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

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. The NCCN Guidelines for HCC provide recommendations for the comprehensive care of patients with HCC, including screening, evaluation, treatment, and surveillance. The multidisciplinary panel of experts meets at least once a year to discuss updates to the NCCN Guidelines based on new and emerging data. These Guidelines Insights focus on some of the recent updates.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma provide multidisciplinary diagnostic workup, staging, and treatment recommendations for resectable, borderline resectable, unresectable, locally advanced, and metastatic disease. This article summarizes the studies and Panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pancreatic Adenocarcinoma.

Background: Treatment for B-cell acute lymphoblastic leukemia (B-ALL) lasts >2 years and can impact families. The Children's Oncology Group multicenter therapeutic trial AALL0932 randomized patients with NCI standard-risk, average-risk B-ALL (NCI-SR AR B-ALL) to receive maintenance vincristine/dexamethasone every 4 or 12 weeks (VCR/DEX4 or VCR/DEX12, respectively). Embedded in AALL0932, this study aimed to (1) longitudinally measure adverse family outcomes overall, and (2) determine whether patients on the VCR/DEX4 regimen (vs VCR/DEX12) had fewer adverse family outcomes.

Methods: Patients with NCI-SR AR B-ALL who were offered enrollment on the multicenter randomized-controlled therapeutic trial AALL0932 were aged ≥4 years with an English-speaking parent. Parent-reported surveys were administered at T1-T5 (approximately 2, 9, 18, 26, and 38 months after diagnosis, respectively; T5 was assessed only in boys) and assessed household changes since leukemia diagnosis, leukemia-related household expenses in the past 4 weeks, unhealthy family functioning (Family Assessment Device score >2), and parents' perceived child vulnerability (Child Vulnerability Scale ≥10). Postrandomization outcomes at T3 and T4 were compared between treatment groups using generalized linear mixed models and multivariable logistic regression models, as appropriate, adjusting for race and ethnicity.

Results: Among 555 participants with completed evaluations, 420 were randomized (mean [SD] age, 6.0 [1.6] years; 45.7% female). At T1, 56.2% of randomized participants reported household changes since diagnosis (81.2% by T4), 88.6% reported ≥$100 in leukemia-related household expenses in the past 4 weeks (61.5% at T4), 19.0% had unhealthy family functioning (23.9% at T4), and 55.8% perceived their child as vulnerable (62.5% at T4). In multivariable models, VCR/DEX4 (vs VCR/DEX12) had an increased likelihood of reporting ≥$100 in leukemia-related expenses in the past 4 weeks (odds ratio, 1.73; 95% CI, 1.03-2.91), but other outcomes were similar between treatment arms.

Conclusions: B-ALL family burdens develop early. Reducing maintenance VCR/DEX frequency may decrease expenses but not other outcomes. Interventions are needed to support families early and throughout ALL therapy.

Background: Optimizing surveillance for the growing population of breast cancer survivors remains a challenge. Although screening guidelines for initial breast cancer are well established, current surveillance guidelines recommending routine provider examinations rely heavily on expert consensus rather than real-world data. Limited evidence exists on how second breast cancer events, including recurrences and contralateral new primary breast cancer, are actually detected in practice.

Methods: We analyzed data from the Pathways Study, a prospective cohort of women diagnosed with stage I-III breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through 2021. We assessed the timing, outcomes, and detection modality of second events, categorized as patient-reported symptoms, surveillance mammogram, provider examination, incidental finding, or ancillary testing.

Results: Of 4,417 eligible women, 792 (17.9%) experienced a second event: 577 (13.1%) had a recurrence and 215 (4.9%) developed a contralateral new primary. Most recurrences were metastatic (70.0%) and symptom-detected (78.0%), with only 9.9% found via surveillance mammogram and 5.0% by provider examination. In contrast, 82.8% of contralateral new primaries were detected via mammogram, with only 0.5% found on provider examination. Recurrences clustered within 5 years postdiagnosis and were associated with poor survival, whereas contralateral primaries occurred steadily over time with more favorable outcomes.

Conclusions: In this large, diverse cohort with high access to survivorship care, routine provider examinations rarely detected second breast cancer events. Detection patterns differed by event type, with recurrences typically early, metastatic, and symptom-detected, whereas contralateral new primaries were found via imaging across the follow-up period. These findings support consideration of more individualized, risk-adapted surveillance strategies that emphasize symptom awareness, patient education, and appropriate use of imaging, rather than uniform examination-based approaches. Further research is needed to evaluate emerging tools, such as circulating tumor DNA and artificial intelligence, to improve the timely detection of second events and survivorship outcomes.

Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of pleural mesothelioma (PM) over the past decade. This review summarizes the history of immunotherapy in PM, covering studies of single-agent immunotherapy, combination checkpoint blockade, the integration of ICIs into frontline therapeutic strategies, and ICI-VEGF combinations. Also discussed are the emerging role of biomarkers in guiding first-line therapy selection for patients with PM and novel therapeutic approaches. Dual checkpoint blockade targeting PD-1 and CTLA-4 demonstrated clinical efficacy in early-phase studies and led to the pivotal phase III CheckMate 743 trial, which established nivolumab and ipilimumab as a standard first-line systemic therapy for PM, particularly in patients with nonepithelioid histology. Since that time, other combination therapy approaches have been explored. For example, chemoimmunotherapy studies have evaluated ICIs, including pembrolizumab and durvalumab, in combination with platinum chemotherapy, with pembrolizumab plus platinum-doublet chemotherapy expanding the approved frontline treatment options for PM. VEGF inhibition, validated in the phase III MAPS study, provided a biologic rationale for combining antiangiogenic agents with ICIs. This prompted investigation of bevacizumab in combination with atezolizumab and chemotherapy in the BEAT-meso study. Unfortunately, this combination did not provide meaningful benefit in this setting. Optimal patient selection and treatment sequencing remain undefined. Although robust data support the use of second-line immunotherapy after first-line chemotherapy, there is a paucity of evidence regarding the efficacy of chemotherapy following frontline ICI. Despite advancements in therapeutic options in PM, biomarker-driven treatment selection remains limited at this time. Future large clinical studies must incorporate validated and standardized biomarker subanalyses, including approaches such as circulating tumor DNA and multiomics, for biomarkers to become clinically relevant in this heterogeneous malignancy. Finally, novel therapeutic strategies, including bispecific antibodies, targeted therapies, perioperative immunotherapy, vaccines, and cellular therapies, are under active investigation and may further expand treatment options for patients with PM.

Background: The combination of radiotherapy (RT) and immune checkpoint inhibitors (ICIs) has become an important therapeutic approach for lung cancer. However, pneumonitis remains a major treatment-related toxicity of this therapeutic approach, and the risk factors for pneumonitis associated with combined RT and ICIs under different treatment sequences have not been clearly defined.

Patients and methods: Patients with lung cancer who received thoracic RT were prospectively enrolled from 3 centers. Pneumonitis was assessed according to CTCAE version 4.0 by a multidisciplinary team. Cox proportional hazards models were used to identify factors associated with pneumonitis.

Results: During a median follow-up of 28.2 months, 133 of 380 (35.0%) patients developed symptomatic pneumonitis (grade ≥2). Treatment with ICIs was associated with an increased risk of symptomatic pneumonitis (hazard ratio [HR], 1.69; 95% CI, 1.20-2.39; P=.003). Among 170 patients treated with ICIs, 89 received ICIs before RT (ICI-first group) and 81 received ICIs after RT (RT-first group). In the ICI-first group, 42 (47.2%) patients developed symptomatic pneumonitis, and an interval of <21 days between ICI administration and RT and a higher percentage of lung volume receiving ≥20 Gy (V20) were associated with an increased risk of pneumonitis. In the RT-first group, 32 (39.5%) patients developed symptomatic pneumonitis, with older age and higher V20 identified as risk factors.

Conclusions: Administration of ICIs before RT significantly increases the risk of pneumonitis in patients receiving thoracic RT. The dosimetric factor V20 consistently emerged as a key determinant of pneumonitis risk in both the ICI-first and RT-first groups. These findings aid in preventing the occurrence of pneumonitis induced by combined RT and ICIs, thereby improving patients' quality of life and survival outcomes.

Background: The use of multiagent immunosuppressive therapy (IST) to treat immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) increases the risk of infection. Time-normalized infection rates in a large cohort have not been previously reported. Predictors of opportunistic and nonopportunistic infections (OIs and non-OIs, respectively) and infection severity are poorly understood.

Methods: We conducted a retrospective chart review of patients treated with ICIs and identified those who received simultaneous multiagent IST for irAE treatment, defined as at least 1 supraphysiologic-dose corticosteroid (steroid) and 2 steroid-sparing ISTs administered within 90 days of one another. Patients who received ≤2 ISTs were not included in the analysis. Total exposure duration and the number of OIs and non-OIs occurring during ICI alone, 1 IST, 2 ISTs, and ≥3 ISTs were used to calculate infection rates per 1,000 exposure-days. Significance was assessed using the Poisson test. The cumulative incidence function and Fine-Gray test were applied to identify clinical features associated with infection risk.

Results: Between June 2011 and February 2024, 20,930 patients received ICI therapy. A total of 142 (0.68%) patients received 3 ISTs and were included in the analysis. Among the 142 patients, 74 experienced a total of 152 infections, including 132 non-OIs in 68 patients and 20 OIs in 17 patients. Cytomegalovirus reactivation accounted for 10 of 20 OIs. Per 1,000 patient-days, the OI density was 0 during ICI alone, 0.06 with 1 IST, 0.57 with 2 ISTs, and 0.42 with ≥3 ISTs (P<.0001). The corresponding non-OI densities were 0.85, 0.90, 2.04, and 4.14, respectively (P<.0001). When mild and moderate infections were omitted, the same trend was observed. In subgroup analyses, age >65 years was a predictor of OIs (P=.046) but not non-OIs, whereas cardiac irAEs were a predictor of non-OIs (P=.018) but not OIs.

Conclusions: These data support the development of improved strategies for infection screening, prophylaxis, and monitoring in patients receiving multiagent IST for irAE treatment.