0.96) for pCR, pOR, and DFS, respectively. At the pseudo-trial level, the R2 was 0.22 (95% CI, 0.20-0.25), 0.33 (95% CI, 0.31-0.36), and 0.83 (95% CI, 0.81-0.84) for the correlation between treatment effects on pCR, pOR, and DFS and OS, respectively. The STE was 0.82 (95% CI, 0.81-0.84) for DFS.

Conclusions: We observed uncertainty regarding the surrogacy of pCR and pOR in patients undergoing RC with or without NAC for localized MIBC. Only DFS consistently mediated the treatment effect on OS, supporting its use as a surrogate for RCT dimensioning when a recurrence or death risk reduction of ≥18% is expected.

Background: Risk of irinotecan-related severe toxicity is significantly higher in patients carrying 2 dysfunctional UGT1A1 gene variants, characterized as poor metabolizers (PMs), following standard irinotecan dosing. Since 2020, we implemented UGT1A1 genotype-guided dosing of irinotecan in routine clinical practice to reduce toxicity in PMs. This study evaluates its impact on severe toxicity in a real-world cohort.

Patients and methods: Our study cohort included adult patients who received UGT1A1 genotype-guided irinotecan dosing at 6 Dutch hospitals between December 2020 and April 2024. Patients were included in the primary analysis if irinotecan was dosed according to UGT1A1 genotype (ie, 100% ±10% dose intensity for intermediate and normal metabolizers [IM/NMs] and 70% ±10% for PMs) in at least cycle 1. Toxicities, hospitalizations, and treatment alterations were collected for cycles 1-3 and graded according to CTCAE version 5.0. Endpoints were compared between PMs with a 70% starting dose and fully dosed IM/NMs.

Results: A total of 501 patients were included in the primary analysis; 54 of whom were PMs (10.8%). Baseline characteristics were evenly distributed between groups. The incidences of overall severe toxicity (29.6% vs 34.0%; P=.52), febrile neutropenia (3.7% vs 5.8%; P=.76), severe neutropenia (17.0% vs 17.8%; P=.88), severe diarrhea (13.0% vs 15.0%; P=.69), and toxicity-related hospitalization (14.8% vs 21.7%; P=.24) were comparable between dose-reduced PMs and fully dosed IM/NMs. In a secondary analysis, 9 UGT1A1 PMs who received an unintended full irinotecan dose experienced more severe toxicity than PMs with a 70% starting dose (overall severe toxicity: 77.8% vs 29.6%; P=.009).

Conclusions: UGT1A1 genotype-guided dosing of irinotecan improves patient safety and treatment tolerability of irinotecan. A 70% starting dose of irinotecan for UGT1A1 PMs is necessary to normalize the risk of severe toxicity to that of IM/NMs.

Background: Cancer-related fatigue (CRF) is a common, distressing symptom in patients undergoing hormone therapy for breast and prostate cancer. Although exercise is recommended, it is not suitable for all patients. Passive therapies such as massage and Reiki may offer accessible alternatives. This study evaluated the feasibility and preliminary efficacy of Reiki and massage therapy in reducing CRF, with Reiki also assessed for potential dose-response effects.

Patients and methods: Adults (age ≥21 years) with breast cancer receiving aromatase inhibitors or with prostate cancer receiving androgen deprivation therapy (ADT) for at least 8 weeks, who reported moderate CRF (score ≥4/10), were enrolled if they had completed other cancer treatments at least 2 months prior. Exclusion criteria included planned nonhormonal cancer treatments, use of erythropoietin or darbepoetin, recent professional massage or energy therapy, or contraindications to massage. CRF was assessed using the Brief Fatigue Inventory (BFI). ANCOVA, adjusted for baseline values, was used to evaluate between-group differences in BFI total score at week 6. Cohen d was used to estimate within-group effect sizes. Feasibility was assessed based on recruitment, retention, and adherence.

Results: A total of 87 participants (breast cancer, n=57; prostate cancer, n=30) were randomized to 2 sessions of massage therapy, 2 sessions of Reiki, or 4 sessions of Reiki. All interventions significantly reduced CRF from baseline (P<.001). Reiki produced greater within-group effect sizes (Cohen d=0.81-1.49 for 2 sessions; 0.99-1.49 for 4 sessions) than massage (d=0.50-0.60). The 4-session Reiki group had the largest reductions in total CRF (d=1.16), worst CRF (d=1.49), and CRF interference (d=0.99). Feasibility was high, with 51% recruitment, 94% retention, and 85% adherence.

Conclusions: Reiki and massage are safe, feasible, and promising interventions for managing CRF in patients receiving hormone therapy. Reiki showed the largest improvements, supporting its clinical relevance. Larger trials are needed to confirm these findings and inform CRF management guidelines.

Clinicaltrials: gov Identifier: NCT02758756.

The recent approval of encorafenib, cetuximab, and FOLFOX based on the phase III BREAKWATER trial has introduced a new standard of care for the first-line treatment of BRAF V600E-mutated metastatic colorectal cancer (mCRC). However, its safety and efficacy in patients with significant liver dysfunction remains unclear and, as such, patients are often excluded from pivotal clinical trials. This report presents a case of BRAF V600E-mutated mCRC presenting with extensive hepatic involvement and liver dysfunction. Despite the absence of guidelines, the patient was initiated on full-dose encorafenib, cetuximab, and FOLFOX. He experienced a rapid clinical and biochemical response, with near-normalization of liver enzymes after cycle 1, and complete functional recovery by cycle 3. Treatment was well tolerated, with no significant adverse events throughout 9 cycles. He subsequently transitioned to maintenance 5-FU, cetuximab, and encorafenib. Posttreatment blood-based next-generation sequencing revealed no residual actionable mutations. The patient then successfully underwent complete surgical resection of his primary tumor and metastatic disease with negative margins. This case highlights the importance of considering encorafenib-based therapy in select patients with BRAF V600E-mutated mCRC in the setting of compromised liver function.

Background: Pathogenic germline variant (PGV) rates in cancer risk genes and their association with clinicopathologic features inform genetic testing practices for patients with prostate cancer (PCa). In this study, we determined the rate of PGVs in PCa risk genes in a real-world, diverse cohort of patients with PCa and identified clinical predictors of carrier status.

Patients and methods: Genetic testing results for 12 PCa risk genes, along with clinical, pathologic, and family history variables, were abstracted from 1,032 patients with PCa who met NCCN genetic testing criteria in oncology clinics, and 3,602 patients with PCa who underwent testing through the VA National Precision Oncology Program. Individual gene PGV rates in patients with PCa were compared with those in individuals assigned male at birth who were cancer-free. Statistical analyses were performed using unpaired t tests and Fisher exact tests.

Results: Among 4,634 patients with PCa, 5.4% had PGVs, with BRCA2 (1.7%), ATM (1.3%), and CHEK2 being the most common. The total PGV rate was significantly higher in 2,825 self-identified White and 1,527 self-identified Black patients (6.3% vs 3.7%; Padjusted=.0024), although rates of BRCA2 and BRCA1 PGVs were similar (1.9% vs 1.3%; Padjusted=.0885 and 0.6% vs 0.5%; Padjusted=.8005, respectively). PGV rates did not differ significantly between 311 self-identified Hispanic and 4,188 self-identified non-Hispanic patients (3.9% vs 5.5%; Padjusted=1.000). In self-identified White and Black patients, PGV rates in BRCA2 and Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2) were significantly higher compared with a cancer-free cohort of individuals assigned male at birth. In a multivariable logistic regression, age at initial PCa diagnosis and self-identified race were significantly associated with the presence of any PGV. In this racially diverse, real-world cohort of individuals with advanced PCa meeting NCCN testing criteria, the overall PGV rate was approximately 5%. Outside of ATM and CHEK2, PGV rates were similar across self-identified race, self-identified ethnicity, and clinical stage.

Conclusions: These data support NCCN Guideline-recommended universal genetic testing for patients with aggressive PCa.

Background: Serious illness conversations (SICs) aim to elicit patient preferences and are associated with improved quality of life and reduced care utilization, but they occur infrequently. Sustainable interventions that encourage SICs are needed.

Patients and methods: This pragmatic 4-arm randomized controlled trial enrolled adult patients at 5 disease-based oncology clinics at 2 sites of an academic cancer center between December 4, 2022, and July 31, 2024. All patients had pathways data indicating they were starting a treatment associated with a poor prognosis without documentation of an SIC in the Advance Care Planning module of the electronic health record (ACP-SICs) in the prior 6 months. Patients were randomized to 1 of 4 groups: (1) a nudge consisting of a mailed letter and questionnaire encouraging SICs; (2) a clinician nudge comprising an email reminder sent the day prior to the clinic visit to prompt an SIC; (3) both nudges; or (4) no nudges. The primary outcome was the proportion of patients with ACP-SICs within 60 days of randomization comparing the control (no-nudge) and combined-nudge arms; a prespecified alternate primary outcome included SICs identified in the free text of clinician notes using natural language processing (ACP + NLP-SIC).

Results: A total of 1,051 patients (median age, 65 years; 60% female; 79% White) were randomized to the control (n=261), clinician-nudge (n=240), patient-nudge (n=273), and combined-nudge arms (n=277). The ACP-SIC rates were 10.7%, 16.7%, 10.6%, and 17.3% for the control, clinician-nudge, patient-nudge, and combined-nudge arms, respectively, and the ACP + NLP-SIC rates were 22.6%, 28.8%, 22.3%, and 32.5%, respectively. Patients in the combined-nudge group had significantly higher ACP-SIC and ACP + NLP-SIC rates than the control group (P=.045 and P=.01, respectively), whereas the clinician-nudge and patient-nudge groups did not.

Conclusions: Combined clinician- and patient-directed nudges resulted in higher SIC rates in 60 days, driven largely by the clinician nudge. NLP increased detection of SICs, demonstrating the importance of evaluating SICs in free-text notes.

As cancer survivorship increases, long-term opioid therapy (LTOT) has become more common in oncology, raising concerns about opioid-related harms. Buprenorphine offers unique pharmacologic advantages that position it as a safer alternative to full agonist opioids (FAOs), yet it remains underutilized in the management of cancer pain (CP). This article reviews the clinical rationale, supporting evidence, and practical considerations for using buprenorphine in managing CP throughout the cancer care continuum, with guidance from the NCCN Adult Cancer Pain Guideline Panel. This review synthesizes findings from pharmacologic research, clinical trials, guideline updates, and expert consensus. It examines the pharmacodynamics, dosing strategies, and safety of buprenorphine in vulnerable populations, as well as its potential to mitigate opioid-related complications. This review also discusses implementation barriers, including prescriber hesitancy, formulary restrictions, and stigma. Buprenorphine provides analgesia comparable to FAOs while reducing the risks of respiratory depression, opioid-induced hyperalgesia, hormonal disruption, and neurocognitive impairment. Buprenorphine may help reduce the neuroadaptive changes associated with LTOT, thereby preserving analgesic efficacy and improving long-term functional outcomes. Multiple formulations and flexible dosing options support personalized care, although regulatory restrictions and clinician unfamiliarity remain significant barriers. Buprenorphine is a viable yet underutilized option for managing CP, particularly when LTOT is anticipated. Broader clinical integration will require more precise guideline recommendations, clinician education, and policy reform. A paradigm shift toward early and proactive buprenorphine use could significantly improve safety, function, and quality of life in oncology patients.