bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin toxicity and treatment compliance of first-line cetuximab with irinotecan, oxaliplatin, and fluoropyrimidines-based chemotherapy in metastatic colorectal cancer (mCRC): The preliminary analysis of observer study.
Authors: Pinto Carmine , Rosati Gerardo , Lolli Ivan , Ruggeri Enzo , Ciuffreda Libero , Ferrari Daris , Di Fabio Francesca , Chiara Silvana , Tralongo Paolo , Ianniello Giovanni Paolo , Frassoldati Antonio , Tumolo Salvatore , DI Costanzo Francesco
Published: February 2017

530

Background: The ObservEr study evaluated the quality of life (QoL), skin toxicity control and treatment compliance of cetuximab plus first-line chemotherapy in a general cohort of patients with mCRC. Methods: ObservEr is a non interventional, observational, multicenter, prospective study. The primary end point is the evaluation of change in QoL during the period in which a first line treatment chemotherapy is given, with specific focus on the impact of the dermatological toxicity of this treatment. Data on QoL (Dermatology Life Quality Index/DLQI and EORTC QLQ C30) is assessed at baseline weekly for the first 8 weeks of treatment. Results: Between April 2011 and September 2012, the expected 210 patients (pts) were enrolled in 31 Italian centers. This preliminary analysis includes 112 pts enrolled to until April 2012. Pt characteristics were: 77(68.7%) males, 35(31.3%) females; median age 70 years (44-80 years); PS ECOG-0 86(76.8%), ECOG-1 36(23.2%); potentially resectable liver metastasis 32(28.6%); chemotherapy regimen FOLFIRI 55(49.1%), XELIRI 13(11.6%), FOLFOX 22(19.6%), XELOX 10(8.9%), irinotecan 4(3.6%), 5FU/AF (de Gramont) 2(1.8%), others 6(5.4%). The interval time between request and result of KRAS test was 10 days (7-16 days). Prophylactic skin toxicity with vitamin K1 cream was performed in 79(70.5%) pts, and reactive skin toxicity treatment included vitamin K1 cream in 32(28.6%). Grade 1-3 skin toxicity was observed in 87(77.7%) pts, and grade 3 in 10(8.9%). No significant difference in grade 3 skin toxicity was detected between males vs females (10.4 vs 5.7%; p=0.722), age <60 vs ≥60 years (9.7 vs 8.6%; p=1.000), and prophylactic vs reactive treatment (7.6 vs 12.5%; p=0.470). Cetuximab temporary and permanent discontinuation relation to skin toxicity was observed in 15(13.4%) and 2(1.8%) pts, respectively. Conclusions: This results suggest that the introduction of K1 cream in the prophylactic or reactive treatment reduce the incidence of grade 3 skin toxicity with improvement of cetuximab compliance. The results of QoL will be available for the 2013 ASCO GI Meeting. Clinical trial information: ID239.
Locally recurrent colorectal cancer and hepatic metastases: Safety, feasibility, and outcomes after concomitant resection.
Authors: Boostrom Sarah York , Mathis Kellie Leanne , Dozois Eric J. , Nagorney David , Cima Robert R , Larson David W , Wolff Bruce G. , Pemberton John H
Published: February 2017

535

Background: The most effective management of locally recurrent colorectal cancer (CRC) is resection. This is also true for hepatic metastases (HM). Data remains limited, however, regarding concomitant resection of recurrent CRC and HM. The aims of this study were to determine the feasibility, safety and outcomes in terms of disease-free survival (DFS) and overall survival (OS) in patients undergoing concomitant resection of recurrent CRC with HM. Methods: All patients who underwent resection of recurrent CRC from 1/1995 to 1/2007 at Mayo Clinic, Rochester were reviewed (n=406). The study group consisted of patients who underwentconcomitant resection of locally recurrent CRC and hepatic resection for metastatic CRC (n= 45). Kaplan-Meier Survival was used to estimate DFS and OS. Results: The study group consisted of 27 men and 18 women. The median age was 59 years. Surgical management involved pelvic dissection in 43 patients and ileotransverse colectomy in two. 17 patients required resection of contiguous organs. 24 patients received intra-operative radiation. 34 patients underwent multiple hepatic wedge resections, 6 patients segmentectomy, 3 left hepatectomy, and 2 right hepatectomy. There was no perioperative mortality. Morbidity was 37%, 2 patients required re-operation. The 1, 3, and 5 year DFS was 72.2, 42.3, and 18.5%, respectively. The 1, 3, and 5 year OS was 87.7, 47.6, and 36.2%, respectively. Conclusions: Synchronous resection of locally recurrent CRC and HM is safe and feasible; morbidity is reasonable and mortality zero. DFS and OS in this patient population appear comparable to that of patients undergoing separate, staged resections.
Differential HER2 expression in resected gastric cancer: Is there prognostic value?
Authors: Fisher Sarah B. , Fisher Kevin E. , Squires Malcolm Hart , Patel Sameer H. , Kooby David A. , Staley Charles A. , Farris Alton B. , Maithel Shishir K.
Published: February 2017

54

Background: For advanced gastric cancer, the ToGA trial established HER2 as an important therapeutic target in the 20% of patients whose tumors exhibited HER2 overexpression or gene amplification. Others have reported that HER2-positive tumors are associated with poor survival in advanced disease. The expression profile and prognostic value of HER2 in resectable gastric cancer are unknown. Methods: 111 pts underwent curative intent resection of gastric adenocarcinoma between 1/00-6/11 and had tissue available for analysis. Immunohistochemistry (IHC) for HER2 was performed on banked tumor specimens and graded by two pathologists blinded to outcomes utilizing ToGA trial criteria. An IHC score of 0+ or 1+ was regarded as negative, 3+ as positive. Fluorescence in-situ hybridization (FISH) for HER2 was performed on equivocal (2+) IHC samples. Primary outcome was differential expression, secondary outcome was overall survival (OS). Results: Median age was 64 years, 54% were male. Median tumor size was 4 cm, 7.2% had a positive margin, 67.6% were poorly differentiated, 23.4% had perineural invasion, 35.1% had lymphovascular invasion, and 61.3% had nodal metastases. 24 patients had stage I disease (21.6%), 32 stage II (28.8%), and 55 stage III (49.6%). Mean follow-up was 28.9 months, median OS was 27.2 months. HER2 expression by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%). Of the 37 equivocal cases, FISH was positive in 8, for a total of 21 HER2-positive cases (18.9%) and 90 HER2-negative cases (81.1%). HER2 status did not correlate with T or N stage, tumor size or location, tumor grade, or perineural or lymphovascular invasion. HER2 status was not associated with OS (p=0.36). Conclusions: Resectable gastric cancer exhibits differential expression of HER2, similar to that of advanced disease. Despite reports suggesting HER2 positive status is associated with aggressive disease and worse outcomes in the advanced setting, HER2 status is not associated with adverse pathologic factors or survival in resectable disease. Although not prognostic, the predictive value of HER2 status for response to trastuzumab in the adjuvant setting requires further investigation.
Correlation of capecitabine associated hand-foot syndrome (HFS) and objective tumor response in patients with metastatic colorectal cancer (mCRC) treated with sorafenib and capecitabine (SorCape).
Authors: Chan Ellie , Ivey Alison Marguerite , Dang Long H. , Daily Karen Colleen , Hou Wei , Viviano Dana Lynn , Watson Scott , Granicz Renee , McEwan Margaret A. , Yan Hui , Allegra Carmen Joseph , George Thomas J.
Published: February 2017

568

Background: Capecitabine (cape) associated hand-foot syndrome (HFS) has been previously reported to be a clinical predictor of improved survival or disease control in metastatic colorectal cancer (mCRC) and breast cancer. This study evaluates the relationship between degree of HFS and objective tumor response in patients (pts) receiving capecitabine and sorafenib (sor) for mCRC as part of an ongoing clinical trial. Methods: Pts with refractory mCRC treated on phase II prospective study with SorCape (NCT01471353) were eligible. 24 of 43 planned pts have been enrolled and all are assessable. Adverse events (AEs) related to HFS were graded by CTACE v4 during the first 3 cycles of therapy and scored as mild (graded 0 or 1), moderate (mod) (grades 2 or 3) or severe (grade 4). Independent RECIST criteria measurements of target tumor volumes were recorded with maximal volumetric regression or progression noted. The correlation between degree of HFS and objective RECIST response was analyzed. Results: Total cohort pt demographics and tumor characteristics are presented separately. 5 (21%) had mild HFS and 19 (79%) developed mod HFS. No pts had severe HFS. Baseline characteristics including age were similar in both groups. Univariate analysis showed no significant correlation between KRAS mutational status, baseline serum CEA, or LDH levels. Pts with mild HFS had a mean 25% (1-68% regression) tumor regression compared to a 20% progression (22% regression to 80% progression) with moderate HFS (p=0.046). Progression free and overall survival data are immature for analysis. Conclusions: In this exploratory analysis of an ongoing clinical trial, the degree of HFS negatively correlated with objective tumor response. The combination of overlapping HFS AEs with this specific dual therapy may impact the previously reported clinical predictor. Ongoing patient enrollment and further analysis of this clinical observation is planned. Clinical trial information: NCT01471353.
Phase II study of first-line combined chemotherapy bevacizumab with modified RPMI regimen for elderly or frail patients with unresectable or metastatic colorectal cancer (OGSG0802).
Authors: Iwamoto Shigeyoshi , Kato Takeshi , Yoshida Motoki , Miyake Yasuhiro , Nakamura Masato , Satoh Taroh , Sakai Daisuke , Matsuoka Masaki , Otsuji Toshio , Furukawa Hiroshi
Published: February 2017

573

Background: The first-line combined chemotherapy RPMI regimen with bevacizumab (Bmab) in AVF2192g trial for elderly or frail patients (Pts) could be active to progression free survival (PFS), the secondary endpoint, although it may not prolong overall survival (OS), the primary endpoint. According to the results of efficacy and safety studies, a fluoropyrimidine (FU) + Bmab regimen is regarded as an option for 1st-line chemotherapy. We planned a phase II study of modified RPMI regimen with Bmab for elderly or frail Pts. Methods: Pts with confirmed unresectable/metastatic colorectal cancer without previous chemotherapy, and not suitable for intensive chemotherapy were enrolled. Pts received modified RPMI regimen (5-FU 600 mg/m2 and l-leucovorin 200 mg/m2 bolus day 1, 8, 15) and Bmab 5 mg/kg day 1, 15, q4w) until disease progression or study withdrawal. The primary endpoint was overall response rate (ORR), and the secondary endpoints were PFS, OS and safety. Results: 41 Pts were enrolled from 13 institutions. Pts characteristics were; median age 76 (range 56-90); male/female, 18/23; ECOG performance status 0/1/2, 21/19/1. The ORR, the rate of best response, the disease control rate (CR+PR+SD) were 36.6%, 56.1%, 85.4%, respectively. Median follow-up period was 14.4 months. 28 Pts (68%) had objective progression and a patient (2.4%) died without progression. The median PFS and OS were 9.0 months (95%CI, 7.5–19.6) and 24.0 months (95%CI, 20.1–NR). The incidences of grade 3 or 4 adverse events were: leukopenia (7%), neutropenia (24%), thrombocytopenia (2%), diarrhea (5%), anorexia (10%), fatigue (5%), stomatitis (7%) and hypertension (5%). Grade 3 febrile neutropenia and grade 4 pulmonary embolism was observed in one pt. Five pts (12%) discontinued the treatment due to severe or uncontrollable adverse event. Conclusions: The modified RPMI regimen with Bmab showed activity, and was well tolerated for elderly or frail Pts. ORR and the median PFS of this regimen were similar to historical data with FU + Bmab. This regimen may be a good option for not requiring percutaneous port placement Pts. Clinical trial information: UMIN000002182.
CEA response as a predictive marker for response according to RECIST in patients with KRAS wild-type metastatic colorectal cancer (KRAS WT mCRC) (pts) treated with panitumumab monotherapy.
Authors: van Hellemond Irene E. G. , Creemers Geert-Jan , van Warmerdam Laurence , de Jong Floris A. , Koornstra Rutger H. T.
Published: February 2017

574

Background: Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR) and is approved as treatment in KRAS WT mCRC in combination with chemotherapy and in chemotherapy-refractory pts as monotherapy. In mCRC, CEA decrease is often used as an early response predictor, but correlative studies with RECIST and formal cutoff criteria are scarcely available. Here we report on an exploratory analysis in KRAS WT mCRC pts treated with monotherapy panitumumab. Methods: A series of 29 KRAS WT mCRC pts who have been treated with panitumumab monotherapy (6 mg/kg once every 2 weeks) as second-line treatment were included (58% male; mean age 65,6 years; performance status was 0-1 in 90%). Every 12 weeks, response evaluation by CT-scan was done routinely. Responses were determined using RECIST v1.1. CEA levels were determined every 6 weeks. A CEA response was defined as two consecutive CEA decreases of ≥10% compared to the previous value. Progression was defined as two consecutive CEA increases of ≥10% compared to the previous value. Pts not meeting these criteria were defined as stable. CEA change at week 6 and CEA response at week 12 week were correlated with RECIST response at week 12 using Spearman’s correlation coefficient. Results: A 10% CEA decrease at week 6 was predictive for response according to RECIST at week 12 (r=0.71, p<0.001). Likewise, at week 12, responses determined by RECIST and CEA strongly correlated (r=0.88, p<0.001). Conclusions: Data from this small study suggest that CEA changes may have predictive potential as early time point response biomarker in pts treated with panitumumab monotherapy. More research is warranted to confirm these retrospective findings. [Table: see text]
Population-based patterns of systemic therapy use in liver-limited metastatic colorectal cancer (mCRC).
Authors: Kellock Trenton Tyler , Gresham Gillian , Cheung Winson Y.
Published: February 2017

576

Background: Treatment of liver-limited mCRC frequently involves systemic therapy and surgery. Our aims were to 1) explore the use and choice of systemic therapy pre- and post-liver resection and 2) examine if specific patient characteristics or therapy regimens were associated with improved outcomes. Methods: Patients diagnosed with liver-limited mCRC from 2006 to 2007 in British Columbia were reviewed. Summary statistics were conducted to describe surgical and systemic treatment patterns. Kaplan-Meier methodology was used to characterize the relationship between systemic regimen and overall survival (OS). Results: Among 374 patients, 42% were aged ≥70 years, 60% were men, 29/39/32% were ECOG 0/1/2+, 80% had primary tumor surgery, and 68% received prior adjuvant chemotherapy. For liver metastases, 95 (26%) were offered hepatic resection. Compared to those who did not receive surgery, resected patients were younger (median 60 vs. 69, p<0.01), better functioning (ECOG 0/1 86% vs. 55%, p<0.01), and had smaller (median 3 vs. 4 cm, p<0.03) and fewer (median 2 vs. 4, p<0.01) lesions. They also had improved median OS (11.0 vs. 9.4 months, p<0.01). Surgical patients having a solitary lesion (p=0.03) or a largest lesion ≤3 cm (p=0.02) experienced better survival. Performance status (HR=0.54, p=0.35), age (HR=0.47, p=0.30), and sex (HR=0.68, p=0.48) did not impact outcomes. Among patients who underwent hepatic resection, 80% received some form of chemotherapy (Table). Median OS did not differ significantly based on choice of chemotherapy: FOLFOX (13.9 months), FOLFIRI (11.5 months), and capecitabine (10.9 months) (p=0.44) or receipt of bevacizumab: yes (14.5 months) vs. no (11.1 months) (p=0.57). Conclusions: In this population-based cohort of liver-limited mCRC patients, hepatic resection was associated with improved survival. Among those offered some form of peri-operative therapy, FOLFOX, FOLFIRI, and capecitabine, either alone or in combination with bevacizumab, appear to be reasonable treatment options. [Table: see text]
Treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with epidermal growth factor receptor (EGFR) therapy in the third-line setting.
Authors: Ho Maria Yi , Renouf Daniel John , Cheung Winson Y. , Zhou Chen , Goktepe Ozge , Lim Howard John , Kennecke Hagen F.
Published: February 2017

579

Background: Monoclonal antibodies targeting the EGFR improve outcomes of patients with mCRC in the first-, second-, and third-line settings. The optimal treatment setting for use of these agents is not yet defined. In British Columbia, cetuximab and panitumumab are limited to patients with KRAS wild type (wt) mCRC previously treated with 5-fluorouracil (5-FU), oxaliplatin (Ox), and irinotecan (Iri). The objective of this study was to describe the treatment and outcomes of patients with mCRC after the introduction of EGFR targeted therapy in the third-line setting. Methods: All patients with newly diagnosed mCRC and referred to 1 of 5 BC Cancer Agency clinics in 2009 were included. Prognostic and treatment information was prospectively collected while KRAS testing information was determined by chart review. Results: 443 patients with a median age of 66 were included of which 59% were men, 73% received any systemic therapy for metastatic disease of which 13% underwent hepatic resection of metastatic disease. Of 117 patients who received 5-FU, Ox and Iri, 10% were not tested for KRAS. Among those tested, 38% were KRAS mutant. In patients who were KRAS wt, 23% did not receive EGFR therapy. On chart review, poor performance status was the dominant reason for not receiving KRAS testing and anti-EGFR therapy in 67% and 50% of cases, respectively. Median survival of 321 patients who received any systemic therapy for metastatic disease was 22.3 months. Conclusions: In this study, when EGFR therapy is limited to patients with KRAS wt mCRC previously treated with 5-FU, Ox and Iri, only 15% received such therapy and poor performance status was the dominant reason for non-treatment. Earlier initiation of EGFR therapy may increase the proportion of patients treated with all active systemic agents. [Table: see text]
Clinical significance of Fas, VEGF, and EGFR expression in advanced gastric carcinoma.
Authors: Ye Sheng , Rong Jian , Fu Xiaohong , Lin Tongyu
Published: February 2017

58

Background: Researches had proved that apoptotic signal proteins Fas-mediated cellular apoptosis influenced development of gastric carcinoma and affected survival of gastric carcinoma patients. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) over expression had been associated with poor survival in several cancers including gastric carcinoma. Methods: Immunohisto-chemistry was performed to detect Fas, EGFR and VEGF protein expression in 60 newly diagnosed patients with gastric carcinoma in the First Affiliated Hospital of Sun Yat-sen University from November 1999 to June 2005. Clinical Data of these patients were reviewed. Time to progression (TTP) and overall survival (OS) were compared by log-rank test according to the expression status of Fas, EGFR and VEGF. Results: There were 40 males and 20 females, all patients were stage IV. All patients were treated with infused fluorouracil plus leucovorin and oxaliplatin or paclitaxel. The positive rate of Fas, EGFR and VEGF in gastric carcinoma was 73.3%, 35% and 40% respectively. TTP for patients with Fas positive was significantly superior to patients with Fas-negative (p<0.05). EGFR and VEGF were not correlated with TTP (p>0.05). Fas, EGFR and VEGF were not associated with overall survival(p>0.05). Conclusions: Fas, EGFR and VEGF are often expressed in gastric carcinoma. Fas expression is correlated with longer TTP. EGFR and VEGF expression were not associated with TTP. Fas, EGFR and VEGF were not a prognostic factor for OS.
A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study): Reports of interim analysis.
Authors: Suenaga Mitsukuni , Mizunuma Nobuyuki , Matsusaka Satoshi , Shinozaki Eiji , Ozaka Masato , Ogura Mariko , Chin Keisho , Yamaguchi Toshiharu
Published: February 2017

580

Background: Re-introduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens including oxaliplatin, irinotecan and fluorouracil (5-FU) was thought to be effective approach, but has not been prospectively explored. Thus, we performed a single arm, open-label phase II study (UMIN ID: 000004884). Methods: Patients with prior chemotherapy including oxaliplatin and irinotecan, achieved tumor response or stable disease during prior oxaliplatin-based therapy, and six months or over from confirmed progression disease during previous oxaliplatin-based therapy were eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response, partial response or stable disease. This trial followed a Simon’s two-stage minimax design. Interim analysis of efficacy was planned after 12 weeks of treatment in 18 patients (Step I). If disease control were confirmed in more than five patients, 15 patients would be newly enrolled in Step II. Results: Between 01-2011 and 07-2012, 18 patients were enrolled in Step I of this study. Characteristics of patients were as follows (N=18): median age, 61 yrs (range 35-75 yrs); male/female, 11/7; ECOG PS0, 94.4%; and colon/rectum, 8/10. All patients were assigned to receive mFOLFOX6 regimen. Disease control was observed in seven patients. There was no benefit in nine patients. Two patients refused to continue treatment and one patient gave up treatment due to oxaliplatin related allergic reaction. According to the interim analysis, DCR after 12 weeks of treatment was 38.9%. There were no severe adverse events and treatment related deaths. Conclusions: In interim analysis, initial efficacy of reintroduction of oxaliplatin after 12 weeks of FOLFOX regimen was confirmed. Step II part of this study is currently ongoing. Clinical trial information: UMIN000004884.
Clinical application of electrogastrography (EGG) in stomach cancer patients with distal gastrectomy.
Authors: Kim Yong Ho , Choi Sung Il , Song Jae Wook
Published: February 2017

59

Background: Electrogastrography (EGG) is a method of measuring action potentials of the stomach. The purposes of this study were to investigate postoperative changes in the EGG and then evaluated gastric motility and to determine the correlation between EGG and quality of life (QOL) of stomach cancer patients with distal gastrectomy. Methods: This study analyzed 20 cases of stomach cancer patients between May 2010 and Dec. 2010. All patients were measured EGG and QOL at 1, 12, and 24 weeks after the operation. The EORTC quality of life questionnaire QOL-C30 version 3.0 and QOL-STO22 were used in this study to assess QOL of gastric cancer patients. Results: Fasting and postprandial mean dominant frequency at 1 week after the operation were 2.7 and 2.6 cycles per minute (cpm), and 2.9 and 2.7 cpm at 12 weeks. Fasting and postprandial dominant power at 1 week were 36.5 and 36.4 dB, and 36.3 and 40.1 dB at 12 weeks. After postoperative week 12, the mean percentage of normal rhythm in both recordings was not changed, whereas the mean percentage of bradygastria was decreased and tachygastria was increased. Regarding QOL, global health, physical, emotional and social status were improved, but pain, insomnia, diarrhea, and financial status was worsened at 12 weeks. On the STO22, the correlation between the QOL and EGG parameters was not significant (p>0.05). Conclusions: These suggest that EGG is a simple and noninvasive method and may be applicated for evaluating motility and autonomic functions of the remnant stomach after distal gastrectomy.
Final results of a phase II multicenter study of neoadjuvant S-1 and irinotecan in patients with locally advanced gastric cancer.
Authors: Terashima Masanori , Saze Zenichiro , Hosotani Ryo , Takahashi Masahiro , Takagane Akinori , Hachiya Osamu , Koeda Keisuke , Matsui Shigeyuki , Fukushima Norimasa , Kawasaki Hitoshi , Gotoh Mitsukazu , Fukushima Masanori
Published: February 2017

65

Background: Combination chemotherapy involving S-1 and irinotecan (IRI-S) has failed to demonstrate a survival benefit over S-1 alone in metastatic gastric cancer. However, the tumor response rate was significantly higher with I-RIS. Therefore, we evaluated the effect of I-RIS as neoadjuvant chemotherapy for locally advanced gastric cancer. Methods: Patients with locally advanced gastric adenocarcinoma, T3-4, N0-3, M0, for whom curative surgery was planned after neoadjuvant chemotherapy, PS 0-1, with adequate organ function were enrolled in this study. Patients received irinotecan 80 mg/m2 on days 1 and 15 and oral S-1 80 mg/m2/day on days 1 to 21. Treatment was repeated every 28 days for 2 courses. Patients then underwent gastrectomy with lymphadenectomy. After surgery, patients resumed treatment with S-1 alone for 1 year. Results: Of the 39 patients enrolled, 37 were eligible. Two cycles of chemotherapy were completed in 34 patients, and surgery was performed in 33 patients. Of 27 RECIST-evaluable patients, 16 (59%) had a partial response and 9 (33%) had stable disease. Major grade 3 toxicities were neutropenia in 6, anorexia in 4, nausea in 3, diarrhea in 2, and fatigue in 2. Resection was performed in 32 (86%) patients and R0 resection was possible in 20 (54%) patients. The reason for R1/R2 were cy+ in 6, M1(LYM) in 5, M1(PER) in 4, M1(HEP) in 1 and PM+ in 2. Postoperative complications were observed in 13 (39%) patients. There were no treatment-related deaths. Pathological response was observed in 13 of 32 patients (41%); 2 patients had pathological CR. Median survival time was 15.9M and median progression-free survival (PFS) was 5.9M. Overall survival and PFS were significantly better in patients underwent R0 resection (p < 0.0001). Neither objective tumor response nor pathologic response predicted the survival. Conclusions: These results show that neoadjuvant S-1 and irinotecan combination chemotherapy was active and feasible for treating locally advanced gastric cancer. R0 resection is essential to achieve long-term survival. Therefore, careful diagnosis with staging laparoscopy before surgery is mandatory to avoid non-curative operation. Clinical trial information: NCT00134095.
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

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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

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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

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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

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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

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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

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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.