JNCI Cancer Spectrum最新文献

While individual-level social determinants of health are associated with pancreatic ductal adenocarcinoma (PDAC), it is currently unknown whether neighborhood-level socioeconomic disadvantage is related to the risk of PDAC diagnosis. Area deprivation index (ADI) is a validated tool to measure neighborhood-level disadvantage. We conducted a retrospective cohort study of 5,069,429 patients in the Veterans Health Administration (VA) between October 1, 2001-December 31, 2021. ADI percentiles were grouped using national ADI decile cutoffs. In multivariable analysis, the lowest ADI group, representing highest neighborhood-level socioeconomic status (SES), was associated with increased hazards for PDAC (adjusted HR, 1.13; 95% CI, 1.06-1.21) compared to those with median ADI percentiles. Differences in PDAC hazards were not seen in the other ADI percentiles. These results suggest that within the VA, a relatively equal access healthcare system, there is limited contribution of neighborhood-level socioeconomic deprivation to PDAC, except for patients with the highest neighborhood-level SES (lowest ADI).

Background: The incidence rates of testicular germ cells tumors (TGCT) are increasing in adolescents and young adults in the United States, especially in Latinos. We investigated the association between TGCT risk and birth levels of phthalates, known endocrine disrupting chemicals, in a diverse population in California.

Methods: Reverse phase chromatography was applied to newborn blood samples of 196 TGCT cases and 190 controls to measure ten phthalates, five of which passed quality control: Mono-2-methyl-2-hydroxypropyl phthalate/mono-3-hydroxy butylphthalate (MHiBP/MHBP), Mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-oxo-isononyl) phthalate (MOiNP), and Mono(2-ethylhexyl) phthalate (MEHP). We conducted single chemical and mixture analyses using weighted quantile sum (WQS) regression, adjusting for birth and sociodemographic characteristics, and hematocrit. We ran repeated holdout analyses splitting data between training and testing sets 100 times.

Results: None of the single phthalates was significantly related to case status. The overall WQS analyses showed a curvilinear mixture effect related to TGCT risk, approximated with linear and quadratic terms, and dominated by MECPP and MEHP mostly in the lower concentration ranges. For Latinos, the curvilinear mixture effect was dominated by MEHP, and the WQS betas were borderline significant (median b1 = 0.37, 95%CI = [-0.25, 1.28]; median b1sq=-0.04, 95%CI = [-0.15, 0.03]), with high level of reproducibility for beta estimations in the repeated analyses (87% to 89%). For non-Latino whites, the mixture effect was dominated by MECPP and MHiBP/MHBP, although the signal for curvilinearity and repeated analyses were less robust.

Conclusions: Prenatal exposure to phthalate mixtures may increase TGCT risk later in life, with some variation by racial/ethnic group.

Background: Radiotherapy (RT) plays a crucial role in managing cancer-related symptoms. This study characterized symptom documentation, especially pain, preceding bone metastasis (BM) diagnosis and initiation of RT for BM, using natural language processing (NLP) approaches.

Methods: A de-identified cohort of patients who received RT for BM at a single tertiary-care institution (2013-2023) was created. Clinical data, notes, and metadata were computationally extracted. A previously validated NLP pipeline based on the clinical Text Analysis and Knowledge Extraction System was used to extract CTCAE-encoded symptoms from all notes in the 30 days preceding BM diagnosis and each course of RT for BM. Logistic regression analyses examined the association between clinical and demographic variables and pain documentation.

Results: 1,061 patients (median [IQR] age, 64 [54-72] years; 582 [54.9%] men) received 1,718 courses of RT for BM. The most common documented symptoms before BM diagnosis and first RT for BM, respectively, were BM-related pain (52.5% vs 91.6%, p < .001), nausea (20.8% vs 48.9%, p < .001), and constipation (12.8% vs 34.2%, p < .001). Prior to BM diagnosis, multiracial/other race (OR = 0.61 [95% CI 0.38-0.99], p = .045) was associated with decreased pain documentation compared to white race. Prior to RT for BM, women (OR = 1.48 [95% CI 1.02-2.15], p = .039) had increased pain documentation compared to men.

Conclusions: Women and multiracial/other race patients experienced a relative increase in pain documentation from BM diagnosis to RT for BM. This may reflect differential decision-making for which patients are offered RT for BM sooner in the symptom trajectory. Interventions are needed to increase equitable distribution of RT.

Background: Weight gain and physical inactivity during chemotherapy for early-stage breast cancer patients are common.

Aim: To investigate the feasibility of a virtual lifestyle (exercise and diet) intervention for breast cancer survivors (BCS) during chemotherapy.

Methods: This single-arm phase II trial delivered 12 weekly 1-hour telehealth sessions of supervised exercise and diet education to BCS (stage I-III) starting (neo)adjuvant chemotherapy. Screening, recruitment, intervention, and study assessments completed at baseline (T0), immediately post-intervention (T1), 3-months post-intervention (T2) were conducted via telehealth in 2022-2023. Primary outcome: ≥60% participants achieved 50% of pre-determined exercise and/or dietary goals. Secondary outcomes: acceptability (participation, attendance, completion), physical health, and lifestyle outcomes.

Results: Of 73 referrals, 60 were eligible, 58 (97%) consented, 51 (85%) commenced intervention, and 34 completed ≥1 post-intervention assessment (completion rate 67%). Mean age 51 years (SD8.8), 50% neoadjuvant chemotherapy. Attendance was lower for exercise than diet sessions (44% vs 62% attended ≥75% sessions). At T1, 36% of participants adhered to ≥ 50% pre-set goals, improving at T2 (62.5%). Weight was not significantly different T0-T1 (p = .199) but significantly increased at T2 (p = .018). Average waist circumference reduced at T1 (-1.9 cm, p = .014) and T2 (-3.3 cm, p < .001). Weekly exercise time increased by 38.5mins T0-T1 (p = .038) and the proportion meeting exercise guidelines improved from 6% (T0) to 41% (T2).

Conclusion: Our primary outcome was not achieved immediately post-intervention but was observed 3-months later. Those completing the intervention attended at least half the diet and exercise sessions during chemotherapy. Results will inform design of a phase III study.

Background: Cancer diagnosis originating in emergency departments (EDs), "emergency presentation" (EP), contributes to poorer cancer survival and reflects both aggressive disease and limited access to routine healthcare. This study characterized EPs for a range of cancers and subclassified by whether patients were hospitalized after the emergency encounter, with the hypothesis that, compared to those hospitalized, patients not requiring hospitalization more specifically represent barriers to timely and adequate care.

Methods: We analyzed SEER-Medicare data for patients aged 66+ years diagnosed with 14 cancer types (2008-2017; N = 614,885). We described EP overall and demographic and clinical characteristics across subgroups using linear regression and assessed differences in healthcare utilization before the EP classification window.

Results: In total, 234,606 (38%) patients were classified as EPs, with 187,439 (80%) hospitalized. EPs were more likely than non-EPs to have pre-diagnostic emergency care (40% (95% CI = 40%-40%) vs. 30% (29%-30%)) and less likely to have non-emergency care for potential cancer symptoms (61% (61%-61%)) vs. 67% (67%-67%)), with minimal variation between inpatient and outpatient EPs. Compared to inpatient EPs, outpatient EPs were more often <70 years old (24% (23%-24%) vs.19% (19%-19%)), non-metropolitan residents (25% (24%-25%) vs. 12% (12%-12%)), with localized cancer (25% (25-26%) vs. 17% (17-17%)).

Conclusion(s): Over one-third of older adult U.S. cancer patients with these cancer types are diagnosed through EP, with most requiring hospitalization. Outpatient EPs are more common among patients in rural areas with less advanced cancers, suggesting they may be an informative indicator of avoidable barriers to care less influenced by underlying health status.

Background: Accumulating evidence suggests that one-carbon nutrient intake reduces the risk of colorectal cancer (CRC), although folate fortification has been associated with a temporary increase in CRC incidence. We hypothesized that one-carbon nutrients might harbor preventive and pro-tumor effects on CRC according to tumor conditions and investigated whether the effect of one-carbon nutrients on CRC risk differs by TP53 status.

Methods: In this prospective study of 21,708 Japanese participants, we applied a multivariable Cox proportional hazards model and examined the associations of dietary intakes of folate, vitamin B6, vitamin B12, and methionine with TP53-overexpressing (N = 192), TP53-non-overexpressing (N = 301), TP53-mutated (N = 180), and TP53 wild-type (N = 134) CRC risk defined by TP53 immunohistochemistry and target sequence.

Results: Vitamin B12 and methionine intakes were not associated with any CRC subtypes defined by TP53 status. Meanwhile, folate intake was marginally associated with decreased TP53-mutated CRC risk (hazard ratio [HR] with 95% confidence interval [CI] for the highest folate intake quartile compared with the lowest: 0.82 [0.46-1.45]) and increased TP53 wild-type CRC risk (HR: 1.50 [0.78-2.90]). A heterogeneous effect of folate on CRC subtypes was detected (Pheterogeneity= 0.03 between TP53 mutation statuses). In women, the association between vitamin B6 and CRC also differed by TP53 mutation status (Pheterogeneity= 0.007). The HR of vitamin B6 was 0.71 [0.30-1.67] for TP53-mutated CRC and 3.89 [1.79-8.49] for TP53 wild-type CRC. However, no heterogeneous effects were observed between TP53 expression statuses.

Conclusion: This study supports the hypothesis that the effect of one-carbon nutrient intake on CRC differs according to tumor conditions.

Background: Patients with incurable gastroesophageal adenocarcinoma (GAC) have an impaired health-related quality of life (HRQoL). Exercise combined with nutritional support may improve this outcome. Careful evaluation of this supportive care strategy is needed to avoid burdening patients at this vulnerable stage with interventions that may offer no (meaningful) benefit. Therefore, this study aims to investigate the effects of a combined exercise and nutritional intervention on HRQoL in.

Patient: s with incurable GAC.

Methods: RADICES is a multicenter randomized controlled trial aiming to include 196 patients with incurable GAC. Participants are randomly assigned (1:1) to a patient tailored intervention or a control group. The intervention group is provided with two training sessions per week and biweekly nutritional consultations, delivered by trained physiotherapists and dietitians, during 12 weeks. The control group receives usual care supplemented with general physical activity advice.The primary outcome is the difference in HRQoL between the intervention group and the control group at 12 weeks, accounting for baseline HRQoL, measured by the EORTC QLQ-C30 summary score. HRQoL is assessed at baseline, 6, 12 weeks, and every 3 months thereafter up to 1 year. Key secondary outcomes include patient-reported outcomes, cardiorespiratory fitness, dietary intake, disease progression, overall survival and cost-effectiveness. Adherence and safety are monitored throughout the intervention period.

Discussion: This study will generate evidence on the effectiveness of a patient tailored combined exercise and nutritional intervention in patients with incurable GAC. If effective for HRQoL, this intervention could be integrated into standard care for patients with incurable GAC.

Cervical cancer elimination (<4 cases per 100,000) is a critical cancer prevention goal in the United States. Implementation of health policies and allocation of health resources occur at regional and state levels; therefore, understanding region- and state-specific cervical cancer incidence, mortality, and progress towards elimination-and remaining gaps-is essential. We estimated hysterectomy-corrected cervical cancer incidence, mortality, and progress toward elimination across all 50 states, the District of Columbia, and Puerto Rico. In 2021, Massachusetts was the only state nearing (4.3 per 100,000) the elimination threshold. Southeastern and Southwestern states were farthest, with the highest incidence rates in Mississippi (14.8), Louisiana (14.2), and Oklahoma (13.8). The mortality rate ranged from 6.8 (Alabama) to 1.4 (Wisconsin). In most states, cervical cancer incidence and mortality did not change from 2007-2011 to 2017-2021. Identifying and addressing regional- and state-level barriers impeding progress will be key to achieving cervical cancer elimination.

Background: Supervised exercise may provide greater functional and quality of life benefits than unsupervised programs after cancer and is recommended for those with or at risk of breast cancer-related lymphedema. These exploratory analyses compared the effect of low- versus high-supervision exercise on the secondary, survivorship outcomes of the SAFE breast cancer trial.

Methods: This randomized study (ANZCTR: ACTRN12616000547448) compared a 12-week, exercise program (target 150 minutes/week, moderate-intensity) supported by either five (LOW) or 20 (HIGH) supervised sessions. Inclusion criteria included: stage ll+ breast cancer within five years, ≥ one comorbidity and/or treatment-related adverse effect and insufficiently active. Outcomes included lymphedema (self-report and bioimpedance spectroscopy), arm symptoms, upper-extremity function (PROMIS Bank v1.2-Upper- Extremity), fatigue, pain, pain interference, pain intensity, physical function, sleep disturbance, anxiety, depression, and satisfaction with social roles (PROMIS-43 Profile v1.0). Chi-square tests evaluated between-group symptom changes. Generalized estimating equations assessed time, group, and time×group effects under an intention-to-treat, two-sided framework.

Results: Sixty women (mean age, 50 years) were randomized to LOW (n = 30) versus HIGH (n = 30). At follow-up, both groups showed similar lymphedema prevalence, comparable rates of maintained or improved arm symptoms, and within-group improvements (p < .05) in fatigue, physical function, sleep, anxiety, depression, and satisfaction with social roles and activities. Potential for superior benefit in HIGH versus LOW was observed for self-reported range of movement, upper-extremity function, and pain interference and intensity (p < .05).

Conclusion: Findings indicate that breast cancer survivors with or at risk of lymphedema can benefit from exercise, even when supervision is limited.

The TMEM173/STING protein is linked to therapeutic resistance in preclinical models of HNSCC. To evaluate STING as a biomarker, quantitative immunofluorescence (QIF) was performed on a tissue microarray (TMA) cohort of primary HNSCC (n = 72). Cytokeratin and DAPI staining were used to differentiate between tumor or stromal compartments and patient groups were dichotomized based on STING QIF scores. HNSCCs display variable STING protein levels in both tumor cell and stromal compartments. STING QIF score in tumor cells is associated with p16 positivity, with similar non-significant trends observed for stromal QIF values. In cohort 1, elevated STING levels in either tumor cells (p=.029) or stroma (p=.023) significantly improved DFS. These findings were validated in a second oropharyngeal HNSCC TMA cohort (n = 92) where borderline or significant differences in DFS were observed for elevated STING in tumor cells (p=.066) or the stroma (p=.028). A more detailed breakdown of failure patterns in cohort 2 revealed that elevated STING in tumor (p=.015) or stroma (p=.054) predicts local-regional control, and a trend for reduced distant failure was also observed for elevated stromal STING (p=.067). Local-regional recurrence was rare in HPV+ tumors and occurred only with low STING expression. In multivariate analysis p16 was a significant predictor for local control while elevated STING was of borderline significance (p=.051). These results suggest that STING protein levels in the tumor cell are a biomarker for predicting HNSCC local control following radiation therapy, while elevated STING in tumor stroma may be associated with a reduced risk of distant failure.