Journal of the National Comprehensive Cancer Network最新文献

With the availability of BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs), outcomes for most individuals with chronic phase chronic myeloid leukemia (CP-CML) are outstanding, with life expectancy similar to age-matched peers. Treatment-emergent adverse events (TEAEs) impair quality of life and many patients struggle with low-level chronic AEs, which for some individuals impact emotional well-being as well as social and work functioning. An emerging body of data supports that many TEAEs are related to therapy dose and can improve with dose reduction. However, it is critical that dose reductions do not alter current outcomes, especially in the rare patients who are at greater risk of losing response or transforming to acute leukemia. Organizations including the National Comprehensive Cancer Network have begun to address when dose reductions may be considered in patients with CP-CML. In this manuscript, we review retrospective and prospective data reporting outcomes in patients after dose reduction and review data supporting lower dose preemptive dosing in first-line and later-line therapy. Switching therapy for intolerance can result in improvements in symptoms and limit toxicity, but other TEAEs may occur. Additionally, emerging therapeutics such as the new class of BCR::ABL1 allosteric inhibitors are under evaluation with a goal of improving tolerability. However, with many TKIs on the cusp of becoming generic, dose reduction becomes an appealing and important cost-effective strategy to minimize TEAEs and improve quality of life while preserving outstanding outcomes in CP-CML.

Background: Hormone receptor (HR)-negative, HER2-positive (also called HER2-enriched) breast cancer has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its association with receipt of care for HR-negative, HER2-positive breast cancer is unknown. We examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment initiation, and survival among nonelderly women newly diagnosed with HR-negative, HER2-positive breast cancer.

Patients and methods: Women aged 18 to 62 years newly diagnosed with HR-negative, HER2-positive breast cancer between 2010 and 2018 were identified from the National Cancer Database. Outcomes included receipt of stage-based guideline-concordant treatment, timely initiation of treatment (<30 days, <60 days, <90 days from diagnosis), and stage-specific 2-year overall survival. A difference-in-differences (DID) analytic approach compared outcome changes following Medicaid expansion in expansion versus nonexpansion states. Multivariable linear probability models were used to estimate treatment outcomes, and flexible parametric survival models were used to evaluate survival, adjusting for sociodemographic and clinical confounders.

Results: A total of 31,401 patients were included. Medicaid expansion was associated with an increase of 0.58 percentage points (ppt; 95% CI, 0.01-1.16) in receipt of guideline-concordant treatment overall, a 2.43-ppt (95% CI, 0.68-4.18) increase in initiating guideline-concordant treatment <60 days after diagnosis, and a 1.17-ppt (95% CI, 0.02-2.32) increase in 2-year survival rate. The increase in 2-year survival associated with Medicaid expansion was most prominent for patients with stage III disease (DID, 3.81; 95% CI, 0.82-6.80).

Conclusions: Medicaid expansion was associated with improved care and survival for patients with HR-negative, HER2-positive breast cancer, an aggressive cancer type for which prognosis largely depends on access to effective treatment.

Background: Patients with intellectual and developmental disabilities (IDD) face unique challenges resulting in disparities in their health care. We sought to define the effect that IDD had on achievement of a "textbook outcome" (TO) following a cancer operation among a nationally representative cohort of patients.

Methods: Data on patients who underwent surgery for a malignant indication, including lung, breast, liver, biliary tract, pancreas, and colorectal, between 2014 and 2020 were extracted from the 100% Medicare Standard Analytical Files database. The association of IDD with TO (defined as the absence of postoperative complications, extended length of stay, 90-day readmission, and 90-day mortality), expenditures, and discharge status was assessed using multivariable logistic regression.

Results: Among 500,472 Medicare beneficiaries, 4,326 (0.9%) with IDD had a cancer diagnosis (breast, n=481; lung, n=419; hepatobiliary, n=194; pancreas, n=145; colorectal, n=3,087). Although overall incidence of TO was 50.5%, patients with IDD were less likely to achieve a TO than those without (37.1% vs 50.6%, respectively; odds ratio [OR], 0.50; 95% CI, 0.46-0.53; P<.001). On multivariable regression, patients with IDD had higher odds of a postoperative complication (OR, 1.53; 95% CI, 1.43-1.64), extended length of stay (OR, 2.06; 95% CI, 1.93-2.21), 90-day readmission (OR, 1.15; 95% CI, 1.07-1.24), 90-day mortality (OR, 1.90; 95% CI, 1.70-2.13), and discharge to a skilled nursing facility (OR, 4.28; 95% CI, 3.97-4.62) (all P<.001).

Conclusions: Patients with IDD had a much lower chance of a postoperative TO, as well as discharge to a nonhome setting. The data highlight the need to improve the care of patients with IDD to assure equitable oncologic surgical care.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.

Background: Although the need to reduce the impact of financial toxicity among patients with cancer is widely acknowledged, few interventions have been developed to address this issue. We tested a novel, multiphase, patient-centered financial navigation (FN) intervention at a large academic medical center.

Methods: We developed a financial toxicity screening tool consisting of the Comprehensive Score for Financial Toxicity (COST) measure plus several additional items based on patient feedback. After systematizing the screening process, 50 patients from the North Carolina Basnight Cancer Hospital were enrolled in the FN intervention following a positive screen for financial distress (COST score <23). The FN intervention involved one-on-one consultations with a trained financial navigator and included an initial comprehensive intake appointment to determine patient eligibility for financial assistance and follow-up appointments to discuss paperwork and application(s) status. We assessed preliminary intervention effectiveness (preintervention and postintervention COST scores) and implementation (ie, fidelity, uptake, acceptability).

Results: All 50 patients assessed for study eligibility screened positive for financial distress. A total of 46 patients completed both the preintervention and postintervention COST instrument and other measures. Postintervention mean COST scores improved from 6.4 at baseline to 13.3 post-FN (P<.0001), indicating a significant decrease in perceived financial toxicity. Fidelity to the intervention was high and 96% of participants received financial assistance.

Conclusions: A patient-centered FN intervention fully integrated into an existing care coordination model can help to decrease the burden of cancer-related financial toxicity among patients with cancer experiencing financial distress. Further studies are needed to test FN interventions in various oncology settings and among targeted populations.

Background: Cancer-related bone pain remains a prevalent and frequently incapacitating ailment. Although conventional approaches effectively alleviate pain in most individuals, a subset of patients may continue to experience intractable pain. Current recommendations for treating cancer-related bone pain include oral analgesics and multimodal adjuvants, radiation therapy, and, in selected cases, intrathecal therapy. Cancer-related bone pain is mediated by a proliferation of sensory and sympathetic fibers. Thus, we believe that this pain can be successfully managed with minimally invasive sympathetic blockade (SB).

Methods: In a retrospective observational cohort, we reviewed patients who underwent single-shot SB for uncontrolled cancer-related bone pain despite receiving opiate analgesics and other interventions. We documented the Edmonton Symptom Assessment Scale (ESAS) ratings, the numeric rating scale (NRS) pain scores, and the morphine equivalent daily dose (MEDD) before and after SB.

Results: The final cohort included 43 patients (median age, 58 years [range, 23-86 years]) with a history of bone pain experienced for a median of 6 months (IQR, 3-12 months). Comparing before and after the SB, patients had pain reduction -6 (IQR, -7 to -4; P<.001), reduction of ESAS scores of -17 (IQR, -23 to -3; P<.001), and reduction of MEDD -57 mg (95% CI, -79 to -34; P<.001). The treatment was well tolerated.

Conclusions: Blockade of sympathetic afferent innervation is an effective and cost-effective modality that can be safely used to palliate intractable pain in patients with malignant bone pain.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The CBCSG010 trial is a prospective and multicenter phase III clinical trial confirming that adding adjuvant capecitabine significantly improved the 5-year disease-free survival (DFS) rate in patients with TNBC by 5.9%. In this study, we attempted to identify the specific population that benefited from adjuvant therapy.

Methods: In this retrospective exploratory analysis, we performed RNA sequencing of tumor tissues from patients with TNBC in the CBCSG010 clinical trial. A single-sample gene set enrichment analysis algorithm and survival analysis were performed to characterize the intrinsic molecular features of the TNBC microenvironment and assess the associations between immune-related gene expression levels or immune cell counts with capecitabine treatment efficacy. Additionally, we performed immunohistochemical staining of 2 markers, PD-L1 and CD8, and hematoxylin-eosin staining of stromal tumor-infiltrating lymphocytes (sTILs) on formalin-fixed, paraffin-embedded specimens to validate findings from bioinformatics analyses.

Results: We found that patients with TNBC with high immune-infiltration treated with capecitabine were more likely to have a better prognosis. We used a cutoff of ≥25 combined positive score (CPS) of PD-L1, ≥10% positive sTILs, and ≥10% positive cells of CD8 to define the "immune-hot" patients. Among immune-hot patients, Kaplan-Meier curves showed that 5-year DFS rates were 96.9% and 79.4% in the capecitabine and control groups, respectively (hazard ratio, 0.13; 95% CI, 0.03-0.52; P=.049 in favor of capecitabine). In the capecitabine group, the 5-year DFS rate was higher for immune-hot patients than for immune-cold patients (96.9% vs 76.4%; hazard ratio, 0.11; 95% CI, 0.04-0.29; P=.028).

Conclusions: Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine, and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients.

CAR T-cell therapy is a recent therapeutic advancement that has transformed the management of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). To date, there are 2 FDA-approved CAR-T products for R/R B-ALL: tisagenlecleucel in patients aged <26 years and brexucabtagene autoleucel in those aged ≥18 years. This review summarizes the pivotal clinical trials that led to FDA approval of these 2 products and highlight emerging data addressing key questions pertinent to CAR-T utilization in the rapidly evolving landscape of R/R ALL management. These include optimal sequencing of CAR-T among other novel immunotherapeutic agents, the role of consolidation and maintenance following CAR-T, novel CAR-T constructs currently under clinical development, and strategies to optimize use of commercially available CAR-T products to improve patient outcomes.