bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604).
Authors: Matsuyama Jin , Tamura Shigeyuki , Fujitani Kazumasa , Kimura Yutaka , Tsuji Takeshi , Iijima Shohei , Imamura Hiroshi , Inoue Kentaro , Kobayashi Kenji , Kurokawa Yukinori , Furukawa Hiroshi ,   Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)
Published: February 2017

108 Background: An adjuvant chemotherapy with S-1 has become the standard treatment for patients (pts) with stage II/III gastric cancer (GC) who have undergone gastrectomy with D2 dissection in Japan, but it is assumed that the survival benefit for stage III pts who received S-1 is modest. S-1 plus docetaxel has shown that the response rate and median overall survival (OS) were 56% and 14.3 months in pts with advanced GC. The aims of this phase II study were to evaluate the feasibility and safety of adjuvant S-1 plus docetaxel in pts with stage III GC with D2 surgery. Methods: Pts with pathological stage III GC who underwent gastrectomy with D2 dissection received oral S-1 (80 mg/m2/day) administration for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks (1 cycle). The treatment was started within 45 days after surgery, and repeated for 4 cycles, followed by S-1 administration until 1 year after surgery. The primary endpoint was feasibility of the 4 cycles administration of S-1 plus docetaxel; secondary endpoints were safety, progression-free survival (PFS), OS, and feasibility of S-1 administration until 1 year after surgery. Results: We enrolled 53 pts, 42 males and 11 females with a median age of 65 years (range, 43-78), between May 2007 and August 2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. The feasibility of planned 4 cycles of treatment was 77.4% (95% CI 63.8-87.7%, p < 0.001) with 41 pts out of 53 pts. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. 3 year overall survival was 78.8% (95% CI 68.4-90.7) and 3 year disease free survival was 50.3% (95% CI 34.4-73.3). Conclusions: Adjuvant S-1 plus docetaxel therapy is feasible and has only moderate toxicity in stage III gastric cancer pts. We believe that this regimen will be a candidate for future phase III trials seeking the optimal adjuvant chemotherapy for stage III gastric cancer patients.
Nonsurgical treatments for stage 0-IA squamous esophageal cancer.
Authors: Ito Hitoshi , Itasaka Satoshi , Miyamoto Shinichi , Ezoe Yasumasa , Muto Manabu , Tanaka Eiji , Sakai Yoshiharu , Chiba Tsutomu , Hiraoka Masahiro 
Published: February 2017

113 Background: Surgery has been the standard treatment for operable squamous esophageal cancer. However, radiation therapy/chemoradiotherapy (RT/CRT) or endoscopic resection (ER) could be an alternative treatment option for stage 0-IA (TNM 7th edition) squamous esophageal cancer, because these treatments are less invasive and can preserve the organ. To evaluate the efficacy of surgery, RT/CRT and EC for stage 0-1A squamous esophageal cancer in clinical practice, we reviewed our experience. Methods: From March 2007 to December 2010, 92 patients with stage 0-IA squamous esophageal cancer were treated in our institute. Overall survival, relapse-free survival, and relapse pattern were evaluated according to the initial treatment modality. Results: Of 92 patients (pts), 76 were male and 16 were women. Median age was 65.5 years old. Tis/T1a/T1b:4/36/52. Median follow up time was 29.1(4.7-55.5) months. As an initial treatment, 9 pts received surgery, 27 pts received RT/CRT and 56 pts received ER. Among the pts underwent ER, one patient underwent esophagectomy and 13 pts were received CRT based on the pathological evaluation for the risk of the lymph node metastasis. Two-year relapse free survival and overall survival of surgery, RT/CRT and ER was 77.8%/100%, 68.6%/100% and 89.8%/95.7%, respectively. After completion of initial therapy, local failures (residual or recurrent disease), regional lymph node relapse and distant metastasis and 1 undetermined relapse were observed in 6, 3 and 5 pts, respectively. Eight out of the 15 pts with recurrence could be disease free after salvage therapy. While 4 pts died during the follow up period, all pts died from other diseases and no pts died from esophageal cancer. Overall esophageal preservation rate was 89.1% (82/92). Conclusions: Although longer follow-up was needed, this study showed that non-surgical treatments (RT/CRT or ER) for stage 0-1A squamous esophageal cancer could be an alternative treatment option and could provide a chance of organ preservation. [Table: see text]
Phase I study of imatinib, cisplatin, and fluoruracil in patients with advanced gastric cancer.
Authors: Mayr Martina , Alberter Barbara , Becker Karin , Schmid Roland M. , Ebert Matthias Philip 
Published: February 2017

115 Background: Combination chemotherapies are established as standard treatment in gastric cancer, but prognosis remains poor. Integration of targeted therapies may provide an additional benefit. Imatinib may inhibit platelet derived growth factor (PDGF) mediated tumor growth and amplify effects of chemotherapy. This Phase I study evaluated dose limiting toxicity (DLT) of imatinib in combination with cisplatin and fluoruracil/ capecitabine therapy in gastric cancer. Methods: The study was designed as a 3-patient cohort dose-escalating trial. Patients (pts) received cisplatin (60 mg/m2 d1 q 21) and capecitabine (1250 mg/m2 bid d1-14 q 21) or cisplatin (50 mg/m2 d1, 15, 29 q 50) and leucovorin (500 mg/m2), followed by a 24-hour 5-fluoruracil infusion (2000 mg/m2 d1,8,15,22,29,36 q 50). Imatinib was started d - 4 and continuously administered with the dose being escalated from 300 to 700 mg QD in 100 mg steps. Results: Characteristics of the 35 enrolled pts: Median age= 61 years (range 39-76). Male: female= 27:8. ECOG 0: 21 pts (60%), ECOG 1: 13 pts (37%), ECOG 2: 1 pt (3%). Localization: carcinoma of the gastroesophageal junction 17 pts (48%), gastric body 18 pts (52%). Histology: intestinal 8 (23%), diffuse 10 (28%), not specified 17 (49%). Metastatic disease: 21 pts (60%). At imatinib dose level 1 (300mg) one DLT was observed and three more pts were enrolled without further DLT. No DLT was encountered up to dose level 4. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Immediate surgery was performed on both with good clinical outcome. Therapy was delivered 14 weeks (range 1- 59) on average. Major grade 3/4 toxicities were nausea (6%), anemia (4%), fatigue (6%) and upper GI hemorrhage (3%). Response evaluation at 6 weeks revealed partial response (PR) in 27%, stable disease (SD) in 43% and progressive disease in 13% of the assessable pts. Conclusions: Combination of imatinib and chemotherapy is a well tolerated therapeutic approach with promising activity. A relationship between study medication and the occurred gastric perforations remains disputable. Further investigations are required to confirm the assumed amplification of chemotherapy effects by imatinib.
Potential factors to explain decreased survival for ethnic subgroups with gastroesophageal adenocarcinoma.
Authors: Ostapoff Katherine , Schwarz Roderich , Mansour John C. 
Published: February 2017

12 Background: Few studies focus on the reasons behind the inferior outcomes in Black and Hispanic patients compared to White and Asian patients. We investigated the association between racial survival differences and social, economic, and health systems factors not often included in large national databases. Methods: Tumor registry data were reviewed at a single cancer program from 1999−2009. Patients with gastric or esophageal adenocarcinoma were included. ANOVA and X2 test were used for continuous and categorical variables. Median survival was estimated using the Kaplan−Meier method with log−rank comparison and Cox regression. Results: Of 515 patients with gastric or esophageal adenocarcinoma, 254 (50%) were Black or Hispanic. Overall survival for Black and Hispanic patients was decreased compared to the rest of study population (8.4 vs 11 months,p=0.002). Black and Hispanic patients are more likely to present with metastatic disease (56% vs 38%,p<0.0001) and signet ring cell histology (p<0.001). On univariate analysis, survival was decreased for patients without insurance (p=0.0003) and lower incomes (p=0.02). Black and Hispanic patients were more likely to have the high risk characteristics of lower income (p<0.001) and lack of insurance (p<0.001). On multivariate analysis, only racial background was associated with differences in survival (HR, 1.4; 95% CI, 1.16 to 1.76; p=0.001). For nonmetastatic gastric cancer patients, rates of curative intent surgery were similar between ethnic groups (80% vs 79%). Blacks and Hispanics with Stage 2−4 disease were less likely to receive or be recommended chemotherapy (53% vs 67%,p=0.009). Conclusions: Differences in survival for patients with gastric and esophageal adenocarcinoma are associated with biologic (signet ring histology and metastatic presentation) and social factors (insurance status and income). Black and Hispanic patients are more likely to belong to these poorer outcome groups. In addition, they may be less likely to receive complete multidisciplinary care. Despite controlling for these imbalances, ethnic status remains associated with inferior survival, indicating that additional factors may partake in this phenomenon.
Preliminary result of a multicenter phase II study of chemoradiotherapy with docetaxel for elderly patients with stage II/III esophageal carcinoma.
Authors: Hashimoto Jun , Kotani Namiko , Hokamura Nobukazu , Ito Yoshinori , Katada Chikatoshi , Ishiyama Hiromichi , Tamaki Yoshio , Nakamura Takayuki , Kato Ken 
Published: February 2017

122 Background: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus cisplatin (CDDP) is one of the most common treatment modalities for esophageal carcinoma (EC). However, there are limited data on CRT in elderly patients, and it is difficult for elderly patients to receive chemotherapy with CDDP due to poor organ function. The aim of this prospective study was to clarify the efficacy and safety of definitive CRT with docetaxel in elderly patients. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) EC, PS 0-1, age over 70 years, and no desire for surgical treatment. A total of 40 patients were planned for enrollment. Chemotherapy consisted of 6 cycles of a 1-h infusion of docetaxel (10 mg/m2) repeated weekly. Radiation was concurrently administered to a dose of 60 Gy in 30 fractions. At this time, we evaluate the preliminary data of efficacy and safety of definitive CRT with docetaxel in elderly patients. Results: A total of 16 patients were enrolled between July 2008 and January 2011, at which point, the trial was closed due to poor accrual. The median age was 77 years (range, 73-81); male/female: 14/2; PS 0/1: 4/12; cStage IIA/IIB/III/IV: 3/4/8/1. Fourteen patients (88%) completed the treatment protocol, 1 patient (6%) could not complete the treatment because of severe toxicities, and 1 (6%) refused to continue the treatment. The complete response (CR) rate was 19% (3/16). In this preliminary analysis, the median follow-up time was 17 months. The 1-year survival rate was 87.5%. The most common grade 3 or 4 toxicities were esophagitis (31%), anorexia (13%), leukopenia (6%), neutropenia (6%), thrombocytopenia (6%), mucositis (6%), and infection (6%). No treatment-related deaths were observed. Grade 3 or 4 esophagitis, pleural effusion, pericardial effusion, and pneumonitis developed as late adverse events in 13%, 13%, 6%, and 6% of patients, respectively. Conclusions: This regimen is considered as feasible on hematological toxicities, however slightly toxic on non-hematological toxicities with modest activity. Lower rate of CR seemed to be due to severe esophagitis. Further follow-up is needed to estimate the efficacy of this treatment.
Retrospective analysis of neoadjuvant chemoradiotherapy for esophageal cancer: The Knight Cancer Institute experience.
Authors: Siddiqui Faisal A , Dolan James P. , Hunter John G. , Douthit Miriam A. , Bloker Lisa M. , Holland John M , Thomas Charles R. 
Published: February 2017

126 Background: Neoadjuvant chemoradiotherapy (NAT) followed by esophagectomy has been established as standard of care for early stage (II – III), resectable esophageal cancer (EC). Patients (pts) treated with NAT are more likely to be downstaged and have a complete (R0) resection. Additionally, pts with aggressive disease are more likely to progress during NAT and, consequently, avoid unnecessary surgery. The aim of the current report was to analyze the outcomes of trimodality therapy at the Knight Cancer Institute. Methods: A retrospective study of 124 pts who underwent NAT followed by esophagectomy for EC from 1999-2010 at our institution was performed. All pts were initially staged by imaging (EUS, CT and/or PET imaging) prior to commencing treatment. After esophagectomy, pathological staging was compared to initial staging to determine the effect of NAT. Results: There were 25 women and 99 men. Initial staging is shown in the table below. Patients received cisplatin, oxaliplatin or carboplatin with 5-FU plus concurrent radiotherapy (RT). RT total dose of 45 Gy to the tumor and regional nodes was given in 1.8 Gy daily fractions, followed by a boost to the tumor for final dose 50.4-54 Gy. 27 (21.8%) of the pts had a pathologic complete response. Additionally, 54 (43.6%) pts were downstaged by chemoradiation. Of the pts that had complete remission or were downstaged, pre-treatment clinical stage was Stage II (22 pts), Stage III (55 pts), and Stage IVa (4 pts). Conclusions: NAT was effective in complete remission or downstaging of two-thirds (81) pts, including 4 pts that were initially unresectable (Stage IVa) and successfully underwent subsequent esophagectomy. As has been shown previously, NAT is effective for downstaging prior to esophagectomy making it more likely that pts will undergo R0 resection. This study also demonstrated that some pts with clinically unresectable tumors could undergo successful esophagectomy after NAT. [Table: see text]
Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.
Authors: Shitara Kohei , Yatabe Yasushi , Sugano Masato , Matsuo Keitaro , Kondo Chihiro , Takahari Daisuke , Ura Takashi , Tajika Masahiro , Muro Kei 
Published: February 2017

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.
Comparison of the clinical benefit of an adjuvant therapy in gastrointestinal stromal tumors (GIST) with other adjuvant cancer therapies.
Authors: Deflin Morgan , Parthan Anju , Taylor Douglas , Coombs John , Sasane Medha , Paolantonio Marc 
Published: February 2017

129 Background: Imatinib in the adjuvant setting for GIST has shown significant improvements in recurrence- free survival (RFS) vs placebo. Number needed to treat (NNT) is a useful measure to compare effectiveness across treatments (txts) from a health policy or population perspective. The objective of this study is to compare the NNT for adjuvant imatinib in GIST with other adjuvant cancer txts at both 1 and 3 yrs of follow-up using RFS. Methods: In the absence of a placebo controlled trial for 3 yr imatinib, data from ACOSOG Z9001 and SSGXVIII/AIO trials were used to indirectly estimate NNT for adjuvant imatinib in GIST. Adjuvant txts in other cancer types were identified from published literature. Studies meeting the following criteria were included in the analysis: (1) study population consisted of cancer patients (pts) who underwent surgical resection of the primary tumor and considered cancer-free, (2) a randomized clinical trial conducted in pts in the US or Europe, (3) comparators were either placebo or no txt (4) RFS was reported and showed benefit with the experimental txt. NNT is defined as the number needed to treat to prevent 1 recurrence or death. NNT was calculated as the inverse of the absolute risk reduction (difference in event rate) between the study groups in each trial. Results: 24 adjuvant txts in 8 different cancer types were identified. With longer follow-up (3 yrs vs 1 yr), 62.5% of txts showed a decreased NNT, including imatinib which decreased from 7 (1 yr) to 4 (3 yrs). The largest relative decrease in NNT over time was 91% for trastuzumab & cyclophosphamide (both used for breast cancer). About 25.0% of the txts had an increase in NNT over time. NNT for imatinib was lower than all other txts at 3 yrs of follow-up and lower than all but 2 txts at 1 yr of follow-up (mitomycin + tegafur [gastric cancer, NNT = 5] and gemcitabine [pancreatic cancer, NNT = 4]). About 28.0% and 41.7% of txts had an NNT less than 10 at 1 and 3 yrs of follow up, respectively. Conclusions: Imatinib has one of the lowest NNTs among other adjuvant txts, at 1 and 3 yrs of follow-up. With longer follow-up duration, most adjuvant cancer txts show a decreased NNT.
Effects of chemotherapy for superficial meso and hypopharyngeal cancers with concomitant esophageal cancer.
Authors: Iizuka Toshiro , Kikuchi Daisuke , Hoteya Shu , Kaise Mitsuru , Udagawa Harushi 
Published: February 2017

134 Background: Recently, the frequency of superficial meso and hypopharyngeal cancer (Ph ca) has increased and elucidation of its biological behaviors is needed. There are no reports to analyze if superficial Ph ca responds to chemotherapy. Therefore, the aim of this study was to clarify the effects of chemotherapy for esophageal cancer on superficial Ph ca. Methods: A total of 48 patients and 57 lesions with superficial Ph ca with concurrent esophageal cancer were enrolled from November 2007 to December 2010. Among these, 29 patients and 31 lesions for which no chemotherapy had been administered for the esophageal cancer, and two patients for whom details of the treatment regimen or evaluation after chemotherapy were not available were excluded. So 17 patients with 24 lesions were included. The maximum diameter of the Ph ca was measured before and after the treatment by endoscopy, the lesion was graded as CR, PR, NC and PD, and the response rate (CR + PR) was analyzed retrospectively. Results: All patients were male with a mean age of 61.1 years. The Ph ca was located in the left piriform sinus in 9 lesions, right piriform sinus in 10 lesions, posterior wall of the hypopharynx in one lesion, and mesopharynx in 4 lesions. The mean diameter of the tumor was 16.3 mm. Among the concurrent esophageal cancers, 6 were classified into the superficial type and 11 into the advanced type. For treatment, DCF was administered for 4 patients and 5 lesions, FP for 8 patients and 11 lesions, FAN (doxorubicin + 5FU + nedaplatin) for one patient and two lesions, CPT11 + CDDP for one patient and one lesion, VP-16 + CDDP for one patient and two lesions, and weekly docetaxel for one patient and one lesion. Radiation therapy for concurrent esophageal cancer was administered in 8 cases. As a treatment response, 7 lesions showed CR, 7 showed PR, 9 showed SD, and one showed PD, so a total response rate was 58.3%. Especially for the 15 lesions whose tumor diameter was less than 20 mm, the response rate was 67%. Conclusions: The response rate was 58.3%, which is relatively good. We believe that the results of this study would serve as important indicators for determining the treatment strategy for superficial Ph ca with concurrent esophageal cancer.
Cost-effectiveness of three years of adjuvant imatinib in gastrointestinal stromal tumors (GIST).
Authors: Sanon Myrlene , Parthan Anju , Taylor Douglas , Coombs John , Paolantonio Marc , Sasane Medha 
Published: February 2017

137 Background: Recent clinical trial data have demonstrated that 3 years (yr) of adjuvant imatinib therapy for patients with surgically resected GIST leads to a significant improvement in recurrence free survival and overall survival vs. 1 yr of therapy. The objective of this study is to assess cost-effectiveness of treating with 3 yrs vs. 1 yr of adjuvant imatinib in the US from a payer’s perspective. Methods: A Markov model was developed to predict GIST recurrence, treatment (txt) costs, and quality-adjusted survival over a lifetime horizon. Patients transitioned between 3 health states: recurrence free GIST, GIST recurrence, and death. Monthly recurrence and mortality rates for 3 yr and 1 yr imatinib were derived from SSGXVIII/AIO clinical trial. The 5-yr recurrence rate observed in the trial was extrapolated for the remaining duration of the model horizon. First recurrence after active txt was treated with imatinib 400mg daily (800mg daily if recurrence during active txt). For subsequent disease progression, patients were treated with imatinib 800mg, sunitinib or best supportive care. After 5 years, txt specific mortality rate was applied for patients with recurrence. Costs and utilities were derived from published literature. Expected costs and quality-adjusted life years (QALYs) were estimated for each txt strategy. Costs and QALYs were discounted at 3% per yr. Extensive sensitivity analyses were conducted. Results: Total lifetime cost per patient was $302,100 with 3 yrs vs. $217,800 for 1 yr of imatinib therapy. Patients on 3 yrs of imatinib had higher QALYs (8.53 vs 7.18) vs. 1yr of imatinib. Incremental cost effectiveness ratio of 3 yrs of imatinib vs 1 yr of imatinib was $62,600/QALY. Model results were sensitive to rate of GIST recurrence beyond 5 yrs and monthly cost of adjuvant imatinib. At a threshold of $100,000/QALY, 3 yr imatinib therapy was cost-effective in 100% of simulations vs. 1 yr of imatinib. Conclusions: Model results suggest that treating patients with 3 yrs of imatinib is cost-effective vs. 1 yr of imatinib below the widely used $100,000/QALY threshold. Both clinical and economic results suggest treating surgically resected GIST patients with 3 yrs of imatinib would result in improved quality-adjusted and overall survival.