JNCI Cancer Spectrum最新文献

Background: Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16-positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7.

Methods: Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase-polymerase chain reaction. Receiver operating characteristic curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome.

Results: The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001).

Conclusion: Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration.

Background: The National Comprehensive Cancer Network (NCCN) financial conflict of interest (FCOI) policy sets dollar maximums for panelists, but violations may occur.

Methods: We studied NCCN Guidelines panelists for the 20 most prevalent cancers, 2013-2022. We included panelists with at least 1 full calendar year of service ("current panelists") and those who began service during the study period ("new panelists"); NCCN FCOI policy limits ($20 000 from any single company or $50 000 across all companies) apply to both groups. Industry payments were obtained from Open Payments and mapped manually via National Provider Identifier. We calculated industry payments received, excluding the same payment categories as does NCCN (research, meals, travel and lodging). We estimated whether panelists received payments exceeding NCCN limits ("violation"). As a proxy for whether panelists were subsequently disqualified as stipulated, we measured continued service for at least 1 full calendar year ("retention") subsequent to an estimated violation. We analyzed retention before and after 2016, due to increased scrutiny on NCCN FCOI in 2016.

Results: The annual proportion of current panelists with estimated violations ranged between 0.5% (2020) and 5.8% (2016). Among panelists who did vs did not have violations, retention was 83.6% vs 88.5% during 2014-2015 (odds ratio [OR] = 0.55, 95% CI = 0.26 to 1.31) and 46.6% vs 89.4% during 2017-2020 (OR = 0.10, 95% CI = 0.06 to 0.17). Among new panelists, 2.7% (5/185) had prior-year violations during 2014-2015, as did 5.5% (18/330) during 2017-2021.

Conclusions: Each year, a small portion of panelists receive industry payments exceeding NCCN limits. Since 2016, the likelihood that such panelists will continue to serve has decreased substantially.

Time toxicity is a considerable burden for oncology patients. This study evaluated the feasibility and acceptability of integrating mobile phlebotomy into standard of care procedures. From September 26, 2022, through December 31, 2023, a total of 345 patients had 1464 home laboratory test collection visits completed. These mobile phlebotomy laboratory collection visits occurred in New York (68.6% of visits), New Jersey (29.9%), Connecticut (1.1%), and Pennsylvania (0.5%). Specimen quality for home laboratory test collection surpassed the Memorial Sloan Kettering Department of Pathology and Laboratory Medicine benchmarks. Acceptability was high, 173 patients were approached, and 149 responded (86% response rate); most respondents (147 of 149, 99%) would use the service again or recommend it to others. This study assessed the integration of mobile phlebotomy into standard of care management for the collection of routine cancer laboratory tests. Mobile phlebotomy results in high patient satisfaction with superior specimen quality, offering a valuable solution to oncology patients for improved efficiency and convenience.

Background: Monitoring toxicities among patients receiving immune checkpoint inhibitors using patient-reported outcome measures (PROMs) is relatively recent. This scoping review aims to guide decision making in the development of PROMs programs for patients receiving immune checkpoint inhibitor therapy.

Methods: Four electronic databases were searched from inception to January 2024. Data on PROM programs for patients receiving immune checkpoint inhibitors (eg, PROMs used, frequency) were extracted. Two authors with established interrater reliability screened titles, abstracts, and full texts. A narrative synthesis identified patterns in the data.

Results: A total of 22 articles described 16 unique multicomponent, electronic PROM programs for patients receiving immune checkpoint inhibitor therapy, mainly developed for remote monitoring of toxicities between appointments. Patients typically completed 18-26 items from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) or Common Terminology Criteria for Adverse Events (CTCAE) weekly, with high adherence and satisfaction. Commonly monitored symptoms were diarrhea, fatigue, shortness of breath, cough, nausea, decreased appetite, rash, joint pain, pain, and mood. Other features of PROMs programs included clinician alerts, with some programs only flagging symptoms that had an impact on treatment. Some programs also or only sent alerts to patients to contact their clinicians and gave access to symptom management information. In terms of efficacy, the only consistent finding was an increase in quality of life.

Conclusions: The findings of this scoping review provide some indication as to which components of a PROM program are promising. However, as the evidence base for using PROMs among patients receiving immune checkpoint inhibitors is growing, many questions remain, including which symptoms to monitor, using which PROM, and at what frequency. More trials are needed to answer these questions and to determine how best to implement PROMs among patients receiving immune checkpoint inhibitor in clinical practice.

Background: In 8 females, 1 will be diagnosed with breast cancer in their lifetime. Although medical advances have increased the likelihood of survival, up to 90% of females will gain weight during and after treatment increasing the risk of breast cancer recurrence and obesity-related comorbidities in survivorship. Behavioral lifestyle interventions focused on diet with or without physical activity can provide breast cancer survivors nonpharmacological options to decrease weight gain and cardiometabolic risk.

Method: A PubMed search was conducted to identify all behavioral lifestyle interventions focused on diet or diet combined with physical activity longer than 4 weeks of duration in breast cancer survivors that included body weight as an outcome. This review aims to summarize the effects on body weight, body composition, and cardiometabolic risk markers.

Results: The review shows there is high heterogeneity in type and duration of the intervention to affect weight and cardiometabolic risk in survivorship. Calorie restriction with and without physical activity appears to promote weight loss among breast cancer survivors. However, the effects on cardiometabolic factors are less clear.

Conclusions: Future studies should be powered for body weight and cardiometabolic effects. Researchers should also consider interventions that (1) are less complex, (2) recruit a more racially and ethnically diverse sample, (3) integrate resistance training, (4) implement the intervention in closer proximity to diagnosis, (5) target weight management in this population before it occurs, and (6) analyze body composition in addition to body weight measurements.

Background: High breast density is an independent risk factor for breast cancer and decreases the sensitivity of mammography. This systematic review synthesizes the international clinical guidelines and the evidence base for screening and supplemental screening recommendations in women with dense breasts.

Methods: A systematic search of CINHAL, Embase, and Medline databases was performed in August 2023 and grey literature searched in January 2024. Two authors independently assessed study eligibility and quality (Appraisal of Guidelines for Research and Evaluation II instrument).

Results: Of 3809 articles, 23 guidelines published from 2014 to 2024 were included. The content and quality varied between the guidelines; the average AGREE II total score was 58% (range = 23%-87%). Most guidelines recommended annual or biennial screening mammography for women more than 40 years old with dense breasts (n = 16). Other guidelines recommended breast tomosynthesis (DBT, n = 6) or magnetic resonance imaging (MRI, n = 1) as the preferred screening modality. One third of the guidelines (n = 8) did not recommend supplemental screening for women with dense breasts. Of those that recommended supplemental screening (n = 14), ultrasound was the preferred modality (n = 7), with MRI (n = 3), DBT (n = 3), and contrast-enhanced mammography (n = 2) also recommended.

Conclusions: Consensus on supplemental screening in women with dense breasts is lacking. The quality of the guidelines is variable, and recommendations are based largely on low-quality evidence. As evidence of the benefits versus harms of supplemental screening in women with dense breasts is evolving, it is imperative to improve the methodological quality of breast cancer screening and supplemental screening guidelines.

The role of immune checkpoint inhibitors for patients with gastroesophageal cancer with liver metastasis remains unclear. Our objective was to investigate whether immune checkpoint inhibitors are beneficial in patients with gastroesophageal cancer with liver metastasis. We searched PubMed, Embase, European Society for Medical Oncology, and American Society of Clinical Oncology meeting abstracts for phase 3 randomized clinical trials testing immune checkpoint inhibitors in metastatic/advanced gastroesophageal cancer from 2017 to 2023. Seven studies were included. Overall survival was similar among all patients (hazard ratio [HR] = 0.72 [95% confidence interval (CI) = 0.67 to 0.77], P < .001), in patients without liver metastases (HR = 0.73 [95% CI = 0.67 to 0.81], P < .001, I2 = 0.0%), and in patients with liver metastases (HR = 0.74 [95% CI = 0.67 to 0.81], P < .001, I2 = 0.0%). Progression-free survival was also similar among all patients (HR = 0.63 [95% CI = 0.57 to 0.70], P < .001), in patients without liver metastases (HR = 0.62 [95% CI = 0.51 to 0.76], P < .001), and in patients with liver metastases (HR = 0.66 [95% CI = 0.57 to 0.76], P < .001). Immune checkpoint inhibitors showed no difference in benefit in patients with gastroesophageal cancer, regardless of liver metastasis. Future studies could focus on deciphering the tumor microenvironment of liver metastasis as an area of translational research.

Background: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

Methods: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad.

Results: Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P = .02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P = .03).

Conclusions: For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use.

Background: Young women with breast cancer (YWBC) face unique challenges that can affect their sexual health. This study aimed to identify factors associated with sexual activity, function, and satisfaction in YWBC up to 5 years postdiagnosis.

Methods: We conducted a prospective cohort study of 474 women 40 years of age or younger diagnosed with nonmetastatic breast cancer in Mexico. Sexual function and satisfaction were assessed using the Female Sexual Function Index and the Sexual Satisfaction Inventory, respectively. Factors associated with sexual health outcomes were examined using mixed-effects models.

Results: The prevalence of sexual dysfunction increased from 33.6% at baseline to 52.9% at 4-5 years postdiagnosis. Factors associated with worse sexual function included older age (mean predicted FSFI score = -1.35, P = .037), treatment-induced amenorrhea (-2.86, P < .001), depression (-4.11, P < .001), and anxiety (-2.13, P < .001). Lower sexual satisfaction was associated with lower educational attainment (mean predicted SSI score = -5.61, P = .002), being single (-6.41, P < .001), treatment-induced amenorrhea (-3.76, P = .004), bilateral oophorectomy (-8.21, P = .017), depression (-11.29, P < .001), and anxiety (-7.50, P < .001). Quality of life, body image, and systemic therapy side effects significantly affected both outcomes. Three distinct trajectories of sexual function were identified: high (62.2%), intermediate (24.3%), and markedly declining (13.5%). Four trajectories of sexual satisfaction were found, ranging from intermediate-to-high (57.3%) to progressively worsening (27.5%).

Conclusion: Sexual dysfunction is prevalent and persistent among YWBC. Multiple biological, psychological, and social factors influence sexual health outcomes in this population. These findings highlight the importance of routine screening and tailored interventions to address the sexual health of YWBC throughout survivorship.

Background: Socioeconomic and demographic factors contribute to disparity in prostate cancer (PCa) outcomes. We examined the impact of Area of Deprivation Index (ADI) and race on PCa incidence and lethality in a North American cohort.

Methods: Our cohort included men who received at least 1 prostate-Specifig Antigen (pSA) test within our Health System (1995-2022). An ADI score was assigned to each patient based on their residential census block, ranked as a percentile of deprivation relative to the national level. Individuals were further categorized into quartiles, where the fourth one (ADI 75-100) represented those living in the most deprived areas. We investigated PCa incidence and lethality, using cumulative incidence estimates and competing-risk regression. An ADI × Race interaction term examined whether the relationship between ADI and outcomes varied based on race.

Results: We included 134 366 patients, 25% of whom were non-Hispanic Black (NHB). Median (IQR) follow-up was 8.8 (5-17) years. At multivariate analysis, individuals from the third quartile (ADI 50-74, 95% CI = 0.83 to 0.95) and the fourth quartile (ADI ≥75, 95% CI = 0.75 to 0.86) showed significant reduced hazard ratios for PCa incidence, when compared with the first quartile (ADI <25, all P < .001). In contrast to the overall cohort, PCa incidence increased with ADI in NHB men, who were persistently at higher hazard for both PCa incidence and lethality than non-Hispanic White (NHW), across all ADI strata (all P < .001).

Conclusions: Living in more deprived areas was associated with lower PCa incidence and higher lethal disease rate. Conversely, PCa incidence increased with ADI for NHB, who consistently showed worse outcomes than NHW individuals, regardless of ADI.