tbuckley/cabot-search huggingface dataset:
Inequity in location and quality of death of advanced cancer patients by immigrant status.
Authors: Ana Isabel Tergas, Megan Johnson Shen, Holly Gwen Prigerson, Andreea Dinicu, Alfred I. Neugut, Jason Dennis Wright, Dawn L. Hershman, Paul K. Maciejewski
Journal: Journal of Clinical Oncology (2021)

12036 Background: Most cancer patients prefer to die at home, a location associated with better quality of death (QoD) and caregiver outcomes. A number of studies demonstrate disparities in end-of-life (EoL) care among immigrant vs non-immigrant populations in the U.S. This study aims to evaluate how immigrant status affects location and QoD among patients with advanced cancer in the U.S. Methods: Data were derived from Coping with Cancer, a federally funded multi-site prospective study of advanced cancer patients and caregivers. The analytic sample of patients who died during the study observation period was weighted (N w =308) to reduce statistically significant sociodemographic differences between immigrant (N w =49) and non-immigrant (N w =259) groups. Immigrant status was determined by patient self-report. Primary outcomes were location of death (intensive care unit, hospital, nursing home, inpatient hospice, home), death at preferred location (yes/no, as per caregiver report in post-mortem interview), and poor QoD (composite score of post-mortem caregiver ratings for patient psychological distress, physical distress, and quality of life in the last week of life). Results: As compared to non-immigrants, immigrants were more likely to die in a hospital as opposed to home [AOR 3.33; 95% CI (1.65-6.71); p=0.001] and less likely to die where they preferred [AOR 0.42, 95% CI (0.20-0.90); p=0.026]. As shown in Table, values-inconsistent aggressive EoL care mediated the effect of immigrant status on death at the patient s preferred location. Further, immigrants were more likely to have poor QoD [AOR 5.47; 95% CI (2.70-11.08); p&lt;0.001]. In particular, among patients who preferred symptom-directed, comfort EoL care, immigrants as opposed to non-immigrants were more likely to have poor QoD [AOR 9.53, 95%CI (4.05-22.40); p&lt;0.001]. Conclusions: Immigrants, as compared to non-immigrants, are more likely to die in hospital settings, less likely to die at their preferred location, and more likely to have poor QoD. These findings are consistent with previously described inequities in EoL care of immigrants and highlight the importance of determining the potential causes and solutions to ensure immigrants receive values-congruent care.[Table: see text]
Thick trust, thin trust, social capital, and health outcomes among trans women of color in New York City
Authors: Sel J. Hwahng, Bennett Allen, Cathy Zadoretzky, Hannah Barber Doucet, Courtney McKnight, Don Des Jarlais
Journal: International Journal of Transgender Health (2021)

Introduction: Many trans women of color communities experience high HIV seroprevalence, extreme poverty, high rates of victimization and substance use, and poor mental health. Greater knowledge of trans women of color social capital may contribute toward more effective services for this marginalized population. Methods: These data come from a mixed-methods study that examined trans/gender-variant people of color who attended transgender support groups at harm reduction programs in NYC. The study was conducted from 2011 to 12, total N = 34. The qualitative portion was derived from six focus group interviews. Results: Two support groups stood out as exhibiting very strong alternative kinship structures. One group was comprised of immigrant trans Latinas, and the other group were trans women of African descent living with HIV. Both groups demonstrated ample cultivation of "trust capital" in the form of "thick trust" (bonding capital) and "thin trust" (bridging/linking capital) both inside and outside/beyond the support groups. Thick trust included the cultivation of intimacy, support in primary romantic relationships, and community leadership. Thin trust included networking with a variety of organizations, increased educational opportunities, and cultural production. Discussion: Participants "opened up to social capital" through the process of trusting as a series of (1) risks; (2) vulnerabilities; and (3) reciprocities. A solid foundation of thick trust resulted in a social, psychological, and emotional "base." Upon this foundation, thin trust was operationalized resulting in positive material, economic, and quality-of-life outcomes, leading to an expanded space of capabilities.
Risk-reducing salpingo-oophorectomy and breast cancer incidence among BRCA-mutation carriers.
Authors: Tamar Perri, Shani Naor-Ravel, Perry Eliassi-Revivo, Dror Lifshitz, Eitan Friedman, Jacob Korach
Journal: Journal of Clinical Oncology (2021)

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.
Protein citrullination as a source of cancer neoantigens
Authors: Hiroyuki Katayama, Makoto Kobayashi, Ehsan Irajizad, Alejandro M Sevillano, Nikul Patel, Xiangying Mao, Leona Rusling, Jody Vykoukal, Yining Cai, Fuchung Hsiao, Chuan-Yih Yu, James Long, Jinsong Liu, Franscisco Esteva, Johannes Fahrmann, Sam Hanash
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Citrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response. Methods Protein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls. Results Proteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p&lt;0.0001); PADI2 protein expression was positively correlated (p&lt;0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen–antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012). Conclusions An immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.
The influence of race on financial toxicity among cancer patients.
Authors: John Panzone, Christopher Welch, Ruben Pinkhasov, Joseph M Jacob, Oleg Shapiro, Alina Basnet, Gennady Bratslavsky, Hanan Goldberg
Journal: Journal of Clinical Oncology (2021)

1525 Background: Studies show that cancer patients and survivors are likely to endure financial toxicity long after being diagnosed. Methods: To examine the influence of race on financial toxicity among individuals with a history of cancer, a US based cross sectional study was conducted using data on 1,328 cancer patients collected from the Health Information National Trends Survey. Multivariable logistic regression analyses were used to analyze the relationship between race and financial toxicity, adjusting for known confounders. Results: Blacks, Hispanics and other races were shown to have a lower rate of insurance compared to Whites. Whites were also more likely to receive cancer treatment than other races (6.1% received no treatment vs 15.0% of Blacks, 17.8% of Hispanics, and 9.7% of other races, p&lt;0.001). Considerably more Whites underwent surgical treatment of their cancer (77%) vs. 60% of Blacks, 55% of Hispanics and 74.2% of other races, p&lt;0.001. Blacks were found to be over 5 times more likely to be denied insurance (OR 5.003, 95% CI 2.451-10.213, p&lt;0.001) and more than twice as likely to be hurt financially than Whites (OR 2.448, 95% CI 1.520-3.941, p&lt;0.001). Other racial minorities were also more than twice as likely to be hurt financially than Whites (OR 2.421, 95% CI 1.248-4.698, p=0.009) (Table). Conclusions: These data suggest that race is significantly associated with increased rates of being hurt financially and being denied insurance due to cancer. Awareness of race inequality should be raised so that equal cancer treatment can be provided, irrespective of race, gender or socioeconomic status.[Table: see text]
Characteristics of patients (pts) and prognostic factors across treatment lines (TL) in metastatic colorectal cancer (mCRC): An analysis from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.
Authors: Jean-Baptiste Bachet, Benoist Chibaudel, Manel Rakez, Richard M. Goldberg, Niall C. Tebbutt, Eric Van Cutsem, Daniel G. Haller, J. Randolph Randolph Hecht, Robert J. Mayer, Stuart M. Lichtman, Al Benson, Alberto F. Sobrero, Josep Tabernero, Richard Adams, John Raymond Zalcberg, Axel Grothey, Takayuki Yoshino, Qian Shi, Aimery De Gramont
Journal: Journal of Clinical Oncology (2021)

3575 Background: Pts with mCRC frequently receive ≥1 sequential treatment TL. Approximately 50%-60% of pts receive second-line (L2) and 20%-30% third-line (L3) regimens in routine practice. We investigated the pts clinical/tumor characteristics and their prognostic impact across TL. Methods: Data from 37,560 pts enrolled in 48 randomized trials (34 in first (L1), 9 in L2, and 5 in L3) were analyzed. Candidate variables (VAR) measured at enrollment were sex, age, body mass index, performance status (PS), bilirubin, hemoglobin (Hb), platelets (Pl), derived white blood cells-to-absolute neutrophil counts ratio (WBC/ANC), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), primary tumor location, and number and location of metastatic sites (MS). Missing data were imputed. VAR with significant value at all TL were selected to construct a prognostic score of overall survival (OS) in training set (TS, n=30,050; 80%). For each TL, the score was calculated as the sum on the estimations of the VAR’ coefficients from the common multivariate model; Cox’s model was used to define risk groups. The discrimination capability was assessed using the Harrell’s C-index. External validation was done in the validation set (VS, n=7,510; 20%). Results: A total of 26,974 pts in L1, 7,693 pts in L2 and 2,893 pts in L3 were analyzed. The following characteristics increased continuously over TL: ≥2 MS (57%, 72%, 82%), lung metastases (50%, 74%, 91%), lymph nodes metastases (51%, 61%, 80%), KRAS mutation (37%, 47%, 51%) and elevated ALP (46%, 52%, 61%). BRAF mutation decreased (9%, 7%, 5%). In L1 vs L3 trials, 70% vs 89% of patients had primary tumor resection, 10% vs 80% had at least one metastasectomy and 31% vs 78% had a late metachronous (&gt;12 months) metastasis. 7 independent VAR were retained in the prognostic score (PS, Hb, Pl, WBC/ANC, LDH, ALP, and the number of MS); four pt groups with significantly different prognoses were defined (table). This score remained valid when excluding pts with PS 2. Third-line oral drugs (vs placebo) and subsequent line (L2/L1 or L3/L2) were effective in all prognostic groups. Conclusions: Clinical/tumor pt characteristics significantly varied over subsequent TL in patients included in randomized trials. The same prognostic model using practical clinical and biological variables can be used in all TL.[Table: see text]
Circulating tumor DNA and circumferential resection margin as key prognostic indicators for survival in rectal cancer.
Authors: Mia Shepherdson, Erin L. Symonds, Susan Byrne, Kirsten Gormly, Christos Stelios Karapetis, Sina Vatandoust, Graeme P. Young, Amitesh Chandra Roy
Journal: Journal of Clinical Oncology (2021)

3579 Background: Recurrence of colorectal cancer has been linked to the presence of epigenetic circulating tumour DNA (ctDNA) in patient plasma after surgery. The prognostic significance of ctDNA prior to treatment remains unknown. This study investigated the correlation between pre-treatment ctDNA and current radiological (MRI) prognostic markers in patients with rectal cancer. Methods: Forty-two patients with rectal cancer were enrolled, with all having staging MRI prior to treatment. Plasma was taken for ctDNA at diagnosis. The presence of either methylated branched-chain amino acid transaminase 1 (BCAT1) or Ikaros family zinc finger (IKZF1) in cell-free DNA from plasma was deemed a positive ctDNA result. Correlation of MRI prognostic indicators and ctDNA results was assessed with chi-square tests. Univariable and multivariable cox regression analyses were performed to determine variables associated with overall survival (OS). Results: Mean age was 64.4 years (SD 12.5) and majority were male (30/42, 71.4%). 11, 13, 9 &amp; 9 patients had stages I, II, III, IV respectively. Patients had a minimum follow-up of 36 months. Thirty-three (78.6%) patients received neoadjuvant chemoradiotherapy. 29 (69.0%) patients underwent surgical resection. 3-year survival rate was 64% in the overall group. 67% (n=28/42) of patients were positive for the methylated ctDNA at diagnosis. 11 out of 12 patients with a positive circumferential resection margin (CRM +) were ctDNA positive (p=0.03). Univariable analysis showed that prognostic indicators for OS were presence of extramural venous invasion (EMVI) (HR 3.0, 95% CI 1.1-8.4), CRM+ (HR 12.2, 95%CI 3.9-37.6), metastatic disease (HR 7.32, 95% CI 2.63-20.37) and ctDNA% methylation (HR 1.1, 95% CI 1.04-1.13) (Table 1). The presence of CRM+ and a positive ctDNA had a HR of 20.5 (95% CI 5.1-82.3). With multivariable analysis, including adjustment for age and EMVI, only CRM+/ctDNA+ variable was an independent predictor for poor survival (HR 20.2, 95% CI 4.5-90.9). Conclusions: In rectal cancer, almost all patients with CRM involvement have ctDNA, and these patients had the worst prognosis. Future studies with longitudinal ctDNA assessment pre and post treatment could potentially inform prognosis and help tailor patients’ treatment.[Table: see text]
Race, subjective social status and metabolic syndrome in women with breast cancer.
Authors: Giampaolo Greco, Emily J. Gallagher, Derek Leroith, Sylvia Lin, Radhi Yagnik, Sheldon M. Feldman, Brigid K. Killelea, Neil B Friedman, Melissa Louise Pilewskie, Lydia Choi, Nina A. Bickell
Journal: Journal of Clinical Oncology (2021)

560 Background: Metabolic syndrome (MS) is associated with worse breast cancer prognosis. Black women have higher rates of advanced breast cancer, as well as MS, diabetes and obesity. As socioeconomic status is associated with MS, we asked whether the subjective perception of social status (SSS), might influence this association in black and white women with a new breast cancer (BC) diagnosis. Methods: We surveyed, obtained serum and conducted anthropometric measures of 1206 women with a new BC diagnosis. Triglycerides, systolic blood pressure (SBP), waist circumference (cm), HDL and glucose were used to calculate a severity index of MS (MS-Zscore: mean=0; sd=1). Women reported their SSS on the 10 rung McArthur US social status ladder, their household income, education attained, diet quality (5 point scale), and exercise measured with metabolic equivalents (METS). Data were analyzed with multivariable generalized linear models. Missing data were imputed with multiple imputation. Results: Average age was 58 yrs of 295 black and 911 white women. BC stage &gt; II was in 11.6% of black and 2.4% of white women. On average black women had higher BMI (31.5 vs 26.6; p&lt;0.001), waist circumference (103 vs 93; p&lt;0.001) glucose (96 vs 92; p&lt;0.001) and SBP (132 vs 126; p&lt;0.001); lower triglycerides (92 vs 104; p&lt;0.001) and HDL (59 vs 68; p&lt;0.001). Black women were more likely than white women to live in poverty (23.7% vs 4.6%; p&lt;.001); report poor diet (32.4% vs 10.4%; p&lt;.001) and less exercise (29.7% v 23.6% in the 25 th %ile), and less likely to graduate college (30.3% vs 70.4%). MSZ-score was positively associated with age (.02 per year; p&lt;.001) and black race (0.35; &lt;.001) and negatively with better diet (-.20 per point in 4 point scale); p&lt;.001), exercise (-.11 per quartile increase in METS; p&lt;.001) and SSS (-.04 per ladder rung; p=.004). SSS was lower in black women within the same levels of income and education). Conclusions: Race, age, diet, exercise and subjective social status all impact metabolic syndrome, a risk factor for breast cancer. Of concern, among breast cancer patients, black women are more likely to rate their SSS below white women, within each education or income level. Subjective social status among women with a new breast cancer diagnosis is associated with MS and may be important to address as a risk factor among breast cancer patients.[Table: see text]
Neoadjuvant chemotherapy to improve colon cancer survival in resectable metastatic colon cancer: A real world NCDB data analysis.
Authors: Saurabh Parasramka, Aasems Jacob, Quan Chen, Bin Huang, Zhonglin Hao
Journal: Journal of Clinical Oncology (2021)

3567 Background: According to the SEER database, approximately 21% of colon cancer patients have synchronous metastatic disease at presentation with a five-year survival of only 14%. Liver is by far the most common site of metastasis. For resectable and borderline resectable metastatic lesions after conversion to surgical resection, five-year survival ranges between 40-70% in different series. Survival advantage of neoadjuvant chemotherapy is not clear. We present here an updated analysis of effect of different variables on survival of 3,247 patients from the National Cancer Database (NCDB) treated from 2010-2015. Methods: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver and/or lung at diagnosis were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy within 1 year of diagnosis. Patients were categorized into 2 cohorts based on whether they received chemotherapy in the pre-operative/peri-operative setting (neoadjuvant chemotherapy –NAC) or post-operative setting (adjuvant chemotherapy AC). Descriptive analysis, Kaplan-Meier plots, Log-Rank tests and Cox regression models for multivariate survival analyses were performed. To assess uncertainty of estimates, a sensitive analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3,247 patients with colon cancer with liver or lung metastases were identified. A large majority 2,527 patients (77.8%) received AC. 54.5% were males and 45.5% females. On multivariate analysis, patients who received NAC had overall survival (OS) advantage with hazard ratio (HR) 0.86 (0.75-0.98). Clinical factors associated with worse survival included age &gt; 75 HR 1.31; positive margin status with R1 HR 1.49 or R2 HR 2.33; Comorbidity index ≥ 2 HR 1.68; positive KRAS status HR 1.20; N2 disease HR1.95; ; having liver metastasis compared to lung HR 1.65 ;. Factors associated with improved survival were CEA less than 30 ng/ml at diagnosis and left sided tumor with HR of 0.64 (0.56-0.72) and 0.75(0.67-0.84) respectively. Conclusions: Metastatic colon cancer with single organ liver or lung lesions benefit from neoadjuvant chemotherapy based on our analysis of the real-world data. The survival advantage in this setting has not been shown before.
Landscape of hyper-progression related gene alterations among Chinese population and their impact on patients’ survival after immunotherapy.
Authors: Wenfan Fu, Si Li, Wenjing Xi, Qidong Yang, Dongsheng Chen, Mingzhe Xiao
Journal: Journal of Clinical Oncology (2021)

e14518 Background: Immune checkpoint inhibitors (ICIs) have demonstrated salutary anticancer effects in patient with cancer. However, more than 10% of treated patients had experienced hyper-progressive disease (HPD), which resulted poor survival. Gene alterations might be associated with HPD, while more studies are needed to clarify their impact on survival and role in tumor progression. Methods: In this analysis, we retrospectively reviewed genomic alterations in 1814 Chinese patients with cancer of lung, liver, colorectal, gastric, pancreatic, biliary duct, melanoma, cervical and esophagus. Next-Generation Sequencing (NGS) by a customized 539-gene panel was performed. Frequency of HPD gene alterations, including amplification of MDM2/4, CCND1 and FGFR3/4, loss of CDKN2A/B, mutations in DNMT3A were investigated. Their impact on progress-free survival (PFS) after immunotherapy were further explored in lung cancer in Rizvi et. 2018 cohort. Results: Of 1814 patients, 449 (24.8%) harbored at least 1 HPD related gene alterations. Esophagus cancer (7/12,58.3%), melanoma (10/23, 43.5%) and liver cancer (108/268, 40.3%) took the largest proportion. The frequencies for each gene were CDKN2A loss (8.5%), CDKN2B loss (8.1%), DNMT3A mutation (7.8%), MDM2 amp (4.9%), MDM4 amp (3.8%), CCND1 amp (3.2%), FGFR4 amp (0.6%), FGFR3 amp (0.3%), respectively. Significant higher TMB in altered group was revealed in EGFR/ALK negative lung cancer (5.88 mut/Mb vs. 2.84 mut/Mb (wild group), P= 0.001). In Rivzi et. 2018 cohort, 46/240 (19.2%) patients had related gene alterations. The TMB was comparable between altered and wild-type groups. Median PFS were 2.5 months and 3.8 months for altered and wild-type group ( P= 0.074). Among altered patients, 17.4% achieved PFS &gt; 6 months (Table 1), two of them had a 1-year PFS (1 with CDKN2A&amp;B loss, 1 with DNMT3A). Conclusions: A considerable proportion of patients harbored HPD related gene alterations. Although they tend to present poorer PFS, there’re patients had the PFS&gt;12 months, the exact impact and underline mechanisms requires more evidence. Distribution of progression-free survival (PFS) for each gene.[Table: see text]