tbuckley/cabot-search huggingface dataset:
The efficacy and toxicity of belotecan (CKD-602) combined with platinum in patients with recurrent epithelial ovarian cancer.
Authors: Y. Kim, S. Lee, S. Kim, D. Kim, J. Kim, J. Nam, Y. T. Kim
Journal: Journal of Clinical Oncology (2010)

5098 Background: This study is to evaluate the efficacy and toxicity of belotecan (CKD-602), a new camptothecin analogue topoisomerase I inhibitor, combined with platinum as the second-line chemotherapy for recurrent epithelial ovarian cancer. Methods: Fifty-four patients with recurrent epithelial ovarian cancer were treated with belotecan combined with cisplatin between January 2005 and December 2008 at Asan Medical Center, Seoul, Korea. These patients' data were collected and analyzed by review of medical records and pathologic and laboratory reports retrospectively. Belotecan (0.5 mg/m2/day, 5 days) with cisplatin (50 mg/m2/day, the last day) were administered intravenously for five days every three weeks as a combination therapy. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and toxicities were evaluated according to NCI Common Toxicity Criteria version 3.0. Results: The median age was 52 years (range, 25-75). Most patients were FIGO stage III/IV (92.7%) and serous adenocarcinoma (92.7%). The overall response rate was 42.6% including 18 patients with CR and the progression-free survival was median 9.7 (2.2 - 30.2) months. Platinum-sensitive patients had significantly higher response rate (70.4% vs. 14.8%) and longer progression free survival (11.7 vs. 6.0 months) than platinum-resistant patients. The most common adverse effect of belotecan combined with platinum was hematologic toxicity, however it was tolerable. Conclusions: As second-line chemotherapy, belotecan combined with platinum was effective in treating recurrent epithelial ovarian cancer, and had acceptable toxicity. Further prospective study regarding efficacy of belotecan in combination with platinum or the other agents, is warranted. No significant financial relationships to disclose.
Proteomic features of colorectal cancer independently predict relapse-free survival.
Authors: Callisia Clarke, Michael Sangmin Lee, Ganiraju C. Manyam, Zhi-Qin Jiang, Feng Tian, Yiling Lu, Jeffrey Morris, Bradley McIntosh Broom, David Menter, Eduardo Vilar Sanchez, Kanwal Pratap Singh Raghav, Cathy Eng, George J. Chang, Michael J. Overman, Dipen M. Maru, Scott Kopetz
Journal: Journal of Clinical Oncology (2015)

616 Background: Proteomic analysis continues to provide major insight into the pathophysiology of colorectal cancer (CRC). Recently, the Cancer Genome Atlas Project and others have utilized reverse-phase protein arrays (RPPAs) to identify critical protein markers and signaling pathways in a variety of tumor types. However, the prognostic relevance of many of these proteins remains unclear. We utilized RPPA to analyze stage 2 and 3 CRC to investigate the prognostic implications of the functional proteome. Methods: Protein extraction was performed on 232 snap frozen stage 2/3 samples from the MD Anderson Cancer Center with a median 5 year follow up. 163 validated proteins and phospho-proteins were analyzed by RPPA (with dichotomization by the median value), and used to identify protein predictors of tumor recurrence. Cox regression was used for univariate analysis with bootstrap validation, followed by inclusion of proteins with corrected p≤ 0.05 into multivariate model with clinical and pathologic variables, including stage, grade, and microsatellite status. Results: 12 proteins were found to be significant predictors of tumor recurrence on univariate analysis after bootstrap validation, which are notable for components of the energy balance/MTOR signaling pathway including AMPK, mTOR, PI3 Kinase p85, FoxO3a. On multivariate analysis, inclusive of known prognostic clinical and pathology variables, phospho-Bad (Ser112), FoxO3a, HER3, and phospho-S6 (Ser240-244) remained significant. Conclusions: Functional proteomic analysis has identified key proteomic features with prognostic importance independent of known clinical/pathological variables. Confirmation studies are ongoing to explore regulators of energy balance and apoptosis in colorectal cancer. [Table: see text]
Predictors of chemotherapy-induced peripheral numbness or tingling in patients with cancer.
Authors: G. Can, A. Aydiner
Journal: Journal of Clinical Oncology (2011)

e19674 Background: Chemotherapy-induced peripheral numbness or tingling (CIPNT) continues to be a substantial problem for many cancer patients. The purpose of this study was to identify the predictors of CIPNT. Methods: This prospective descriptive study was conducted at Adnan Aydiner Oncology Center with 490 cancer patients between December 2005 and January 2011. Personal characteristics, illness related characteristics and symptom severity of the patients were assessed by using Patients Clinical Record Forms. The severity of CIPNT and other chemotherapy related side effects was graded by the NCI Common Toxicity Criteria at each treatment of the patient. Frozen gloves were applied only in hourly taxane based treatment. Descriptive statistics and nonparametric tests were used during the data analysis. Logistic regression analysis was performed to predict the factors affecting the CIPNT. For all statistical analyses, a two-sided p value of less than 0.05 was considered to be statistically significant. Results: Most of the patients were women and their mean age was 55.72±11.63. Most of them had breast (36.9%) and lung (36.1%) cancer diagnosis and 51.8% had received taxan based therapy. Grade 1 CIPNT was found in 288 out of 490 patients (58,8%), grade 2 in 67 (13,7%), and grade 3 in 43 (8,8%) patients. In univariate analysis the factors affecting CIPNT were gender, age, body mass index, occupation, hypertension, primary tumor, stage of disease, type of chemotherapy agent, interval or number of the chemotherapy cycles, and baseline level of leukocyte or hemoglobin. Frozen glove did not prevent CIPNT. A multivariate analysis of 12 out of 22 clinical and biological factors selected after univariate analysis showed a higher risk of CIPNT in patients who had colorectal or ovarian cancer (OR 3,35 [1.82-6.14]), metastatic disease (OR 3,39 [1.87-6.17]), hypertension (OR 4,94 [1.96-12.29]), women (OR 4,34 [2.16-8.71]), weekly-biweekly therapy (OR 2,37 [1.16-4.83]) and old age (OR 1,03 [1.01-1.06]), respectively. Conclusions: Our data showed that many clinical and biological factors of the patients could predict a higher risk of CIPNT. In contrast to our thoughts frozen gloves did not reduced CIPNT associated with taxane.
B7H1 expression and association with clinical response to sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC).
Authors: Jenny J. Kim, Haiying Xu, Housam Haddad, Robert Anders, Sehbal Arslankoz, Hang Wang, Zhe Zhang, Sarah Rapp, Laura S. Wood, George J. Netto, Charles G. Drake, Gary L. Rosner, Brian I. Rini
Journal: Journal of Clinical Oncology (2013)

416 Background: Preliminary data support that B7H1 expression is associated with objective response (OR) to anti-PD-1 antibody treatment in multiple solid tumors. The aim of this study was to retrospectively evaluate a possible association between B7H1 expression and clinical response to sunitinib therapy in mRCC patients. Methods: mRCC patients receiving sunitinib therapy (50mg 4/2) were identified and data regarding patient characteristics and clinical outcome to sunitinib were recorded. Immunohistochemistry (IHC) staining of B7H1 was done on pretreatment formalin fixed paraffin embedded (FFPE) tissue sections according to available protocol at Hopkins. IHC scorings were done by 2 independent pathologists who were blinded to outcomes and a 3 rd pathologist was used if there was a discrepancy between the first 2. Association of B7H1 expression with OR was assessed using Fisher’s exact test. Progression free survivals (PFS) were estimated using the Kaplan-Meier method and compared using log-rank test. Multivariate analyses were performed using logistic regression and Cox regression. Results: 20 cases were identified of which 18 had available FFPE for IHC analysis. 78% were male; median age was 55 (range 35-79); 72% ECOG PS of 0; 94% had prior nephrectomy; 89% were therapy naïve. 50% were intermediate risk category according to Heng criteria and the rest were poor risk. 55.6% (10/18) were positive for B7H1 expression (&gt;5% positive cell membranous staining). 30% of B7H1 positive patients had OR whereas 50% of B7H1 negative patients had OR (p = 0.63). Median PFS were 19.3 and 6.2 mos for B7H1 negative and positive groups, respectively (p = 0.56). In multivariate models, B7H1 expression was neither associated with OR (odds ratio = 0.54, 95% CI = 0.07-4.23, p = 0.56) nor PFS (hazard ratio =1.06, 95% CI = 0.34-3.34, p = 0.92) after adjusting for Heng risk classification. Conclusions: In this study, B7H1 expression was not associated with clinical outcome to sunitinib therapy in metastatic RCC patients.
Patient-derived AVATAR mouse models to predict prognosis in advanced renal cell carcinoma.
Authors: Cristina Suarez, Mar Martinez, Enrique Trilla, Gabriela Jimenez-Valerio, Ines de Torres, Rafael Morales, Jose Jimenez, David Lorente, Ana Vivancos, Paolo Nuciforo, Juan Morote, Joan Carles, Oriol Casanovas
Journal: Journal of Clinical Oncology (2016)

551 Background: Anti-angiogenic (AA) drugs are the cornerstone of first-line (FL) treatment in renal cell carcinoma (RCC). While several mechanisms of resistance to AA have been described, second line (SL) therapies are disappointing with short PFS reported. A recent strategy makes use of individual patient-derived tumor models in animals for drug testing simultaneously with that patient’s FL and SL treatments (AVATARs). The predictive value of each specific AVATAR for that same original patient will be key in order to predict SL treatment response in the clinic trying to help in decision making in this setting. Methods: We generated a unique panel of patient-derived mouse models of RCC based on the orthotopic implantation of primary renal tumor biopsies or metastasis directly obtained from patients. Sunitinib FL treatment followed by different SL treatments are evaluated in each mouse model. Response to treatments in these models and molecular profiling in search of predictive factors of response/resistance will be performed. Results: In this subset of 12 advanced RCC patients, tumor take rate in mice to develop AVATARs was 75% at 5 months after implantation. Previous data demonstrated a positive association of grafting capacity with tumor stage and Fuhrman grade (p &lt; 0.0001). AVATAR models faithfully reproduced each patient’s histological characteristics and metastatic capacity. Time to tumor growth in AVATAR models significantly correlated to clinical outcome in each patient (spearman correlation, p &lt; 0.0001). These advanced AVATAR models are treated FL with AA drugs and, at the moment of emergence of resistance to therapy, treatment is switched to known and experimental SL treatments in different animal cohorts. Updated results on AVATAR treatment and prediction of patient’s responses will be presented. Conclusions: Thorough characterization of these AVATAR models together with their response to AA treatments we will be able to predict response/resistance to new SL treatments for our RCC patients as a personalized cancer therapy approach.
SBRT outcomes for primary and metastatic liver lesions.
Authors: M. H. Stenmark, E. Liu, M. J. Schipper, E. Ben-Josef, T. S. Lawrence, M. U. Feng
Journal: Journal of Clinical Oncology (2011)

262 Background: Stereotactic body radiation therapy (SBRT) permits precise delivery of 1-5 high doses of radiation to liver tumors with low risk of toxicity. This study aims to evaluate local control and overall survival (OS) in patients treated with SBRT for primary and metastatic liver lesions. Methods: From 2006 to 2010, 62 patients with 106 liver lesions (71 metastatic, 35 primary) were treated with SBRT. Lesions were most commonly from primary hepatocellular carcinoma (29%), or colorectal (23%), breast (8%), or esophageal metastases (8%). Patients were heavily pretreated: 51% received ≥1 prior form of liver-directed therapy and 54% received ≥1 prior systemic therapy regimen. The number of active hepatic lesions at the time of SBRT was 1 in 49%, 2 in 23%, 3 in 22%, and ≥4 in 7%. Of the metastatic lesions, 42% were accompanied by active extrahepatic disease. Of the primary liver lesions, 69% were Child-Pugh class A, 26% class B, and 6% class C. Median gross tumor volume (GTV) was 8.8 cm 3 (range 0.2-222.4). Median biological equivalent prescription dose (BED 10 ) was 100 Gy (42.6-180). The majority of patients received either 3 or 5 fractions (47% and 48%, respectively). Results: Median follow-up for all lesions was 18 months (4.6-46.8). Local tumor control was observed in 92/106 treated lesions with 1- and 2-yr local control rates of 88% and 74%. No correlation was found between local control and lesion type (primary vs metastatic), lesion size, or prior liver directed therapy. Median survival for all patients was 25.2 months, with 1- and 2-year OS of 81% and 52%. Survival was longer among patients with metastatic lesions compared to primary lesions (2-yr OS 63% vs 29%, HR 0.46, p=0.02). The number of active hepatic lesions was an independent prognostic factor for survival (HR 1.77, p=0.002). For patients with metastatic liver lesions, the presence of active extrahepatic disease yielded significantly worse survival (2-yr OS 37% vs 83%). Among HCC patients, a lower CLIP score was associated with improved survival with 2-yr OS of 55% for CLIP score 0, 44% for score 1, 17% for score 2, and 0% for score 3. No patients experienced RILD. Conclusions: Treatment of liver tumors with SBRT provides excellent local control, necessitating further improvements in systemic therapy. No significant financial relationships to disclose.
Targeted therapies for metastatic colorectal cancer (mCRC): A systematic review of cost-effectiveness (CE).
Authors: Tanya G. Bentley, Michael Samuel Broder, Lopamudra Das, Jesse Ortendahl, Yun Su, Samuel Wagner
Journal: Journal of Clinical Oncology (2012)

583 Background: Currently three targeted agents are available for the treatment of mCRC. Making the right choice requires balancing efficacy, safety, quality of life, and, in cost-constrained systems, cost. This study aims to determine the most cost effective treatment in each line of therapy for mCRC through systematic review of published CE analyses (CEA). Methods: Literature was searched in Medline, Cancerlit, EMBASE, Cochrane, CINAHL, BIOSIS, Web of Science, Tufts CEA registry, ASCO and ASCO GI for CEAs of the three mCRC targeted agents, cetuximab, bevacizumab, and panitumumab. Manuscripts from 2004-2011 and abstracts from 2009-2011, published in English and considering payer/societal perspectives were included. Incremental CE ratios (ICERs) were converted to US$ using 2010 purchasing power parity. Results: 15 models from six countries were identified. Mean incremental costs per quality adjusted life year (QALY) and per life year (LY) gained are shown in the Table. All four models evaluating cetuximab in 1st line therapy, and only one of the six in 2nd+ line therapy, were done among biomarker selected KRAS wild type patients. Cetuximab’s cost effectiveness in 1st line therapy was driven by its ability to convert initially unresectable liver metastasis to resectable. Conclusions: Lower ICERs appear to be associated with the use of a predictive biomarker and / or a sub patient population that can benefit the most from a treatment. With the KRAS biomarker and its potential curative benefit in patients with initially unresectable liver metastasis, cetuximab appears to be the most cost-effective targeted agent in 1st line mCRC treatment. In 2nd or later lines, direct CEA between the three agents in comparable biomarker selected patients are needed to determine the most cost effective agent. [Table: see text]
Biweekly docetaxel and vinorelbine as second-line treatment in advanced (stage IIIB+IV) non-small-cell lung cancer (NSCLC). A phase II study of the Galician Lung Cancer Group
Authors: S. Vázquez, G. Huidobro, M. Amenedo, J. L. Fírvida, M. Lázaro, L. Del Río, M. J. Villanueva, E. Álvarez, M. Ramos, J. Casal
Journal: Journal of Clinical Oncology (2005)

7334 Purpose: To evaluate the efficacy and safety of biweekly docetaxel and vinorelbine in previously treated patients with advanced NSCLC. Patients and Methods: Patients with stage IIIB and IV NSCLC which progressed after or during first-line chemotherapy, measurable disease, ECOG PS=0–2 and adequate organ function were included. Previous treatment with paclitaxel was allowed. Docetaxel was administered at 40 mg/m2 and Vinorelbine was administered at 20 mg/m2 days 1 and 14. Cycles were repeated every 28 days until disease progression, occurrence of unacceptable toxicity or voluntary withdrawal. Both, toxicity and efficacy analyses were performed on the intent-to-treat (ITT) population. Results: A total of 50 patients were included (M/F, 40/10), with median age 59 years (31–89) and ECOG PS 0–1 in 75% of patients. Tumor histology mainly included epidermoid (50%)and adenocarcinoma (25%). Tumor stage was IIIB (35%) and IV (65%). Median number of metastatic lesions was 2 (51% 2 or more), located mainly in lymph nodes(33%), adrenal glands (31%), and lung (31%). Previous chemotherapy included platinum (97.8%), gemcitabine (82.6%) and paclitaxel (71.3%). A total of 153 cycles (median 3, range 1–6) were administered. Median relative dose intensity for docetaxel and vinorebine was 86%. Toxicity: Grade III/IV hematologic toxicity per patient was neutropenia (20.8%) and anemia (4.2%). One patient died due to neutropenia grade 3 and sepsis. Febrile neutropenia was observed in 2 patients. Grade III/IV non-hematologic toxicity per patient was asthenia (4.2%), vomiting (2.1%), mucositis (2.1%) and diarrhea (2.1%).Efficacy: Of 44 ITT patients (6 patients have just begun chemotherapy), 1 achieved CR, 4 PR, 10 SD and 19 progressed resulting in an ORR of 11.4% (95% CI; 1.7–19%).10 patients could not be evaluated for response due to early withdrawal (6 tumor-related exitus, 1 P.S. deterioration., 1 toxic death and 2 pneumonias). Median TTP and OS were 89 days (95% CI: 34–143) and 198 days (95% CI: 109–286), respectively. Conclusion: Biweekly docetaxel and vinorelbine is an active and feasible regimen in previously treated patients with advanced NSCLC. No significant financial relationships to disclose.
Potential role of chemoradiotherapy for metastatic pancreatic cancer.
Authors: D. Y. Lee, J. M. Robertson, J. Huang, J. H. Margolis, S. Balaraman, L. Nadeau
Journal: Journal of Clinical Oncology (2011)

344 Background: Patients with metastatic pancreatic cancer have a poor outcome and the radiotherapy is typically only given to patients requiring palliation. We analyzed our institutional pancreas database to compare the outcome between chemotherapy alone vs. chemoradiotherapy. Methods: From January 2000 to December 2008, 199 metastatic pancreatic cancer patients were retrospectively analyzed. 13 (6.5%) patients received chemoradiotherapy and 186 (93.5%) patients received chemotherapy alone. Chemotherapy regimens consisted of 5-fluorouracil, gemcitabine, erlotinib, or cisplatin. The follow-up time was calculated from the time of diagnosis to the date of death or the last contact. Kaplan-Meier analysis was used to calculate the overall survival (OS). Results: Median OS was 5.3 months for all patients. Median OS was 4.9 months (0.4–27.0) for patients treated with chemotherapy alone and 7.8 months (0.6–44.1) for those treated with chemoradiotherapy (p = 0.013). Univariate survival analysis of categorical variables for patients treated with chemoradiotherapy revealed that age, race, gender, location of metastatic site, T stage (T3 v. T4) or nodal stage were not significant. However, ECOG performance status (1 v. 2/3) and the dose of radiation (&lt;35 v. &gt;35 Gy) received were associated with improved survival (p = 0.013, p=0.049). Median OS was 12.9 months for ECOG 1 vs. 5.6 months for ECOG 2/3. Median OS was 11.1 months for patients treated with radiotherapy dose &gt; 35 Gy vs. 5.9 months for those who received less than 35 Gy. 3/13 (23%) patients who received chemoradiotherapy lived nearly two years or more. Conclusions: Metastatic pancreatic cancer patients with good performance score may benefit from chemoradiotherapy. Long-term survival was observed in this selected group. No significant financial relationships to disclose.
Association of single nucleotide polymorphisms (SNPs) in <i>SULT1E1 </i>with response to treatment with abiraterone acetate (AA) in men with metastatic castration refractory prostate cancer (mCRPC).
Authors: Tyler Howard Buckley, Anitha Alex, James M. Farnham, David Gill, Shiven B. Patel, Craig Teerlink, Frederick S. Albright, Robert A Stephenson, Lisa A Cannon-Albright, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2016)

222 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict response to AA in men with mCRPC, serve as prognostic and predictive biomarkers, and guide towards more individualized therapy. Methods: 836 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 61 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to treatment failure (TTF) in 68 Caucasian men with mCRPC undergoing treatment with AA. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Three SNPs in SULT1E1 were associated with TTF on AA therapy after correcting for multiple testing (p &lt; .00007) while controlling for Gleason Score (Table). Conclusions: SNPs in SULT1E1(estrogen sulfotransferase gene) were significantly associated with TTF on AA therapy, and may serve as predictive markers to treatment with AA. Further validation is being performed in a larger cohort of men with mCRPC. [Table: see text]