tbuckley/cabot-search huggingface dataset:
Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.
Authors: Avani Satish Dholakia, Muhammad Ali Chaudhry, Jeffrey P. Leal, Daniel Tandel Chang, Siva P. Raman, Zheng Su, Amy Hacker-Prietz, Jonathan Pai, Mary E Griffith, Richard L. Wahl, Erik Tryggestad, Timothy M. Pawlik, Daniel A. Laheru, Christopher Lee Wolfgang, Albert Koong, Joseph M. Herman
Journal: Journal of Clinical Oncology (2014)

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV max and SUV peak ) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Liver mean + (2 * Liver sd ). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm 3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p &lt; 0.003) and TLG of 70.9 cm 3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p &lt; 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.
How sensitive are epidermal growth factor receptor tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring epidermal growth factor receptor gene–sensitive mutations?
Authors: A. Hata, N. Katakami, K. Kunimasa, H. Yoshioka, S. Fujita, R. Kaji, Y. Imai, K. Tomii, M. Iwasaku, A. Nishiyama, T. Ishida
Journal: Journal of Clinical Oncology (2011)

7609 Background: The efficacy of epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs; gefitinib and erlotinib) has been demonstrated in patients with non-small cell lung cancers (NSCLC) harboring EGFR sensitive mutations. EGFR mutations are found in 30-40% of adenocarcinoma, but rarely in other histologic subtypes. EGFR mutations are occasionally found in squamous cell carcinoma (SCC) in our clinical practice. However, there is little data demonstrating the efficacy of EGFR-TKIs in SCC harboring EGFR mutations. Methods: We investigated the frequency of EGFR mutation positive SCC of the lung between April 2006 and October 2010. The efficacy of EGFR-TKIs in lung cancer patients with SCC harboring EGFR mutations was retrospectively evaluated. Results: Thirty of 249 patients with SCC (13.3%) had EGFR mutations. The types of EGFR mutation were exon 19 deletion (19/33, 58%), L858R point mutation in exon 21 (12/33, 36%), and G719S point mutation in exon 18 (2/33, 6%). Twenty of these 33 patients were treated with EGFR-TKIs (gefitinib 18; erlotinib 2). Five of 20 EGFR mutation positive patients responded to EGFR-TKIs with the response rate of 25.0% (95% confidence interval [CI], 8.7 to 49.1%). Median progression-free survival (PFS) and median overall survival were 1.4 months (95% CI, 0.7 to 5.8 months), and 14.6 months (95% CI, 2.9 months to undeterminable), respectively. Approximately one third of EGFR mutation positive SCC patients obtained PFS greater than six months. Conclusions: Although EGFR-TKIs seem to be less effective in EGFR mutation positive SCC than EGFR mutation positive adenocarcinoma, some EGFR mutation positive patients with SCC can obtain clinical benefit from EGFR-TKIs. EGFR mutational analysis is recommended even in patients with SCC to select and treat patients properly.
Interim safety results from the all cases post-marketing study (PMS) of sunitinib in 1,027 Japanese patients with renal cell carcinoma (RCC) or gastrointestinal stromal tumor (GIST).
Authors: N. Agata, N. Ueno, H. Houzawa, E. Ueda, Y. Komatsu, T. Nishida, S. Naito, H. Akaza
Journal: Journal of Clinical Oncology (2011)

e15133 Background: In Japan, sunitinib malate (SUTENT) was approved in April 2008 for unresectable or metastatic RCC and GIST. As recommended by the Japanese Ministry of Health Labor and Welfare guidance, we conducted an all-cases PMS to further evaluate the safety of sunitinib following its approval in Japan to supplement the information already available for this agent. We report here interim safety results from the PMS for sunitinib in 1,027 Japanese patients (773 patients with RCC and 254 patients with GIST). Methods: All 1,027 patients were examined for eligibility and registered for this study before initial treatment with sunitinib. Patients were followed for up to 1.5 years. We used descriptive statistics and logistic regression analyses to determine the incidences of adverse events (AEs) and the impact of related factors. Results: The incidence of all-grade AEs reported was 95.6% (982/1,027 patients). The most frequent grade 3/4 AEs (MedDRA) included: platelet count decrease (32.7%), white blood cell count decrease (11.2%), hypertension (10.6%), neutrophil count decrease (9.4%), thrombocytopenia (4.6%), lipase increase (4.6%), anemia (4.5%), hand-foot syndrome (4.3%), anorexia (3.8%) and hypothyroidism (2.6%). Based on an analysis of the incidences of grade 3/4 AEs after risk factor adjustment, significant contextual factors associated with a higher incidence were: gender (female), age (>55 yrs old), concomitant drug (presence), ECOG performance status (0 or 1) and initial dose (37.5 or 50 mg). Conclusions: Evidence from this interim analysis of the PMS in Japanese patients suggests that the safety profile of sunitinib in the post-marketing setting is similar to that previously reported in clinical trials with Japanese patients. Hematological AEs appeared to be more common in Japanese patients than in Western patients treated with sunitinib.
Implementation of a statewide quality assessment program for rectal cancer.
Authors: Samantha K. Hendren, Ellen McKeown, Sandra L. Wong, Mary Oerline, Darrell A. Campbell, Nancy J. Birkmeyer
Journal: Journal of Clinical Oncology (2013)

4 Background: The quality of surgical care for rectal cancer (RC) has been extensively studied in Europe; however, efforts in the United States are limited by the lack of detail about surgical care in available registries. We describe a unique quality assessment program for RC designed within the Michigan Surgical Quality Collaborative (MSQC), a collaborative quality improvement organization that includes community and academic medical centers. Methods: 10 MSQC hospitals contributed to this retrospective cohort study (2007-2012). Experienced nurse reviewers were trained to abstract cancer surgery-specific data from hospital medical records and local tumor registries. Five RC surgery-specific quality measures were designed based on literature review and current guidelines: adequate lymph node (LN) procurement (&gt;=12); use of mesorectal excision; rate of margin positivity; use of neoadjuvant therapy for clinical stage II/III; and sphincter preservation rate for mid/upper RC. Results: 353 RC cases were studied (333 radical surgery, 20 local surgery). Participating hospitals varied in size (5 &lt;400 beds), teaching status (6 major teaching, 2 minor teaching, 2 non-teaching), and urban/rural location (9 urban). Challenges encountered in the data abstraction training process included overcoming technical jargon in pathology and operative reports. Regular conference calls, access to a specialist for questions, and modifications to definitions helped overcome difficulties; 9 of 10 abstractors scored &gt;90% correct on test cases. Analysis reveals wide variation between hospitals on quality measures. 75% of cases had adequate LN procurement (range by hospital 64-100%); mesorectal excision was performed in 76% of cases (38-97%); 9% had positive margins (0-17%); 94% of clinical stage II/III cases had neoadjuvant therapy (67-100%); and 86% of eligible cases had sphincter preservation (62-100%). Conclusions: A program designed to provide salient feedback to surgeons regarding RC treatment is feasible, and reveals that high-quality processes of care are not consistently used. These data suggest opportunities for process improvement. The program will be disseminated statewide for prospective data feedback and quality assessment.
Sucessful Outcome in Poor-Prognosis Acute Thrombotic Thrombocitopenic Purpura Treated with Plasma Exchange and Rituximab.
Authors: Cesar Almeida Neto, Mirianceli C. Mendonça, Marcelo C. Braga, Fabiana S. Ghaname, Fernanda Gobette, Luis F.F. Silva, Jorge N. Ghaname, Anis Gamne
Journal: Blood (2005)
Comparison of outcomes for the elderly patients treated with single agent versus doublet regimen as first-line chemotherapy for recurrent or metastatic gastric cancer.
Authors: Der Sheng Sun, Yoon Ho Ko, Eun Kyoung Jeon, Hye Sung Won, Byoung Young Shim, Sang Young Roh, Ji Chan Park, Hoon Kyo KIM, Young Seon Hong, Suk Young Park
Journal: Journal of Clinical Oncology (2014)

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.
Plasma MN (carbonic anhydrase IX) and outcome in sunitinib-treated metastatic renal cell cancer.
Authors: Nicholas E. Lamparella, Suhail M. Ali, Kim Leitzel, Walter P. Carney, Allan Lipton
Journal: Journal of Clinical Oncology (2013)

405 Background: The transmembrane protein MN (carbonic anhydrase IX)(CAIX) catalyzes the hydration of carbon dioxide to carbonic acid and decreases pH. In cancer, up-regulation of CAIX gene expression occurs under hypoxic conditions within tumors. Significant levels of CAIX protein have been detected in a variety of cancers including kidney, cervix, lung, bladder, colon, breast, liver, gall bladder, and pancreas. Methods: Pretreatment plasma CAIX and VEGF-A levels were determined from 52 metastatic renal cell cancer patients enrolled in a phase III first-line trial of sunitinib vs. interferon alpha (IF). The CAIX and VEGF-A ELISAs (WILEX/Oncogene Science, Cambridge MA) were used for determination of plasma biomarker levels. 51 of 52 patients had an MSKCC score of 0 or 1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) plasma CAIX and VEGF levels. Results: Pretreatment plasma CAIX levels averaged 371 pg/ml, with a median of 194 pg/ml and 25 th and 75 th percentile values of 125 and 298 pg/ml, respectively. In the whole population, higher plasma CAIX was significant on a continuous basis for predicting reduced PFS (p &lt; 0.007) and shorter OS (p &lt;0.0001). When analyzed using the median as cutpoint, the elevated plasma CAIX cohort trended for reduced PFS (p = 0. 13) and had a significantly reduced OS (HR 2.77, p = 0.026) (median 94 vs. 115 weeks). In univariate analysis plasma VEGF-A did not predict for PFS or OS when analyzed as a continuous or dichotomous variable. In multivariate analysis for PFS (including treatment arm, CAIX, and MSKCC score), treatment with sunitinib (vs. IF) (p = 0.006) and lower plasma CAIX (p = 0.04) resulted in a significantly longer PFS. In multivariate analysis for OS, again treatment with sunitinib (vs. IF) (p=0.037), and lower plasma CAIX (p &lt; 0.0001) resulted in a significantly longer OS. Conclusions: Elevated pretreatment plasma CAIX predicted for reduced PFS and overall survival in metastatic renal cancer patients. In addition, sunitinib was superior to interferon, regardless of plasma CAIX status.
Quality of life (QOL) for patients treated with FOLFOX with or without cetuximab (Cmab) following complete resection of colorectal cancer (CRC): Results from North Central Cancer Treatment Group (NCCTG) phase III trial N0147.
Authors: M. R. Mahoney, J. A. Sloan, J. M. Hubbard, H. Liu, A. F. Shields, E. Chan, R. M. Goldberg, S. Gill, M. S. Kahlenberg, S. G. Nair, D. J. Sargent, S. R. Alberts
Journal: Journal of Clinical Oncology (2011)

3541 Background: QOL has been demonstrated to be a key outcome in CRC. This study reports on the QOL-related findings for our recent (ASCO 2010) phase III study, N0147. Methods: Patients (pts) with completely resected, histologically proven stage III (any T, N1 or N2, M0) adenocarcinoma of the colon received 12 bi-weekly cycles of FOLFOX alone (1337 pts) or with Cmab (1349 pts). Overall QOL was measured via a validated single-item numerical analogue self-assessment (LASA) measure with similar LASA items for mental, and physical well-being (WB). LASA was completed prior to treatment, at 3 months post-treatment initiation, and at treatment discontinuation.Comparisons across treatment groups were assessed using two-sample t-tests and analysis of covariance models, with 80% power to detect a difference of 1 point on the 100 point scale at a 0.05 level of significance (2-sided t-test). Results: QOL data was provided by 1,422 pts. Significant differences in WB (Mental, Physical) and overall QOL over time and across treatment arms were observed, favoring FOLFOX alone and by 1-8 points. Similar results were seen at the time of treatment discontinuation: Overall (0.3, p=0.001), Mental WB (0.3, p=0.01), Physical WB (0.2, p=0.05). FOLFOX treated pts aged 70+ reported Mental/Physical WB at the end of treatment 5 points higher than those aged <70 (p=0.01, p=0.02). Elderly pts reported higher Mental/Physical WB on FOLFOX (5 points, p<0.02) and Mental WB with Cmab (4 points, p=0.02), although more fatigued with Cmab (7 points, p=0.01). Conclusions: Consistent with the primary survival findings, pts receiving FOLFOX alone also reported significantly better QOL than those pts who also received Cmab. These results were consistent across gender and age. Patients aged over 70 appear to have stable to improved QOL during adjuvant CRC therapy with FOLFOX; the QOL was reported lower for pts receiving Cmab. These data support inclusion of elderly patients for studies in this population. Supported by NIH Grant CA25224. ClinicalTrials.gov #NCT00079274.
Prognostic model in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
Authors: D. Z. Radosavljevic, D. Gavrilovic, I. Golubicic, S. Jelic
Journal: Journal of Clinical Oncology (2011)

e18046 Background: Advanced NSCLC represents a poor prognosis disease, usually treated with combination chemotherapy, which is of limited efficacy. Median survival of patients (pts) is about 8 to 10 months. The purpose of this study is to analyse clinical pretreatment prognostic factors for survival (OS) and time to progression (TTP), but also the importance of response rate (RR=complete+partial response), as a therapeutic prognostic factor. Methods: 362 pts (318 m/44 f), stage IIIB/IV, performance status (PS) 0-2 (60% in PS0/1) received chemotherapy in four previously conducted clinical studies, with cisplatin dose of 120mg/m2 q 4wks, or carboplatin AUC 5. For the whole group, median number of cycles received was 4 and median survival was 7 months. Results: Univariate and multivariate analyses demonstrated that clinical stage of disease (IIIb vs IV), PS (PS0 vs PS1, PS2) and RR (RR vs SD, PD) are significant prognostic factors for OS and TTP (univariate: p<0.01; multivariate: p<0.05). Age and gender were not statisticaly proven to be of importance, neither for OS, nor for TTP. Landmark time method (on 3 months) was applied to remove the bias for differences in OS by tumor response. After this correction, in Cox model for OS, as independant factors of prognosis, remain PS and RR. HR (95%CI) for SD:RR pts was 1.32 (1.01-1.72) and for PD:RR was 2.12 (1.49-3.00) : risk of death was greater for 32% in pts with stable disease and as much as twice in progressive disease pts, both compared with RR pts (p<0.05). HR (95%CI) for PS2:PS0 pts was 2.07 (1.33-3.22) which confirmed more than twice greater risk of death for PS2 compared to PS0 pts (p<0.05). Based on the Cox model for OS, the probabilities of OS from 1. to 12. month from the beginning of the chemotherapy, were made for 12 different groups of pts obtained by combining patients’ response and PS categories. Among these categories, the best probability of surviving 12 months have SD/PS0 pts (41%), followed by RR/PS0 pts (37%), while PD/PS0 pts have only 14% of probability to survive 12 months. Conclusions: It seems that response to chemotherapy, along with pretretment factors, has an influence on length of survival in advanced NSCLC.
To screen or not to screen: Colonoscopy, a story of successful population-based screening.
Authors: Catalina Mosquera, C. Suzanne Lea, Satomi Imai, Timothy Louis Fitzgerald
Journal: Journal of Clinical Oncology (2016)

508 Background: Screening for neoplasia of the breast and prostate has come under increasing scrutiny. However, little is understood regarding the temporal impact of screening on incidence and mortality for colorectal cancer (CRC). Methods: We selected states that had both CRC screening prevalence estimates from The Behavioral Risk Factor Surveillance System (BRFSS) and cancer registry data from The Surveillance, Epidemiology, and End Results (SEER) data from 1988-2012. We used SEER*Stat to compute age-adjusted incidence and mortality rates by state.Correlation coefficients were computed for change in screening. Results: The states California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, and Utah were included. Each statehad unique population and tumor characteristics for age, gender, race, socioeconomic status, stage of presentation,and location of the primary, &lt; 0.0001. Over the study period for ages 50 +, there was an increase in screening endoscopy (41 to 64%, R2 = 0.77, p &lt; 0.0001) and a slight decrease in fecal occult blood testing (25 to 23%, R2 = 0.28, p &lt; 0.0001). Similar trends were noted by state. There was an inverse relationship between increased screening endoscopy and incidence of CRC (60.03 to 34.68/100.000, R2 = 0.95 and p = &lt; 0.0001); this was pronounced for early disease (45.4 to 25.7/100,000, p = &lt; 0.0001) and minimal for late stage disease (10.5 to 7.2/100,000, p = 0.014). There was comparable trend in mortality (23.27 to 13.47 per 100.000). When evaluating states individually, the association between increasing endoscopic screening and the trends in incidence and mortality were robust (R2 0.75 – 0.92 and R2 0.65-0.95, respectively p &lt; 0.0001). However, when states were analyzed collectively the association of screening with decreases in incidence and mortality was weaker (R2 = 0.27, p = 0.005 and R2 = 0.65, p = 0.06, respectively). Conclusions: Increased screening for CRC coincides with a decrease in incidence and mortality, disproportionality decreasing early stage cancer. This correlation is very strong within states but diminished between states, suggesting factors in addition to creening are influencing the epidemiology of CRC.
A Novel Combination of Chicken Hypersensitive Site-4 Insulator Elements Improves Titers and Restores Full Insulator Activity.
Authors: Paritha Arumugam, Fabrizia Urbinati, Chinavenmeni S. Velu, Tomoyasu Higashimoto, H. Leighton Grimes, Punam Malik
Journal: Blood (2009)
A phase I study of hepatic arterial infusion of oxaliplatin plus intravenous fluorouracil, leucovorin, and bevacizumab in patients with predominant hepatic metastases
Authors: S. Fu, L. Chintala, D. Madoff, D. S. Hong, A. Naing, S. L. Moulder, J. J. Wheler, C. S. Ng, J. Lim, M. Patterson, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

2534 Background: The liver is a common site of metastatic involvement in advanced cancer patients. Hepatic arterial infusion (HAI) displayed benefit on overall and progression-free survival. HAI oxaliplatin plus intravenous fluorouracil (5FU) and leucovorin (LV) was well tolerated and effective in those with inoperable colorectal cancer. Pilot data from our group suggested that this proposed regimen could induce responses in patients who had failed systemic therapy including those with compromised hepatic function. We therefore initiated a formal trial of this regimen. Methods: Cohorts of 3–6 patients with predominant hepatic metastases with serum bilirubin less than 3.0 mg/dL will receive escalating dose of HAI oxaliplatin (ranging from 60 mg/m2 to 150 mg/m2 over 2 hours) followed by the standard LV/5FU2 protocol plus intravenous bevacizumab 10 mg/kg once every 3 weeks. Results: Of enrolled 38 patients, toxicities and responses were evaluated. Six dose levels were escalated. DLT was observed in 2 out of 5 patients receiving HAI oxaliplatin at 150 mg/m2: grade 3 hyperbilirubinemia and grade 4 thrombocytopenia. Additional 11 patients have tolerated HAI oxaliplatin 140 mg/m2 well in the expansion phase. Common adverse events included fatigue, transient hepatic functional abnormality, hypokalemia, and myelosuppresion. Clinical benefits were identified in patients with colorectal cancer, hepatoma, adenocarcinoma of duodenum, ovarian and breast cancer. Conclusions: HAI oxaliplatin at 140 mg/m2 plus the standard LV/5FU2 protocol and bevacizumab 10 mg/kg once every 3 weeks was well tolerated and effective in wide range of hepatic metastases. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmion, Inc. Pharmion, Inc Pharmion, Inc.