tbuckley/cabot-search huggingface dataset:
Experiences of underrepresented adolescent and young adult (AYA) cancer survivors engaging in research-related activities.
Authors: Lauren Victoria Ghazal, Anao Zhang
Journal: Journal of Clinical Oncology (2024)

10073 Background: Adolescent and young adult (AYA) cancer survivors are an age-defined cohort (15-39 years at diagnosis) confronting unique biopsychosocial needs throughout their cancer experience. Underrepresented (sexual and gender minority [SGM] and/or Black, Indigenous, and People of Color [BIPOC]) AYAs face additional challenges associated with discrimination, mistrust of providers, and culturally incongruent services. As a result, many underrepresented AYAs experience suboptimal oncological care and disparate outcomes when compared to cis-gendered heterosexual and/or white peers. This study explored the experiences of underrepresented AYA cancer survivors engaging in research-related activities. Methods: This study is part of a larger Patient Centered Outcomes Research Institute (PCORI)-funded project that is evaluating multilevel facilitators and barriers to oncological care and research for underrepresented AYA cancer survivors. With support from five academic cancer centers and five community-based organizations supporting AYAs across the US, we have assembled an intersectional community advisory panel (CAP) of 10 AYAs who identify as BIPOC and/or SGM. Together with the CAP, a semistructured interview guide was developed, and from January to February 2024, we conducted video interviews. Data were analyzed using thematic analysis of verbatim transcribed interview scripts. The CAP assisted the investigative team in the analyses and interpretation of data. Results: Of the 20 participants interviewed, roughly 70% identified as BIPOC, 40% as SGM, and 10% as both BIPOC and SGM. Participants included underrepresented AYA cancer survivors who, prior to this specific study, had or had not participated in cancer-related research. Three major themes affecting underrepresented AYAs and engagement in research-related activities were discovered, and included: 1) Layering of identities, culture, and stigma; 2) The role of trusted conduits in facilitating engagement; and 3) Beyond compensation: reasons of pursuance. Conclusions: The resultant themes illuminate multilevel facilitators and barriers to research engagement among underrepresented AYA cancer survivors. Findings will assist in guiding researchers, oncology care providers and program administrators both in academic and community settings in the design of inclusive and equitable cancer care delivery programs for underrepresented AYA cancer survivors.
Phase I dose escalation and pharmacokinetics clinical trial of mitoxantrone hydrochloride liposome in children with relapsed and refractory solid tumors.
Authors: Junting Huang, Mingqing Ji, Hui Li, Yanpeng Wu, Ruiqing Cai, Juan Wang, Suying Lu, Jia Zhu, Feifei Sun, Zijun Zhen, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2024)

10047 Background: Compared with solvent-based mitoxantrone, mitoxantrone hydrochloride liposome has been found to reduce bone marrow toxicity. This open-label, muti-center, single-arm phase I clinical trial aims to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in pediatric with solid tumors. Methods: The study was divided into Phase Ia and Ib. Phase Ia was the dose escalation study, with a "3+3" design. Patients received mitoxantrone hydrochloride liposome at three dose levels (16 mg/m 2 , 20mg/m 2 , 24mg/m 2 , d1) in combination with irinotecan (50mg/m 2 , d1-5) and vincristine (1.5mg/m 2 , d1) every 3 weeks. Pharmacokinetic studies were conducted simultaneously. The primary endpoint of Phase Ia was the maximum tolerated dose (MTD). In phase Ib, patients received the combination therapy of mitoxantrone hydrochloride liposome at the MTD dose. The primary endpoint of Phase Ib was the incidence and severity of hematological adverse events. Secondary endpoints in both phases included objective response rate (ORR), pharmacokinetic (PK) parameters, and others. Results: From October 2022 to January 2024, a total of 51 pediatric patients with relapsed and refractory solid tumors were enrolled, 28 patients in Phase Ia and 23 patients in Phase Ib. The median age was 10.0 years (range: 3, 21). All Patients could be evaluated for toxicity and 40 for efficacy. The MTD of mitoxantrone hydrochloride liposome was determined to be 24mg/m 2 . The results of pharmacokinetic analysis were not returned. Highest incidence of hematological and non-hematological adverse events (AEs) were anaemia (88.2%), diarrhea (84.3%). The newly found or aggravated TnIUtra, BNP value abnormality and lower LV function after medication were 4 (11.8%), 5 (14.3%) and 0 (0.0%), respectively. The overall ORR and DCR were 50.0% (95% CI: 33.8% - 66.2%) and 90.0% (95% CI: 76.3% -97.2%). 13 patients (25.0%) treated with mitoxantrone hydrochloride liposome combination regimen received the opportunity of surgery. Conclusions: The mitoxantrone hydrochloride liposome combination regimen has demonstrated an acceptable toxicity profile and promising clinical efficacy in pediatric patients with solid tumors, especially in sarcomas. Clinical trial information: NCT05620862 .
Association of germline polygenic risk for thyroid autoimmunity with overall survival in the I-SPY2 Trial.
Authors: Kirkpatrick B Fergus, Pooja Middha, Zoe Quandt, Yiwey Shieh, Amrita B Basu, Rosalyn Sayaman, Paula R Pohlmann, Douglas Yee, Rebecca Arielle Shatsky, Claudine Isaacs, Michael J. Campbell, Gillian L. Hirst, Lamorna Brown Swigart, Laura van 't Veer, Elad Ziv, Laura Esserman
Journal: Journal of Clinical Oncology (2024)

10600 Background: Germline genetic variation influences immune activity and risk of autoimmunity, and has been hypothesized to play a role in response to cancer therapeutics and survival. Prior studies of breast cancer have reported associations between genetic variation in thyroid autoimmunity and overall survival (OS). Here, we aim to investigate the association between a polygenic risk score for hypothyroidism (PRS-H) and response to therapy in women with early-stage breast cancer, and hypothesize that high PRS-H will be associated with better treatment response and survival. Methods: This study includes 1,368 women aged 18 years and above with stage II-III breast cancer of size &gt; 2.5cm by clinical exam, with germline data available. It is an approved biomarker analysis of the I-SPY 2 trial, which is a phase II, adaptive, randomized platform trial across multiple sites studying novel cancer therapeutics across multiple arms for use as neoadjuvant chemotherapy for early-stage breast cancer. The outcome of survival is defined as alive at the most recent follow-up. Using the Cox proportional hazards model, we evaluate the association between a previously published PRS-H and overall survival. Models are adjusted for age at screening, immunotherapy status, and five principal components. Results: Among 1,368 early-stage breast cancer women, 33% (n=447) had pCR, and 85% (n=1,157) were alive at the last follow-up. Additionally, 16% (n=219) of women received immunotherapy. We observe a significant association between PRS-H and OS (HR = 0.78, 95% CI 0.66-0.92, p=0.004). Individuals in the top 10th percentile of the PRS-H (highest genetic risk) have improved survival (log rank p=0.04). Conclusions: Germline genetic variation in thyroid autoimmunity proclivity is associated with improved overall survival in our cohort of women with early-stage breast cancer receiving neoadjuvant chemotherapy. Our findings suggest that the genetic risk for autoimmunity may be important for long-term survival. We will expand this analysis to include the entire I SPY 2 population when all patients have completed genotyping. We plan to further characterize the role of germline autoimmunity profiles and survival. Clinical trial information: NCT01042379 .
Effect of polygenic risk score for clinically significant prostate cancer in a screening program: The BARCODE 1 study results.
Authors: Ros A. Eeles, Elizabeth Kathryn Bancroft, Jana Kathlyn McHugh, Edward Saunders, Mark Brook, Eva McGrowder, Sarah Wakerell, Denzil James, Elizabeth Page, Andrea Osborne, Netty Kinsella, Syed Aslam Sohaib, Declan Cahill, Stephen Hazell, Sam Withey, Imran Rafi, Pardeep Kumar, Nicholas D. James, Sarah Benafif, Zsofia Kote-Jarai
Journal: Journal of Clinical Oncology (2024)

10500 Background: Incidence of prostate cancer (PCa) is increasing, but there is no internationally agreed population screening program. Studies using an age-based PSA approach show a high rate of false-positive results as well as over-diagnosis of indolent PCa. Genome wide association studies identify common germline variants to calculate a polygenic risk score (PRS) associated with PCa risk. The BARCODE1 study used PRS to target PCa screening to those at higher risk based on genotype. Methods: European men aged 55-69yrs were recruited via Primary Care in the UK. PRS was constructed by summing weighted risk alleles for 130 PCa risk variants using germline DNA from saliva samples via mailed kits. Men with a PRS &gt; 90 th centile were invited for PCa screening using MRI and 12-core transperineal biopsy (including MRI fusion to target additional lesions where identified) irrespective of PSA result. Results: Invitation letters were sent to 40,292 men. 8,953 (22%) expressed an interest; 8,014 were eligible and sent a saliva kit. 6,644 consented; 6,393 were genotyped; 251 failed QC. A total of 6,142 participants had PRS calculated: 745 (12.1%) had a PRS &gt; 90th centile and were invited to screening. 558/745 participants attended screening (121 declined, 66 excluded on health grounds). 551 underwent MRI and 468 had prostate biopsy resulting in 187 (40.0%) diagnoses of PCa, overall PCa detection rate 2.8%. Mean age at diagnosis 64.1yrs (range 57-73; median 64). Using NCCN criteria (2023) 103/187 (55.1%) of cancers were Intermediate or High Risk; 40/187 (21.4%) were Intermediate Unfavourable/High/Very High Risk. 119/187 (63.6%) men had a PSA &lt;3.0ug/L; PPV of biopsy for PSA &gt; 3.0ug/L was 49.6%. PPV of MRI (presence of PI-RADS 3-5 lesion) 60.4%. PPV of PRS alone 40%. 103/187 (55.1%) had Gleason &gt;7; compared with 360/1014 (35.5%) p &lt; 0.001 in the PSA directed ERSPC study. Conclusions: A population PCa screening program using PRS risk-stratification enriches for clinically significant PCa requiring treatment. It detects a high proportion of clinically significant disease compared with PSA or MRI based screening programs and MRI missed a significant proportion (17-67%) of cancers found on biopsy. This is the first study to assess if this approach will be useful in population screening programs. Clinical trial information: NCT03857477 . [Table: see text]
Testicular germ cell tumor survival among children, adolescents, and young adults: A population-based retrospective cohort study.
Authors: Rand Ajaj, Cindy Lau, Sumit Gupta, Nancy N. Baxter, Rinku Sutradhar, Jason D. Pole, Sarah Malkiel, Furqan Shaikh, Paul C. Nathan
Journal: Journal of Clinical Oncology (2024)

10035 Background: While testicular germ cell tumor (TGCT) overall survival (OS) exceeds 90%, some patient groups, such as adolescents, have inferior event free survival (EFS) outcomes. There is a paucity of granular, population-derived data about outcomes in children, adolescents, and young adults (CAYA) with TGCT, limiting a deeper understanding of the factors that impact their survival. Methods: All male CAYA (ages 11-21 years) in Ontario, Canada diagnosed with TGCT between 1992-2021 were identified using provincial cancer registries. Detailed disease and treatment characteristics were chart abstracted for ~2/3 of the cohort and determined through health administrative databases for the remainder. We assessed 5-year OS and EFS (first of death, recurrence/progression, or subsequent malignant neoplasm [SMN]) using Kaplan-Meier analysis and the log rank test. Follow-up started at TGCT diagnosis, except for survival after SMN or recurrence, where follow-up started at event date. Results: 748 TGCT patients were identified; 521 were chart abstracted and thus had EFS data available. Median age at diagnosis was 19 years (interquartile range:18-21) and 83.6% had non-seminoma histology. OS and EFS ± standard error (SE) were (94.7 ± 0.8 %, n=748) and (76.4 ± 1.9%, n=521), respectively. Among patients with chart abstracted data, OS and EFS differed by cancer extent at diagnosis and were lowest among CAYA with non-lung organ metastases (Table). Patients who underwent retroperitoneal lymph node dissection (RPLND) for initial treatment (91/521) had higher survival than those who did not (OS 96.6 ± 1.9% vs 93.7 ± 1.2%, p=0.04; EFS 87.6 ± 3.5 % vs 74.1 ± 2.1 %, p=0.0008), particularly CAYA with lung-only organ metastases. OS post SMN (n=28) was 77.3 ± 8.2%, with lower OS after non-TGCT SMN (50.8 ± 14.4%, n=13) than second primary TGCT (100 ± 0%, n=15), p=0.002. OS after recurrence/progression (n=116) was superior in the 59 who did not receive chemotherapy at initial diagnosis (89.7 ± 4%) compared to the 57 who had initial chemotherapy (65.9 ± 6.4%; p=0.0001). Conclusions: CAYA with TGCT have low EFS, consistent with previous studies. The extent of metastasis is a significant predictor. Efforts are needed to improve the survival outcomes of young TGCT patients with organ metastasis at diagnosis, and those who recur or develop a non-TGCT SMN. [Table: see text]
Estimating risk for pancreatic cancer among 9.4 million veterans in care.
Authors: Louise Wang, Navid Rahimi Larki, Melissa Skanderson, Janet Tate, Ronald G Hauser, Cynthia Brandt, Yu-Xiao Yang, Amy C. Justice
Journal: Journal of Clinical Oncology (2024)

10544 Background: Screening for pancreatic ductal adenocarcinoma (PDAC) has focused on individuals with a hereditary component, accounting for only 10% of PDAC events. Using the electronic health record, we developed a PDAC risk prediction model in a general population in the Veterans Health Administration (VA), the largest integrated health system in the US. Methods: We included all individuals from 2002- 2021 with ≥1 inpatient or outpatient VA encounter and recorded race, starting follow-up 1.5 years after first VA encounter. We excluded those who developed PDAC before start of follow-up. We used the multivariable Cox proportional hazards model in the derivation dataset (random 70% of cohort) to estimate the coefficients associated with each predictor for our outcome, time to PDAC (3 and 10 years), censoring at loss to follow-up or 12/31/2021. Candidate predictors included age, gender, race/ethnicity, sex, BMI, smoking status, alcohol use (alcohol use/related disorders and AUDIT-C), diabetes, pancreatitis, Hepatitis C, HIV, liver disease, cholecystectomy, pancreatic cysts, Charlson comorbidity index and common laboratory values. Selection of predictors was based on clinical reasoning, extent of missing values and model fit (Akaike Information Criterion and Harrell’s c–statistic). We evaluated model discrimination using c – statistic and model calibration comparing observed Kaplan – Meier estimated incidence vs. predicted risk score. Results: Among 9.4 million individuals, we observed 19,839 cases of PDAC within 10 years (6,022 cases within 3 years). Median baseline age was 58.5 years, 75.0% were White, and 16.3% were Black. Final predictors included age, gender, smoking, alcohol use (alcohol use/related disorders and AUDIT-C), BMI, diabetes, pancreatitis, pancreatic cyst, and history of cancer (Table, c-statistic in the derivation cohort 3 years: 0.79; 10 years: 0.77). Ten-year risk ranged maximally from 0-5.5%. Preliminary studies suggest labs do not clinically improve model performance. Conclusions: We developed a novel prediction model using available clinical data in a general population that identifies PDAC with high accuracy. Future work will try to identify additional predictors to improve the range of risk predicted. We will validate our findings in the testing set and in external cohorts. [Table: see text]
Real-world cancer care utilization among patients with breast cancer with germline variants of uncertain significance.
Authors: Allison W. Kurian, Kevin S. Hughes, Sarah M. Nielsen Young, Emily M. Russell, Flavia Facio, Chad Moretz, Rachel Ellsworth, Daniel Esteban Pineda Alvarez, Ed Esplin, W. Michael Korn
Journal: Journal of Clinical Oncology (2024)

10512 Background: Receipt of variant of uncertain significance (VUS) results from germline genetic testing (GGT) is common, but should not influence treatment or surveillance interventions. We examined treatment and surveillance uptake among breast (BC) patients (pts) undergoing GGT. Methods: GGT (Invitae Corporation) and insurance claims (Komodo Healthcare Map) data were assembled for female pts with ICD code(s) for BC or DCIS from 2015-2023, GGT &lt;120 days post-diagnosis (dx) and &gt;1 year of claims pre- and post-GGT. Inclusion/exclusion criteria followed prior work (PMID 32027353). Genes analyzed for VUS and positive (&gt;1 pathogenic germline variant, PGV) results were those with high ( &gt; 50%; BRCA1/ 2, CDH1, PALB2, PTEN, TP53) or moderate (20-50%; ATM, BARD1, CHEK2, NF1, STK11, RAD51C/D) BC risk. Multivariable logistic regression models of the association between GGT results and interventions included race/ethnicity, age, family history, local/distant metastasis, and log-transformed time from BC dx to GGT. Chi-square tests were used to compare demographics of VUS pts to other pts. Significance was set to p &lt; 0.05. Results: The cohort consisted of 19,334 pts (2005 VUS, 16,062 negative, 1,267 positive): 68% White, 25% lymph node involvement, 63% cancer family history, 28% Medicare/Medicaid, mean (SD) age at testing: 53 (11) and mean (SD) days from dx to GGT: 37 (25). VUS pts were more likely to be non-White (p &lt; 0.001). VUS pts were not more likely than negative pts to undergo BC-related therapies or surveillance, except for (anthracycline) chemotherapy (Table). In contrast, positive pts had significantly greater odds than negative pts of bilateral mastectomy, platinum/anthracycline chemotherapy, PARP inhibitors, and breast MRI. Conclusions: In a contemporary, real-world cohort of nearly 20,000 BC patients, receipt of BC-related interventions was similar in VUS and negative pts. VUS results do not appear to prompt guideline-discordant management, though the finding of increased anthracycline use needs further study. [Table: see text]
Naxitamab chemo-immunotherapy regimens other than with irinotecan/temozolomide for patients with relapsed/refractory high-risk neuroblastoma.
Authors: Cristina Larrosa, Margarida Simao Rafael, Juan Pablo Muñoz, Maite Gorostegui, Alicia Castaneda Heredia, Moira Garraus, Jaume Mora
Journal: Journal of Clinical Oncology (2024)

10037 Background: Patients with relapsed/refractory (R/R) high-risk neuroblastoma (HR-NB) have dismal prognosis with chemotherapy-only salvage regimens. Naxitamab, a humanized anti-GD2 monoclonal antibody (mAb), when combined with Irinotecan and Temozolomide (I/T), has demonstrated clinically meaningful efficacy in R/R HR-NB patients (NCT03189706). We aimed to investigate the potential synergy of naxitamab with other cytotoxics. Methods: In this retrospective analysis, we examined patients treated at SJD with chemo-refractory disease, who received naxitamab in combination with chemotherapeutics other than I/T. Each cycle comprised naxitamab 2.25 mg/kg/day IV over 30 minutes, days 2, 4, 9 and 11 (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously, days 6-10 combined with either a) cyclophosphamide (250mg/m2) and topotecan (0.75mg/m2) D1 to D5 (C/T), b) ifosfamide (1500mg/m2), etoposide (100mg/m2) D1-D3 and carboplatin (400mg/m2) D1 (ICE) or c) doxorubicin 37.5mg/m2 D1-D2 and cyclophosphamide (250mg/m2) D1-D3 (C/D). Toxicity was measured by CTCAE v4.0 and responses by INRC. Results: Twenty-nine patients received naxitamab plus GM-CSF with C/T (n=23), ICE (n=6) and C/D (n=1). One patient received both ICE and C/T. Seventeen patients had a variable number of prior relapses (1 n=14, 2 n=1, and 3 n=2). Twelve patients had refractory disease, most having received additional therapy post-induction. All but 4 patients had received naxitamab and I/T (n=20), and/or ICE (n=3/n=1), and dinutuximab-beta and I/T (n=1). Toxicities of the new regimens included myelosuppression expected with chemotherapy, and pain and hypertension expected with naxitamab. Hemorrhagic cystitis occurred in 2 patients treated with C/T, BK infection documented in one. A total of 113 cycles (median 2; 1-8) were administered, outpatient. Out of the 30 treatments, 5 achieved complete response (CR), 2 partial response (PR), and 2 mixed response (MR), providing an objective response (OR) of 30%. Eight patients achieved stable disease (SD) and 13 progressed on treatment. Disease control rate (DCR) (OR or SD) after 2 cycles was 56.6%. Patients who never responded with prior chemo-immunotherapy progressed through the new combinations. Contrary, patients who showed initial stabilization with I/T or ICE but ultimately progressed, switching drugs resulted in 60% DCR and 30% OR. Most favourable OR (75%) was seen in patients who achieved CR with prior chemoimmunotherapy and relapsed (3 out of 4). Conclusions: Naxitamab-based chemo-immunotherapy with regimens other than I/T exhibited similar and manageable toxicity profiles. Switching chemotherapeutics provided objective responses only to patients who had previously shown efficacy with I/T chemo-immunotherapy.
Intravitreal chemotherapy (IVC) in retinoblastoma: A study of clinical variables and ocular preservation outcomes.
Authors: Sidnei Epelman, Thamires MJ Mutran, Luiz Fernando Teixeira, Ethel Fernandes Gorender, Neviçolino Pereira de Carvalho Filho
Journal: Journal of Clinical Oncology (2024)

10059 Background: Retinoblastoma, a primary intraocular malignancy, poses unique challenges in preserving life and vision. This retrospective study aims to analyze the impact of IVC in a population of retinoblastoma patients. The primary objective to avoid external radiotherapy, a recognized risk factor for second neoplasms, particularly in germline retinoblastoma cases. Methods: We conducted an analysis of retinoblastoma patients from 2011 to 2024. Clinical variables, including sex, age, laterality, intraocular retinoblastoma staging, and therapies employed, were prospectively documented. Results: The study included 59 patients (37 male; 22 female). Thirty-three percent of patients had unilateral tumors and an average age of 28 months at diagnosis, and 67% had bilateral tumors with an average age of 15 months. Sixty-one eyes were treated and classified at diagnosis as follow: 6 (9.8%) in groups A and B, 10(18%) in group C, 37(64%) in group D, 6(11%) in group E, and 2(3%) without initial information. IVC was administered as part of a multimodal treatment approach. A total of 203 cycles of IVC were performed, averaging 3.4 cycles per patient. Melphalan was used in 39% of cycles, followed by the combination of melphalan and topotecan in 35%, and topotecan alone in 26%. Seven of 61 (11.5%) were enucleated. Three of 61 eyes (4.9%) received radiotherapy. Control of vitreous seeds and vision preservation were achieved in 57/61 eyes (93%). No grade 3 or 4 adverse events occurred. Conclusions: IVC emerges as a crucial component in the management of retinoblastoma, offering a viable alternative to external radiotherapy. The analysis highlights the importance of this approach in preserving ocular integrity, thereby avoiding enucleation and reducing the risk of second neoplasms, particularly in germline retinoblastoma patients.