tbuckley/cabot-search huggingface dataset:
Randomized trial of irinotecan and cetuximab (IC) versus irinotecan, cetuximab and ramucirumab (ICR) as 2nd line therapy of advanced colorectal cancer (CRC) following oxaliplatin and bevacizumb based therapy: Result of E7208.
Authors: Howard S. Hochster, Paul J. Catalano, Peter J. O'Dwyer, Edith P. Mitchell, Deirdre Jill Cohen, Bryan Andrew Faller, Jeremy S. Kortmansky, Sheetal Mehta Kircher, Jill Lacy, Heinz-Josef Lenz, Udit N. Verma, Al Bowen Benson
Journal: Journal of Clinical Oncology (2018)

3504 Background: While both anti-VEGF(R) and EGFR antibodies have activity in metastatic RAS wild type CRC, the combination of the two appeared to be detrimental when combined with chemotherapy in unselected CRC patients. We undertook this study to determine whether the anti-VEGFR antibody, ramucirumab, improved activity of Irinotecan and Cetuximab as 2nd line therapy in KRASwt CRC patients, who previously received FOLFOX or CAPOX with bevacizumab (bev) first line therapy, and were now progressing. Methods: Patients with advanced and measurable (RECIST 1.1) CRC who had previously been treated with a fluoropyrimidine and oxaliplatin (ox) with bev, and recently showed progression on CT scan were randomized to IC (180 mg/m2 and 500 mg/m2 respectively) or ICR (R = 8 mg/kg) every 2 weeks. After 35 pt were randomized, planned interim analysis showed excess gr 3-5 toxicity for ICR. Therefore a modified ICR (150 mg/m2, 400 mg/m2 and 6 mg/kg) arm was instituted after study hold. Patients were stratified by PS (0 vs 1), progression on ox (Y vs N), and progression within 6 months of last treatment (or longer). 100 patients were then accrued to IC vs mICR, with 85% power to detect improvement in median PFS from 4.5 to 7.65 months (with 15% type I error or p < 0.15) by stratified log-rank test. Results: Results: 102 patients were randomized and evaluable from June, 2014 - July, 2017. Patients were 65% male, 9% black and 8% Hispanic with med age 60 years, PS 0 = 52%, with 24% progressing while on ox and 15% progressing more than 6 months off rx. Gr 3-4 overall toxicity for IC vs mICR was 47% vs 54% with diarrhea = 10 v 15%; rash = 13 vs 8%; neutropenia = 9 vs 10%. Reasons off study were: 60% progression, 18% adverse events and 10% patient choice. Stratified log rank analysis showed a HR = 0.65 for PFS of mICR vs IC (overall med 5.8 months; p = 0.068), which met primary endpoint of p < 0.15. Survival appears to be equal with med = 20.5 months. Conclusion: In KRAS selected, wildtype CRC, 2nd line therapy (following ox and bev based treatment), an anti-VEGFR antibody, combined with anti-EGFR and irinotecan, prolongs PFS. This effect is similar to the reported improvement in PFS in other 2nd line anti-VEGF trials and supports the fact that antibodies against these two targets can be combined for additional benefit in the appropriate patient population. This study was coordinated by ECOG-ACRIN & supported by NCI awards: CA180820, CA180794, CA180826, CA180830, CA180888, CA180870, CA189830. Clinical trial information: NCT01079780.
Disparities in prognosis communication among parents of children with cancer: The impact of race and ethnicity.
Authors: Maya Ilowite, Angel M. Cronin, Tammy I Kang, Jennifer W. Mack
Journal: Journal of Clinical Oncology (2017)

6562 Background: Most parents of children with cancer say they want detailed prognostic information about their child’s cancer. However, prior work has been conducted in populations of limited diversity. We sought to evaluate the impact of parental race/ethnicity on prognosis communication experiences amongst parents of children with cancer. Methods: We surveyed 357 parents of children with cancer, and the children’s physicians at Dana-Farber Cancer Institute/Boston Children’s Hospital and Children’s Hospital of Philadelphia. Our outcome measures were parental preferences for prognostic information, physician beliefs about parental preferences, prognosis communication processes and communication outcomes. Except where noted, associations were assessed by logistic regression with generalized estimating equations to correct for physician clustering. Results: 87% of parents wanted as much detail as possible about their child’s prognosis, with no significant differences by race/ethnicity (P = .50). Physician beliefs about parental preferences for prognosis communication varied based on parent race/ethnicity. 60% of physicians for White parents reported they believed parents wanted as much detail as possible about their child’s prognosis, versus 36%, 38%, and 64% of physicians, respectively, for Black, Hispanic, and Asian/Other parents (P = .04). Parent race/ethnicity was not associated with actual prognostic disclosure as reported by parents (P = .79) or by physicians (P = .61). Accurate understanding of prognosis was higher amongst White (51%) versus non-White parents (range 22%-29%), although this difference was not statistically significant (P = .13, unadjusted). Conclusions: The majority of parents, regardless of racial and ethnic background, want detailed prognostic information about their child’s cancer. However, physicians rarely recognize the information needs of Black and Hispanic parents. Despite this discrepancy, prognosis communication outcomes were largely equivalent. Our findings suggest that in order to meet parents’ information needs, physicians should ask about the information preferences of parents of children with cancer prior to prognosis discussions.
Thirty-day readmissions in metastatic cancer patients: Room for improvement?
Authors: Rachel Solomon, Natalia Egorova, Rebeca Franco, Nina A. Bickell
Journal: Journal of Clinical Oncology (2017)

6541 Background: To date, cancer has been excused from most readmission reduction efforts. Yet reported readmission rates for cancer patients discharged from medical services are as high as 27%. Some readmissions for patients with metastatic disease may be avoidable. We assessed the prevalence of potentially preventable readmissions and associated factors in adult patients with metastatic cancer. Methods: We measured 30 day readmissions for dehydration, cancer-related pain, and failure to thrive in patients with primary diagnosis metastatic cancer on index admission to a New York State hospital between December 1, 2012 and December 31, 2014. We used competing risk models to assess the effects of demographics, comorbidities, hospital type, payor, and discharge disposition. Results: During the study period, 11,275 patients had 19,307 index hospitalizations with primary diagnosis, metastatic cancer. The 30 day readmission rate was 24.5% of which 8.9% (424) were potentially preventable. Black (HR 1.26, 1.17-1.35) and Hispanic patients (HR 1.19, 1.09-1.31) had higher rates of readmission than whites. Being older (HR per 10 years of age 0.94, 0.90-0.97), female (HR 0.95, 0.91-0.99), having private insurance (HR 0.87, 0.87-0.81) and discharge to hospice (HR 0.62, 0.42-0.91) decreased risk of readmission. Discharge home with services (HR 1.21, 1.14-1.27) or to a skilled nursing facility (SNF) (HR 1.11, 1.01-1.23) conferred higher risk than going home unaided. Index hospitalization at public hospitals increased risk (HR 1.1, 1.02-1.18); teaching hospitals were protective (HR 0.84, 0.774-0.92). Patients with potentially preventable readmissions were younger (HR per 10 years of age 0.85, 0.78-0.93). Compared to those who went home unaided, patients discharged with services were more likely (HR 1.31, 1.05-1.64) and those discharged to SNF were less likely to have avoidable returns (HR 0.55, 0.37-0.81). Payor, gender, race, comorbidities, and index hospital type did not contribute. Conclusions: While the overall rate of potentially preventable admissions among metastatic cancer patients is low, higher readmission rates among those discharged home with help suggests that services supplied are not sufficient to address their health needs.
Paclitaxel With Inhibitor of Apoptosis Antagonist, LCL161, for Localized Triple-Negative Breast Cancer, Prospectively Stratified by Gene Signature in a Biomarker-Driven Neoadjuvant Trial
Authors: Aditya Bardia, Marina Parton, Sherko Kümmel, Laura G. Estévez, Chiun-Sheng Huang, Javier Cortés, Manuel Ruiz-Borrego, Melinda L. Telli, Paloma Martin-Martorell, Rafael López, J. Thaddeus Beck, Roohi Ismail-Khan, Shin-Cheh Chen, Sara A. Hurvitz, Ingrid A. Mayer, Daniel Carreon, Scott Cameron, Serena Liao, José Baselga, Sung-Bae Kim
Journal: Journal of Clinical Oncology (2018)

There are currently no targeted therapies approved for triple-negative breast cancer (TNBC). A tumor necrosis factor α ( TNFα)-based gene expression signature (GS) predictive of sensitivity to LCL161, inhibitor of apoptosis antagonist, was translated into a clinical assay and evaluated in a neoadjuvant trial.
KEYNOTE-046: ADXS-PSA plus pembrolizumab (pembro) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Mark N. Stein, Lawrence Fong, Ronald F Tutrone, Anthony E. Mega, Maurice Lobo, Quan Hong, Naomi B. Haas
Journal: Journal of Clinical Oncology (2018)

5019 Background: ADXS--PSA, an attenuated Listeria monocytogenes-based immunotherapy that targets prostate-specific antigen (PSA), is designed to generate antigen-specific T cell effectors that kill tumor cells. Published data has shown synergy of ADXS Lm-LLO-TAA treatment with a PD-1 blocking antibody in an animal model. Methods: This phase 1/2 trial studied pts with progressive mCRPC, ≥18 yrs who received ≤2 prior chemo-/targeted-/immunotherapies or ≤1 prior chemotherapy in a metastatic setting. Part A (PA; n = 14) pts received ADXS-PSA doses 1x109; 5 x109 and 1x1010 colony forming units (CFU) IV every 3 wks and Part B (PB; n = 37) pts received 1x109 CFU + 200 mg pembro IV every 3 wks with a 4th pembro dose 3 wks later, for up to 2 yrs or until progression/toxicity. The 1◦ endpoint was safety/tolerability. Anti-tumor activity and effect on PSA level were evaluated. Preliminary results are presented. Results: At entry, PA and PB pts were similar in age (~70 yrs), Gleason score (~8.3) and prior abirateroneuse. PB pts had higher median BL PSA (40.6 v 20.8 ng/ml), and more prior enzalutamide (53 v 26%) and chemotherapy (49 v 36%) use v PA. 46 pts (94%) experienced treatment-related AEs (TRAE) with 16 pts having grade 3-4 events: fatigue, hypotension, hypertension, anemia. TRAEs ≥10% of any grade were cytokine release symptoms including chills, fever, nausea and hypotension. TRAE incidence was similar between groups and all resolved with supportive care. Accrual is complete but pts remain on trial. Overall, 2 PA (14%) v 16 PB pts (43%) had a decreased PSA post-BL. Of these, 8 PB (22%) v 0 PA pts achieved a PSA reduction ≥50% from BL; which was confirmed in 3 PB pts (38%). At the time of analysis, tumor measurements were available for 5 PA and 23 PB pts. One PA pt (20%) and 10 PB pts (43%) had SD (RECIST 1.1). Four PB pts (40%) with SD also had a decreased PSA post-BL; a confirmed response was seen in 2 of these pts. 9 PA and 14 PB pts had non-measurable disease at BL; 33% (3/9) and 79% (11/14) had disease stabilization (non-CR/non-PD). Conclusions: In this population of heavily pretreated mCRPC pts ADXS-PSA + pembro had a manageable safety profile and showed promising activity compared to monotherapy. These preliminary data warrant further study. Clinical trial information: NCT02325557.
Overexpression of satellite alpha transcript in breast cancer patients to impair specific chromosomes.
Authors: Kosuke Ichida, Koichi Suzuki, Nao Kakizawa, Taro Fukui, Yuji Takayama, Fumiaki Watanabe, Takaharu Kato, Masaaki Saito, Kazushige Futsuhara, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2017)

e23216 Background: Impairment of stability in chromosomal structure facilitates abnormal segregation of chromosomes, increasing the risk of carcinogenesis. Chromosomal stability during segregation is managed by appropriate methylation in the centromere region of chromosomes, which is associated with heterochromatin structures. Insufficient methylation, or demethylation, results in chromosomal instability. Satellite alpha transcript (Sat-A) is non-coding RNA transcribed from satellite alpha repetitive sequences at centromere, which is overexpressed by demethylated status of centromere. We have reported that increased levels of Sat-A were observed in patients with colorectal cancer, resulting in chromosomal instability. Difference levels of demethylation were reported in breast cancer patients but their association with Sat-A expression and chromosomal instability are not well known. In this study, we determined if Sat-A was involved in the chromosomal instability of breast cancer. Methods: We constructed lentiviral vectors expressing Sat-A and control viruses, which were infected in human mammary epithelial cells. The expression levels of Sat-A were determined by qRT-PCR and copy number alterations were evaluated by array CGH. Demethylation levels of satellite alpha sequences were determined by Methylight PCR. Then, these results were verified by using clinical specimens of 45 breast cancer patients. Results: Array CGH analysis revealed that copy number alterations were frequently seen at specific chromosomes of 8q and 20q in infected cells, despite no alteration in control, which was consistent with results in the clinical specimens. Patients with high levels of Sat-A expression showed more alterations than patients with low. Regression analysis exhibited that levels of Sat-A expression were significantly collated with demethylation levels of satellite alpha sequences. Conclusions: Overexpression of Sat-A impaired stability of chromosome 8q and 20q in human mammary epithelial cells, which was also recognized in clinical specimens of breast cancer patients. Chromosomal instability induced by Sat-A is involved in the development of breast cancer.
P06 Competing CNS or Systemic Progression Analysis for EGFR Mutation-Positive NSCLC Patients on Afatinib in LUX-Lung 3, 6, and 7
Authors: J.C.-. Yang, Y. Wu, V. Hirsh, K. O’Byrne, N. Yamamoto, S. Popat, A. Tamiya, D. Kaen, A. Märten, M. Schuler
Journal: Journal of Thoracic Oncology (2018)
Exploring a possible relationship of germline <i>CDKN2A</i> mutations with breast cancer in a multigene panel cohort.
Authors: Darling J Horcasitas, Holly LaDuca, Amal Yussuf, Ginger Chisholm, Jonah R Chavez, Annette Campbell Fontaine, Laura Panos Smith
Journal: Journal of Clinical Oncology (2017)

e23218 Background: Germline mutations in CDKN2A have been known to increase the risk of melanoma and pancreatic cancer compared to the general population. With the advent of multi-gene panels, individuals who may not have melanoma or pancreatic cancer are undergoing CDKN2A analysis. Previous studies in homogenous populations have suggested that breast cancer risks may also be increased in CDKN2A. This study aims to further evaluate a possible relationship of CDKN2A mutations with breast cancer through a series of case-control comparisons. Methods: Clinical histories and molecular results were retrospectively reviewed for patients undergoing CDKN2A analysis as part of two diagnostic pan-cancer panels at a single laboratory to ascertain CDKN2A mutation carriers (n = 104) and patients negative for all genes analyzed (n = 20,280). Patients with a personal and/or family history (1 st and 2 nd degree relatives) of pancreatic cancer and/or melanoma were excluded from case-control analysis. Results: The majority of CDKN2A mutation carriers (82.6%, n = 86/104) had a personal history of cancer documented on the test requisition form. The most common cancers were breast (n = 38, 52.8%), melanoma (n = 37, 43.0%) and pancreatic (n = 6, 7.1%). The average age of breast cancer diagnosis in this cohort was 49.3 years (range 25-84). Family history of breast, melanoma, and/or pancreatic cancer was reported for 54.9%, 46.1%, and 34.3% of CDKN2A mutation carriers, respectively. Females with breast cancer were not more likely to test positive for a CDKN2A mutation than females with cancer other than breast (OR = 0.84, p = 0.79) or unaffected females (OR = 1.02, p = 1). Conclusions: Although CDKN2A mutations were not significantly associated with breast cancer in this cohort, these findings do not necessarily rule out an association of CDKN2A mutations with breast cancer, particularly if risks are moderate or if genotype-phenotype correlations exist. Additional studies involving breast cancer cases unselected for age and family history and/or longitudinal studies of CDKN2A carriers are needed to better understand the relationship between CDKN2A and breast cancer risk.
Clinical characteristics of melanoma in an ethnically diverse population of adolescents and young adults.
Authors: Kimberly Ann Miller, Anthony Pham, Jacob Stephen Thomas, Myles G Cockburn, David Robert Freyer, James Hu, Joel Milam, Katherine Wojcik, Gino Kim In
Journal: Journal of Clinical Oncology (2017)

e21043 Background: Melanoma is the third most common cancer among adolescents and young adults (AYAs; aged 15-39). Disease characteristics have not been well-described in this age group, particularly among diverse populations. We describe clinical features of AYAs diagnosed with melanoma at a large public hospital serving an ethnically diverse population. Methods: We reviewed medical chart data from patients diagnosed with melanoma between 2001-2016 at Los Angeles County + USC Medical Center. We describe clinical characteristics of AYA patients and compare to non-AYAs (aged ≥40) using Fisher’s exact test. A p-value &lt; 0.05 was considered statistically significant. Results: Of the 273 melanoma patients identified, 47 (17.3%) were AYAs (mean age 32.3; SD±4.45; lower age range 18). The majority of patients were Hispanic (AYA, 53.2%; non-AYA, 51.1%), followed by non-Hispanic whites (AYA, 38.3%; non-AYA, 38.7%). A greater proportion of AYA patients were female (59.6%) compared to non-AYAs (38.2%) (p &lt; 0.01). No AYA patients reported prior skin cancer compared to 19.9% of non-AYAs; 8.5% of AYAs reported family history of melanoma compared to 6.3% of non-AYAs. For all patients, superficial spreading melanoma was the most common histological subtype (AYA, 21.3%; non-AYA, 20.9%). Nodular melanoma was the second most common subtype in AYAs (17.02%) in contrast to acral lentiginous melanoma among non-AYAs (20.9%). Median Breslow depth was 3.0 mm for AYAs and 2.55 mm among non-AYAs. A slightly higher percentage of AYAs were diagnosed with regional disease (31.9%) than non-AYAs (24.4%), and a greater proportion of non-AYAs presented with distant metastases (AYA, 6.4%; non-AYA, 18.7%). The most common site of diagnosis were the extremities for all patients (AYA, 45.0%; non-AYA, 29.3%). Conclusions: We found similar clinical characteristics between AYA and non-AYA melanoma patients. However, we found a statistically significant difference for gender. The increased incidence of melanoma in female AYAs may be driven by biological factors such as sex hormones or genotype, or tanning behaviors. Further research is warranted to identify predictive and prognostic factors of melanoma among diverse AYAs, particularly females.
Rotavirus Gastroenteritis Infection Among Children Vaccinated and Unvaccinated With Rotavirus Vaccine in Southern China
Authors: Chuanxi Fu, Zhiqiang Dong, Jichuan Shen, Zhicong Yang, Ying Liao, Wensui Hu, Sen Pei, Jeffrey Shaman
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Since 2000, the Lanzhou lamb rotavirus vaccine has been exclusively licensed in China for voluntary rotavirus gastroenteritis (RV-GE) prevention. <h3>Objective</h3> To evaluate the association of the Lanzhou lamb rotavirus vaccination with RV-GE among children in southern China. <h3>Design, Setting, and Participants</h3> This cross-sectional, ecological study was set in Guangzhou, China. Participants were infants possibly vaccinated (aged 2 months to 3 years) and the children ineligible for vaccination (aged ≥4 years). The study was conducted from May 1, 2007, to April 30, 2016, and the data analysis was conducted in July 2016. <h3>Main Outcomes and Measures</h3> Annual median age at onset of RV-GE and seasonal distribution of incidence. Cases of RV-GE in Guangzhou, China, diagnosed from May 1, 2007, to April 30, 2016, and reported to the National Information System for Disease Control and Prevention were examined. Poisson regression models were fitted among 32 452 children younger than 4 years and among 450 children who had been ineligible for vaccination, while controlling for secular trends, socioeconomic status, and meteorological factors. Logistic regression was used to assess the indirect effects provided by the vaccinated infants from 2009 to 2011 on unvaccinated infants aged 2 to 35 months based on a separate case-control data set. <h3>Results</h3> During 9 seasons, 119 705 patients with gastroenteritis were reported; 33 407 were confirmed for RV-GE (21 202 [63.5%] male, 32 022 [95.8%] aged &lt;4 years, and 31 306 [93.8%] residing in urban districts). The median age at onset for all patients with RV-GE increased from 11 months during the 2007 season to 15 months during the 2015 season, and the onset, peak, and cessation of incidence were delayed. When citywide vaccination coverage in the prior 12 months was classified into high and low groups (≥8.36% vs &lt;8.36%), the incidence rate ratio for the high coverage group decreased by 32.4% among children younger than 4 years (incidence rate ratio, 0.676; 95% CI, 0.659-0.693;<i>P</i> &lt; .001). Among the children ineligible for vaccination, the incidence rate ratio in higher coverage periods was 0.790 (95% CI, 0.351-0.915;<i>P</i> &lt; .001) compared with the lower coverage. Compared with districts with 14% or less vaccination coverage, the adjusted odds ratio for RV-GE among unvaccinated children younger than 3 years was 0.85 (95% CI, 0.73-0.99;<i>P</i> = .03) for districts with 15% to 19% of coverage, and 0.79 (95% CI, 0.67-0.93;<i>P</i> = .004) for districts with more than 20% of coverage. <h3>Conclusions and Relevance</h3> This study provides evidence of the population health benefits of the Lanzhou lamb rotavirus vaccination in preventing RV-GE among children in China younger than 4 years, including herd effects.