tbuckley/cabot-search huggingface dataset:
Difference between duration of treatment (DOT) and progression-free survival (PFS) as a marker of unbalanced censoring.
Authors: Laleh Amiri-Kordestani, Julia Wilkerson, Sanjeeve Balasubramaniam, Susan Elaine Bates, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2012)

2548 Background: In the conduct of randomized trials Kaplan and Meier envisioned rates of censoring as similar between arms, providing accurate assessment of clinical trial results. Censoring is used when patients withdraw consent, leave study due to toxicity, or reach data cut-off without disease progression or death. Censoring can lead to erroneous conclusions as it can be either beneficial or detrimental to the arm under study. Such censoring can also explain how a statistically valid difference in PFS “disappears” when overall survival (OS) is examined. We hypothesized that censoring, especially that due to toxicity, would lead to a discrepancy between DOT and PFS since two different patient populations would be scored. Methods: We reviewed all phase III randomized studies of drugs approved by FDA since 2005 for pts with metastatic solid tumors, looking for DOT and PFS. We used standard statistical analyses using SAS. Results: We identified 55 Phase III studies conducted with abiraterone, axitinib, bevacizumab, cabazitaxel, cetuximab, eribulin, erlotinib, everolimus, ipilimumab, ixabepilone, lapatinib, panitumumab, pazopanib, sorafenib, sunitinib, temsirolimus and vandetinib. DOT was not provided in 27%. Forty-four comparisons (88 arms) were included in the analysis. The median PFS, DOT, delta PFS (difference in PFS between experimental and control arms) and delta DOT were: 161, 126, 51 and 36 days, respectively. The slopes of PFS vs DOT and delta PFS vs delta DOT were 1.16 and 1.03, respectively close to the ideal of 1.0. Five trials fell above the 90% CI boundary with delta PFS/delta DOT of 3 to 36, including two everolimus studies (PNET and breast cancer) two sunitinb studies (RCC and PNET) and one bevacizumab study (E2100, breast cancer). Conclusions: PFS and DOT as well as delta PFS and delta DOT should be concordant. The most likely explanation for a discordance between these values is toxicity-driven censoring and its occurrence raises concerns regarding the degree of efficacy. A greater utilization of “Time to Treatment Failure”, an endpoint that includes toxicity in its definition would be valuable in oncology trials, particularly those with high levels of toxicities.
Molecular profiling (MP) programs to increase access to targeted therapies in a rural setting.
Authors: Steven Francis Powell, Lora Jane Black, Chun-Hung Chan, Megan L Landsverk, Jessica Vandermark, Christie Ellison, Kathryn Morberg, Paul A. Thompson, James M. Ford, Anu G. Gaba
Journal: Journal of Clinical Oncology (2015)

e17576 Background: Nearly 85% of cancer patients (pts) are treated in the community. In order to advance our understanding of cancer genomics and the impact of targeted therapy, this research needs to expand in the community. Community-based MP programs can improve access to targeted therapies and support genomic research. Methods: From June 1st, 2014 through January 15th, 2015 we instituted a prospective MP study at Sanford Health. Sanford Health is a multi-center, predominantly rural health system centered in the Dakotas. Patients with incurable, advanced solid tumors who had progressed after exhausting standard treatment options were offered enrollment in a MP program. All patients enrolled had MP performed on a recent tumor biopsy ( < 14 weeks from enrollment) using the Foundation One targeted sequencing panel. Results were reviewed at a multi-center, video-conferenced, weekly genomic tumor board. Treatment options were offered based on actionable alterations (AA) identified through MP. FDA approved on-label agents, FDA approved off-label agents, and clinical trials agents targeting the AA were considered treatment options. Clinical trials with targeted agents were opened through industry and cooperative groups to interface with this screening program. Tumor specific, MP, and patient outcome data was prospectively monitored, regardless of treatment. Results: A total of 43 pts were enrolled in the program over the study period. 37 of the 43 pts (86%) had successful MP. 34 of these pts (92%) had an AA. Of those with successful MP, 18 pts (48.6%) were treated based on their MP data. 9 pts (24.3%) were treated on clinical trials with an agent aimed at their specific alteration(s). The other 9 pts (24.3%) were treated with FDA on-label or off-label drug based on their MP data. Treatment specific outcomes including, progression-free survival, overall survival, best overall response, and severe adverse events are being prospectively followed. Conclusions: Prospective MP programs are feasible and effective in facilitating enrollment into targeted therapy trials in the community setting. Development of similar MP programs could substantially increase our understanding of cancer genomics and the impact of targeted therapies.
Impact of location to repeat mobile mammography utilization trends: 10-year analysis of a comprehensive urban cancer center.
Authors: Elizabeth Carloss Riley, Lane Roland, Laura Barkley, Jianmin Pan, Shesh Rai, Sarah Mizuguchi
Journal: Journal of Clinical Oncology (2014)

6577 Background: Mobile Mammography Units (MMU) are a model of community outreach through targeted locations. The purpose of this study was to analyze the association between MMU utilization and screening location in the largest county in Kentucky. Methods: From January 2001- December 2010, 48,324 screening mammograms were performed with 21,587 unique subjects. Locations were divided into three categories: Corporate, Partnership Clinics (public health clinics) and Partnership Community (local events.) Utilization was defined as once, twice or more than 3 times in a 10 year period. The p-values were computed using the Pearson Chi-square test. The comparison with a p-value < 0.05 was considered statistically significant. Results: Partnership Clinic accounted for the majority of encounters (40.6%) and was most likely to repeat twice (19.1%) or 3 or more times (30.2%) in a 10 year period. Partnership Community accounted for the least at 24% and was least likely to utilize the van repeatedly (p=<.001.) The majority of screens occurred only once in a 10 year period regardless of location. Conclusions: To our knowledge this is the largest database of MMU reported in the literature. We previously reported on race and insurance status as predictors of repeat utilization. The current dataset suggests women referred from the Partnership Clinic (Public Health Clinics) are most likely to repeat utilize the van which would be consistent with the intended purpose of the MMU as these patients are most likely to be uninsured or underinsured. Partnership Community are the least likely to repeat utilize however further analysis is needed to determine whether consistency of offered location from year to year could impact these trends as the Community group locations may be less consistent annually. Analysis of the trends of utilization of MMU based on location has implications for funding and outreach. Total N= 21857 1 screen N=11816 2 screens N=3983 >/= 3 screens N=6058 P value <.001 Corporate (%) 7741 (35.4) 4223 (54.6) 1385 (17.9) 2133 (27.6) Partnership clinic (%) 8874 (40.6) 4499 (50.7) 1694 (19.1) 2681 (30.2) Partnership community (%) 5242 (24.0) 3094 (59.0) 904 (17.2) 1244 (23.7)
A single genomic HER2 assay for the protein expression and the DNA amplification status
Authors: S. Carpentier, F. Bertucci, R. Tagett, P. Finetti, J. Jacquemier, J. M. Le Doussal, F. Hermitte
Journal: Journal of Clinical Oncology (2009)

e22082 Background: Currently, up to 20% of HER2 tests in breast cancer may be inaccurate. To address this situation, the 2007 ASCO/CAP guideline for HER2 testing recommended using standardized IHC (for HER2 protein expression) and FISH (for HER2 DNA amplification) in a sequential testing algorithm. However, test standardization and equivocal results still remain an issue potentially leading to inappropriate treatment decisions. A new genomic HER2 (gHER2) assay was designed to address these issues. Methods: Frozen samples of 152 primary breast cancers with a positive or negative IHC result (126 IHC 0+ and 26 IHC 3+ determined by tissue microarray) were profiled using Affymetrix U133 Plus 2.0 gene chips. Recursive feature elimination algorithm by support vector machines (RFE-SVM) was used to select probesets correlated to IHC status; to compute a genomic HER2 (gHER2) expression index; and to set a threshold discriminating between IHC 0+ from IHC 3+ samples. This gHER2 assay was validated in 4 independent datasets (n=309) and tested for its ability to reclassify HER2 equivocal cases (IHC 2+, n=21). The assay was standardized using Ipsogen MapQuant Dx. Results: RFE-SVM identified 6 known and 1 unknown genes correlating with the IHC status, all located within the HER2 DNA amplicon. The gHER2 assay gave unequivoqual HER2 status in 96.2 % of samples. The genomic HER2 assay was concordant with IHC status in 94.5% of cases. 95 % of samples with equivocal IHC status (IHC 2+) could be re-classified in accordance with FISH status in 95 % of cases. Conclusions: We could identify a genomic signature of both HER2 DNA amplification and HER2 protein expression. A new standardized genomic HER2 assay was derived that matches the ASCO/CAP guideline requirements of 95 % concordance with validated techniques. It may contribute to reduce the number of equivocal results. [Table: see text]
Serial neutrophil to lymphocyte ratios (NLR) in relation to weight change and overall survival in patients (Pts) with metastatic non-small cell lung cancer (NSCLC).
Authors: Jason Nathaniel Macklis, Mary J. Fidler, Philip Bonomi, Sanjib Basu, Jeffrey Allen Borgia, Mohammed S. Azeem, David Sher, Marta Batus
Journal: Journal of Clinical Oncology (2015)

e19143 Background: We previously observed a significant relationship between overall survival (OS) in stage III/IV NSCLC patients and weight change during chemotherapy or chemoradiation. A high neutrophil/lymphocyte ratio (NLR) at baseline and at follow-up is associated with shorter survival in cancer patients and may be a surrogate for ongoing inflammation which is implicated in promoting cancer cachexia and tumor progression. The objective of this study is to explore potential relationships between OS, serial weights, and serial NLRs in advanced NSCLC patients receiving chemotherapy. Methods: 139 stage III/IV NSCLC pts were treated with first-line platinum doublets from June, 2011 to August, 2012. NLR and body weight were recorded at baseline, 6, and 12 weeks from initiation of therapy and correlated with OS. The association between NLR and OS was assessed using Cox PH analysis, and the association between NLR and weight change was assessed using a simple regression analysis. Results: 139 pts with median age 68, PS 0-1/2 = 83/17%, male/ female = 48%/52%. NLR at baseline median 3.6, range 0.1898 to 30.910; at 6wks median 3.11, range 0.2703 to 42.11; at 12wks median 3.52 range 0.2147 to 42.93. Increase in the NLR at baseline, 6, and 12 weeks were associated with a decrease in OS (baseline HR 1.06, p < 0.001; 6 wks HR 1.07, p = 0.001; 12wks HR 1.05, p < 0.001). The effect of NLR on hazard is multiplicative (i.e. a change of 5 in baseline NLR results in a HR of 1.065). Initial weight and NLR were negatively correlated (cor = -0.267, p = 0.001), and weight change and NLR were also negatively correlated at 12wks (cor = -0.371, p < 0.001; weight change -13.17kg to +16.61kg, median -0.5kg, mean -0.89kg). Conclusions: High baseline and progressive increase in NLRs are associated with inferior OS and weight loss in advanced NSCLC patients. In addition to having prognostic significance, these observations suggest that studying molecular mediators of cachexia/inflammation and their relationships to tumor progression may identify new therapeutic targets in the large subset of NSCLC patients who have cancer cachexia.
The final report of a phase I trial of surgical resection with biodegradable carmustine (BCNU) wafer placement followed by vaccination with dendritic cells pulsed with tumor lysate for patients with glioblastoma.
Authors: Jeremy Rudnick, Jethro Lisien Hu, Anne Luptrawan, Mia Mazer, Chris Wheeler, Miriam Nuno, Ray M Chu, Surasak Phuphanich, Keith L. Black, John Yu
Journal: Journal of Clinical Oncology (2012)

2084 Background: Our prior immunotherapy trials demonstrated efficacy in generating a tumor specific immune response in malignant glioma and the potential for high tumor-specific toxicity and sustained tumoricidal activity. Immunotherapy may synergize with chemotherapy and biodegradable carmustine (BCNU) wafers and have a modest impact to extend overall survival. We exploited this synergistic effect to maintain a cytotoxic environment around the tumor milieu, and this is a presentation of the final results of our clinical trial. Methods: Patients with glioblastoma were eligible after maximal resection with biodegradable carmustine (BCNU) wafer placement. Screening leukapheresis was used to isolate mononuclear cells which were differentiated into dendritic cells, pulsed with tumor lysate, and then 3 intradermal vaccines administered at 2-week intervals. Patients continued systemic chemotherapy after vaccine or at progression. Results: Twenty three patient with glioblastoma received therapy including 8 with newly diagnosed disease (35%) and 15 with recurrent disease (65%) were evaluable. Immune response data is available for 20/23 patients although survival data is present for all. One grade 3 SAE of fever and chills was noted otherwise therapy was well tolerated. Within the newly diagnosed GBM cohort the median overall survival (OS) was 25.5 months (15,31+), and within the recurrent GBM cohort, the median OS was 16 months (8,23+). Among the recurrent GBM an increase of &gt;1.5 X baseline interferon gamma production post vaccination was associated with a prolonged median OS 22 months (8,40) in 4/12 patients versus 17 months (9,27) in 8/12 patients. Conclusions: We were able to generate an immune response in 25% of patients which is lower than what we have seen in previous trials and suggests a limited synergy with local control. However, within the recurrent GBM cohort we did find prolonged survival in both groups with an increased survival noted in immune responders demonstrating the potential for this therapy.
The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.
Authors: Zhi-tao Xiao, Rong-xin Zhang, Yang Zhao, Jian-Hong Peng, Pei-Rong Ding, Xiao Jun Wu, Zhen-hai LU, Li-ren LI, Desen Wan, Zhi-zhong Pan, Hui-Zhong Zhang, Shi-xun Lu, Gong Chen
Journal: Journal of Clinical Oncology (2017)

544 Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P &lt; 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P &lt; 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P &lt; 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P &lt; 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.
Using the NCCN survivor assessment questionnaire as a tool to tailor educational needs of cancer survivors.
Authors: Wendy Crabbe, Praveena Iruku
Journal: Journal of Clinical Oncology (2017)

156 Background: Survivor care after cancer treatment includes assessment of fatigue, pain, cognitive dysfunction, cardiac toxicity, sexual function, and the patient’s habits related to nutrition, physical activity, sleep and stress management. Using a tool to evaluate these symptoms and lifestyle habits is needed to determine the educational needs of the cancer survivor for the survivor treatment summary visit. Methods: We have used the National Comprehensive Cancer Network (NCCN) Survivorship Assessment tool for the past 12 months to develop a survivor care plan. It is a pre-visit 25 question survey completed by the patient. The patient responses help focus education based on current symptoms and lifestyle habits. A total of 50 questionnaires were completed over the past year. Results: Of the 50 patients, 46 were women, 45 had breast cancer, 3 colorectal and 2 other. The average age was 56 years old, 70% were Hispanic, 86% received chemotherapy and there were 4 recurrences. The average time from finishing adjuvant therapy to the survivor treatment summary visit was 7 months. Fifty percent of patients were on adjuvant hormonal therapy (Aromatase Inhibitor or Tamoxifen). Persistent symptoms at the time of the survivor visit are detailed in the table below. Regarding nutrition and physical activity, 44% of survivors were obese with 44% who said they get regular physical activity. Of the 44% who get regular physical activity, it can be further broken down to 1-3 days a week (10%), 4-7 days a week (28%) and 46% of patients said they ate 2.5 cups of fruits and vegetables per day. Conclusions: At the time of the survivor treatment summary visit there are still residual side effects from treatment including cognitive dysfunction, pain, fatigue, trouble sleeping and problems with sexual function. The NCCN Survivor Assessment questionnaire is a good tool to determine persistent side effects from treatment and educational needs of cancer survivors.[Table: see text]
Phase Ib/II study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.
Authors: Jared David Acoba, Amy Rock, Hing C. Wong
Journal: Journal of Clinical Oncology (2017)

TPS510 Background: IL-15 is one of the most promising new candidates in cancer immunotherapy. Similar to IL-2, IL-15 stimulates natural killer (NK) and CD8+ T cells, however IL-15 may be a more effective and safer therapy as it does not trigger regulatory T cells or induce capillary leak syndrome. Preclinical data also show that IL-15 is effective in eradicating murine pancreatic cancers. However, the use of rhIL-15 in the clinic however has been limited by its short half-life (30 minutes) and cytokine related adverse effects, such as fever and hypotension. Compared with IL-15, ALT-803, a novel IL-15 superagonist complex (IL-15N72D:IL-15RαSu/Fc), has a prolonged serum half-life and is capable of potently inducing NK and CD8+ T cell proliferation in vivo. Pancreatic cancer remains one of the most common causes of cancer death and novel therapies are needed. This study represents the first clinical experience of ALT-803 in the treatment of pancreatic cancer. Methods: This is a Phase Ib/II, multi-institution study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The study involves a phase Ib dose escalation phase to determine the MTD using a standard 3+3 design. Patients will receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 D1, 8, 15 and ALT-803 at assigned dose on D2, 9, 16 of a 28d cycle. Primary endpoints are safety and tolerability. Phase II will be a two-stage expansion phase using a Simon two-stage design with a primary endpoint of survival at 8.5 months. Secondary endpoints include response rate, progression free survival, and overall survival. Response will be assessed q8 weeks by RECIST v1.1. Major inclusion criteria include: locally advanced (Phase Ib only) or metastatic pancreatic adenocarcinoma, adequate organ function, PS ECOG 0-2, and 0 or 1 (Phase Ib only) line of prior therapy for advanced pancreatic cancer. Prior nab-paclitaxel is not allowed Current enrollment: Enrollment to the first dose level is ongoing. Complete accrual of phase Ib is expected within nine months. Clinical trial information: NCT02559674.
Reasons for delay in time to initiation of adjuvant chemotherapy for colon cancer: A multi-institution study.
Authors: James Joseph Biagi, Ronald L. Burkes, Christine B. Brezden, Kevin M. Zbuk, Brandon Matthew Meyers, Oren Hannun Levine, Silvana Spadafora, Stephen Welch, Sukaina Davdani, Wilma Hopman, Christopher M. Booth, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2014)

e14504 Background: Although adjuvant chemotherapy (AC) has been shown to improve survival in patients with colon cancer (CC), meta-analyses have suggested decreased survival with increasing Time To AC (TTAC). We examined the predominant factors leading to delayed TTAC in routine clinical practice. Methods: Individual medical records were reviewed for 1,608 patients with CC who initiated AC 2005-2012 at eight cancer centers in the Province of Ontario. Patient, disease, and treatment characteristics, plus time intervals between each step in the cancer care pathway from surgery to AC, were captured. Patients were then categorized into three groups for comparison: (I) inter-current illness and/or post-operative complications, (II) oncologist/patient-initiated delay, (III) no medical reason for delay. Groups were compared using chi square tests and one-way ANOVA. A multivariate logistic regression analysis (MVA) was used to determine factors associated with TTAC >8 weeks (wks) for each cohort. Results: The proportion of patients in each group was: (I) 24.7%, (II) 19.5%, (III) 55.8%; mean TTAC was: (I) 10.1±2.7, (II) 10.5±3.6, (III) 8.5±2.1 wks (p<0.001); the proportion of cases with TTAC>8 wks was: (I) 76.4%; (II) 81.4%; (III) 57.9%. The most common post-operative complication in Group I was ileus (34.2%). The only significant predictor of TTAC >8 wks by MVA in group I was AC via central venous catheter (OR=2.4, 95%, CI:1.2-4.9). Median length of stay in hospital after surgery was 10, 6 and 6 days for Group I, II, and III, respectively (p<0.001). When MVA was performed on all patients, the presence of post-operative complications (OR=2.4, 95%CI:1.6-3.8) and oncologist/patient-initiated delay (OR=3.5, 95%CI:2.1-6.0) were the strongest predictors of delay. There was no effect on TTAC if surgery was performed in peripheral versus academic hospital (p=0.32). Conclusions: Although the majority of patients had no medical reason for delay, the average TTAC was > 8 wks. Our findings suggest that health-system factors such as waiting for consultations and chemotherapy booking cause the majority of delays in TTAC. These are modifiable and quality improvement initiatives should focus on how to reduce these delays.