JNCI Cancer Spectrum最新文献

Background: In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.

Methods: Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.

Results: The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo.

Conclusions: Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.

Trial registration: ClinicalTrials.gov: NCT04607668.

Background: Black/African Americans experience disproportionate cancer burden and mortality rates. Racial and ethnic variation in cancer burden reflects systemic and health-care inequities, cancer risk factors, and heredity and genomic diversity. Multiple systemic, sociocultural, economic, and individual factors also contribute to disproportionately low Black/African American participation in cancer clinical trials.

Methods: The Participatory Action for Access to Clinical Trials project used a community-based participatory research approach inclusive of Black/African American community-based organizations, Henry Ford Health, and the University of Michigan Urban Research Center. The project aims were to understand Black/African Americans' behavioral intentions to participate in cancer clinical trials and to obtain recommendations for improving participation. Audio-recorded focus group data were transcribed and coded, and searches were conducted to identify themes and subthemes. Representative text was extracted from the transcripts.

Results: Six community focus group discussions (70 participants) and 6 Henry Ford Health patient/survivor focus group discussions (29 participants) were completed. General themes related to trial participation were identified, including (1) systemic issues related to racism, health disparities, and trust in government, health systems, and clinical research; (2) firsthand experiences with health care and health systems; (3) perceived and experienced advantages and disadvantages of clinical trial participation; and (4) recruitment procedures and personal decision-making processes. Specific recommendations on how to address barriers were obtained.

Conclusions: Community-based participatory research is effective in bringing communities equitably to the table. To build trust, health systems must provide opportunities for patients and communities to jointly identify factors affecting cancer clinical trial participation, implement recommendations, and address health disparities.

Background: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4504 women diagnosed with invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their physical activities during the previous 6 months, which were dichotomized as meeting the Centers for Disease Control and Prevention's Physical Activity Guidelines for Americans (≥150 minutes of moderate-intensity or ≥75 minutes of vigorous-intensity activity per week) vs not. Incident CVD events (heart failure, cardiomyopathy, cardiac arrest, ischemic heart disease, stroke) occurring between enrollment and December 2021 were identified from electronic health records. Covariate-adjusted, competing-risks Cox regression models estimated associations between meeting physical activity guidelines and CVD risk.

Results: Compared with women who did not meet physical activity guidelines at their diagnosis, those who did had a 25% lower risk of CVD (HR = 0.75, 95% CI = 0.60 to 0.94). Among the individual CVD outcomes, meeting physical activity guidelines was protective against incident cardiomyopathy (hazard ratio [HR] = 0.54, 95% CI = 0.31 to 0.95), heart failure (HR = 0.66, 95% CI = 0.50 to 0.87), and cardiac arrest (HR = 0.68, 95% CI = 0.49 to 0.99).

Conclusions: Meeting physical activity guidelines at breast cancer diagnosis was associated with lower risk of CVD after diagnosis. Studies investigating changes in physical activity after a breast cancer diagnosis and CVD risk are warranted.

Background: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Methods: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions.

Results: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant.

Conclusions: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.

Background: Black women have a 40% higher breast cancer (BC) mortality rate than White women and are at a higher risk of acquiring cardiovascular disease. Proton therapy (PT) can be used to mitigate cardiac radiation exposure; however, PT remains a scarce resource in the United States. We report on the cardiovascular profiles of patients undergoing PT to determine the potential benefit of PT for Black women when compared to non-Black patients.

Methods: We retrospectively analyzed 599 BC patients who received PT from June 2016 to December 2021 at the Maryland Proton Treatment Center. A variety of sociodemographic, disease, and treatment variables were analyzed using descriptive statistics.

Results: With a median follow-up of 26 months (range: 0.47-90 months), Black patients comprised 31.6% of the population and presented with higher rates of hypertension (p < .001), cardiopulmonary conditions (p < .001), and a larger median BMI (p = .015) when compared to the other cohort, a trend that persisted at time of post-PT follow-up. Black women had higher rates of triple negative disease (p < .001) with subsequent greater receipt of neoadjuvant chemotherapy (p = .039). Pulmonary events were 2.6-times more likely to occur in Black patients vs the non-Black cohort after PT (OR : 2.60; CI: 1.39-4.88; p = .003).

Conclusions: Black women presenting for PT had higher baseline risks of cardiovascular co-morbidities combined with more aggressive BC biology and a subsequent 2.6-fold increased risk of pulmonary events after PT. Our findings support the use of advanced radiation techniques as means to spare important organs-at-risk, especially in historically marginalized populations.

Background: Maintenance niraparib at an individualized starting dose (ISD) is established in platinum-sensitive recurrent ovarian cancer (PSROC). However, patients' perspectives on the burden of prolonged maintenance therapy have not been reported in prospective trials or routine practice.

Methods: In the real-life multicenter NiQoLe study, patients with PSROC received ISD maintenance niraparib. The primary objective was to describe physician-reported adverse events (AEs) leading to treatment modification during the first 3 months. Secondary endpoints included patient-reported outcomes (symptomatic AEs using PRO-CTCAE, self-reported fatigue and impact on daily activities/function using FACT-F) collected remotely weekly using a specifically designed electronic device.

Results: Most (80%) of 139 treated patients (median age 70 years) began niraparib at 200 mg/day. Median treatment duration was 5.7 (range 0.2-21.4) months. During the first 3 months, 86 patients (62%) required treatment modification (median 27 days to modification). Physician-reported grade ≥3 niraparib-related AEs occurred in 34 patients (24%); 68 patients (49%) had treatment modification for AEs, predominantly thrombocytopenia. The most frequent patient-reported AEs (PRO-CTCAE) were fatigue, insomnia, constipation, and dry mouth. Self-reported AEs were severe in 66% of patients. At baseline, 33% of patients reported severe fatigue (FACT-F), which generally persisted during niraparib. Physicians systematically underestimated major patient-reported symptoms.

Conclusions: In routine practice, dose modification was often required during the first 3 months despite individualized dosing. Physicians underestimated the burden of fatigue and symptomatic AEs. Digital self-reporting of AEs is feasible, provides patient-centered information complementing physician-reported AEs, and allows fuller appreciation of toxicity in real-world studies.

Clinical trial information: NCT03752216.

Background: In non-small cell lung cancer (NSCLC), social determinants of health (SDOHs) influence treatment, but SDOHs with geographic precision are infrequently used in real-world research due to privacy considerations. This research aims to characterize the influence of census-tract level SDOHs on treatment for stage I and IIa NSCLC.

Methods: Patients diagnosed between 1/1/17 and 9/30/22 with stages I and IIa NSCLC in the Syapse Learning Health Network had their addresses geocoded and linked to five census tract-level indicators of SDOH (social vulnerability index (SVI), percent (%) housing burden, % broadband internet access, primary care shortage area, and rurality). Clinical and demographic characteristics were ascertained from medical records. Nested multinomial logistic regression models estimated associations between SDOHs and initial treatment using two-sided Wald tests. The collective statistical significance of SDOHs was assessed with a likelihood ratio test (LRT) comparing nested models. Descriptive statistics described time-to-treatment-initiation.

Results: Among 3595 patients, 58% were initially treated with surgery, 29% with radiation, and 12% with "other." Two SDOH variables were associated with increased relative risk ratios (RRR) for radiation therapy compared to surgery: living in primary care shortage areas (RRR 1.61, 95% CI: (1.23-2.10)) and living in non-metropolitan areas (RRR 1.45 (1.02-2.07)). The LRT suggested that the five SDOH variables collectively improved the treatment model. Further, patients in areas with high SVI, low internet access, and high housing-burden initiated treatment later.

Conclusion: When using precise estimates of geospatial SDOHs, these measures were associated with treatment, and should be considered in analyses of cancer outcomes.

Background: People with HIV (PWH) diagnosed with stage-IV cancer are less likely to receive palliative care (PC) compared to those without HIV. Our objective was to evaluate inequities in PC receipt among PWH with stage IV cancer in the US.

Methods: We used the National Cancer Database (2004-2020), including adult (18-89 years) PWH with the 14 most common cancers that occur among PWH. PC was defined as treatment provided with non-curative intent. Our main exposures included % quartiles of adults without a high school degree (educational attainment) and median income quartiles within the patient's zip code. We used hierarchical multivariable Poisson regression to estimate adjusted prevalence ratios(aPR) with 95% confidence intervals (95% CI), adjusting for age, sex, year of diagnosis, race/ethnicity, and cancer type.

Results: Among the included 10,120 PWH with stage IV cancer, 72% were men, 51% were either non-Hispanic(NH)-Black or Hispanic/Latinx, 38% were aged ≥60 years, and 97% resided in urban areas. Fourteen percent received PC. NH-Black PWH living in zip-codes with lower quartiles of educational attainment were more likely to receive PC compared to those in the highest quartile (Q1vs.Q4: aPR:1.93;95% CI:1.29-2,86) For income overall, compared to those in the highest quartile (Q4) of income, those in the lowest quartile had 26% higher likelihood of receiving PC (Q1vs.Q4: aPR:1.26;95% CI:1.05-1.52), particularly among NH-Black adults (Q1vs.Q4: aPR:1.67;95% CI:1.25-2.22; Q2 vs.Q4; aPR:1.48;95% CI:1.09-2.01).

Conclusions: PC use among PWH with stage-IV cancer is low. Contextual poverty plays a role in PC delivery to PWH and cancer, particularly among NH-Black PWH.

Recent studies have shown that de novo metastatic prostate cancer incidence in the United States increased from 2010 to 2019. Plausible explanations include delayed detection after recommendations against prostate cancer screening or upstaging associated with use of more sensitive imaging technologies. Using Surveillance, Epidemiology, and End Results patient cases and controlling for aging of the population, we found the median age and prostate-specific antigen (PSA) level at prostate cancer diagnosis increased by 1.4 years of age (95% CI = 1.3 to 1.5 years) and 1.4 ng/mL (95% CI = 1.4 to 1.5 ng/mL) over this period, consistent with the delayed detection hypothesis. Racial differences were noted, with 75th percentiles of PSA at diagnosis increasing by 4.3 ng/mL (95% CI = 3.7 to 4.8 ng/mL) over this time period for non-Hispanic Black men compared with 3.0 ng/mL (95% CI = 2.8 to 3.2 ng/mL) for non-Hispanic White men. Overall, patient characteristics at diagnosis suggest that delayed detection contributed at least in part to increases in de novo metastatic disease.