JNCI Cancer Spectrum最新文献

Background: Despite long-standing efforts to improve breast cancer care quality, wide performance gaps persist. We sought to identify regions demonstrating meaningfully low performance and characterize health-system and health-profession factors associated with geospatial disparities.

Methods: We used the Surveillance, Epidemiology, and End Results-Medicare linked database and the Health Resources and Services Administration area health resource file to characterize performance across health-care service areas using 4 metrics: diagnosis stage, chemotherapy, radiation, and endocrine therapy. We used principal component analysis to identify health-care facility and provider characteristics associated with performance; and hierarchical multivariable modeling to attribute total variance proportionally to 5 domains: patient characteristics, health service area region, health-care facility and provider characteristics, randomness, and unexplained.

Results: Among 31,571 women aged 66-79 diagnosed 2007-2013 with stage I-III breast cancer and treated with surgery, 61% had stage I disease, 23% received chemotherapy, 54% received radiation therapy, and 42% received endocrine therapy. Health system factors explained more variance for endocrine therapy (21%), chemotherapy (12%), and radiation therapy (12%), compared with geospatial region or patient characteristics. Health profession factors were associated with quality for stage, radiation therapy, and chemotherapy; health-care facility factors were associated with quality for stage, endocrine therapy, and chemotherapy. Patient characteristics explained <5% of observed variance.

Conclusions: Reassuringly, only a small number of regions demonstrated suboptimal breast cancer care. Optimal performance was associated with multidisciplinary teams and facilities with robust resources and higher volumes. Incorporating geospatial and health system factors into quality measurement efforts could foster the design of impactful quality improvement programs.

Background: The INTEGRATE phase 3 trial in advanced gastric and esophagogastric junction cancer involved pooling overall survival data with its preceding phase 2 trial, raising concerns about misalignment due to treatment switching in phase 2, or the "winner's curse." We evaluated phase 2 results, adjusted for these opposing effects, against phase 3 according to the prespecified statistical analysis plan.

Methods: Overall survival estimates were adjusted for treatment switching using the rank-preserving structural failure time model (RPSFTM) and inverse probability of censoring weights (IPCW) method. A novel shrinkage approach mitigated overestimation from the winner's curse, and Bayesian prediction methods predicted phase 3 outcomes from phase 2 estimates. A simulation study modeled 10 000 seamless phase 2/3 trials to quantify bias in the pooled estimate.

Results: The observed phase 3 hazard ratio (HR = 0.71, 95% CI = 0.54 to 0.93) for overall survival was more conservative than the adjusted phase 2 estimates (RPSFTM and novel shrinkage approach: HR = 0.61, 95% CI = 0.29 to 1.29; RPSFTM and Bayesian prediction: HR = 0.59, 95% CI = 0.48 to 0.73; IPCW and novel shrinkage approach: HR = 0.55, 95% CI = 0.31 to 0.99; IPCW and Bayesian prediction: HR = 0.58, 95% CI = 0.46 to 0.72). Simulations indicated negligible bias in the pooled log hazard ratio of ‒0.011 and 0.005 under the null and alternative hypotheses, respectively.

Conclusion: Adjusting phase 2 estimates for both treatment switching and the winner's curse produced point estimates similar to the unadjusted phase 3 results. A prospective plan to pool trial data under a closed testing procedure may be a reasonable strategy when a recruitment shortfall in phase 3 is anticipated, provided that potential sources of misalignment are thoroughly assessed.

Clinical trial information: ACTRN12612000239864 (INTEGRATE I)NCT02773524 (INTEGRATE IIA).

Background: Residual or recurrent cancer after surgery but prior to adjuvant therapy occurs in a proportion of patients with head and neck cancer and may warrant treatment changes. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) may help to identify residual or recurrent disease but is not routinely obtained. We evaluated the relevance of postoperative FDG-PET/CT in this clinical context.

Methods: This single-institution, retrospective study identified patients with head and neck cancer who underwent definitive surgery between January 1, 2013, and April 1, 2023, and received a postoperative FDG-PET/CT prior to adjuvant treatment. We measured the rates of management changes resulting from postoperative FDG-PET/CT findings and the association between having a postoperative FDG-PET/CT which resulted in a management change and oncologic outcomes with selected multivariable competing-risks and proportional hazards regressions.

Results: Of 150 patients, 66 (44.0%) had a management change because of the postoperative FDG-PET/CT findings; 62 (93.8%) had radiotherapy plan changes, 20 (30.3%) underwent additional diagnostic testing, 11 (16.7%) had systemic therapy added or changed, 3 (4.6%) underwent reresection, and 15 (10.0%) switched to palliative-intent treatment. Having a postoperative FDG-PET/CT that resulted in a management change was not significantly associated with cancer recurrence or overall survival (both P > .05).

Conclusions: In patients with resected head and neck cancer, postoperative, pre-adjuvant therapy FDG-PET/CT can alter clinical management and may enable additional personalization of treatment. When practical to obtain without delaying treatment, postoperative FDG-PET/CT may have clinical utility though requires careful interpretation due to the risks of false positives.

Background: Patients with cancer are at a higher risk of tuberculosis (TB) infection because of the immunosuppressive effect of prolonged chemotherapy. This study determined the prevalence of TB and TB-related deaths among patients with cancer from a global perspective.

Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct the current study. Extracted data from relevant articles were analyzed using Stata, version 17.0, software (StataCorp LP). The effect size estimate was computed using a random-effects model, considering a 95% confidence interval (CI). The I2 statistic and Galbraith plot were used to confirm heterogeneity. A univariate meta-regression, sensitivity, and subgroup analyses were conducted to identify the source of heterogeneity. The Egger test and a funnel plot were used to check publication bias.

Results: In the 13 articles, of the 2 135 402 patients with malignancy, 31 073 had TB. The pooled estimate of TB was 3.69% (95% CI = 1.79% to 5.58%), with high heterogeneity (I2 = 99.99%). The pooled TB prevalence in Europe was 7.04 (95% CI = 1.09% to 12.99%). The prevalence of TB in a single study in North America was 8.78% (95% CI = 8.45% to 9.10%). A higher TB prevalence was observed in patients with solid tumors (6.84%, 95% CI = 4.30% to 9.38%), followed by hematologic malignancies and solid tumors (3.63%, 95% CI = 1.46% to 5.80%). Pulmonary and extrapulmonary TB were 3.05% and 0.77%, respectively. The rate of TB-related death was 0.04%. In meta-regression, publication year and sample size did not affect heterogeneity.

Conclusion: There is a considerable burden of TB (3.69%) in patients with cancer, which calls for routine TB screening and early treatment of cases to reduce complications.

Background: Retrospective analyses of studies of IO-containing combinations for advanced renal cell carcinoma (RCC) suggest that depth of response is associated with overall survival but have methodological limitations. We investigated the relationship of week 12 depth of response as a continuous variable with overall survival.

Methods: Pooling data from patients with treatment-naïve advanced RCC enrolled in randomized IO-containing frontline advanced RCC trials submitted to the US Food and Drug Administration that included week 12 imaging assessment, we developed 36-month overall survival prediction models based on week 12 depth of response (reduction from baseline in target lesion diameter) using Cox proportional hazards with natural spline in an IO combination group and a sunitinib group. To avoid guarantee-time bias, only patients in follow-up at the week 12 scan were included. Overall survival was defined from the week 12 imaging date.

Results: Among the 4 trials that met our inclusion criteria, 1364 patients in the IO combination group and 1267 patients in the sunitinib group had week 12 imaging. Depth of response and 36-month overall survival were correlated throughout the entire range of depth of response in both treatment groups, with no plateau in overall survival as depth of response approached complete response. Across this range, estimated 36-month overall survival was higher in the IO combination group.

Conclusions: Deeper response was associated with better 36-month overall survival in this pooled exploratory analysis of treatment-naïve patients with advanced RCC treated with IO combination or sunitinib. Further work characterizing the relationship between depth of response and overall survival at the trial level may advance understanding of the utility of depth of response as a pharmacodynamic response biomarker or early endpoint in signal-seeking trials and to facilitate efficient drug development.

Background: Personalized therapeutic approaches for localized prostate cancer have evolved significantly, with tissue-based biomarker tests supplementing traditional risk stratification tools. However, national testing patterns and geographic variability remain limited a decade after coverage implementation. We aimed to assess current nationwide utilization and urban-rural differences in tissue-based biomarker testing.

Methods: Using full Medicare claims data, we retrospectively identified patients with newly diagnosed prostate cancer and tissue-based biomarker testing claims from 2019 to 2023. Patients' county of residence was categorized as metro, urban, or rural. Regional testing rates were further assessed across hospital referral regions. A multivariable logistic regression model was performed to assess the effect of residence on test receipt.

Results: Our final cohort included 749 202 patients, of whom 79.5% lived in metro, 11.4% in urban and 8.00% in rural counties. Overall, 86 908 (11.6%) patients underwent tissue-based biomarker tests. Hospital referral region-level testing rates ranged from 2.4% to 42.7%. Rural patients were 18% less likely to undergo testing compared to metro patients (odds ratio [OR] 0.82, 95% CI = 0.73 to 0.91). Independently, the odds of undergoing testing were lower among Black (OR 0.82, 95% CI = 0.77 to 0.88) and Hispanic patients (OR 0.80, 95% CI = 0.73 to 0.88) compared to White patients.

Conclusion: This study reveals high geographic variability in tissue-based biomarker testing for prostate cancer. Further, Black and Hispanic patients were less likely to receive testing. Our findings highlight regional practice variation in the use of advanced, not routinely recommended tests and underscore the need to minimize disparities in diagnostic access.

Background: Bladder cancer is the ninth most common cancer worldwide. Despite its prevalence, large-scale studies on the relationship between socioeconomic disparities and disease stage at presentation are lacking. This study examines the association between the Area Deprivation Index (ADI), a robust measure of socioeconomic status, and stage at diagnosis among bladder cancer patients.

Methods: Patients diagnosed with bladder cancer (any TNM stage) from the Michigan Department of Health and Human Services (2004-2019) were retrospectively analyzed. ADI was assigned based on patients' residential census-block group and stratified into quartiles, with the fourth quartile (ADI 75-100) representing the most deprived. Multivariable logistic regression tested the impact of ADI on advanced disease stages (muscle invasive disease [≥T2], positive nodal status [cN+], metastatic disease [cM+]).

Results: Among 29 010 patients, the majority were non-Hispanic White (92%), males (75%), and residents in metropolitan areas (81%). Patients in the third and fourth ADI quartiles had higher rates of ≥T2 (22%, 24.5%) compared with the first and second quartiles (18%, 19.5%) (P < .001), as well as increased rates of cN+ (3.4%, 3.7%) and cM+ (2.8%, 3.2%) (P < .001). Multivariable regression showed that each 10-unit rise in ADI increased odds of T2 by 4% (95% CI = 1.03 to 1.06, P < .001), cN+ by 4% (95% CI = 1.01 to 1.07, P = .038), and cM+ by 6% (95% CI = 1.02 to 1.09, P = .003).

Conclusion: Higher ADI correlates with advanced bladder cancer stages at diagnosis. Addressing these disparities is essential to improve outcomes in bladder cancer care.

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death and age at diagnosis, sex, race and ethnicity, socioeconomic status, rurality, acute leukemia type, and year of diagnosis were evaluated with logistic regression.

Results: Overall, 6.0% of AYAs experienced early death and there was a significant annual decrease in the odds of early death (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.95 to 0.98, P < .0001) across the study period. Over the entire study period, AYAs diagnosed with acute promyelocytic leukemia (9.6%, 95% CI = 8.4 to 11.1) or other acute leukemias (13.3%, 95% CI = 10.5 to 16.7) had the highest proportion of early death and AYAs diagnosed with T lymphoblastic leukemia/lymphoma had the lowest (2.6%, 95% CI = 1.9 to 3.7). Older age at diagnosis, male sex, and Hispanic ethnicity were all associated with increased risk of early death.

Conclusions: A high proportion of AYAs with acute leukemia experience early death and risk varies by leukemia type and sociodemographic factors. A better understanding of the complex interplay between disease biology and sociodemographic factors is needed to guide risk prediction and prevention.

Background: We investigated the relationship between intakes of red, white, and processed meats with liver cancer-including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, gallbladder cancer, and other biliary tract cancers.

Methods: The analytic cohort consisted of 480 347 US adults in the prospective National Institutes of Health-AARP Diet and Health Study who were cancer-free at baseline at ages 50-71 years. With a median follow-up of 19.68 years, we identified 1150 participants with incident liver cancer (219 intrahepatic cholangiocarcinomas and 931 hepatocellular carcinomas), 231 with incident gallbladder cancer, and 472 with other incident biliary tract cancers (272 extrahepatic cholangiocarcinomas). At baseline, a self-administered food frequency questionnaire assessed usual dietary intake. We used multivariable Cox proportional hazards models to estimate the associations of meat type with hepatobiliary cancers. We used substitution models with the "leave-one-out" approach as our primary analysis and addition models as a supplemental analysis.

Results: Replacing red meat with white meat was inversely associated with liver cancer (hazard ratio [HR]50 g/1000 kcal = 0.62, 95% CI = 0.51 to 0.77), hepatocellular carcinoma (HR50 g/1000 kcal = 0.63, 95% CI = 0.50 to 0.80), and intrahepatic cholangiocarcinoma (HR50 g/1000 kcal = 0.56, 95% CI = 0.35 to 0.90). Because of the symmetry of substitution models, replacing white meat with red meat yielded hazard ratios equal to the reciprocal of these values, indicating increased risk for the same cancer sites. No associations were observed for meat intake and gallbladder or other biliary tract cancers.

Conclusions: Our study indicates replacing intake of red meat with white meat could lower risk of liver cancer by nearly 40%, whereas replacing white meat with red meat could increase the risk by more than 60%.

Background: Evidence of the success of in vitro fertilization (IVF) procedures is critical for informed decision making before and after cancer treatment. We compared IVF outcomes between women with and without cancer.

Methods: Using data from a national IVF database-the Society for Assisted Reproductive Clinic Outcomes Reporting System, linked to statewide cancer registries and birth certificates in 9 states-we identified women who initiated IVF after a cancer diagnosis. Fertility preservation was defined as oocyte retrieval ≤90 days after cancer diagnosis, and IVF after cancer treatment as retrieval >90 days postdiagnosis. Number of oocytes retrieved and conception and livebirth rates were compared between these groups and a comparison group of women without cancer in couples with male factor infertility only.

Results: Compared with retrievals for male factor infertility only (n = 81 370), the number of oocytes retrieved was not significantly different for women who underwent retrieval for fertility preservation (n = 2941) but was significantly lower for women who underwent retrievals after cancer treatment (n = 2479) (mean difference = -2.99, 95% confidence interval [CI] = -3.40 to 2.59). Rate of conception as a function of transfer attempts and likelihood of livebirth after conception also did not significantly differ for fertility preservation (n = 291) compared with male factor infertility only (n = 34 410). Women with IVF after cancer treatment (n = 672) had a lower rate of conception (hazard ratio = 0.70, 95% CI = 0.61 to 0.79) but a similar overall likelihood of a livebirth after conception, relative to the group with male factor infertility only.

Conclusion: IVF outcomes may be maximized when ovarian retrieval is initiated before cancer treatment.