JNCI Cancer Spectrum最新文献

Background: Comorbidities worsen cancer survival, but patterns of preexisting and new-onset comorbidities among cancer survivors are unknown.

Methods: We investigated self-reported and clinically diagnosed comorbidity among cancer survivors in the All-of-Us program's national database. Eight highly prevalent comorbidities were identified using self-reported data from the personal health history survey among cancer survivors (n = 20 534) and noncancer adults (n = 113 628) and validated among cancer survivors (n = 26 978) using data from electronic health records (EHRs). Among 5-year survivors (n = 9174) documented in EHR, we further estimated the incidence of new-onset comorbidities.

Results: The most prevalent comorbidities identified in personal health history data were hypertension (40.5%), osteoarthritis (28.4%), depression (28.0%), and obesity (23.2%). EHR data identified preexisting comorbidities: hypertension (43.3%), osteoarthritis (29.4%), depression (19.4%), and obesity (19.1%). During 5-year survival, more than 50% of cancer survivors developed at least one new comorbidity, and more than 25% developed two or more. The onset of new comorbidities showed a sharp increase in the first-year postdiagnosis. Incidence rates varied by age, race, and ethnicity.

Conclusion: Future research is needed to develop effective strategies to prevent new-onset comorbidities during and after cancer treatment.

Background: Cancer survivors experience symptoms that can often be managed with moderate-to-vigorous physical activity. Most studies are short, small, and in-person, limiting scalability. This study evaluated a 12-month digital moderate-to-vigorous physical activity intervention and its impact on long-term physical health outcomes in a large sample of cancer survivors.

Methods: This 2-arm trial was embedded within the Cancer Prevention Study-3 prospective cohort study and included survivors with cancers associated with physical inactivity. Eligible participants were randomly assigned to a digital moderate-to-vigorous physical activity intervention or control group and completed 4 assessments (including surveys and accelerometry) across the 12-month intervention. Primary outcomes were total steps, step cadence (peak 1 minute and 30 minutes), 30-second sit-to-stand, self-reported mobility, walking pace, and pain. The primary analysis followed an intention-to-treat approach, with subgroup analyses by website engagement and among those with poor outcomes at baseline.

Results: In total, 415 were randomly assigned (intervention: n = 286; control participants: n = 129), and 391 were included in the analysis. The intervention did not statistically significantly affect total steps, mobility, walk pace, or pain. However, website-adherent participants showed higher peak cadence (adherent: 125 steps per minute vs nonadherent or control participants: 121-122 steps per minute) and clinically meaningful improvement in sit-to-stand performance (average increase: 13-16, P < .001).

Conclusions: In intention-to-treat analyses, there were no statistically significant changes in most physical health outcomes. Among participants who adhered to the website protocol, the intervention was associated with improvements in cadence and 30-second sit-to-stand performance.

Implications: Our findings support the potential of scalable digital interventions to promote moderate-to-vigorous physical activity, with benefits more apparent among engaged users.

Background: Childhood cancer survivors face long-term psychological challenges, including depression, trauma/stress, and anxiety. However, objective assessments of mental health service utilization among child and young adult (YA) survivors of childhood cancer remain limited. We examined mental health care utilization among publicly insured childhood cancer survivors and disparities by sociodemographic and neighborhood-level factors.

Methods: Using multistate public insurance claims data, we identified 5946 survivors (diagnosed ≤21 years) who completed cancer therapy; initiated treatment episode(s) for depression, trauma/stress, or anxiety post cancer therapy; and maintained continuous coverage. Logistic regressions examined factors associated with having any mental health visit and ≥4 visits within 12 weeks of treatment episode initiation in children (ages 3-17) and YAs (ages 18-39).

Results: Among 4052 child treatment episodes, 54.6% were in female survivors, 41.5% non-Hispanic White survivors, and 27.4% Hispanic survivors; demographics were similar across 3871 YA episodes. Utilization was highest among survivors aged 3-11 years (any visit: 73.4%; ≥4 visits: 39.8%), followed by those aged 12-17 years (67.8%; 33.2%), 18-26 years (51.9%; 20.2%), and 27-39 years (43.3%; 16.4%). Hispanic children were less likely than non-Hispanic White peers to have ≥4 mental health visits (marginal effect = -8.73 percentage points; 95% CI = -12.78 to -4.68), as were children in most (vs least) deprived neighborhoods (marginal effect = -8.80 percentage points; 95% CI = -14.07 to -3.53). Similar disparities were observed for any mental health visit.

Conclusion: Mental health service utilization was low among publicly insured childhood cancer survivors after mental health diagnosis, with notable disparities by age, ethnicity, and geographic location, underscoring the need for interventions to improve psychological support in this underserved population.

Background: Firefighters display increased risk of colorectal cancer (CRC). The distribution for CRC stage at diagnosis among firefighters compared to other occupational groups is unknown.

Methods: Colorectal cancer cases from the Florida Cancer Data System cancer registry (2001-2014) for males ≥20 years were ascertained. Firefighters were identified through either direct linkage with Florida Fire Marshal's Office employment and certification records or Standard Occupation Codes annotated at diagnosis. White-collar, blue-collar, and service workers were also identified according to these codes. Stage at diagnosis was classified as localized, regional, or distant. Bivariate tabulations of occupational groups and clinicodemographic covariates were conducted using contingency tables. The association between occupational group and stage at diagnosis was assessed by multivariable multinomial logistic regression adjusting for year of diagnosis, age, race and ethnicity, tobacco use and cancer diagnosis sequence. Adjusted odds ratios (aORs) are reported.

Results: In total, 13 813 CRC cases, including 346 cases among firefighters, were analyzed. Firefighters were more likely to be non-Hispanic white and be diagnosed with a single primary cancer. One hundred and forty (40.5%) firefighter CRC cases were localized. Using firefighters as the referent group, only blue-collar workers approached 50% increased odds of later-stage diagnoses (aORRegional = 1.44; 95% CI = 1.12 to 1.84; P = .004; aORDistant =1.49; 95% CI = 1.11 to 2.01; P = .008). Individuals ≥50 years and the first among multiple primary cancers were more likely to have localized CRC (P < .001).

Conclusion: Although firefighters have increased CRC risk, they tend to be diagnosed more localized. Improved screening across worker groups can increase the percentage of localized CRCs.

Background: Once considered "undruggable," protein phosphatases are now recognized as potential therapeutic targets. The serine and threonine-protein phosphatase 1 regulates key cellular processes and enhances androgen receptor activity in prostate cancer, even under castration-resistant conditions, suggesting a role in disease progression.

Methods: LNCaP and PC3 cells were treated with peptides mimicking protein phosphatase 1-docking motifs in androgen receptor, alongside known bioportides (MSS1 and mitoparan). Cellular uptake was assessed by confocal microscopy and fluorescence assays. Viability was measured with PrestoBlue, and androgen receptor and Prostate-Specific Antigen expression was analyzed by quantitative reverse transcription-polymerase chain reaction and Western blot.

Results: Androgen receptor sequence contains 3 protein phosphatase 1-docking motifs: KVFF (binding site 1), HVVKW (binding site 2), and KPIYF (binding site 3). Binding site 1 and binding site 2 peptides were modified for better solubility, while binding site 3 was combined with the Tat sequence to enhance cellular uptake. Fluorophore-conjugated peptides successfully entered cells, with androgen receptor-binding site 3 showing the highest internalization in LNCaP cells (P = .0495). Treatment with the 3 androgen receptor-binding site peptides individually reduced cell viability in LNCaP and PC3 cells (P = .0352 and P = .0298, respectively). Combining androgen receptor-binding site peptides statistically reduced cell viability, particularly with all 3 peptides together (LNCaP: 68%, P = .0369; PC3: 80%, P = .0369). No statistically significant changes in androgen receptor or prostate-specific antigen expression were observed.

Conclusion: Bioportides targeting protein phosphatase 1-docking motifs, especially when combined, decrease prostate cancer cell viability, and additional protein phosphatase 1-interfering peptides such as MSS1 and mitoparan display potent cytotoxic effects. The absence of changes in androgen receptor and prostate-specific antigen expression highlights the need to further investigate their mechanisms of action.

Background: Comprehensive, multidisciplinary care is crucial for managing early-stage non-small cell lung cancer (NSCLC), typically treated via lung resection or stereotactic body radiation therapy (SBRT). We evaluated how variable access to on-site SBRT may be associated with clinical outcomes for patients with stage I NSCLC receiving surgical resection within an integrated health-care system.

Methods: We performed a retrospective cohort study of patients with stage I NSCLC treated with lung resection at Veterans Health Administration (VHA) facilities between 2006 and 2016. The VHA provides thoracic surgery at approximately 100 facilities, whereas lung SBRT is currently available at approximately 20 facilities. We compared short- and long-term outcomes for patients treated at surgery-only facilities vs those at facilities offering surgery and SBRT.

Results: We identified 6289 patients undergoing lung resection, with 4673 (74.3%) treated at surgery-only sites and 1616 (25.7%) at surgery + SBRT sites. Sociodemographic factors were similar between cohorts. Surgery + SBRT sites showed higher adherence to operative quality metrics and improved patient selection. Short-term outcomes were better at surgery + SBRT sites with lower rates of 30-day major complications, 30-day mortality, and 90-day mortality. With a median follow-up of 6.3 years, 5-year overall survival was higher at surgery + SBRT sites (59.4% vs 56.9%; adjusted hazard ratio 1.12, 95% CI = 1.02 to 1.23).

Conclusion: Short- and long-term outcomes were better for patients with stage I NSCLC who underwent lung resection at facilities delivering thoracic surgery and SBRT. These findings support recommendations to increase SBRT availability at medical centers offering lung resection to ensure comprehensive multidisciplinary care is provided.

Background: Socioeconomic position (SEP) is a fundamental social determinant of health (SDoH) contributing to observed disparities in cancer and cardiovascular (CV) care among individuals with prostate cancer (PC). Understanding the influence of SEP on CV health is essential for addressing outcome inequities within this population.

Methods: We conducted a retrospective study utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare to evaluate CV outcomes in patients ≥65 years with PC from 2009 to 2017. We studied the impact of SEP on cardiovascular events (CVEs), cardiovascular mortality (CVm), PC-specific mortality (PCsm), and all-cause mortality. CVE, CVm, and PCsm were analyzed using competing risk models and all-cause mortality with Cox proportional hazards models. A subgroup analysis was performed in Non-Hispanic Black and Non-Hispanic White individuals.

Results: We included 141 242 patients of whom 76 844 were in high SEP areas (45.6%) and 64 398 in low SEP ones (54.4%). Both groups had a mean age of 72 years; patients in low SEP areas were 67.5% Non-Hispanic White, 34.4% having diabetes, 73.3% hypertension, and 67.7% dyslipidemia versus the high SEP group with 85.6% Non-Hispanic White, 30.4% diabetes, 69.9% hypertension, and 70.7% dyslipidemia. Patients in low SEP areas had higher risks of CVm (subdistribution hazard ratio [sHR] = 1.18, 95% CI = 1.12 to 1.25), PCsm (sHR = 1.12, 95% CI = 1.06 to 1.17), CVE (sHR = 1.07, 95% CI = 1.04 to 1.09), and all-cause mortality (HR 1.16, 95% CI = 1.13 to 1.20). Accentuated results were shown in the Non-Hispanic Black subgroup.

Conclusion: Adverse SEP plays a significant role in shaping outcomes among older patients with PC, contributing to elevated risks of adverse CV and survival outcomes.

Background: Black men in the United States bear a disproportionate share of the prostate cancer (PCa) burden, with more than 50% higher incidence and double the mortality compared with White men. Previous studies have examined racial disparities in the incidence of fatal PCa (fPCa), defined as diagnosis leading to disease-specific death within 10 years, and found that they are greater in younger vs older men. However, the extent to which these trends are driven by disparities in incidence or survival is unknown.

Methods: We conduct a retrospective analysis of data from the Surveillance, Epidemiology, and End Results program over the period 1980-2009 to decompose the incidence of fPCa into incidence and 10-year probability of death and quantify the relative disparities in these metrics by age at diagnosis.

Findings: We find that relative PCa incidence for Black vs White men significantly decreases by 0.116 units with each successive 5-year age group (95% CI = -0.183 to -0.049) but the relative probability of death within 10 years does not differ significantly by age (slope = -0.012, 95% CI = -0.060 to 0.035). Further, this deconstruction is similar before and after the introduction of prostate-specific antigen screening.

Conclusion: We conclude that higher relative incidence of fPCa in young Black men vs young White men appears to be largely driven by their significantly increased incidence of disease. This finding supports investigating targeted screening of Black men beginning at younger ages than White men.

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: 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.