tbuckley/cabot-search huggingface dataset:
Association of social determinants of health (SDH), allostatic load (AL) and incident cancers in the multi-ethnic study of atherosclerosis (MESA).
Authors: Ruth C. Carlos, Sarah Bell, Hassan Mirboluk, Paniz Charkhchi, Maya C Doyle, Jana A Hirsch, Wendy S Post, Gelareh Sadigh
Journal: Journal of Clinical Oncology (2024)

10562 Background: AL may represent accumulated physiologic stress from adverse SDH. We assess the relationship of AL and incident cancer risk in MESA, a cohort free of cardiovascular disease (CVD) at baseline. Methods: MESA participants at Exam 1 (July 2000-August 2002) were included, except those with prevalent cancers other than non-melanoma skin, median follow-up, 16.5 years. We assigned the composite AL measure 1 point for each individual biomarker in the worst quartile for total cholesterol, high density lipoprotein cholesterol, C-reactive protein, and IL-6. One point each was assigned for BMI&gt;25 or &lt;18kg/m 2 ; creatinine&gt;1.2mg/dL (women) or &gt;1.4mg/dL(men), systolic (≥140mmHg), diastolic (≥90mmHg) blood pressure; heart rate&gt;100bpm; coronary artery calcium score&gt;0 and history of diabetes. AL score (mean=3.09, SD=1.76) ranged 0-12. Other covariates included sociodemographic variables. Where missing, data for individual biomarkers were imputed using Multivariate Imputation by Chained Equations in R prior to calculating AL score. Cox regression models assessed AL in the whole population and stratified by race/ethnicity. Results: 6808 participants comprised the analytic sample; 1022 (15%) were diagnosed with new cancer during follow-up. Chinese (adjusted hazard ratio [aHR], 95% confidence interval [95%CI], 0.46,0.36-0.60) and Hispanic/Latino (aHR,95%CI 0.60,0.50-0.72) participants were less likely to develop new cancers compared with White participants. Each AL point increase was associated with increased new cancer risk (aHR,95%CI 1.07,1.03-1.11). In models stratified by race/ethnicity, AL association with new cancer risk persisted only for Black (aHR,95%CI 1.07, 1.00-1.14, p=0.04) and Hispanic/Latino (aHR,95%CI 1.17, 1.07-1.28, p=0.001) participants. Conclusions: AL as a composite measure of physiologic stress and self-reported Chinese and Hispanic/Latino race/ethnicity independently correlated with incident cancer risk in a cohort free of CVD at baseline. Race/ethnicity may moderate the effects of AL. [Table: see text]
Timing of genetic testing referral and genetic testing results in patients with multiple primary cancers.
Authors: Rachel Hodan, Victor Ritter, Summer S. Han, Shilpa Narayan, Mina Satoyoshi, Allison W. Kurian
Journal: Journal of Clinical Oncology (2024)

10592 Background: An individual diagnosed with a metachronous or synchronous cancer that arises independently, not due to recurrence or metastasis, has multiple primary cancers (MPC). Practice guidelines recommend germline genetic testing based on specific combinations of primary cancers and ages of diagnoses but do not recommend testing for all patients with MPC. In prior work (PubMed ID 37276540), we found that patients with breast cancer are more likely to receive testing than patients with other primary cancer types. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral. Methods: Using Oncoshare, a breast cancer research database that integrates data from electronic medical records and the California Cancer Registry, we identified female patients with MPC diagnosed between January 2000 and June 2023 with breast cancer as either the first or second cancer and seen at Stanford University. We analyzed testing rates after first vs. second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and the timing of breast cancer (1 st or 2 nd ), using both univariate and multivariable logistic regression that adjusted for age at first diagnosis, race/ethnicity, and time between the first and second diagnoses. Results: 1,069 patients met the study eligibility; 75% were non-Hispanic White, and 73% had breast as the first cancer. 342 (32%) patients had testing, and 113 (33%) had at least one PV. Most patients had testing after the first cancer (44%, n=150) or after the second cancer (48%, n=165) (Table). Those with breast cancer as their first primary tended to have a higher testing rate, (OR 1.62, 95% CI 0.9-3.0), however, the statistical significance of this association was attenuated in the multivariable model with more parameters (P=0.11), possibly due to small sample size. Overall PV yield (33%) was high, consistent with a tertiary referral center. Conclusions: In this academic clinic-based sample of patients with MPC, we observed a higher testing rate when breast vs. another cancer was the first primary although it did not reach statistical significance. Additional research is needed to validate this finding in a larger cohort and determine whether similar referral patterns are observed in community practice, where most U.S. patients receive cancer care. [Table: see text]
Increasing cancer-related mortality and demographic disparities in young adults in the United States between 1999 and 2020.
Authors: Alexander James Didier, Alan Fahoury, Swamroop Nandwani, Andrew Campbell, Macelyn Batten, Jeffrey M. Sutton
Journal: Journal of Clinical Oncology (2024)

10569 Background: The global rise in cancer incidence in the young adult population (≤ 45 years), particularly in obesity-related cancers, is of growing concern. As the demographic afflicted by cancer expands beyond traditional boundaries, a nuanced understanding of the unique characteristics and challenges specific to young adults is imperative for developing interventions that address their distinct needs. In this study, we characterize cancer mortality rates in the young adult population to assess for emerging trends and cancer burden in the United States. Methods: The Centers for Disease Control database was queried for all underlying causes of death due to cancer (ICD 10 codes C00-C97) between 1999 and 2020. Malignancies that primarily affect the elderly, such as prostate and multiple myeloma, were excluded. Age-adjusted mortality (AAMR) rates per 100,000 people were extracted for adult patients between 25 and 44 years of age. AAMR was assessed by demographic and clinical variables, including race, geographic density, sex, and primary site. Joinpoint trend analysis was used to identify the presence of statistically significant temporal trends. Average annual percent change (AAPC) was considered statistically significant if p &lt; 0.05. Results: Between 1999 and 2020, 366,478 cancer-related deaths occurred in young adults in the United States. The overall AAMR was 20.7, decreasing from 24.8 in 1999 to 17.5 in 2020 at a rate of -1.6% annually (p&lt;0.05). However, increasing mortality was seen in a number of primary sites, including uterine cancer with an increase of 2.6% annually (p&lt;0.05) and colorectal cancer with an increase of 0.8% annually (p&lt;0.05). Overall AAMR was highest for non-Hispanic Black individuals at 28.3, 29% higher than the next highest group (non-Hispanic White) at 21.2 and almost double that of non-Hispanic Asians at 14.7. Individuals residing in rural populations experienced the highest AAMRs at 24.3 and the slowest rates of decrease at -1.6% annually (p&lt;0.05), compared with urban individuals whose AAMR was 19.8 with a decrease of -1.9% annually (p&lt;0.05). Primary sites with the highest AAMRs included breast (3.1), lung (2.1), and colorectal (1.8) cancers. Conclusions: The current study sheds light on the evolving landscape of cancer mortality among young adults in the United States. The overall decrease in age-adjusted mortality rates is promising, reflecting advancements in cancer care and prevention strategies. However, the alarming increase in mortality rates for specific cancer types, such as uterine and colorectal cancers, underscores the need for targeted interventions and heightened awareness, especially in at-risk populations. The identified racial and geographic disparities further emphasize the importance of implementing tailored approaches to address the unique challenges faced by diverse populations.
Efficacy and safety of the use of dinutuximab in newly diagnosed or relapse high risk neuroblastoma: Single arm systematic review and meta-analysis.
Authors: Lorena Escalante Romero, Davi Said Gonçalves Celso, Isadora Mamede Mendes da Silva, Pedro Cotta Abrahão Reis, Maria Inez Dacoregio, Carlos Stecca, Eliana Maria Monteiro Caran
Journal: Journal of Clinical Oncology (2024)

10044 Background: Patients with high-risk Neuroblastoma have a poor prognosis, with 43% experiencing a 3-year survival rate in newly diagnosed cases and a 21% 1-year event-free survival in relapsed patients. Dinutuximab, an immunotherapy targeting anti-disialoganglioside (GD2), emerges as a promising treatment for high-risk Neuroblastoma. This single arm meta-analysis aims to assess the efficacy and safety of dinutuximab, providing insights into its impact on survival rates among neuroblastoma patients. Methods: We systematically searched Pubmed, Cochrane and EMBASE for clinical trials between 1988 to 2023 utilizing Dinutuximab (ch14.18 or ch14.18/CHO) in patients with newly diagnosed or relapsed/refractory high-risk neuroblastoma. We pooled the prevalence and the 95% confidence intervals (CI) for the outcomes of interest: overall survival (OS), event-free survival (EFS) and progression-free survival (PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE). Heterogeneity was assessed using I² analysis and all statistical analyses were employed using R software version 4.3.2 and a random-effects model. Results: The analysis included 2214 patients from 13 clinical trials, comprising four phase III trials and six phase II. Six studies included Interleukin 2 (IL-2). Among the patients, 364 (16.5%) had relapsed or refractory disease. Dinutuximab was applied as post-consolidation treatment in 1809 patients (81.1%). The age of patients ranged from 1 to 21 years. In a pooled analysis, the 3-year OS rate was 69% (CI 0.62-0.76; I² = 85%), and the 3-year EFS rate was 61% (CI 0.52-0.69; I² = 77%). In the group of newly diagnosed patients, the 3-year EFS rate was 62% (CI 0.58-0.66; I² = 52%) and 3-year OS rate of 74% (CI 0.69-0.79; I² = 71%). Among patients with relapse, there was a 3-year OS rate of 57% (CI 0.50-0.64; I² = 0%). The overall ORR was 47% (CI 0.37-0.57; I² = 69%), of which 38 newly diagnosed patients using Dinutuximab during induction chemotherapy showed an ORR of 86%. TEAEs of grade ≥ 3 were 70% (CI 0.44-0.88; I² = 94%), and in the subgroup without IL-2 use, it was 43% (CI 0.29-0.57; I² = 85%). Conclusions: This single-arm meta-analysis suggests that both newly diagnosed or relapsed/refractory high-risk Neuroblastoma patients benefit from Dinutuximab, with a promising impact on 3-year OS and EFS. Dinutuximab appears to be a safer option; however, concomitant use of IL2 is associated with a higher rate of adverse effects.
Association between wildfire PM2.5 and genitourinary cancer survival in California.
Authors: Shuchi Gulati, Mariela Alaniz, Nicholas Mitsiades, Mamta Parikh, Sean Raffuse, Theresa Keegan, Irva Hertz-Picciotto, Primo N Lara, Shehnaz K Hussain
Journal: Journal of Clinical Oncology (2024)

10567 Background: Aerosolized particulate matter (PM) 2.5 (i.e., particles ≤ 2.5 µm in diameter or fine particles), including those that emanate from wildfires, has been previously associated with cancer risk and survival. While prior studies have focused primarily on etiology, little is known about the effects of wildfire PM2.5 on cancer prognosis. We sought to explore the effects of wildfire PM2.5 on genitourinary (GU) cancer survival in the state of California where episodic wildfires are considered a component of its climate. Methods: Using the California Cancer Registry, we identified incident prostate (n=81,261), urothelial (n=26,689), and kidney (n=26,303) cancers diagnosed between 2017-2020. Daily PM2.5 was estimated over the same period. Random forests regression was used to fuse diverse datasets (official air quality monitoring, satellite observations, meteorological modeling, predictive smoke modeling, and low-cost sensor networks [PurpleAir]) and produce a consensus estimate of PM2.5 for each centroid of a 1-square kilometer grid across California. We used home address at the time of cancer diagnosis to map each cancer case to the nearest centroid, and averaged PM2.5 exposures over the 6 months preceding cancer diagnosis for each case. Cox-proportional hazards regression was used to quantify the hazard ratio (HR) for death from any cause following cancer diagnosis associated with PM2.5, adjusting for key covariates including age, sex, race/ethnicity, neighborhood socioeconomic status, comorbidity, smoking status, rural/urban residence, and stage at diagnosis. Results: In patients with prostate cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with an 18% increased hazard of death (HR=1.18; 95% confidence interval (CI)= 1.02-1.36, p=0.023). When stratified by stage at diagnosis, the association of PM2.5 and survival was limited to stages I, II, and III (HR=1.39; CI= 1.11-1.74, p=0.005) versus stage IV (HR=1.06; CI= 0.87-1.27, p=0.566). For urothelial cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with a non-statistically significant 11% increased hazard of death (HR=1.11; CI= 0.96-1.29, p=0.151), which did not differ by stage at diagnosis. Kidney cancer survival was not associated with PM2.5 (HR= 0.94; CI= 0.79-1.11, p= 0.44). Conclusions: These findings suggest that higher PM2.5 exposure could influence prostate and urothelial cancer prognosis, perhaps through alteration of physiological pathways relevant to cancer aggressiveness or impairing response to treatment, including cellular immune response, inflammation, angiogenesis, or cell-signaling pathways. Further studies should look into the mechanisms and design mitigating strategies in patients diagnosed with these high-risk cancers who have been exposed to wildfire PM2.5.
Clinical characteristics, prognosis, and immunotherapy outcome in pediatric melanoma: Analysis from a large Chinese cohort.
Authors: Juan Wang, Mengjia Song, Yingxia Lan, Junting Huang, Jia Zhu, Suying Lu, Feifei Sun, Zijun Zhen, Yi Que, Wanming Hu, Yu Zhang, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2024)

10050 Background: Malignant melanoma in children and adolescents is rare, with limited data on Chinese populations.To assess the clinical characteristics, survival, prognostic factors, and the efficacy of immunotherapy in a real-world cohort of Chinese pediatric patients with melanoma. Methods: This is a retrospective, cohort study included pediatric melanoma patients between February, 2005 and May, 2021, with a median follow-up time of 76.7 months. Data analyses were conducted in May, 2023. This study enrolled patients from Sun Yat-sen University Cancer Center, the biggest cancer institution in South China for cancer prevention, diagnosis and treatment. Inclusion criteria for this study were as follows: 1) histopathologically confirmed diagnosis of melanoma; 2) Age ≤18 year; 3) with complete clinical data on sex, age, histopathological features, etc. The exclusion criteria was secondary malignant melanoma. Main outcomes and measures were patient’s OS and EFS. Results: 43 patients were enrolled, with median age of 138.9 (range 13.1-215.0) months, including 30 cutaneous melanoma, 7 meningeal melanoma, 5 mucosal melanoma, and 1 uveal melanoma. The frequency of BRAF V600E mutation was 16.7% (4/24). Mismatch repair proteins were normally expressed (7/7), and the positive rate of programmed cell death ligand 1 expression was 55.6% (5/9). The event-free survival and overall survival of cutaneous, mucosal and meningeal melanoma were 46.7±9.1% vs 75.0±21.7% vs 16.7±15.2% ( P = 0.010), 65.5±8.9% vs 75.0±21.7% vs 16.7±15.2% (P&lt; 0.001), respectively. Survival of cutaneous melanoma were associated with pathological type, ulceration, Clark level, disease spread, sentinel lymph node status, tumor stage and Ki-67 expression. 5 of 9 patients who were treated with PD-1 inhibitors (5 with PD-1 inhibitors alone, 3 with PD-1 inhibitors plus angiogenesis inhibitors, 1 with combination of anti-PD1, anti-angiogenic inhibitors plus chemotherapy) were evaluable with the overall response rate of 20%. The most common immune-related adverse event was hypothyroidism. Conclusions: This is the largest real-world study in pediatric melanoma patients in Asia. The prognosis of mucosal melanoma was favorable, followed by cutaneous melanoma, and meningeal melanoma had the worst prognosis. PD-1 antibody combined with angiogenesis inhibitors maybe a promising choice in pediatric melanoma.
RMS13: A phase II trial using risk adapted focal proton beam radiation and/or surgery with the addition of maintenance chemotherapy in intermediate risk rhabdomyosarcoma.
Authors: Jessica Gartrell, Alberto S. Pappo, Yimei Li, Tushar Patni, Daniel J. Indelicato, Sara Michele Federico, Elizabeth Stewart, Christopher L Tinkle, Sara Helmig, John Thomas Lucas, Michael W. Bishop, Mary B McCarville, Karen H. Albritton, Matthew J. Krasin
Journal: Journal of Clinical Oncology (2024)

10008 Background: European trials have demonstrated improved outcomes in SIOP high-risk/COG intermediate risk (IR) rhabdomyosarcoma (RMS) when 6 months of maintenance therapy (MTC) was added to ifosfamide, vincristine (VCR), dactinomycin (DAC) +/-doxorubicin chemotherapy. The effectiveness of MTC integrated with VCR, DAC and cyclophosphamide (CYC), standard North American chemotherapy, remains unclear. Methods: RMS13 is a phase II multicenter trial evaluating the safety and efficacy of risk adapted proton radiation therapy (RT) and the addition of MTC in patients with IR RMS (embryonal stage 1, Group III non-orbit, and stage 3 Group I, II were not eligible for MTC). Patients received 12 cycles of VCR (1.5mg/m 2 weekly), DAC (0.045mg/kg q3weeks), and CYC (1200mg/m 2 q3weeks) (VAC) followed by MTC with 4 cycles of oral CYC (50mg/m 2 daily), bevacizumab (15mg/kg) q3wks, and sorafenib (90mg/m 2 bid) (CBvSor). RT was prescribed based on local tumor status at the time of RT (Table 1). Five-year disease-free survival (DFS) using the Kaplan-Meier method and the cumulative incidence (CI) of primary site local failure (LF) was described. Results: 46 patients were enrolled (Table 1). One patient refused further therapy and was removed from the analysis. 5-year DFS for the entire cohort was 67.5% with a median follow up of 54 mo. The trial was halted since &lt; 75% of enrolled patients received all prescribed CBvSor MTC. Of the 35 who were eligible for MTC, 24 initiated MTC and 18 completed protocol-directed MTC. Three pts received vinorelbine/CYC MTC after enrollment was stopped. Reasons for not completing CBvSor MTC included: progression prior (6), toxicity (5), refusal (3). The 5-year DFS for the 24 patients that started cycle 3 was 70.3%. When limited to patients classified as high-risk in RMS2005 trial, the 5-year DFS was 81.4%. No patients experienced LF after margin negative surgery. The CI of LF was: 0% following 36GyRBE RT for microscopic residual disease, 8% for patients with unresected tumors &lt; 5cm receiving standard dose RT (50.4GyRBE), and 10% for patients with unresected tumors &gt; = 5cm receiving dose escalated RT (59.4GyRBE). 5/6 patients with alveolar N1 disease recurred. Conclusions: Local control with risk adapted dose-escalated RT was excellent in IR patients. Those with nodal involvement fared poorly. While 4-cycles of MTC with CBvSor was not feasible, those who underwent at least 3 cycles experienced enhanced DFS outcomes, aligning with the positive results seen in other trials incorporating MTC. Clinical trial information: NCT01871766 . [Table: see text]
Phase I trial of chidamide, an oral HDAC inhibitor, in combination with oral etoposide in patients with refractory/recurrent neuroblastoma.
Authors: Feifei Sun, Zijun Zhen, Suying Lu, Jia Zhu, Juan Wang, Junting Huang, Yi Que, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2024)

10034 Background: Chidamide, an oral subtype-selective histone deacetylase (HDAC) inhibitor, has been shown to be effective in adult patients with hematological tumors. However, there is no data on its safety and efficacy in pediatric cancer patients. Combination of HDAC inhibitors and etoposide have shown synergistic anti-tumor effects in preclinical studies of neuroblastoma. We conducted a phase I trial in pediatric patients with recurrent or refractory neuroblastoma to determine the maximum tolerable dose (MTD) of chidamide combined with oral etoposide treatment. Methods: Daily oral etoposide 35 mg/m 2 /dose was administered on days 1–21 in combination with escalating doses of chidamide (14 and 17 mg/m 2 /d) twice weekly in each 28-day cycle using the standard 3 + 3 design. Patients with response or stable disease after two cycles would maintain treatment until disease progression or unacceptable toxicity occurred. Chidamide pharmacokinetic testing was performed. Results: 31 patients were enrolled in this study. The median age was 7 years (range 3 – 18). 14 patients were included in the dose escalation phase (Ia), 17 patients in the expansion cohort (Ib). The MTD of chidamide was 14 mg/m 2 /d, with dose limiting neutropenia and thrombocytopenia observed at 17 mg/m 2 /d. Median number of cycles completed was 2.5 (range 1–11). A total of 19 patients (61.3%) experienced treatment-related grade 3/4 hematologic toxicity, and no grade 3/4 non-hematological toxicity was observed. No objective responses were seen. Conclusions: In children with refractory/recurrent neuroblastoma, chidamide is well-tolerated at 14 mg/m 2 /d twice weekly when combining with oral etoposide 35 mg/m 2 /d daily. Prolonged disease stability achieved in patients with minimal residual diseases deserves further investigation. Clinical trial information: NCT05338541 .