tbuckley/cabot-search huggingface dataset:
Outcomes and patient-related reported urinary toxicity of low dose rate brachytherapy for localized prostate cancer.
Authors: Marshall Meeks, Jeff M. Michalski, Stephanie Subasic Markovina, Todd A. DeWees
Journal: Journal of Clinical Oncology (2016)

29 Background: Brachytherapy (BT) is a common treatment modality for localized prostate cancer (LPCa). Here we report our institutional outcomes and patient-reported genitourinary (GU) toxicity following BT for LPCa. Methods: Medical records of patients with LPCa treated with low dose rate (LDR) BT at our institution from 1997-2011 were reviewed. BT prescriptions were 145 Gray (Gy) and 109Gy for mono- and combined iodine 125 ( 125 I) therapy, and 125Gy and 100Gy for mono- and combined palladium 103 ( 103 Pd) therapy. Biochemical failure was defined by the Phoenix definition. Kaplan Meier curves were used to compare biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). Patient-reported GU toxicity was evaluated by the American Urological Association Symptom Score (AUAS), and results binned into three time intervals, 1, 6, and 12 months post-BT. Repeated measures analysis determined a trend in AUAS score over time. Effect of age as a continuous variable, prostate specific antigen, Gleason score, clinical T stage, combined external beam radiotherapy + BT and use of neoadjuvant androgen deprivation therapy (nADT) on AUAS score was determined. Results: Of 459 patients identified, 400 received BT monotherapy and 8% received nADT. Median follow-up was 5.8 years. Nine-year bRFS, MFS, and OS were 92.8%, 97.9%, and 79.7%. Pretreatment AUAS scores were available for 252 patients. For 69 patients with all four values, median baseline AUAS scores rose from 6 to 14 at one month following BT (p &lt; 0.0001). AUAS scores did not change from one-month to 6 months post-BT (p = 0.99), but decreased to a median of 8 (p &lt; 0.0001) by 12 months post-BT. In the 69 patients with all values, no factors were found significant for change in AUAS scores. For 252 patients with pre-treatment AUAS and at least one additional value (assuming values missing at random), analysis revealed older age and use of nADT were associated with higher AUAS scores at all time points. Conclusions: LDRBT for LPCa offers excellent bRFS, MFS, and OS. AUAS scores rose in the first 6 months following BT but returned to pre-treatment baseline by 12 months post-BT. Older age and nADT use may be associated with higher AUAS scores.
Long-term tolerance of neoadjuvant docetaxel/estramustine chemotherapy in patients with high-risk localized prostate cancer treated at IGR in the GETUG 12 phase III trial.
Authors: Pierre-Olivier Bosset, Laurence Albiges, Agnes Laplanche, Christophe Massard, Yohann Loriot, Mario Di Palma, Karim Fizazi
Journal: Journal of Clinical Oncology (2013)

168 Background: The GETUG 12 phase III trial tested the adjunction of docetaxel-estramustine to standard treatment in 413 patients with high-risk prostate cancer (Eur J Cancer 2012, 48: 209-17). Patients in both arms received androgen deprivation therapy (ADT) for 3 years plus local treatment (radiotherapy: 87%, median dose: 74 Gy). Pts in the chemotherapy arm also received 4 cycles of docetaxel 70mg/m2 /3weeks + estramustine 10 mg/kg/d d1-5, repeated every 3 weeks. Immediate tolerance was acceptable with only 2% of febrile neutropenia and no toxic deaths. As the long-term impact of chemotherapy in this setting is unknown, long-term side effect assessment was undertaken in pts from GETUG 12 who were treated at the Institut Gustave Roussy (n=81). Methods: After pts had completed the planned 3 years of ADT, they were followed-up every 6 months. Data on weight, sexual function, serum testosterone, and cardiac complications were obtained prospectively, in parallel with efficacy data. Pts requiring salvage therapy for cancer progression were censored in this analysis. Results: The median follow-up is 71.6 months (range: 36- 108 months). The main long-term side effects are listed in the table below. 4 (4.9%) and 1(1.2%) cardiovascular events occurred in the ADT and the ADT + chemotherapy arm, respectively. Conclusions: Docetaxel-estramustine chemotherapy had no adverse long-term impact on serum testosterone, weight, and sexual function in patients with high-risk localized prostate cancer treated with ADT and radiotherapy. [Table: see text]
First-line clinical trials and metastatic colorectal cancer: How selected are clinical trial participants?
Authors: Kathryn M Field, Joseph James McKendrick, Jeremy David Shapiro, Jeanne Tie, Susie Bae, Matthew E. Burge, Desmond Yip, Louise M. Nott, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

524 Background: Guidelines recommend that oncology patients have the opportunity to participate in a clinical trial wherever possible. It is purported that as trial participants are often younger and fitter, data extrapolation from trial outcomes to patients seen in routine care may be difficult. We compared characteristics of patients with metastatic colorectal cancer (mCRC) participating in a first-line clinical trial with those treated in routine care. Methods: The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed mCRC comprehensive database, was used to identify patients treated on a first-line trial compared with those receiving combination chemotherapy; single-agent therapy; or no chemotherapy. Data collection began in June 2009 and is ongoing at 15 Australian centres to date. Results: Of 671 patients, 49 (7.3%) participated in a first-line clinical trial. Patients on trial were significantly younger, with 49% (n=24) trial participants being under 60 years, compared with 33% (n=128) receiving combination chemotherapy off study (p=0.047), 13% (n=13) single-agent therapy (p&lt;0.0001) and 10% (n=15) no treatment (p&lt;0.0001). All trial participants were ECOG performance status 0-1, compared with 87% (n=335) of non-trial patients receiving combination chemotherapy (p&lt;0.0001), 80% (n=82) receiving single-agent therapy (p&lt;0.0001) and 52% (n=76) no treatment (p&lt;0.0001). Similarly, Charlson comorbidity score was significantly lower in trial participants, with 88% (n=43) having a score 0-3 (less comorbidity) versus 71% (n=272) receiving combination chemotherapy, 39% (n=40) receiving single-agent therapy and 25% (n=36) no treatment. Preliminary analysis suggests significant overall survival benefit for the clinical trial cohort. Conclusions: Consistent with available literature, trial participants with mCRC are significantly younger, fitter and of better performance status than those who receive similar chemotherapy off-trial or no treatment. The impact of trial participation on survival may be thus subject to multiple factors biasing for a better outcome, including the contributing benefit of younger age and less comorbidity.
Efficacy of erlotinib for CNS relapse in non-small cell lung cancer patients after gefitinib treatment.
Authors: N. Yanagitani, H. Tanaka, E. Miyauchi, I. Motokawa, K. Kudo, F. Ohyanagi, A. Horiike, T. Horai, M. Nishio
Journal: Journal of Clinical Oncology (2010)

e18005 Background: Two active epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib and erlotinib are available for NSCLC patients. In Japan, gefitinib was commonly used as first EGFR-TKI and 30% of non-selected NSCLC patients experienced dramatic tumor regressions with gefitinib. However, the majority of these patients eventually develop disease progression after a median of about 10 months. Because of poor drug penetration, the central nervous system (CNS) is a common relapsed site after gefitinib treatment failure. Another EGFR-TKI, erlotinib was used at 150mg daily dose which is maximum tolerated dose and this setting was higher than setting of gefitinib. Therefore, erlotinib may be still effective for CNS metastases after gefitinib treatment failure. In this study, we evaluated the efficacy of erlotinib in NSCLC patients who had CNS relapse after gefitinib treatment failure. Methods: We identified 27 NSCLC patients who had disease progression of CNS metastases during or after gefitinib treatment and received erlotinib monotherapy. Characteristics of these patients were followed, 24 women and 3 men, median age 60 y.o., PS 0/1/2; 9/11/7, 26 adenocarcinoma/1 large cell carcinoma, 6 smoker/21 non-smoker. Results: Response of CNS metastases with erlotinib treatment was evaluated in 25 of 27 patients. 11 PR, 10 SD and 2 PD of CNS metastases were observed. While response rate (RR) of extra CNS disease was 24%, RR of CNS metastases were 40.1%. Disease control rate (DCR) was 77.8%, respectively. The median duration of erlotinib treatment was 16 weeks. The symptom improvements of CNS metastases were observed in 6 of 27 patients (22.2%). Conclusions: CNS relapse in NSCLC patients after gefitinib treatment may still have tumors that remain sensitive to erlotinib. After gefitinib treatment failure, erlotinib may prolong EGFR-TKI efficacy, especially for CNS relapse. No significant financial relationships to disclose.
Situation analysis of treatment procedures for laryngeal cancer in Japan based on national administrative database of case-mix system.
Authors: Y. Ichimiya, S. Matsuda
Journal: Journal of Clinical Oncology (2010)

e16022 Background: Japanese national administrative database of case-mix system can be important source to reveal the recent circumstances surrounding cancers, considering the volume of data widely collected from all over the country. Methods: We obtained 14,232 discharge data of head and neck cancers between July and December of 2008 from 587 acute care hospitals which participated in the national case-mix project. The database includes various clinical information such as diagnosis, cancer staging, comorbidities, treatment and short term outcome. We analyzed the details of treatment procedures for 2,790 cases (1 case = 1 hospitalization) from 2,319 patients of laryngeal cancer according to the Japanese procedure codes. Results: There were 2,156 male and 163 female patients. The majority were between the ages of 60 and 79 years, and the median age was 69 years (range 22-96). More than half of the newly diagnosed patients were at the early stages (Stage I: 32.7% and Stage II: 22.9% according to UICC TNM classification). Open surgery was performed for 606 cases, endoscopic resection without open surgery (microlaryngectomy mostly) for 781, and other supportive surgical procedures for 280. Radiotherapy (RT) was used for 485, chemotherapy (CT) for 248 and both RT and CT for 506. There were 260 cases who did not receive any surgical procedures or RT/CT. CT was used in 31.6% of cases in the <60 age group, 28.2% in the 60-79, and 14.1% in the >= 80. Among 669 patients who received CT, 394 (58.9%) received a single agent and tegafur/gimeracil/oteracil potassium was the most frequently used (35.8%). Double agents were used for 179 (26.8%), and 138 (77.1%) received the combination of platinum and fluorouracil. Three or more agents were used for 96 (14.3%) and the most common regimen was the combination of cisplatin, fluorouracil and docetaxel. The single agent tegafur/gimeracil/oteracil potassium was more frequently used in the >=70 age group. Conclusions: The most frequent surgical procedure for inpatient due to laryngeal cancer was microlaryngectomy. Chemotherapy was used in 27.0% of the cases and the most frequently used regimen was the single agent tegafur/gimeracil/oteracil potassium. No significant financial relationships to disclose.
Comparison of stereotactic body radiotherapy and conventional external beam radiotherapy in renal cell carcinoma.
Authors: Christopher L. Tinkle, Stephen Lawrence Shiao, Vivian K. Weinberg, Amy M. Lin, Alexander R. Gottschalk
Journal: Journal of Clinical Oncology (2015)

434 Background: Renal cell carcinoma (RCC) is considered a radiation-resistant histology, often with poor response to conventionally fractionated external beam radiotherapy (EBRT). We compared outcomes for patients treated with EBRT versus stereotactic body radiotherapy (SBRT) for RCC. Methods: From 2004 and 2012, a total of 89 patients were treated with either EBRT or SBRT and retrospectively reviewed. Patients with locally recurrent RCC, bone or soft tissue RCC metastases, or primary RCC in a solitary kidney were included. 51 patients received EBRT, while 38 patients received SBRT. The median biologically effective dose (BED), assuming an α/β ratio of 10, was 32.6 Gy 10 for the EBRT group and 48.0 Gy 10 for the SBRT group. Local failure (LC) was defined pathologically or by imaging according to RECIST 1.1 and toxicity reported according to CTCAE v4.0 guidelines. Univariable and multivariable analyses using Cox’s regression model was performed to determine predictors of local control. Results: Median follow up from RT was 9.8 mo (range: &lt;1-73 mo) with EBRT and 19.7 mo (range: &lt;1-61 mo) with SBRT (p=0.26). EBRT patients were younger (p=0.02) and more were M1 (p=0.04), yet other baseline features did not differ significantly. Total RT dose, dose/fraction, and BED 10 were significantly higher in the SBRT group (p≤0.002 for each), while number of fractions was significantly fewer (p&lt;0.001). The 1-year LC estimate was 88% (95% CI, 72-96%) with SBRT and 50% (95% CI, 32-65%) with EBRT (p=0.001), with no significant difference in rate of distant recurrences (p=0.37). The 1-year progression free survival (PFS) and overall survival (OS) between the EBRT and SBRT groups were 17% (95% CI, 8-29%) vs. 39% (95% CI, 24-54%) (p=0.06) and 39% (95% CI, 25-52%) vs. 82% (95% CI, 65-91%) (p=0.002), respectively. The use of SBRT was the most important independent factor significantly predictive of local control on multivariable analysis (p=0.001, LLR test; HR=0.29, 95% CI, 0.13-0.61), while neither age nor metastasis at diagnosis was predictive. No drade 3-4 toxicity was observed in either RT group. Conclusions: The data support that SBRT improves local control over standard fractionation schemes. Higher dose per fraction, with a BED in the range of 48 Gy 10 , is a safe and effective local treatment modality for RCC.
Clinicopathologic comparison of resected pulmonary adenocarcinoma according to the <i>EGFR</i> mutation status.
Authors: T. Yano, T. Yoshida, Y. Morodomi, K. Ito, A. Haro, Y. Shikada, R. Maruyama, M. Takenoyama, Y. Maehara
Journal: Journal of Clinical Oncology (2011)

e17524 Background: Gene mutations of epidermal growth factor receptor (EGFR) are largely limited to tumors in never smokers, light smokers, and adenocarcinoma. The presence of this gene mutation is the clinical indication for the administration of EGFR-tyrosine kinase inhibitors. The present study compared the clinicopathologic features of surgical pulmonary adenocarcinoma according to EGFR mutation status. Methods: The medical records of 102 patients with EGFR mutation status-known adenocarcinoma who underwent a complete resection from 2008 through 2010 were reviewed for the clinicopathologic variables. The patients ranged in age from 37 to 85 years old with a mean of 67.3. The male:female ratio was 44:58. The EGFR mutation positive -negative ratio was 45:57. Results: The comparison between the EGFR mutation positive and EGFR mutation negative patients in various clinicopathological variables is summarized in the table.Significant differences were observed in gender, smoking status, pleural invasion, and histological differentiation. No difference was observed in the postoperative recurrence-free survival associated with the EGFR mutation status (p=0.124). Conclusions: No remarkable difference was found in the potential of tumor extension, although there were significant clinicopathologic differences between the patients with an EGFR mutation positive status and those with an EGFR mutation negative status. Variables Positive (n=45) Negative (n=57) P value Age (mean + SD) 66 + 8.5 68 + 9.9 0.374 Gender (female : male) 36 : 9 23 : 34 <0.01 Never smoker : ex-smoker 31 : 14 15 : 42 <0.01 PET-SUVmax (mean + SD) 4.3 + 3.85 5.9 + 4.80 0.112 Diameter (mean + SD) 2.4 + 1.02 2.8 + 1.56 0.084 Vascular invasion (+/-) 12 : 33 18 : 39 0.589 Lymphatic permeation (+/-) 5 : 40 7 : 50 0.856 Pleural invasion (+/-) 4 : 41 15 : 42 0.025 Differentiation (G1/G2/G3) 33 : 11 : 1 29 : 18 : 10 0.018 pT (T1 : T2 : T3-4) 34 : 10 : 1 36 : 19 : 2 0.480 pN (N0 : N1: N2) 37 : 4 : 4 50 : 3 : 4 0.711
Coamplification of receptor tyrosine kinases and downstream targets in Japanese gastric cancers.
Authors: Arnaldo Neves Santos Silva, Jordy Coffa, Yohei Miyagi, Varsha Menon, Daniel Bottomley, Lindsay C. Ward, Toru Aoyama, Jeremy D. Hayden, Tomio Arai, Iain BeeHuat Tan, NianTao Deng, Xiu Bin Chan, Suling Joyce Lin, Patrick Tan, Takaki Yoshikawa, Ilse Zondervan, Suvi Savola, Heike I. Grabsch
Journal: Journal of Clinical Oncology (2014)

41 Background: Amplifications of receptor tyrosine kinases genes (RTKs), EGFR, ERBB2, FGFR2, MET, have been associated with the pathogenesis and progression of gastric cancer (GC). Recent studies have found that coamplifications of RTKs are rare in GC. Two phase III trials using RTK targeted therapy have failed to achieve survival benefit in GC patients. Co-amplification of RTKs and downstream targets genes (DSTs), PIK3CA, KRAS, MYC, CCNE1 may be related to resistance to RTK targeted therapy. We tested the hypothesis whether RTKs and DSTs genes are coamplified in GC. Methods: DNA and RNA were extracted from 221 GC from the Kanagawa Cancer Center Hospital (Yokohama, Japan). Copy number of EGFR, ERBB2, FGFR2, PIK3CA, KRAS, MYC, CCNE1 was investigated by a newly developed multiplex ligation dependent probe amplification (MLPA) assay. RNA expression of the same genes was measured using the NanoString platform and compared to DNA copy number status. The frequency of RTK and DST co-amplifications was established and related to KRAS mutation status. Results: RTK amplification was associated with high levels of RNA expression except MYC (all p&lt;0.05). 68% of GC had no RTK amplification. 9% of GC had RTK amplification and no DST amplification. 10% of GC had RTKs co-amplified. 23% of GC had RTK and DST co-amplified. There was no overlap between KRAS mutations and amplifications of KRAS, PIK3CA, FGFR2 or MET. Conclusions: This is the first study reporting that RTK and DST co-amplification are more frequent than RTK co-amplification in GC. These results indicate that GC patients considered for RTK targeting therapy might require DNA copy number assessment of RTKs as well as key DSTs and KRAS mutation testing in order to identify those patients who benefit most from treatment.
Quality indicators of end-of-life cancer care: What rate is right?
Authors: Lisa Catherine Barbera, Rinku Sutradhar, Fred Burge, Kim McGrail, Konrad Fassbender, Beverley Lawson, Reka Pataky, Alex Potapov, Stuart Peacock, Anna Chu, Ying Liu, Hsien Seow
Journal: Journal of Clinical Oncology (2014)

57 Background: Many publications use administrative health care data to describe quality of care indicators at the end of life (EOL). However, very little is available to help decide on optimal rates for these indicators. The purpose of this abstract is to develop data-driven and achievable benchmark rates for EOL quality indicators using administrative data from 4 provinces in Canada. Methods: Five quality indicators of EOL care were defined and measured using linked administrative data for each of the 33 regions across British Columbia, Alberta, Ontario and Nova Scotia. These were: emergency department (ED) use, intensive care unit (ICU) admission, physician house calls (MD) and nursing visits at home (RN) prior to death, and death in hospital (DH). First, an empiric benchmark was defined by determining indicator rates among the top ranked regions to include the top decile of patients overall. Second, funnel plots were used to graph the age and sex adjusted indicator rates for each region along with the overall average value and 95% confidence limits (CL) that accounted for region size. Results: There was significant variation in rates for each indicator among the regions. Minimum and maximum rates for ED, ICU, RN, MD and DH varied approximately 2 to 4 fold across the regions with MD showing the greatest variation. Benchmark rates based on the top decile performers were: ED 34%, ICU 2%, MD 34%, RN 63%, DH 38%. With the exception of ICU, funnel plots demonstrated that mean indicator rates and their 95% CL were uniformly worse than these benchmarks even after adjusting for age and sex. Additionally, few regions met the benchmark rates. Conclusions: There is significant variation in EOL quality indicators across regions in 4 provinces in Canada. The combination of these two methods allows each region to determine its performance relative to both a benchmark and the overall average. As a result, each region is then able to gauge their performance with greater context which facilitates priority setting and resource deployment. These two methods demonstrate how decreasing variation and striving for a target can drive quality improvement. Deriving benchmark values from ‘real world’ data offers the advantage of realistically achievable targets.
Fluorodeoxiglucose (FDG)-avidity at positron emission computed tomography/computed tomography (PET/CT) during adjuvant hormone therapy (HT) in patients (pts) with breast cancer (BC).
Authors: S. Redana, A. Gucalp, C. Ghiotto, L. Vinante, G. Zago, M. N. Fornier, L. Evangelista
Journal: Journal of Clinical Oncology (2011)

e21172 Background: Reduced FDG avidity in metastasis of BC pts receiving HT may suggest a lower sensitivity of PET/CT in the detection of disease recurrence in these pts. We aim to evaluate the impact of HT on glucose metabolism of metastatic lesions with FDG PET/CT imaging in BC pts. Methods: We retrospectively evaluated imaging and charts of 166 BC pts scanned with PET/CT at a median time of 4 years (range 1-26) from primary surgery. The main indications for PET/CT were: persistent elevation of tumor markers and clinical suspicion of relapse. The diagnostic accuracy of FDG PET/CT was computed according to standard method. The mean difference between the groups was assessed using Student's t test, whereas categorical data were compared with chi-square. Significance was set at p<0.05. Results: 142/166 (86%) received adjuvant HT and were included in the analysis. At the time of PET/CT scan, 89 (63%) pts were still on HT and 53 (37%) had completed HT. PET/CT was positive in 60 patients, 29 (33%) on HT and 31 (58%) off HT. PET/CT was negative in 82 pts, 60 on HT and 22 off HT. After a median follow-up of 8.5 months (range 1-25), disease relapse was clinically and radiologically confirmed in 50/142 (35%) pts; 22/89 (25%) vs. 28/53 (53%) pts on and off HT, respectively p<0.001.PET/CT yielded true-positive results in 81% and 82% of pts with and without HT, respectively (p=not significant (NS)); whereas it failed to identify disease relapse in 4/60 and 5/22 pts (18% and 19%, p=NS; on and off HT, respectively). Furthermore, no differences for mean value of the maximum Standardized Uptake Value (SUV max) for visceral and non-visceral metastatic sites between pts with and without HT were reported (Table). Conclusions: The diagnostic accuracy of FDG PET/CT in BC pts on adjuvant HT vs those who have completed therapy appears equivalent. These preliminary results suggest that the glucose metabolism is not altered by hormonal suppression. Further evaluation is warranted. SUV max PET/CT sites On HT Off HT P value Skeletal (n=29) 7.3±3.0 7.7±3.9 NS No visceral (skeletal + lymph node + soft tissue) (n=55) 7.8±6.7 7.3±3.9 NS Visceral (n=30) 6.4±3.4 6.4±3.2 NS