JNCI Cancer Spectrum最新文献

Background: Granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, are associated with bone pain, potentially impacting treatment adherence. This study hypothesized that a 5-day regimen of filgrastim would result in less bone pain than single-dose pegfilgrastim in patients receiving chemotherapy for early breast cancer.

Methods: In this multicenter, open-label, randomized controlled trial, patients requiring prophylactic G-CSF during chemotherapy were randomly assigned 1:1 to receive either 5-day filgrastim or pegfilgrastim. The primary outcome was patient-reported bone pain, assessed as area under the curve of daily pain scores (0 = no pain to 10 = worst pain) over the first 5 days following G-CSF in cycle 1. Secondary outcomes included bone pain in cycles 2-4, febrile neutropenia, hospitalizations, chemotherapy delays, dose reductions, early discontinuations, chemotherapy-related deaths, health-related quality of life, and health-care resource utilization.

Results: From June 2021 to March 2023, a total of 233 patients were randomly assigned, with 219 analyzed (110 filgrastim and 109 pegfilgrastim) after excluding those who withdrew before receiving treatment. Adjusting for stratification factors and prespecified baseline covariates using repeated measures linear regression, the mean area under the curve (0-40) for cycle 1 bone pain was 10.2 (11.2) for 5-day filgrastim and 10.2 (9.81) for pegfilgrastim, with an adjusted mean difference of 0.70 (95% confidence interval = 1.62 to 3.02; P = .556). Although no clinically significant differences were observed in most secondary outcomes, the 5-day filgrastim group exhibited a numerically higher incidence of febrile neutropenia (6.4% vs 0.9%, P = .065) and hospitalization (10.0% vs 3.7%, P = .106).

Conclusion: There was no significant difference in bone pain between 5-day filgrastim and pegfilgrastim.

Background: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry.

Methods: The study evaluated 1002 patients treated with endocrine therapy (ET) only or ET with chemotherapy (ET+CT) enrolled in FLEX (NCT03053193) with 5-year median follow-up. Propensity-score matching balanced treatment groups by menopausal status, T-stage, and nodal status. The primary endpoint was distant recurrence-free interval (DRFI). Regression and Cox proportional hazards models assessed chemotherapy benefit across MammaPrint Index (MPI) risk.

Results: Most patients were postmenopausal (70.1%), node-negative (70.0%), and had grade 2 tumors (51.2%). The regression models showed that MPI strongly predicted 5-year DRFI in ET only (R2 = 0.99, P < .001) and ET + CT (R2 = 0.90, P < .001) groups, corresponding to an average absolute chemotherapy benefit of 5.6% in High 1 and 10.9% in High 2. Minimal improvement in DRFI with chemotherapy was observed for Low (1.7%) and UltraLow (<1.0%) risk groups. A multivariate Cox model with an MPI-by-treatment interaction term demonstrated that increasing MPI risk was associated with greater chemotherapy benefit on DRFI (HR = 0.15, P = .047). Chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status, or grade.

Conclusions: These RWD from the FLEX Registry demonstrate that MPI is predictive of both DRFI prognosis and chemotherapy benefit in HR+HER2- EBC. (NCT03053193).

Background: Human papillomavirus infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix, a rare aggressive subtype without human papillomavirus infection.

Methods: To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma in 3 independent cohorts of patients with gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma. The first cohort comprised 8 gastric-type adenocarcinoma of the cervix and 22 patients with usual-type endocervical adenocarcinoma treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing. The other 2 cohorts comprised 52 patients with gastric-type adenocarcinoma of the cervix and 109 patients with usual-type endocervical adenocarcinoma and 39 patients with gastric-type adenocarcinoma of the cervix and 232 patients with usual-type endocervical adenocarcinoma, whose mutational data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (Japanese patients) and Genomics Evidence Neoplasia Information Exchange (US patients) public databases, respectively. Metabolomic analysis was performed in 8 patients, including 5 with gastric-type adenocarcinoma of the cervix.

Results: TP53 mutations were more prevalent in gastric-type adenocarcinoma of the cervix than in usual-type endocervical adenocarcinoma in all 3 cohorts. Transcriptome analysis consistently revealed frequent suppression of TP53-related pathways in gastric-type adenocarcinoma of the cervix. Metabolites preferentially detected in gastric-type adenocarcinoma of the cervix tissues suggest TP53 alterations are implicated in intratumoral metabolic properties.

Conclusion: The development of gastric-type adenocarcinoma of the cervix is likely driven by TP53 mutations, which play a large role in shaping intracellular signaling and metabolic profiles within tumor cells.

Background: Cancer survivors may be more likely to experience accelerated declines in physical function compared to cancer-free controls, but objective data and knowledge of preventive interventions are limited.

Methods: The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, single-blinded, randomized trial conducted at 8 centers across the United States that enrolled 1635 sedentary adults aged 70-89 years and with physical limitations but who could walk 400 m at baseline, of which 371 (22.7%) reported a history of cancer. Participants were randomized in a 1:1 ratio to a health education or physical activity program. The primary endpoint was time to major mobility disability, defined objectively by the inability to walk 400 m in less than 15 minutes.

Results: Cancer history modified the effect of randomized group on major mobility disability (P = .006). Among those randomized to the health education program, participants with a history of cancer were 53% more likely to develop major mobility disability compared with participants who did not have a history of cancer (Hazard Ratio (HR) = 1.53; 95% CI = 1.18 to 1.99; P = .001). Among participants with a history of cancer, those randomized to the physical activity program were 43% less likely to develop major mobility disability compared with the health education program (HR = 0.57; 95% CI = 0.40 to 0.82; P = .003).

Conclusion: In this analysis of a randomized clinical trial, cancer survivors had an increased risk of mobility disability compared with non-cancer controls, and physical activity attenuated this risk.

Socioeconomically disadvantaged counties exhibit higher cervical cancer incidence and poorer survival. However, the specific impact of the magnitude of persistent poverty on these outcomes remains largely unexamined. Using national cancer registry data, we observed that women living in persistent poverty counties who have experienced extreme poverty (≥40% poverty) have more than 1.5 times higher cervical cancer incidence and twice the mortality rate as women who lived in nonpersistent poverty counties. Furthermore, stage-specific incidence was consistently higher in persistent poverty counties across localized, regional, and distant diagnoses. Five-year mortality for localized cervical cancer diagnoses was nearly twice as high in extreme poverty counties (11% vs 6%, 2-sided P = .03). These findings highlight substantial disparities in cervical cancer outcomes associated with increasing magnitude of persistent poverty and underscore the need for targeted interventions in economically vulnerable communities to reduce disparities and achieve cervical cancer elimination goals.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.

Methods: We conducted a systematic review and meta-analysis of RW studies on HR+/HER2- MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs' 95% confidence intervals (CIs). Similar criteria applied to pooled hazard ratios (HRs) of PFS/OS for palbociclib+AI vs AI in visceral/nonvisceral subgroups.

Results: Twelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95% CI = 19.5 to 31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI = 20.2 to 27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95% CI = 11.6 to 28.5) exceeded PALOMA-3 (11.2, 95% CI = 9.5 to 12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95% CI = 6.3 to 15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95% CI = 49.1 to 53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95% CI = 37.5 to 53.8). WMOS (49.1 months, 95% CI = 49.1 to 53.3) was slightly lower than RCTs (53.7, 95% CI = 37.5 to 53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in nonvisceral disease.

Conclusions: RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.

Solid organ transplant recipients (SOTRs) in the United States have lower risks for breast and prostate cancers than the general population. To explore whether pretransplant screening explains this observation, we conducted a case-control study of US adults aged 65 years or older using the SEER-Medicare database (2000-2019). We included 252 279 breast cancer cases, 3 855 275 female controls, 316 981 prostate cancer cases, and 2 361 846 male controls. We used Medicare claims to identify solid organ transplant procedures and screening with mammography or prostate-specific antigen testing before case/control selection. SOTRs exhibited reduced risks for breast cancer (adjusted odds ratio = 0.60, 95% CI = 0.45 to 0.80) and prostate cancer (0.84, 95% CI = 0.71 to 1.00). These inverse associations were significant among screened individuals, although a borderline association for breast cancer was suggested in unscreened women. Pretransplant cancer screening probably largely explains the reduced risks of breast and prostate cancer among US SOTRs, but there may also be other protective factors.

Background: Obesity is highly prevalent among Hispanic and Latino adults and is an established risk factor for 13 cancers; however, studies focused on Hispanic and Latino adults are limited. We examined 6 anthropometric measures in association with incidence of obesity-related cancers among Hispanic and Latino adults, overall and by sex, age, and heritage.

Methods: We included 16 415 Hispanic and Latino adults from the Hispanic Community Health Study/Study of Latinos. Baseline (2008-2011) anthropometric measures included body mass index (BMI), waist circumference, waist-to-height ratio, waist-to-hip ratio, fat mass index, and percent body fat. The incidence of 13 obesity-related cancers was ascertained through linkages with 4 state cancer registries (n = 330 incident obesity-related cancer diagnosed over a mean follow-up of 10.7 years). Survey-weighted Cox models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between each anthropometric measure and latent class analysis-derived groups and obesity-related cancer risk.

Results: Hazard ratios were elevated among adults with the highest levels of anthropometric measures and more so among women than among men. For example, a BMI of at least 30 (vs <25) kg/m2 was associated with an adjusted hazard ratio of 1.42 (95% CI = 0.88 to 2.30) overall and adjusted hazard ratios of 2.22 (95% CI = 1.18 to 4.16) in women and 0.46 (95% CI = 0.20 to 1.02) in men. Adjusted hazard ratios also varied by Hispanic and Latino heritage. For example, a 1-standard deviation increase in BMI was associated with a 63% (HR = 1.63, 95% CI = 1.10 to 2.41) increase in obesity-related cancer risk among South American adults but not among Central American adults (HR = 1.03, 95% CI = 0.53 to 2.00).

Conclusions: Multiple anthropometric measures were positively associated with obesity-related cancer risk, particularly among women. Efforts to reduce obesity may be important for cancer prevention in Hispanic and Latino adults.

Background: Political determinants of cancer risk are largely unexplored, conceptually and empirically.

Methods: Observational analysis of associations present in 2017-2021 between 5 state-level political metrics and 4 age-standardized cancer outcomes (regional and distant stage at diagnosis for breast, cervical, and colorectal cancer among screening-age adults and premature cancer mortality), overall and in standardized linear regression models adjusting for state-level poverty and medical uninsurance.

Results: In fully adjusted models (adjusted for state-level poverty and state-level medical uninsurance variables: % working age adults [age 35-64] without medical insurance; number of years of state Medicaid expansion), each 1 SD shift toward a more liberal political ideology (measured by voting record) among elected officials in the US House of Representatives was associated with decreased risk of diagnosis with regional and distant breast and colorectal cancer (respectively: -0.76, 95% confidence interval [CI] = -1.26 to -0.25; -0.75; 95% CI = -1.5 to 0). Risk of premature cancer mortality likewise was lower, in the fully adjusted models, with each 1 SD shift toward more liberal scores for the state electoral college vote (-2.01, 95% CI = -3.68 to -0.33), the state liberalism policy index (-2.51, 95% CI = -4.48 to -0.54), and political ideology of elected officials in the US Senate (-1.93, 95% CI = -3.71 to -0.14).

Conclusion: Our state-level analyses suggest that political metrics are associated with preventable cancer outcomes. Efforts to reduce population burdens of cancer and inequities in these burdens could benefit from analyses of sociopolitical drivers of cancer risk across the cancer continuum.