JNCI Cancer Spectrum最新文献

Background: The 2024 American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology practice guidelines recommend early salvage radiation therapy (RT) for biochemical recurrence after radical prostatectomy and androgen deprivation therapy for high-risk features. Increasingly, men with high-risk disease are undergoing radical prostatectomy. We therefore characterized contemporary RT and androgen deprivation therapy practices within the Michigan Radiation Oncology Quality Consortium and Michigan Urological Surgery Improvement Collaborative.

Methods: Patients receiving postprostatectomy RT from June 9, 2020, to June 9, 2024, were eligible. Prospectively collected data included surgical pathology, RT, and androgen deprivation therapy details. RT was adjuvant (pre-RT prostate-specific antigen [PSA] <0.1 ng/mL), consolidative (persistent PSA ≥0.1), or salvage (all others). Multivariable analyses evaluated associations between clinicopathologic features and androgen deprivation therapy use.

Results: Among 345 patients across 26 centers, 56% had at least 1 high-risk feature: pT3b/T4 (24%), pN1 (6%), grade group 4/5 (30%), pre-RT PSA greater than 0.5 ng/mL (27%). RT was adjuvant (10%), consolidative (28%), or salvage (62%), initiated at median PSA of 0.07 ng/mL (interquartile range [IQR] = 0.03-0.09 ng/mL), 0.5 ng/mL (IQR = 0.3-1.5 ng/mL), and 0.3 ng/mL (IQR = 0.2-0.5 ng/mL), respectively. Median time to RT was 8, 6, and 29 months. A minority were recommended 24 months of androgen deprivation therapy (17%), and very few were recommended intensification with AR-pathway inhibitors (5%). On multivariate analysis, androgen deprivation therapy was associated with pT3b/T4 (odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.34 to 5.93), pN1 (OR = 6.22, 95% CI = 1.35 to 47.57), grade group 4/5 (OR = 2.87, 95% CI = 1.51 to 5.56), and pre-RT PSA more than 0.5 (OR = 2.11, 95% CI = 1.17 to 3.91).

Conclusions: Within the Michigan Radiation Oncology Quality Consortium, more than half who received postprostatectomy RT had high-risk features; nearly 30% required consolidation for persistently positive PSA. Androgen deprivation therapy was associated with high-risk features, but few received androgen deprivation therapy prolongation or intensification. Studies are needed to personalize androgen deprivation therapy, especially for those with persistent PSA, who are frequently treated yet underrepresented in trials.

Background: We examined late effects clustering among adolescent and young adult (AYA; age 15-39 years at diagnosis) Hodgkin lymphoma (HL) survivors and identified characteristics associated with each cluster.

Methods: We included AYAs with HL in 2006-2018 from the California and Utah Cancer Registries linked to statewide hospitalization, emergency department, and ambulatory surgery visit data. We identified severe late effects >2 years after cancer diagnosis in 9 late effects categories. Latent class analysis (LCA) was used to identify late effects clusters. Multinomial logistic regression models estimated adjusted associations of demographic and treatment characteristics with LCA late effect group.

Results: We identified 4635 AYA HL survivors with median follow-up of 8.2 years and 4 late effects groups: 77.1% had a low probability of any late effect (Low Morbidity), 12.8% had high probability of Thyroid disorders, 8.0% had high probability of Cardiovascular Disease (CVD), and 2.1% had high probability of Multiple Conditions (CVD, diabetes/pancreatic, thyroid, and renal diseases). Publicly insured AYAs were more likely than those with private insurance to be in the CVD (OR = 1.53, 95% CI = 1.18 to 1.98) and Multiple Conditions (OR = 2.17, 95% CI = 1.29 to 3.66) than the Low Morbidity group. AYAs with radiation were more likely to be in the Multiple Conditions (OR = 2.31, 95% CI = 1.41 to 3.78) and Thyroid (OR = 2.81, 95% CI = 2.20 to 3.58) groups. Hematopoietic cell transplantation was associated with Multiple Conditions (OR = 9.50, 95% CI = 5.82 to 15.50), CVD (OR = 3.82, 95% CI = 2.96 to 4.93), and Thyroid (OR = 2.86, 95% CI = 2.12 to 3.85) groups.

Conclusions: While most AYA HL survivors were in the Low Morbidity group, those with public insurance or intense treatment may be at higher risk for multiple conditions.

Background: Cancer-related cognitive impairment is a significant concern, yet data assessing long-term changes from pretreatment baselines are limited.

Methods: In this large nationwide study, patients with breast cancer and lymphoma and controls were assessed at pre-chemotherapy, post-chemotherapy, 6-month, 1-year, and 2-year follow-ups. Cognitive function was measured using self-reported and performance-based assessments. The analysis included 225 participants: breast cancer (41 patients/36 controls) and lymphoma (73 patients/75 controls). Cognitive trajectories were estimated using longitudinal linear mixed models, adjusting for demographic, clinical, and psychosocial factors. A minimal clinically important difference cutoff identified changes over time in perceived cognitive impairment.

Results: Patients with breast cancer reported greater cognitive complaints than controls, with declines in FACT-Cog Total (β = -17.17, P < .001), Perceived Cognitive Impairment (β = -11.09, P < .001), and Perceived Cognitive Abilities (β = -3.60, P = .03) from pre-chemotherapy to 2-year follow-up. Declines were observed in memory (Rey Auditory Verbal Learning Test [RAVLT] Immediate Recall: β = -1.53, P = .04) and executive function (phone fluency: β = -1.53, P = .02) at 1 year. Patients with lymphoma also showed more complaints, with declines in Perceived Cognitive Impairment (β = -6.19, P = .01), poorer RAVLT Immediate (β = -1.62, P < .001), Delayed Recall (β = -1.72, P < .001), and phone fluency (β = -2.46, P < .001) from pre-chemotherapy to 1-year follow-up.

Conclusion: Compared with controls, patients with breast cancer and lymphoma showed persistent cognitive worsening up to 1-year posttreatment, and patients with breast cancer reported perceived impairment at 2 years compared with controls.

Background: There are substantial historical racial and ethnic differences in treatment survival for patients with hepatocellular carcinoma (HCC) that may have changed with approval of 9 novel systemic HCC therapies between 2017 and 2022.

Methods: This retrospective cohort study included patients from the Flatiron Health Research Database who received systemic therapy between 2011 and 2023. We identified receipt of systemic therapy, including novel systemic therapies receiving US Food and Drug Adminstration approval ≥2017, and determined overall survival (OS) from start of first-line systemic therapy until death. Multivariable models adjusted for sociodemographic and clinical factors.

Results: The study included 4198 patients who were 53.0% White, 11.8% Black, and 5.2% Asian, and 11.2% were Hispanic. Asian patients were more likely than White patients to receive novel systemic therapies (odds ratio [OR] = 1.78, 95% confidence interval [CI] = 1.12 to 2.83), while Black and Hispanic patients had similar receipt of treatment. Asian and Hispanic patients had median OS of 10.3 and 10.5 months compared with 8.0 and 8.3 months for White and non-Hispanic patients. Asian (HR = 0.79, 95% CI = 0.65 to 0.96) and Hispanic patients (HR = 0.72, 95% CI = 0.62 to 0.83) had better OS than White and non-Hispanic patients, respectively, which did not substantially change with stepwise adjustment. Racial differences in survival worsened over time. Receipt of novel therapy was associated with improved survival.

Conclusions: Asian and Hispanic patients had the best survival, and Asian patients were more likely to receive novel therapies. As adjustment for many social and clinical factors had minimal impact on these findings, additional research is needed to understand these survival differences.

Background: Diagnosis, treatment, and outcomes of colon cancer in the United States differ between patients younger than age 50 (early-onset colon cancer [EOCC]) and those age 50 or older (average-onset [AOCC]) and may be impacted by access to care. Less is known about surgical quality and postoperative outcomes between patients with EOCC and AOCC. This study aimed to compare patients with EOCC and AOCC in surgical aspects and 30-day postoperative complications and readmissions in the Military Health System.

Methods: The cohort included patients diagnosed with stage I-III colon adenocarcinoma between 2001 and 2014 who received surgery. Poisson regression with robust standard errors estimated the adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) in association with age at diagnosis for the outcomes.

Results: Among 333 patients with EOCC and 1369 patients with AOCC, there were no statistically significant differences in surgical delay, positive margins, or inadequate lymphadenectomy. Patients with EOCC had statistically higher adjusted 30-day risk of any complication (ARR = 1.31, 95% CI = 1.05 to 1.63), inclusive of general surgical (ARR = 1.64, 95% CI = 1.14 to 2.38) and gastrointestinal (ARR = 1.29, 95% CI = 1.00 to 1.65) complications, relative to patients with AOCC. There was no statistically significant difference in 30-day readmission for patients with EOCC (ARR = 1.30, 95% CI = 0.84 to 202) compared with patients with AOCC.

Conclusion: In the Military Health System, patients with EOCC had higher adjusted 30-day risk of complications following surgery compared with patients with AOCC. This finding may have implications for care delivery and postoperative management of patients with EOCC to reduce complication burden and achieve optimal outcomes.

Background: In the development of breast cancer and ovarian cancer there may be an influence of lifestyle and environmental factors. This influence could be relevant also in patients with genetic predisposition such as in carriers of germline pathogenic variants in the BRCA genes. However, this issue has been addressed in only a few studies so far.

Methods: In this retrospective, multicenter case-control study, we enrolled participants with a pathogenic variant BRCA gene and divided into 2 groups: group 1, patients with breast cancer and/or ovarian cancer, and group 2, subjects without cancer. We compared these groups regarding demographic data as age, body mass index, smoking habits, estroprogestinic use, Mediterranean diet, and physical activity. Multivariable analyses were used to identify predisposing factors. All evaluations were 2-tailed and considered statistically significant if the P value was less than .05.

Results: We enrolled 281 participants, 135 (79.4%) with breast cancer, 32 (18.8%) with ovarian cancer, 3 (1.8%) with both, and 111 unaffected (39.5%) women. Independent risk factors associated with cancer were age (P < .0001); body mass index (P = .007); family history (P = .002); occupation (P = .003); smoking habits (P = .012), number of cigarettes smoked (P = .016), and pack-year index (P = .022); and estroprogestinic use (P = .032) and years of estroprogestinic use (P = .029). At multivariate analysis, age (odds ratio [OR] = 1.062; P < .0001), family history (OR = 0.129; P = .001), number of cigarettes smoked (P = .014), and estroprogestinic use (OR = 2.009; P = .025) were statistically significant risk factors associated with cancer development.

Conclusions: In the development of breast cancer and ovarian cancer, lifestyle and environmental factors seem to play a statistically significant role in the presence of genetic predisposition associated with BRCA1 and BRCA2 gene mutations.

Background: Breast cancer survivors (BCSs) are at increased risk of late effects. While research has reported positive effects of exercise therapy on fatigue and health-related quality of life (HRQoL) among short-term BCSs, evidence in long-term survivors remains scarce.

Methods: The CAUSE (CArdiovascUlar Survivors Exercise) trial was a 2-armed randomized controlled trial. Long-term BCSs were assigned to 5 months of thrice-weekly supervised aerobic exercise or usual care. Late effects and HRQoL were assessed by Chalder Fatigue Questionnaire, European Organization for Research and Treatment of Cancer QLQ-BR23 and QLQ-C30 questionnaires, and Scale for Chemotherapy-Induced Long-term Neurotoxicity at baseline (T0), post-intervention (T1), and 1-year follow-up (T2).

Results: In total, 140 BCSs (mean age 59.0 ± 6.4 years, 11 ± 1 years post-treatment) were included. Loss to follow-up at T1 was 6% and 19% in the exercise- and usual care group, respectively. From T0 to T1, the exercise group significantly improved total fatigue (between groups mean difference [MD] = -3.0, P < .001), body image (MD = 6.7, P = .043), physical- (MD = 3.2, P ≤ .001), role- (MD = 9.6, P = .019), and cognitive function (MD = 3.4, P = .038), insomnia (MD = -9.0, P = .017), and global health/QoL (MD = 5.3, P ≤ .001) compared to usual care. The exercise benefits were more pronounced in BCSs experiencing versus not experiencing late effects at baseline. At 1-year follow-up, most improvements regressed toward baseline values.

Conclusion: Aerobic exercise significantly improves fatigue, body image, physical-, role-, and cognitive function, insomnia, and HRQoL in long-term BCSs. These findings suggest that exercise therapy should be a core component of managing late effects and enhancing HRQoL in long-term BCSs.

Clinical trial registration: URL: https://www.clinicaltrials.gov/. Registration number: NCT04307407.

Background: Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.

Methods: Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests.

Results: In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC.

Conclusions: Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

Background: Metastasis-directed radiotherapy (MDT) is the mainstay in management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for localizing PCa metastases. The efficacy of MDT guided by PSMA-PET imaging with and without androgen deprivation therapy (ADT) ± androgen-receptor pathway inhibitor (ARPI) has not yet been well characterized. We sought to evaluate the efficacy of PSMA PET-guided MDT.

Methods: This is a single-institutional retrospective study of patients diagnosed with metastatic PCa by PSMA-PET imaging who were treated with MDT. Survival analyses were performed using the Kaplan-Meier method with Cox proportional hazards testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance.

Results: One hundred and ninety-four metastatic lesions from 101 patients identified by PSMA PET were irradiated with MDT. Forty-seven of the 79 (59%) patients with hormone-sensitive PCa (HSPC) received ADT ± ARPI along with MDT. Four of 194 lesions (2.1%) demonstrated radiographic progression after MDT, with a median follow-up of 22.4 months. Two-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT ± ARPI and 35% in those who did not (P = .027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT or ARPI, and HSPC treated with ADT ± ARPI was 5.4, 7.6, and 43.9 months, respectively (P < .0001). No Grade 3-5 adverse effects were observed.

Conclusions: MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT ± ARPI.

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.