tbuckley/cabot-search huggingface dataset:
Concurrent chemoradiotherapy using carboplatin/cetuximab regimen in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) not eligible for high-dose cisplatin (HD-DDP).
Authors: Kunal Saigal, Sean Warsch, Amar Mandalia, Michael Samuels, Khaled A. Tolba, Chukwuemeka Ikpeazu, Deukwoo Kwon, Edgardo S. Santos
Journal: Journal of Clinical Oncology (2012)

e16001 Background: Cetuximab (Cx) + radiation therapy (RT) is well tolerated and has improved survival in patients (pts) with LA-HNSCC. However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin (Carbo) is added to Cx + RT for pts unsuitable for HD-DDP. Methods: We reviewed records of 16 pts with LA-HNSCC treated with definitive Cx + Carbo + RT at the University of Miami from 2007-2011. Median follow-up was 9.4 months (range: 1-50 months). Results: Median age: 71.5 years (range: 57-90 years); 15 male, 1 female.ECOG PS 0=15, 1=1. TNM staging was: T1= 1, T2= 5, T3=8, T4=2; N stage: N0=8, N1=5, N2a=2, N2b=1. All pts received weekly Carbo (AUC 1.5-2), Cx given conventionally and daily conventionally-fractionated RT. Median total weeks of concurrent systemic therapy= 7 (range: 3-8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of the 15 evaluable pts, there were: 12 CR, 2 PR, and 1 PD. There were 2 local in-field failures, 1 regional failure, and 3 distant failures. At last follow-up, 11/16 pts remained with NED. 3-year locoregional recurrence was 29.5% (95% CI: 5.3%-45.9%). Toxicity (NCI-CTCAE v4.0): Mean percentage of weight loss was 14% (range: 6-26%). Two pts required systemic therapy dose-reduction. Three pts experienced a treatment delay and 3 did not finish RT as planned including one pt who received only 30Gy due to death secondary to MI during treatment. Conclusions: In this small retrospective series, Carbo/Cx/RT was well-tolerated and efficacious in pts unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio of Cx + RT in pts who are poor candidates for more aggressive therapies and warrants evaluation in a prospective manner. [Table: see text]
Longitudinal study of hope, meaning/peace (M/P), and quality of life (QOL) in patients (pts) with ovarian cancer (OC).
Authors: Lois M. Ramondetta, Diana Urbauer, Donna S. Zhukovsky, Michael W. Bevers, Jubilee Brown, Diane C. Bodurka, Premal H. Thaker, Sonya Anderson, Jessica Gallegos, Charlotte C. Sun
Journal: Journal of Clinical Oncology (2012)

9134 Background: M/P may be the most valued end point of life. How hope, faith, physical and psychological factors impact M/P is unknown. We evaluated factors affecting M/P in pts with OC. Methods: OC pts at a cancer center (CC), academic hospital (AH) and county hospital (CH for primarily uninsured) participated. Surveys completed at initiation of chemotherapy (CTX); completion of CTX; and 1 yr later. Surveys included FACT-O, -SP, Herth Hope Index, Hospital Anxiety and Depression Scale (HADS), ESAS, and Locus of Control (LOC). Results: N=115. Median age=55 yrs, married 64%, Christian 96%. CH had more AA/Hispanics pts (p=.001) and unmarried pts (p=.001). QOL and symptoms improved for all sites over time (p =.03); CH pts had the worst scores (p= &lt;.001). CC pts expressed more hope, less anxiety and depression (A/D) compared to CH and AC pts for all time points (p=.03). CH pts had higher and increasing A/D over time while CC pts had the least (p=.02). LOC scores differed by site (p=.01). CH pts held strongest belief that life was controlled by chance and “others”; CC pts had the least. There was no association between site/time for belief of internal control over one’s life. CH pts consistently had the lowest M/P scores (p=004). Adjusting for site, disease status and time, higher M/P associated with higher hope, better QOL, symptoms and faith (p= &lt;.0001). Lower M/P associated with increased A/D (p=.003) and symptoms (p&lt;.0001). Poorer M/P over time correlated with belief that life was controlled by chance (p=.01) and "powerful others"(p=.02). Level of M/P did not correlate with belief of internal control over one’s life. Conclusions: M/P did not change over time. CC pts had highest M/P. Higher M/P associated with higher hope and faith, better QOL, less symptoms and A/D. Lower M/P associated with sense that life is controlled by chance and powerful others. Data show medically underserved pts have poorer QOL, more symptoms and A/D and may believe the future is determined by luck/chance and by “others”. Triaging for spiritual crisis may be important in these pts. Interventions to decrease A/D and symptoms may improve pts’ sense of M/P over the cancer journey.
A phase II study of cisplatin (CDDP) and oral vinorelbine (NVBO) concomitantly with radiotherapy (RT) in locally advanced (LA) non-small cell lung cancer (NSCLC) treatment: Interim analysis.
Authors: Oscar Juan Vidal, Sergio Vazquez-Estevez, Vicente Giner, Joaquin Casal Rubio, Jose-luis Firvida, Francisco Aparisi, José Muñoz-Langa, Jose Garcia Sanchez, Regina Girones, Francisco Javier Perez, Alfredo Sanchez-Hernandez
Journal: Journal of Clinical Oncology (2012)

e17545 Background: CDDP+NVBO as induction and concomitant regimen with RT has shown good efficacy outcomes and safety profile (Krzakowski, J Thor Oncol. 2008). The objective of this study was to evaluate the effectiveness and toxicities of the combination of CDDP and NVBO given at full doses concomitantly with RT in LA-NSCLC. Methods: Between February 2010 and May 2011, 26 chemo-naive patients (p) with histologically confirmed stage IIIA/IIIB unresectable LA NSCLC were treated. Treatment consisted of 4 cycles (cy) of NVBO 60 mg/m 2 on days 1 and 8 and CDDP 80 mg/m 2 every 3 weeks plus RT 66 Gy starting on day 1, cy 2. A standard Fleming two stage design is being used. The sample size is calculated with a power of 90% and a two-sided type 1 error allowance of 5%. Stage 1 included 25 pts, with subsequent expansion to a total of 45. Results: Patient’s characteristics were: Median age, 59 years (range 48-71); males, 92%; smokers, 60%; adenocarcinoma, 28% / squamous, 64%; stage IIIA, 54% / IIIB, 46%. 21 p completed the 4 cy treatment as per protocol. We analyzed 92 cy. Hematological toxicities (% cy): grade (g) 3/4 neutropenia, 42.3%; g3 anemia, 3.3%; g3 thrombocytopenia, 2.2%; febrile neutropenia, 1 p. Non-hematological toxicities (% cy): g3 oesophagitis, 6.5%; g4 diarrhea, 1.1%. 21 p were evaluable for response. 1 CR (4.8%), 17 PR (81%) and 1 SD (4.5%) were reported. ORR 85.8%. Survival analysis has not been performed due to short follow-up. Conclusions: The findings of this interim analysis confirm the previously reported outcomes of efficacy and safety with NVBO plus CDDP when administered concurrently with RT in stage IIIA/IIIB p. The trial has met the criteria for continuation into stage 2.
Patterns of CD8+ T-cell infiltration and immune escape mechanisms in head and neck cancer.
Authors: Vassiliki Saloura, Zhixiang Zuo, Arun Khattri, Holbrook Edwin Kohrt, Mark W. Lingen, Thomas Gajewski, Marcin Kowanetz, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2015)

6078 Background: Immunotherapy with PD-1/PD-L1 axis blockade has shown promising preliminary results in patients with head and neck squamous cell carcinomas (HNSCC) (Seiwert ASCO 2014). Using a 12-gene chemokine expression signature (Harlin/Gajewski 2009) 33-47% of HNC have a T-cell inflamed phenotype (TCIP-High) characterized by CD8+ TIL enrichment and PD-L1 expression in both HPV(+) and HPV(-) HNC. In this study, we sought to identify patterns of CD8+ tumor infiltration and describe immune escape mechanisms. Methods: We evaluated the patterns of infiltration of CD8+ TILs in a subset of tumors (N = 73) from the Chicago HNC Genomics (CHGC) cohort using IHC. 58 were also stained for PD-L1 expression. 55 tissues were evaluated with dual CD8/FOXP3 staining. To assess potential mechanisms of immune escape, we interrogated the different patterns of CD8+ TIL infiltration in conjunction with the TCIP-high signature. Results: 27% (20/73) of CHGC tumors showed either no CD8+ T-cells (Immunologic Ignorance (II), 8%, 6/73) or CD8+ T-cells limited to the tumor periphery (Excluded Immune Infiltrate (EII), 19%, 14/73). Of these tumors, 75% (15/20) were PD-L1 negative and 25% (5/20) were PD-L1+. 73% (53/73) of tumors showed intratumoral CD8+ TILs. Of these tumors, 38 had available PD-L1 staining results and 63% (24/38) were PD-L1+ (Functional Immune Response (FIR)), while 37% (14/38) were PD-L1 negative (Non-Functional Immune Response (NFIR)). FIR tumors (intratumoral CD8+, PD-L1+) with strong PD-L1 positivity showed significantly higher immune cytolytic activity, by GZMA and PRF1 gene expression, compared to NFIR tumors. Tumors with intratumoral CD8+ TIL infiltrate correlated with the TCIP-High phenotype in both HPV(+) and HPV(-) tumors. FOXP3 staining was significantly higher in HPV(+) tumors. Conclusions: 73% of HNC attract intratumoral CD8+ TILs and 63% of these tumors seem to activate a functional immune response. PD-L1 upregulation may serve as a compensatory immune escape mechanism, making this subset a rational target for PD-L1 blockade. T-regulatory cells seem to play an additional role in immune evasion of HPV+ HNC, suggesting that a combinatorial approach with a T-reg depleting strategy warrants clinical investigation.
Clustered genomic variants specific to patients who develop immune-related colitis after ipilimumab for prediction of toxicity.
Authors: Ahmad A. Tarhini, William A LaFramboise, Patricia Petrosko, Christopher G Deamont, John M. Kirkwood
Journal: Journal of Clinical Oncology (2014)

9024 Background: Ipilimumab (Ipi) is approved for metastatic melanoma based on significant survival benefits shown in phase III trials. Ipi can result in immune-mediated effects on various organ systems, leading to adverse events (AE) including diarrhea/colitis reported in 30-40% patients (pts) that can be serious and life-threatening. The ability to predict the risk of this AE may lead to new monitoring and improved management. Methods: Targeted, deep sequencing of DNA from the blood of 34 pts who underwent neoadjuvant Ipi for regionally advanced melanoma (Tarhini et al, PLOS One, 2014) was performed to detect the 21 pts who experienced diarrhea/colitis. Sequencing was focused on the coding region of 10 genes and genomic domains surrounding 9 SNPs previously associated with IBS, Crohn's Disease and ulcerative colitis in GWAS studies. Selected amplicon libraries derived from locations on 5 chromosomes were sequenced on Ion Torrent PGM at high base density (318 chip: >1000X) and BAM files interrogated using GATK algorithm (UGT v.2.3, Broad Institute, Boston, MA) to identify SNPs, single base substitutions and INDELs (<5 bases). Variants were selected for specificity to pts with grade 1-3 colitis vs pts without. All calls were verified by manual curation of BAM files using Integrated Genomics Viewer (Broad Institute). Results: We identified 132 variants specific to pts with colitis (X =6.1; range=1-20). The most parsimonious variant signature (11 variants, 3 chromosomes) comprised 3 INDELs shared by 13 pts including an intronic 5 base DEL in CDKAL1 gene and 2 INS in KIF21B. While 11 pts were classified by 6 unique INDELs and 2 rare SNPs (rs55770822, rs140589352). Alternatively, a 34Kb chromosome 1 "hot spot" in KIF21B gene captured variants specific to 18 pts including multiple frameshift and other coding mutations predicted to alter protein translation. Conclusions: These data suggestthat unique INDELs and SNPs specific to pts with colitis after Ipi may provide a predictive biomarker signature. The predominance of these variants within the KIF21B gene previously implicated in inflammatory bowel disease suggests an important role in Ipi induced colitis. (Supported by NIH award P50CA121973). Clinical trial information: NCT01608594.
Racial and Ethnic Disparities in Oncotype DX Test Receipt in a Statewide Population-Based Study
Authors: Brigette A. Davis, Jenerius A. Aminawung, Maysa M. Abu-Khalaf, Suzanne B. Evans, Kevin Su, Rajni Mehta, Shi-Yi Wang, Cary P. Gross
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Racial disparities have been reported in breast cancer care, yet little is known about disparities in access to gene expression profiling (GEP) tests. Given the impact of GEP test results, such as those of Oncotype DX (ODx), on treatment decision-making for hormone receptor–positive (HR+) breast cancer, it is particularly important to assess disparities in its use. Methods: We conducted a retrospective population-based study of 8,784 patients diagnosed with breast cancer in Connecticut during 2011 through 2013. We assessed the association between race, ethnicity, and ODx receipt among women with HR+ breast cancer for whom NCCN does and does not recommend ODx testing, using bivariate and multivariate logistic analyses. Results: We identified 5,294 women who met study inclusion criteria: 83.8% were white, 6.3% black, and 7.4% Hispanic. Overall, 50.9% (n=4,131) of women in the guideline-recommended group received ODx testing compared with 18.5% (n=1,163) in the nonrecommended group. More white women received the ODx test compared with black and Hispanic women in the recommended and nonrecommended groups (51.4% vs 44.6% and 47.7%; and 21.2% vs 9.0% and 9.7%, respectively). After adjusting for tumor and clinical characteristics, we observed significantly lower ODx use among black (odds ratio [OR], 0.64; 95% CI, 0.47–0.88) and Hispanic women (OR, 0.59; 95% CI, 0.45–0.77) compared with white women in the recommended group and in the guideline-discordant group (blacks: OR, 0.39; 95% CI, 0.20–0.78, and Hispanics: OR, 0.44; 95% CI, 0.23–0.85). Conclusions: In this population-based study, we identified racial disparities in ODx testing. Disparities in access to innovative cancer care technologies may further exacerbate existing disparities in breast cancer outcomes.
Prospective clinical experience with research biopsies in breast cancer patients.
Authors: Catherine A. Zeghibe, Ines Maria Vaz Duarte Luis, Elizabeth S. Frank, Jessica Sohl, Kimberly E. Washington, Stuart G. Silverman, Joseph M. Fonte, Erica L. Mayer, Beth Overmoyer, Andrea L. Richardson, Ian E. Krop, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2013)

e17574 Background: There is active debate concerning the ethics and risks of non-clinically indicated biopsies (bxs) in patients (pts) with cancer. In this analysis we examined our single institution experience regarding acceptance, safety, and success rate with research biopsies in pts with breast cancer (BC). Methods: An IRB-approved ongoing prospective study at the Dana-Farber Cancer Institute collects research bxs from pts with BC. Research bxs are performed as additional passes at the time of a clinical bx (cohort 1) or as a separate procedure for banking purposes only (cohort 2) on known tumor or suspicious lesions. Bxs are not linked to a specific therapeutic or correlative trial. Bx-site related risks are pre-specified in consent forms. Grade 2-5 adverse events (AEs) associated with the procedure are prospectively collected. Chart review for bxs between 2005-2013 was performed in this analysis. Results: As of January 2013, 158 pts had consented to the study; 3 pts withdrew consent and 4 pts did not have bxs. 151 pts are in the analytic cohort (total bxs performed= 161); 82% in cohort 1, 18% in cohort 2. Most pts were white (89%) with a performance status of 0-1 (98%). A majority of pts (96%) underwent a bx in the setting of known or suspected metastatic disease. 39% of bxs were performed at time of diagnosis or first recurrence. The most common sites for bx were liver (38%, n=61), skin (24%, n=39) and breast (18%, n=29). Lung was uncommon (3%, n=4). Research biopsies were successfully performed in 114 (92%) pts in cohort 1 and 27 (100%) pts in cohort 2. In cohort 1, research biopsies were not successful in 10 pts. In 9 pts the clinical samples had insufficient material, leading to the forfeit of the banked research sample for clinical purposes; in 1 pt the bx was suspended for severe pain. Only 3 (1.9%) pts had AEs ≥ grade 2: 1 with grade 2 pain; 1 with grade 2 pneumothorax; and 1 with grade 3 pain. Conclusions: Our experience in an academic medical center suggests that pts with BC are willing to undergo research bxs outside the context of a therapeutic or translational trial. These procedures can be performed safely with a high rate of successful tissue collection. Additional data are needed to fully quantify the risks and to demonstrate the value of these procedures.
Accuracy, bias, self-fulfilling prophecies, and scientific self-correction
Authors: Lee Jussim
Journal: Behavioral and Brain Sciences (2017)

Abstract In my Précis of Social Perception and Social Reality (Jussim 2012, henceforth abbreviated as SPSR ), I argued that the social science scholarship on social perception and interpersonal expectancies was characterized by a tripartite pattern: (1) Errors, biases, and self-fulfilling prophecies in person perception were generally weak, fragile, and fleeting; (2) Social perceptions were often quite accurate; and (3) Conclusions appearing throughout the social psychology scientific literature routinely overstated the power and pervasiveness of expectancy effects, and ignored evidence of accuracy. Most commentators concurred with the validity of these conclusions. Two, however, strongly disagreed with the conclusion that the evidence consistently has shown that stereotypes are moderately to highly accurate. Several others, while agreeing with most of the specifics, also suggested that those arguments did not necessarily apply to contexts outside of those covered in SPSR. In this response, I consider all these aspects: the limitations to the tripartite pattern, the role of politics and confirmation biases in distorting scientific conclusions, common obstructions to effective scientific self-correction, and how to limit them.
Breast cancer and DNA epair gene SNPs in a family cancer registry population
Authors: L. R. Langer, J. Papp, J. S. Sinsheimer, L. Kwan, J. Seldon, E. F. Reed, S. Dandekar, Y. Korin, Z. F. Zhang, P. A. Ganz
Journal: Journal of Clinical Oncology (2007)

10514 Background: Alterations in the DNA double-strand break repair (DSBR) pathway are associated with cancer risk. Mutations in the genes BRCA1/2 disrupt DNA DSBR. Variations in breast cancer penetrance among BRCA1/2 mutation carriers, and familial patterns among women without known BRCA1/2 mutations may be related to polymorphisms of genes in the DNA-DSBR pathway. Methods: Using a case-control study design with individuals in the UCLA Family Cancer Registry (FCR), we examined the independent effects of 100 SNPs in 19 DNA-DSBR genes. SNPs were assayed using the Applied Biosystems SNPlex™ assay. Results: 630 consecutive females from 508 families in the UCLA FCR selected for familial risk of breast cancer were included in the study. Table 1 describes select subject characteristics. Preliminary association analysis of the Caucasian subset using a nonparametric permutation method, which controls for Ashkenazi Jewish heritage and dependencies among relatives, suggests that polymorphisms within RAD21 (p=0.0044, p=0.0005), XRCC2 (p = 0.0069), XRCC4 (p =0.0511), and BRIP1 (p =0.0107) may be associated with a change in risk of breast cancer. Using only unrelated Caucasian subjects in a logistic regression analysis with covariates such as age, BMI, and Ashkenazi Jewish heritage, the effects of these polymorphisms remain significant, with 32% to 74% change in the odds of breast cancer. Conclusions: We have identified five potential SNPs in genes in the DNA-DSBR pathway that appear to be associated with a change in risk of breast cancer. This hypothesis generating study lends support to a role for polymorphisms of the DNA-repair pathway in breast carcinogenesis. Assessment of gene-environment and gene-gene interactions will help to elucidate carcinogenic mechanisms. Further validation in similar populations is warranted. (Funded by the Breast Cancer Research Foundation and NIH/NCI CA87949 R25 Career Development Program.) [Table: see text] No significant financial relationships to disclose.
Stage II non-small cell lung cancer treated with nonsurgical approaches.
Authors: Xiaofu Zhu, Tinghua Zhang, Jason R. Pantarotto, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2014)

e18507 Background: The standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy (CT). However, some patients (pts) do not undergo surgery due to refusal or other reasons. We examined the outcome of stage II NSCLC pts who were treated with curative non-surgical approaches. Methods: We performed a single institution chart review of pts with stage II lung NSCLC treated non-surgically with curative intent between January 1, 2002 and December 31, 2012. Data on demographics, staging, therapy, and outcome were collected. Primary endpoint was overall survival (OS), and factors associated with survival and choice of therapy. Results: Overall, 550 stage II pts were identified, of whom 80 received radical non-surgical treatment. Median age was 73. Forty-six percent of patients were female; 73% had ECOG performance status (PS) of 0-1. Stage II was defined by T2b-T3 N0 in 55% of pts and N1 in 45%. Where documented, the most common reasons for no surgery were inadequate pulmonary reserve (51%) and medical comorbidities (19%). All pts received radical radiotherapy (median 66 Gy [range 45-70]). Twenty-five pts received concurrent chemoradiotherapy (CRT); 3 received sequential CRT. At time of analysis, 64% have died. Median OS was 22.9 months. Recurrence occurred in 41%, and median recurrence-free survival was 15.9 months. Factors associated with longer survival include good PS (0-1 vs 2-3, HR 0.38, 95% CI 0.21-0.69, p=0.0015), <5% weight loss (HR 0.55, 95% CI 0.31-0.98, p=0.0414), and low (<median) WBC (HR 0.37, 95% CI 0.20-0.69, p=0.0017). Combined modality therapy was less likely in pts ≥70 years old (OR 0.27, 95% CI 0.10-0.73, p=0.0096) or higher (>median) Charlson comorbidity scores (OR 0.08, 95% CI 0.02-0.36, p=0.0011), but more likely in those with PS 0-1 (OR 4.80, 95% CI 1.28-18.03, p=0.0203) and those with T3 tumors (OR 10.00, 95% CI 1.16-86.02, p=0.0360). Conclusions: Non-surgical approaches to management of stage II NSCLC are varied. Factors associated with longer survival are similar to those seen in stage III disease.