tbuckley/cabot-search huggingface dataset:
Rectal toxicity after permanent iodine-125 seed implantation: Nationwide cohort study in Japan (J-POPS).
Authors: Norihisa Katayama, Atsunori Yorozu, Shinichiro Maruo, Shinsuke Kojima, Toshio Ohashi, Nobumichi Tanaka, Shiro Saito, Takushi Dokiya, Masanori Fukushima, Hidetoshi Yamanaka
Journal: Journal of Clinical Oncology (2014)

73 Background: The purpose of this report is to describe acute and late rectal toxicities and to evaluate factors associated with rectal toxicity in permanent seed implantation (PI) patients enrolled in a nationwide cohort study in Japan. Methods: A total of 2,339 patients in 46 institutes were evaluated. They were treated in the nationwide cohort study entitled Japanese Prostate Cancer Outcome Study of Permanent I-125 Seed Implantation (J-POPS) during the first two years, until June 2007. Rectal toxicities were evaluated using the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, which were obtained at 3, 12, 24, and 36 months after completion of radiotherapy. The odds ratios (OR) of factors associated with greater than or equal to grade 2 rectal toxicity were calculated using a logistic regression model, and the 95% confidence intervals (CI) were estimated. Results: Greater than or equal to grade 2 rectal toxicities were seen in 2.8% of all patients (1.7% in the PI monotherapy group and 6.4% in the external beam radiation therapy [EBRT] combination therapy group). On multivariate analysis, among all patients, greater than or equal to grade 2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100) (OR, 1.93; 95% CI, 1.39–2.68) and EBRT addition (OR, 3.00; 95% CI, 1.39–6.32). R100 in the PI monotherapy group (OR, 1.67; 95% CI, 1.06–2.64), and R100 (OR, 2.07; 95% CI, 1.30–3.30) and interactive planning (OR, 0.46; 95% CI, 0.23–0.92) in the EBRT combination therapy group were also associated with greater than or equal to grade 2 toxicity. Greater than or equal to grade 2 toxicity was seen in 3.7% and 1.4% of patients with R100 greater than or equal to 1 ml and R100 less than 1 ml, respectively, in the PI monotherapy group (OR, 2.78; 95% CI, 1.28–6.05) and in 14.1% and 5.4% of patients with R100 greater than or equal to 1 ml and R100 less than 1 ml, respectively, in the EBRT combination therapy group (OR, 2.88; 95% CI, 1.28–6.45). Conclusions: Rectal toxicity was relatively limited compared to other reports. For Japanese PI patients, R100 should be less than 1 ml, both in PI monotherapy and in EBRT combination therapy, and interactive planning should be performed for EBRT combination therapy.
Using information technology to improve cancer care.
Authors: Amy Tarnower, Barbara S. Kraft
Journal: Journal of Clinical Oncology (2012)

322 Background: Since 1996, the U.S. federal government has passed several laws aimed at improving the health care system, specifically health care quality, safety, and efficiency. Among these laws is the Health Information Technology for Economic and Clinical Health (HITECH) Act, enacted as part of the American Recovery and Reinvestment Act of 2009, which mandates the adoption and meaningful use of information technology (IT) for clinical purposes. The HITECH Act further defines meaningful use objectives as Improving Quality, Safety, Efficiency; Engaging Patients and Families; Improving Care Coordination; Improving Public and Population Health; Ensuring Privacy and Security for Personal Health Information. To meet the adoption requirement, the University of New Mexico Hospital system implemented Powerchart by Cerner in 1999. In addition, the UNM Cancer Center (UNMCC) implemented MOSAIQ by Elektra in 2010. Both meet Meaningful Use requirements. This abstract describes how UNMCC improves clinical quality with these two IT systems. Methods: UNMCC uses Powerchart to capture patient data such as charting, medications and test results. MOSAIQ is used to manage the patients therapy orders. Because these IT systems capture all patient data and treatment plans, clinic physicians have access to all the information when making treatment decisions either in the clinic or in the hospital. Additionally, UNMCC uses continuous quality assessments to design appropriate clinical process interventions and to document safety and accuracy improvements in patient care. Results: In the 18 months since implementing both IT systems and continuous assessments, UNMCC can demonstrate the following improvements in quality of patient care: Fewer clinic errors in ordering lab tests, dispensing medication, billing, and modifying chemotherapy doses; Improved authorization processes with insurance providers, resulting in more timely consultations with patients; Optimization of molecular tests ordered and performed, resulting in cost savings; Reductions in staff and overhead. Conclusions: By using IT as part of its clinical quality systems, UNMCC has achieved overall improvements in patient care.
Relationship of duration of androgen blockade and response to antiandrogen withdrawal: A retrospective study.
Authors: I. Nunez, C. Suarez, R. Morales, M. Gallén, J. Planas, X. Maldonado, C. M. Valverde, C. Serrano, J. Morote, J. Bellmunt, J. Carles
Journal: Journal of Clinical Oncology (2011)

e15104 Background: Patients with progressive prostate cancer treated with androgen blockade, might achieve prostate-specific antigen (PSA) decline or stabilization after discontinuation of antiandrogen treatment. This phenomenon is called antiandrogen withdrawal response and is often associated with clinical improvement. Methods: PSA response of 170 patients from two different centers was retrospectively analyzed. Eligible patients had progressive prostate cancer during treatment with androgen blockade (orchiectomy or LHRH agonist plus antiandrogen). Patients were stratified according to Gleason grade (≤6 vs >6), stage at diagnosis (II, III, IV), type of antiandrogen (bicalutamide, flutamide or steroidal antiandrogens) and duration of treatment blockade (≤12 or >12 months). Clinical benefit (CB) was defined as a confirmed PSA decline ≥50% or stabilization for ≥3 months. Results: Median age was 71 years (range 48 - 91). One hundred forty-one patients had a Karnofsky performance status (K PS) ≥ 80%. Of the 170 patients, 108 (63.5%) had PSA progression after antiandrogen withdrawal and 62 (36.5%) had PSA stabilization or decline. No significant correlation between stage, Gleason grade or K PS and CB was found. Ninety-eight (57.6%) patients had previously received bicalutamide, 52 (30.6%) flutamide and 20 (11.8%) steroidal antiandrogens. CB after antiandrogen withdrawal was observed in 37.8% (37/98), 44.2% (23/52) and 10% (2/20) of patients in the group of bicalutamide, flutamide and steroidal antiandrogens respectively (p=0.024). Longer duration of antiandrogen blockade was associated with CB: 40.5% (53/131) of patients who had received more than 12 months of antiandrogen blockade vs 23.1% (9/39) among patients who had received ≤ 12 months (p=0.0478). Median duration of response was 7 months (range 3 – 52). Conclusions: In patients with progressive prostate cancer, antiandrogen withdrawal may be a useful maneuver resulting, in some cases, in prolonged responses. According to this study, duration of androgen blockade treatment and use of non steroidal antiandrogen may predict a favorable response to antiandrogen withdrawal.
A Phase I/II trial of weekly gemcitabine with celecoxib and thalidomide for patients with advanced pancreatic cancer
Authors: J. J. Densmore, J. R. Fox, G. Kannarkat, J. K. Morgan, G. Petroni, T. Blount, K. Sullivan, M. E. Williams
Journal: Journal of Clinical Oncology (2005)

4241 Gemcitabine-based combination regimens have been utilized in the treatment of advanced disease with minimal effect on survival. VEGF and COX-2 overexpression in pancreatic tumor tissue suggest that an anti-angiogenic agent such as thalidomide and a COX-2 inhibitor such as celecoxib may improve response. Addition of celecoxib (C) to thalidomide (T) and gemcitabine (G) was therefore evaluated in a Phase I/II trial. Methods: Twelve patients with unresectable, locally-advanced or metastatic adenocarcinoma of pancreas were enrolled in Phase I/II trial of weekly G(1,000mg/m2) on days 1 and 8 every 21 days. Patients received C 400mg PO BID and T 200mg PO QHS and titrating to 300mg PO QHS if tolerated after one week. C and T were started 2 weeks prior to the first dose of G and continued throughout the treatment. To assess possible response from C and T alone, tumor markers CEA and CA19–9 were followed prior to initiation of G and throughout the course of therapy. Patients were followed closely for major toxicities including neutropenia, renal failure, gastrointestinal hemorrhage, thrombotic events, thrombocytopenia, peripheral neuropathy, somnolence, and rash. Therapy was held or discontinued if significant toxicities developed or if disease had progressed upon clinical or radiographic evaluation. Results: Twelve patients were enrolled. Mean age was 57 years (range 45 to 72) with ECOG status 0,1, or 2 at initiation. Mean number of cycles received was 2.3. Five patients were noted to have a partial biochemical response to C and T alone as evidenced by a decrease in CA19–9 levels. No radiographic responses were noted, although several patients had improvement in metastatic disease or stable disease. Mean survival of patients from time of diagnosis was 10 months. Toxicities included 3 patients with a skin rash and 1 patient with pulmonary embolism. Conclusions: The partial biochemical CA19–9 response of advanced pancreatic cancer to oral C and T alone or in combination with G in a significant fraction of patients suggests anti-tumor activity. Measureable radiographic responses from the combination of G, C and T appear to be no better than single agent G, but the regimen was well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Tumor shrinkage during VEGF inhibitor therapy as an independent predictor of PFS and OS in renal cell carcinoma (RCC).
Authors: Viktor Gruenwald, Jonas Busch, Steffen Weikert, Christoph Seidel
Journal: Journal of Clinical Oncology (2013)

423 Background: Response to VEGF targeted therapies has been recently shown to be an important prognostic and predictive marker in metastatic RCC. However, whether the extent of tumor shrinkage (TS) correlates with distinct clinical outcome remains unknown. We investigated the role of early TS fractions on median progression free survival (PFS) and median overall survival (OS). Methods: Tumor evaluations according to RECIST 1.1 were performed within 3 months (mo) of targeted therapy with a VEGF inhibitor in 108 patients (pts). Pts were then categorized in fractions of TS: a) -100% to -60%; b) -60 % to -30% and c) -30% to 0% or gain in tumour size: d) 0% to +20% and e) &gt; +20%. Kaplan-Meier and log-rank analyses were performed to estimate PFS and OS with a landmark set to 6 mo. Multivariate Cox proportional hazard model was utilized for evaluation of prognostic factors. Results: First-line VEGF inhibition achieved a PFS of 10.6 mo (95% CI 8.7 – 12.5) and an OS of 29.8 mo (95% CI 23.9 – 35.6) in all pts. 5 pts achieved a complete remission (4.6%), 28 pts a partial remission (25.9%), 52 pts. stable disease (48.2%), and 23 pts. had progressive disease (21.3%) as best response. In univariate analyses histology (clear cell differentiation vs. others) and TS were associated with PFS (p = 0.026; p &lt;0.0001) and OS (p = 0.017; p = 0.009). Multivariate analyses confirmed the relevance of TS as a prognostic variable for OS (p = 0.021; HR 1.49) and PFS (p = &lt;0.001; HR 1.91). Conclusions: TS is an independent predictive and prognostic marker in first-line treatment with VEGF inhibitors in mRCC. [Table: see text]
Adjuvant chemoradiotherapy in 450 patients with gastric cancer: The multicenter retrospective study.
Authors: M. Kucukoner, A. Isikdogan, M. Bilici, S. B. Tekin, D. Uncu, B. Cetin, F. Dane, M. Inanc, M. A. Kaplan, K. Cayir, S. Buyukberber, N. Ozdemir, N. S. Turhal, M. Ozkan, A. Inal, S. Aksoy, M. Benekli
Journal: Journal of Clinical Oncology (2011)

e14623 Background: The use of adjuvant therapy for resectable gastric adenocarcinoma has become standard, after the publication of the Intergroup (INT)-0116 data. The aims of this study are to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 450 patients with gastric cancer. Methods: This retrospective analysis included 450 patients from 6 Medical Centers between 2003 and 2009. The patients with resactable gastric cancer and stage IB-IV (M0) and who had completed the adjuvant chemo-radiotherapy were evaluated retrospectively. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. The survival was calculated with the Kaplan–Meier and life table method. Total overall survival (OS), disease-free survival (DFS), 1, 2, 3 and 5-year survivals were determined. Results: Of 450 patients were 67.8% (n=305) men and 32.2% (145) women, and median age 57 years (range 26-85). According to Lauren classification, intestinal, diffuse and unknown types were 28%, 26.4%, and 45.6%, respectively. According to TNM staging system, T1 and T2 were 29%; T3 and T4 were 70.9 %. N0, 1, 2 and 3 were 14.2%, 42.6%, 35.4% and 7.9%, respectively. Relapse rate was %49.3. Loco regional recurrences rate, distant metastasis and unknown relapse were 13.4%, %24.2 and 62.4 % of the relapsing patients, respectively. In intestinal and diffuse types, DFS medians were 48 and 21 months (p: 0.002) and OS medians were 53 and 22 (p: 0.001), respectively. In T1, T2, T3 and T4 stages, DFS medians were 96, 57, 23, and 19, and OS medians were 96, 73, 26 and 22,respectively (p: 0.001). In N0, 1, 2 and 3 stages, DFS medians were 78, 36, 26, and 9, and OS medians were 72, 37, 28 and 15, respectively (p: 0.001). For all patients, the medians of OS and DFS were 34.4 and 33.1 months, and OS rates were 82%, 62%, 48%, 35%, and DFS rates was 74%- 57%-43%-32% in 1, 2, 3 and 5-year, respectively. Conclusions: This study shows that OS and DFS results were similar to the results of INT-0116 and adjuvant chemo-radiotherapy is still standard treatment in patients with operable gastric cancer.
Molecular studies support the association between germ-line genetic variants in the vascular endothelial growth factor (VEGF) pathway and survival in non-small cell lung cancer (NSCLC) patients.
Authors: D. M. Glubb, W. Zhang, K. Owzar, C. Jiang, O. Mirza, S. Kashyap, W. Rzyman, J. Jassem, F. R. Hirsch, R. Dziadziuszko, F. Innocenti
Journal: Journal of Clinical Oncology (2011)

7059 Background: The VEGF-pathway plays an important role in angiogenesis and is a therapeutic target. Germline genetic variation in this pathway has been associated with disease prognosis but variants with established molecular function are lacking. Thus, we have selected putatively functional variants in the VEGF-pathway genes for testing their association with progression-free survival (PFS) in NSCLC patients. Methods: We selected 11 single-nucleotide polymorphisms (SNPs) in 23 genes of the VEGF-pathway (www.pharmgkb.org) due to their association with gene expression in lymphoblastoid cell lines (Paré-Brunet et al., AACR 2008;#4332), and a further 21 SNPs were identified from the literature and bioinformatics. These 32 SNPs were genotyped in 154 Caucasian stage I-III NSCLC patients by TaqMan. Associations with PFS were tested by Cox regression using an additive model and controlling for disease stage. SNPs were also examined for association with gene expression in tumor samples from a subset of patients and luciferase assays. Results: Five SNPs in KRAS, two in FLT1, one in HIF1A and one in VEGFA associated with PFS (p<0.05, additive model). For three of these variants, the associations were supported by a correlation with gene expression. VEGFA -1154GG genotype patients had greater median PFS (55.3 months) than AG (14.6) and AA patients (11.0; p<0.05), and 39% lower VEGFA tumor expression than AG/AA patients (p<0.05). KRAS 26478TT patients had shorter PFS (5.8) than CT (11.6) and CC patients (25.6; p<0.02), and 175% greater KRAS tumor expression (p<0.01) than CT/TT patients. KRAS 9489GG genotype patients had greater PFS (39.0) than GA (25.7) and AA patients (9.1; p<0.01), and the G allele was associated with a 50% reduction of KRAS promoter expression in luciferase assays (p<0.01). Conclusions: In this exploratory study, we have identified germline variants in the VEGF pathway which associate with PFS in NSCLC. Molecular studies have supported these associations, which seem to be mediated through an effect on gene expression. This study proposes novel prognostic germline markers for testing in future studies.
Treatment and outcomes of goblet cell adenocarcinomas (GCAs) of the appendix.
Authors: Erica Tsang, Yarrow Jean McConnell, David Schaeffer, Lawrence Lee, Siham Zerhouni, Kimberly Schaff, Caroline Speers, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2015)

551 Background: GCAs are rare mucinous neoplasms with mixed epithelial and endocrine differentiation, which behave more like mucinous adenocarcinomas than appendiceal neuroendocrine tumors. Optimal therapy is poorly described. Objectives of this study were to define prognostic factors and describe management of patients presenting with stage I-IV disease. Methods: Patients diagnosed with GCAs between 1990-2010 were identified from the British Columbia province-wide cancer registry and linked to an electronic pathology archive. Pathology was reviewed in 79 of 87 cases where archival tissue was available. Treatment and outcome data were obtained from the BC Cancer Agency, GI Cancer Outcomes Unit, and Provincial Pharmacy databases, combined with chart review. Kaplan Meier survival analysis was used to compare outcomes. There were insufficient events for robust multivariate analysis. Results: 87 cases of appendiceal GCAs were identified for an annual population incidence of 0.2/200,000. Median age was 54 (range 25-91) years, and 42 (48%) were male. There were no stage I patients. For stage II-III (n=68) and stage IV (n=19) patients, median overall survival (OS) was 42.8 and 15.4 months, respectively (p=0.009). Of stage II-III patients, 51 (76%) underwent right hemicolectomy and 9 (16%) received adjuvant chemotherapy: 5-FU (n=5), 5FU/oxaliplatin (n=4). Median recurrence-free survival (RFS) was 38.2 months (10 recurrences: 9 peritoneal, 1 hepatic). Univariate analysis demonstrated no prognostic effect of adjuvant chemotherapy, surgical approach (hemicolectomy vs. appendectomy), T4 tumors, number of nodes resected, or lymph node positivity. 5-year RFS was 90.2% in patients who presented with appendicitis, compared to 63.7% in those without appendicitis (p=0.016). Of 19 patients with stage IV disease, 10 (63%) received palliative chemotherapy including FOLFOX (n=4), FOLFIRI (n=1), FOLFIRI/bevacizumab (n=2), and capecitabine (n=2). Only high mitotic rate was associated with reduced OS. Conclusions: GCAs are rare tumors and the majority present with non-metastatic disease. Presentation with metastatic disease carries a poor prognosis and chemotherapy agents used for advanced colorectal tumors are most commonly applied.
Temozolomide and thalidomide in the treatment of advanced melanoma, a phase II study
Authors: I. R. Okeke, D. A. Laber, T. Bev, K. M. McMasters, D. M. Miller
Journal: Journal of Clinical Oncology (2005)

7573 Background: Temozolomide and thalidomide (TT) are active agents in the treatment of melanoma. The optimal dose and schedule have not been defined. Methods: Temozolomide was administered at 75 mg/m2/day for 6 out of 8-weeks cycle. Thalidomide was given at 200 mg daily for the first two weeks and increased by 100 mg/day weekly up to a maximum of 400 mg/day without interruption. Responses were assessed every 2 cycles by using the RECIST guidelines. Results: From May 2002 through December 2004, 30 patients with advanced and symptomatic melanoma were enrolled. 17 subjects are evaluable for toxicity and 9 for response. Median age 59.3 years (39–79), PS 1 (0–2). Sites of metastasis: 3 skin, 8 lymph nodes, 4 brain, 3 liver, 2 bones, 3 adrenals, 15 lungs, 1 kidney, 2 spleen, 1 heart 2 mesenteric and 1 tongue. Prior therapies: 5 surgeries (3 local, 2 brain), 2 brain radiotherapy, 3 adjuvant interferon, 7 biochemotherapy, 2 vaccine. 47 cycles of TT have been administered (range 1–8 cycles). 70% of the patients received the maximum thalidomide dose whereas 17% had dose reduction due to fatigue and neuropathy, the rest could not be escalated. Out of 9 patients, 1 had a complete response after 2 cycles, 1 partial response, 1 stable disease after 2 cycles and 6 patients progressed after 1 cycle of TT. Toxicity grade 3: anemia 5%, thrombocytopenia 17%, thromboembolic disease 5% and shingles 5%; grade 2: constipation 17%, fatigue 17%. 1 patient with brain metastasis developed seizures attributed to a low level of antiepileptic and 1 had gastrointestinal bleed due to gastric melanoma. No other hematologic or non-hematologic toxicities were observed. Results will be updated for the meeting. Conclusions: TT is an active and well tolerated treatment for patients with advanced melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering
Outcomes of patients with late relapse metastatic renal cell carcinoma treated with targeted therapies: A single-institution experience.
Authors: Kamal Kishore Mandalapu, Marc Ryan Matrana, Teja Poosarla
Journal: Journal of Clinical Oncology (2015)

498 Background: Approximately 20-30% of patients (pts) with renal cell carcinoma (RCC) develop recurrence after treatment of localized disease. Of these pts, the great majority recur within the first few years following surgery. Rarely, late recurrences are seen after 5 years of disease free survival. The outcome of metastatic RCC has improved markedly with targeted therapies (TT). Little data are available about outcomes of pts with metastatic RCC from late recurrences who are treated with TT. Methods: We retrospectively reviewed records of consecutive pts with metastatic RCC who had late recurrence &gt;5 years and were treated with TT between 11/1/2006 and 11/1/2013. All the pts had prior nephrectomies. Outcomes were tabulated using basic statistical techniques. Adverse events (AEs) were graded using CTCAE v4.0. Results: 24 pts (100% clear-cell, median age 69 years, 83% males, all with prior nephrectomies) met inclusion criteria with late recurrence &gt;5 years. 79% had favorable risk and 21% intermediate risk by MSKCC criteria. 11 pts died. Estimated median overall survival time for all pts was 50.2 months (95% CI: 23.93–NR) .The 3-year overall survival rate was 71.78% (95% CI: 47.98-84.77). The median number of sequential TT received was 2 (range 1-4). Median time on first line TT was 20.7 months. 45% of pts received pazopanib in the frontline setting, 29% received sunitnib, and 25% received sorafenib. 68% received TT in the second-line and subsequent settings. Common adverse events of TT included fatigue (52%), diarrhea (36%), hypertension (36%), anorexia (28%), hair and skin changes (24%), increased liver function tests (20%), nausea/vomiting (16%), and 95% of adverse events were grade 1/2. Conclusions: In this retrospective study, pts diagnosed with metastatic RCC after disease free interval &gt;5 years have prolonged survival when treated with TT. Overall survival and 3-year survival rates were better than historical controls. Adverse events were mild/moderate and manageable.