bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of docetaxel (DTX) and S-1 as neoadjuvant chemotherapy for potentially R0 advanced gastric cancer.
Authors: Emi Yasunori , Oki Eiji , Saeki Hiroshi , Morita Masaru , Kusumoto Tetsuya , Matsuura Hiroshi , Shimokawa Mototsugu , Kakeji Yoshihiro , Baba Hideo , Maehara Yoshihiko 
Published: February 2017

74 Background: This trial sought to evaluate the efficacy and safety of preoperative chemotherapy with DTX plus S-1 for advanced gastric cancer with poor prognosis even after R0 curative resection. We show the 2 years follow-up data. Methods: Preoperative staging was confirmed by laparoscopy. Eligibility criteria included 1) negative peritoneal cytology, H0, P0 and M0, 2) possible curative resection, and 3) ECOG PS 0-1. Patients received DTX (35 mg/m2) on days 1 and 15, and daily oral administration of S-1 (80 mg/m2/day) for days 1–14 every 4 weeks of 2 courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). A sample size of 45 was planned for the expected pRR of 40% and threshold value of 20%, with one-sided alpha of 0.05 and beta of approximately 0.1. Results: A total of 47 patients were centrally registered between November 2007 and November 2009 from 14 centers. All patients were eligible for analysis. The median age was 63 (range 37–79); male/female: 36/11; PS0/1:41/6; and clinical stage IIIA/IIIB: 31/16. The target pRR was 47% (90%CI, 34–60%; p<0.0001). Forty six patients (98%) underwent surgery, in whom curative resection was performed in 44 patients, and 37 patients completed the protocol treatment. The response to preoperative chemotherapy was PR/SD/PD/NE in 16/24/2/5 with a response rate of 34%. The rate of 2 years and 3 years DFS were 53.9%, and 49.3%, respectively. The rate of 2 years and 3 years Overall survival were 69.6%, and 55.1%, respectively. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42%), febrile neutropenia (4%), grade 2 anorexia (21%), and fatigue (15%). Major operative morbidity included pancreatic fistula (9%), abdominal abscess (11%), pneumonia (2%), and anastomotic leakage (0%). No patients died due to surgical complications. Conclusions: The combination of DTX and S-1 was well tolerated and promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer. Clinical trial information: UMIN000000875.
The impact of positive margins on outcome among patients with gastric cancer treated with radiation.
Authors: Schoenfeld Jonathan D. , Wo Jennifer Yon-Li , Mamon Harvey J. , Kwak Eunice Lee , Mullen John Thomas , Enzinger Peter C. , Blaszkowsky Lawrence Scott , Ryan David P. , Hong Theodore S. 
Published: February 2017

81 Background: Positive surgical margins (PM) have been associated with worse outcomes in gastric cancer patients. We sought to evaluate the impact of PM among a modern cohort of gastric cancer patients treated with radiotherapy (RT), some of who also received epirubicin-based chemotherapy (CTX). Methods: We performed a retrospective analysis of patients with gastric adenocarcinoma treated at Massachusetts General Hospital from November 2005 and the Dana-Farber Cancer Institute from August 1998 through 2010. All underwent definitive surgery and RT and were followed through July 2012 for recurrence and survival. We assessed associations with PM using Chi-Squared tests and Cox proportional hazard models. Results: We followed 91 patients for a median of 42 months (interquartile range, IQR 15 – 61 months). Median age at surgery was 60 years (IQR 49 – 68 years). Seven patients were treated with neoadjuvant RT; 84 received adjuvant RT a median 88 days after surgery (IQR 73-108 days). Thirty-three patients received epirubicin-based CTX including 8 perioperatively and 25 postoperatively. PM were identified in 22 patients (24%), including two patients (25%) who received epirubicin-based CTX perioperatively (p = 0.95 versus no perioperative epirubicin-based CTX) and in no patients (0%) who received neoadjuvant RT (p = 0.19 versus adjuvant RT). There were 41 recurrences and 26 deaths. PM were associated with an increased crude risk of overall recurrence (36% versus 73%; p = 0.003). Adjusting for age, positive lymph nodes, pT stage and tumor differentiation, PM were associated with an increased hazard for time to recurrence (HR 2.3; 95% CI 1.2 – 4.3; p = 0.02) and marginally increased hazard for time to all-cause mortality (HR 2.2; 95% 0.9 – 5.2; p = 0.08). Conclusions: We confirm PM following surgical resection of gastric adenocarcinoma are associated with increased risk of recurrence and a trend towards reduced survival, despite aggressive multimodality therapy including RT and, in some cases, epirubicin-based CTX. These findings suggest that strategies that maximize the likelihood of achieving negative margins at the time of surgery, such as neoadjuvant chemoradiation, should continue to be evaluated.
Different recurrence pattern after neoadjuvant chemoradiotherapy compared to surgery alone in esophageal cancer patients.
Authors: Plukker John Theodorus , Smit Justin , Guler Sahin , Beukema Jannet , Mul Veronique E. , Burgerhof Johannes , Hospers Geke A. 
Published: February 2017

82 Background: Neoadjuvant chemoradiotherapy (CRT) is currently considered standard treatment in esophageal cancer patients who are eligible for surgical resection with curative intent. Objective was to evaluate the recurrence pattern after neoadjuvant CRT in patients with esophageal cancer. Methods: We analyzed the results and recurrence patterns from a single center (N=152) in a propensity score matched study between patients treated with neoadjuvant CRT (N=44) and surgery alone (44 from the 108),in the period 2002-2010. Patients treated with neoadjuvant (CROSS schedule) carboplatin/paclitaxel and 41.4 Gy radiotherapy, were compared with a historical cohort of patients with curative intended surgery alone. Surgery was performed through a transthoracic approach with 2-field lymphadenectomy. Results: After matching, the baseline characteristics were equally distributed between both groups (table 1). The response to CRT was 63%, with a pathological complete response of 26%. After a median follow-up of 23 months (7-74 months), lung was the most common site of distant recurrence (16%, N=7), followed by distant lymph nodes (11%, N=5) in the neoadjuvant CRT group, whereas skeletal metastases were the most common site of distant recurrence (18%, N=8), followed by skin or soft tissue (16%, N=7) in the surgical alone group. The estimated 3 and 5 year overall survival was 62% and 55% in the neoadjuvant CRT group, compared to 37% and 31% in the surgery group (Log-rank test: P=0.018). The estimated locoregional free recurrence survival (LRFS) after 3 and 5 years was 79% and 68% in the neoadjuvant CRT group, compared to 44% and 40% in the surgery alone group (Log-rank test: P=0.049). The estimated distant recurrence free survival (DRFS) was 63% and 54% after 3 and 5 years in the neoadjuvant CRT group, compared to 50% and 35% in the surgery alone group (Log-rank test: P=0.314). Conclusions: This neoadjuvant CRT regimen significantly improved oncological outcome compared to surgery alone. An important shift in recurrence pattern was observed from relatively high locoregional recurrences (LRFS) to relatively more distant recurrences (DRFS) in the CRT group compared to the surgery alone group.
Early decline of CA125 to chemotherapy in advanced gastric cancer with peritoneal effusion.
Authors: Ando Takayuki , Hosokawa Ayumu , Ueda Yuko , Yoshita Hiroki , Ueda Akira , Mihara Hiroshi , Hasumoto Yuushi , Fujinami Haruka , Kajiura Shinya , Nishikawa Jun , Ogawa Kohei , Tsukioka Yuji , Kobayashi Takashi , Horikawa Naoki , Sugiyama Toshiro 
Published: February 2017

97 Background: Serum cancer antigen 125 (CA125) has been shown to be elevated in gastric cancer with peritoneal effusion, and to be a biomarker for monitoring the efficacy of chemotherapy in ovarian cancer. Therefore, we retrospectively evaluated the hypotheses that an early decline of CA125 to chemotherapy predicted the response of peritoneal effusion and survival in advanced gastric cancer with peritoneal effusion. Methods: CA125 concentration was measured at baseline and 4 to 7 weeks after induction of chemotherapy. The patients whose CA125 decreased at least 25% after chemotherapy were categorized as a decline group, and the other patients were defined as non-decline group. Baseline peritoneal effusion was classified in three levels with CT scan: none; mild; severe. Mild effusion was localized in the pelvic cavity or surface of the liver, and severe effusion was extended throughout the abdominal cavity. CT scan was followed every 2 months after chemotherapy, and the response in peritoneal effusion was defined to decrease at least one level. The median PFS and OS were also evaluated in two groups. Results: 121 advanced gastric cancer patients were assessable for analysis of CA125 concentration between April 2006 and April 2012. In 59 patients with a baseline CA125 below the upper limit of normal (ULN), 16 patients (27%) had peritoneal effusion, and in 75 patients with a baseline CA125 equal to above ULN, 54 patients (73%) had peritoneal effusion (P < 0.0001). Baseline characteristics of 54 patients with effusion and elevated CA125 were as follows: median age = 63 years (range 38-81), male : female = 38 : 16, PS 0-1 : 2-3 = 35 : 19, diffuse: intestinal = 40 : 14, mild effusion : severe effusion = 41 : 13. In 26 patients of the decline group, the response of effusion was 45%, the median PFS was 146 days, and the OS was 308 days. In 28 patients of the non-decline group, the response of effusion was 4%, the median PFS was 67 days, and the OS was 192 days. There were significant differences in response of peritoneal effusion (P = 0.001), PFS (P = 0.0002), and OS (P = 0.005). Conclusions: Early decline of CA125 has potential clinical utility in predicting favorable response and survival to chemotherapy in advanced gastric cancer patients with peritoneal effusion.
Bone health among prostate cancer survivors: Long-term follow-up from the Prostate Cancer Outcomes Study (PCOS).
Authors: Morgans Alicia Katherine , Fan Kang-Hsien , Koyama Tatsuki , Albertsen Peter C. , Goodman Michael , Hamilton Ann S. , Hoffman Richard M. , Stanford Janet L. , Stroup Antoinette M. , Derleth Christina Louise , Penson David F. 
Published: February 2017

106 Background: Bone complications of androgen deprivation therapy (ADT) have been described using administrative databases and smaller prospective studies with relatively short follow-up. Prospectively acquired data with long term follow-up are lacking. We assessed the relationship of patient-reported bone health and ADT exposure in a population-based prospective cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. Methods: Using PCOS 15 year patient-reported survey data, we identified men with non-metastatic prostate cancer diagnosed from 1994-1995 and followed through 2009-2010. We evaluated subgroups receiving >1 yr, ≤1 yr, and no ADT. We then queried participants regarding the development of osteoporosis, fracture, and use of osteoporosis medications. We assessed the relationship between duration of ADT and bone health outcomes using univariable logistic regression models, and evaluated the association between ADT and osteoporosis medications using multivariable logistic regression adjusted for PSA and geographic location. Results: Among 961 men who completed 15 year surveys, 157 received >1 yr ADT, 120 received ≤1 yr ADT, and 684 did not receive ADT. During the study period, 12 men developed bone metastases and were excluded from the fracture analysis (7 received >1 yr ADT, 2 received ≤1 yr ADT, and 3 did not receive ADT). Men receiving >1 yr ADT were more likely to report osteoporosis (OR 4.29, 95% CI 2.38-7.71) or fracture (OR 1.73, 95% CI 1.04-2.89) than men not receiving ADT. When compared with men not receiving ADT, men receiving >1 yr ADT were more likely to report bone mineral density testing (OR 4.59, 95% CI 3.09-6.83), and bone medication use (OR 3.22, 95% CI 2.19-4.72). Half (50.3%) of men treated for >1 yr ADT reported bone medication use. Among men who reported use of bone medications, 94% reported calcium or vitamin D use and 6% reported bisphosphonate use. Conclusions: Men treated with prolonged ADT (>1 yr) reported higher rates of osteoporosis and fracture at 15 year follow up. Accordingly, they reported more frequent screening and treatment for osteoporosis, with 50% of men receiving prolonged ADT reporting use of bone medications.
Utilization and cancer detection by U.S. prostate biopsies (2005-2011).
Authors: Olsson Carl A. , Kapoor Deepak A. , Mendrinos Savvas E. , Anderson Ann E. , Bostwick David G. 
Published: February 2017

107 Background: To assess the positive biopsy rate and core sampling pattern in patients undergoing prostate biopsy in the US at a national reference laboratory and pathology laboratories integrated into urology group practices and analyze the relationship between positive biopsy rates and number of specimen vials per biopsy (sv/b). Methods: For the years 2005-11, we collected pathology data from a national reference laboratory (NRL) including number of urologists and urology practices referring samples, total specimen vials submitted per prostate biopsy, and final diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia or atypical small acinar proliferation. Over the same period, similar data was gathered from urology practices with in-house laboratories performing global pathology services (urology practice labs, UPL) identified by a member survey of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials/biopsy were calculated in aggregate and separately for each site of service. Results: From 2005-11, 437,937 biopsies were submitted in 4,230,129 vials (9.4 sv/b); overall positive biopsy rate was 40.3%, identical at both the NRL and UPL (p=0.97). Nationally, the number of specimen vials/biopsy increased sharply from a mean of 8.8 during 2005-8 to 10.3 from 2009-11 (difference 1.5 sv/b, p=0.03). For the most recent 3 year period (2009-11), there was no significant difference between the NRL (10.0 sv/b) and UPL (10.6 sv/b) (p=0.08). Positive biopsy rate correlated strongly (p<0.01) with number of specimen vials/biopsy. Conclusions: The positive prostate biopsy rate of 40.3% is identical across sites of service. Although there was a national trend towards increased specimen vials/biopsy from 2005-11, from 2009-11 there was no significant difference in specimen vials/biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10-12 unique specimen vials has been adopted by urologists across sites of service and can be considered the de facto national standard of care.
Comparision of survival rates of patients (pts) with localized prostate cancer (T1-2N0M0) treated with brachytherapy (BT) and external beam radiation therapy (EBRT): Surveillance Epidemiology and End Results (SEER) database review.
Authors: Tesfaye Anteneh A. 
Published: February 2017

124 Background: Unlike in localized prostate cancer with low recurrence risk features, the role of BT in localized prostate cancer with intermediate and high risk features is not well defined. The aim of this study is to compare the survival rates of such pts treated with BT & EBRT using the SEER database in the 3 different risk levels. Methods: The 1973-2009 SEER database was reviewed for men with T1-2N0M0 prostate cancer treated with radiation therapy alone between 2004-2009. Pts with additional malignancies and combination radiation therapy were excluded. Localized Prostate cancer was stratified into low (T1, T2a and PSA<10 and Gleason ≤6), intermediate (T2b or PSA=10-20 or Gleason =7) and high (T2c or PSA >20 or Gleason ≥8) risk for recurrence. Results: A total of 73,867 pts were retrieved from the database, of which 24,661 (33.4%) were treated with BT and 49,206 (66.6%) with EBRT. Pts treated with BT had younger median age, lower PSA, Gleason’s score, and T staging than EBRT. Five year overall survival (OS) and cancer specific survival (CSS) rates are shown in the table. On multivariate analyses, T staging, PSA level, Gleason’s score and type of radiation therapy were independent prognostic factors for 5 year CSS & OS. In pts with localized prostate cancer, those treated with EBRT had 47% higher odds of dying from prostate cancer compared to those treated with BT at the end of 5 years. (HR (95% CI) =1.47 (1.113-1.94); p=0.007). Conclusions: In patients with localized prostate cancer treated with radiation alone, BT is seen to have superior 5 year OS over EBRT in all 3 risk levels. BT also has superior 5 year CSS in low and high risk levels, while being comparable in intermediate risk levels. Prospective randomized controlled trials are needed to validate this finding. [Table: see text]
Rate of hot flashes in patients with advanced prostate cancer treated with GTx-758.
Authors: Yu Evan Y. , Gittelman Marc , Keane Thomas E. , Tutrone Ronald , Belkoff Laurence , Bass Joel , Chu Franklin , Gambla Mike , Gaylis Franklin , Bailen James , Getzenberg Robert H. , Coss Christopher , Hancock Michael L. , Dalton James T. , Steiner Mitchell S. 
Published: February 2017

129 Background: When androgen deprivation therapy (ADT) for prostate cancer was first developed, life expectancy for men with advanced disease was short and the systemic effects were of limited relevance. GTx-758 is a selective ERα agonist that effects serum total testosterone (T), free T, SHBG and PSA. Herein we compare the effects of GTx-758 and leuprolide on hot flashes, one of the common side effects in men on ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Utilizing a standardized instrument to measure the frequency and severity of hot flashes, data was compiled at baseline, day 28 and day 90. The number of men experiencing hot flashes were those reporting any in the period between the respective time point and the prior patient visit. All p values describe the comparison of both GTx-758 treatment groups to the leuprolide treated men. Results: At the baseline, there were no significant differences in the number of men reporting hot flashes in any of the treatment groups (p=0.065). The percentage of men who experienced a hot flash while receiving leuprolide increased significantly to 60.4% (p<0.0001) by Day 28 and increased further to 80.9% (p<0.0001) by Day 90. Although some subjects experienced hot flashes while receiving GTx-758, these men were a significantly lower percentage, 18.8 and 5.6% at the 1000 mg and 2000 mg doses of GTx-758 respectively at day 90. As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion and not all of the men on the study reached the 90 day treatment date (99 evaluable). Conclusions: Men with advanced prostate cancer, receiving GTx-758 experienced a greater than 4-fold reduction in their reported hot flashes at day 90. Since hot flashes are a major side effect that impacts the quality of life in men on ADT, the ability to significantly decrease their likelihood would seem to be of great benefit. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed that will determine if similar effects on serum free testosterone, PSA and hot flashes can be shown with a lower rate of VTEs. Clinical trial information: NCT01326312.
Early response assessment and bone flare phenomenon on 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in patients (pts) with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone acetate.
Authors: Burgio Salvatore Luca , Matteucci Federica , Menna Cecilia , Caroli Paola , Moretti Andrea , Bianchi Emanuela , Rossi Lorena , Kopf Barbara , Masini Carla , Fabbri Francesca , Amadori Dino , De Giorgi Ugo 
Published: February 2017

134 Background: In this prospective study, in patients with CRPC previously treated with docetaxel, we evaluated prostate specific antigen (PSA) and FCH-PET/CT for early response assessment to abiraterone acetate, and assessed frequency of early FCH-PET/CT discordant with PSA and clinical response. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was repeated after 4-6 weeks and a CT scan was done after 3 months of abiraterone acetate. FCH-PET/CT bone flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist’s report indicating progressive disease (PD) in context of a ≥50% decline in PSA, no PD at 3-month CT scan, with FCH-PET/CT improvement or stability 2-3 months later. Results: Three of 29 patients treated with abiraterone acetate did not perform the follow-up FCH-PET/CT due to rapidly PD with a decline in performance status. Of the remaining 26 patients, 4 are still undergoing early response evaluation. Twenty two pts, median age was 71 yrs (range, 57-86 yrs) were evaluable for this analysis. A ≥50% PSA decline was observed in 15/22 (68%) evaluable pts. Undetectable PSA levels (≤0.1 ng/mL) occurred in one case. Early FCH PET/CT response assessment was as follows: complete response (n=2, 9%), partial response (n=7, 32%), stable disease (n=3, 14%), PD (n=10, 45%), but in 4 of 10 pts with PD a bone flare phenomenon on FCH PET/CT was observed. PSA decline ≥50% and FCH PET/CT response correlated in 19 of 22 pts (86%). Conclusions: Discordant findings between serologic PSA response and increases in early FCH-PET/CT bone lesion intensity are reported here for the first time in CRPC. Further investigation is needed to clarify the confounding effect of FCH-PET/CT bone flare on patient management and interpretation of results.