bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of end of life cancer care in the elderly population in Qatar: A retrospective cohort study.
Authors: Hassan Azza Adel , Allam Ayman , Jacob Cicy Mary
Published: February 2017

87

Background: Managing cancer in the elderly ( ≥ 65 years of age) is quite challenging as a result of associated comorbidities, poor performance status and the expected lower tolerance to treatment. The aim of the present study is to report on the demographics of cancer in the elderly population at NCCCR, also to analyze different indicators constituting End of Life (EoL) care in this subgroup of patients. Methods: Elderly patients ( ≥ 65 years of age) presenting with cancer diagnosis to NCCCR between January 01, 2009 till December 31, 2013 constituted the cohort study group. Their medical records were reviewed for the following items: Diagnosis, Performance status, age, comorbidities, treatment received, place of death, Length of Stay (LOS) during last hospitalizations as well as aggressiveness of care at EoL. Patients were then subdivided into 3 age groups: 65-74 years (n = 175), 75-79 years (n = 63) and ≥ 80 years (n = 54). Results: The most common diagnosis was colorectal cancer (42%, 35% and 46% in the 3 age groups respectively). The palliative ward was the most common place of death (43%, 46% and 36% respectively) followed by Medical ICU (26%, 14% and 20% respectively). The median survival from the date of admission in last hospitalization was not different in the 3 age groups (9.4 days vs 9.11 days vs 8.8 days respectively). There was no statisticallly significant differences between the 3 age groups as regards any of the 6 indicators of aggressive care. However, a high percentage of ICU admissions (ranging between 20% - 29%) was reported across all age groups. Conclusions: Colorectal cancer is the most common type of cancer in elderly population in Qatar. Admission to ICU in the last month of life was high, ranging between 20-29%. The mean LOS of last hospitalization was short ranging between 8.8 - 9.4 days. These findings would warrant the development of a needed community palliative care service that would allow this group of patients to receive their EOL care at home, rather than in hospital.
Stereotactic body radiation therapy and patient-reported quality of life prospectively evaluated in patients with unresectable or recurrent pancreatic cancer.
Authors: Rosati Lauren M. , Cheng Zhi , Robertson Scott P. , Kummerlowe Megan N. , Hacker-Prietz Amy , Wolfgang Christopher Lee , Pawlik Timothy M. , Le Dung T , Zheng Lei , Laheru Dan , Herman Joseph M.
Published: February 2017

92

Background: The impact of fractionated stereotactic body radiation therapy (SBRT) on patient-reported quality of life (QOL) and physician-reported toxicity in patients with recurrent or locally advanced pancreatic cancer (PCA) was prospectively evaluated. Methods: Forty-two PCA patients were treated with 25-33 Gy using SBRT in 5 fractions on a single-institution study. Both patient- and physician-reported outcomes were evaluated prior to SBRT and 4-6 weeks post-SBRT. Eight outcomes were consistently evaluated among both groups—performance status, fatigue, pain, anorexia, nausea, vomiting, constipation, and diarrhea. Patient-reported QOL metrics were assessed using a 4-point Likert scale on the EORTC QLQ-C30 and QLQ-PAN26, while physician-reported toxicities were graded using the NCI CTCAE version 4.0. Comparisons between those with paired patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT were made using the Wilcoxon signed-rank test. Results: Of the 42 patients currently enrolled onto the study, 29 had both patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT. Fifty-five percent were female and 83% were Caucasian. The median age at diagnosis was 65.6 years (range, 40.8-86.6). There was no significant impairment of any of the 8 physician-reported toxicities, nor were significant changes observed in patient-reported overall health (p = 0.66) or QOL (p = 0.18) scores following SBRT. Patients felt less worried about their future health (mean change [mD] = -0.45, p = 0.02), and an improvement in feeling less attractive as a result of disease and treatment reached borderline significance (mD= 0.31, p = 0.09). However, patients felt limited in planning activities in advance (mD= 0.45, p = 0.02) and were more constipated (mD= 0.38, p = 0.01) 4-6 weeks post-SBRT. Conclusions: Although the numbers are small, patients with unresectable or locally recurrent PCA do not appear to suffer any detriment of overall health or QOL after receiving a five-day course of SBRT. Moreover, this regimen may lead to a more optimistic point of view on future health and/or level of physical attraction. Clinical trial information: NCT01781728.
Quality of life and its correlates after pelvic exenteration for gynecologic cancer.
Authors: Donovan Kristine A. , Albizu-Rivera Alexandra , Chon Hye Sook , Wenham Robert Michael
Published: February 2017

93

Background: Pelvic exenteration (PE) has been performed historically in women with gynecologic cancer for palliation of recurrent disease. With advances in operative methods, PE in the well-selected patient can produce 5-year survival rates as high as 60%. Despite a recent increase in rate of PE performed with curative intent, there is a paucity of data on its long-term physical and emotional effects. We sought to characterize women’s long-term quality of life (QOL) and its correlates after PE for recurrent gynecologic cancer. Methods: We conducted a mixed methods study combining quantitative measurement of QOL and its demographic, clinical and psychological correlates with concurrent qualitative assessment to probe women’s cognitive and behavioral responses to PE. Results: From 2005 to 2014, 85 women underwent PE at our institution; 44% were still alive at study initiation. Among eligible women, 72% completed their participation. Mean age of the sample at time of study participation was 57.3 (SD = 9.5) years (range = 43 to 75) and median time since surgery was 3.0 years (range = .9 to 8). Women’s self-reported global QOL score was average (54.4 (23); range = 33.3 to 100) and the relationship between QOL and current age or time since surgery was not significant (p > .05). Women reported mild sleep disturbance, mild to moderate pain, moderate fatigue and anxiety and severe depressive symptoms. All of the women exceeded the cut-off for clinically significant depressive symptoms. Qualitatively, women described profound negative changes in their physical and emotional well-being after PE. In nearly all of the women, the extended survival after PE helped to buffer the effects of these changes. Conclusions: Results suggest women’s health-related QOL may return to, or near, pre-surgical levels in long-term survivorship but that symptom control is suboptimal. Findings should facilitate more informed decision making prior to PE and suggest targets for clinical intervention to enhance QOL and improve symptom control after PE. This study highlights the need for more comprehensive assessments pre- and post-PE to examine the effects of disease- and PE-related variables, cultural norms and social support on patient-reported outcomes.
Impact of sleep disturbance in myelodysplastic syndromes (MDS).
Authors: Solis Roxanne M. , Cronin Angel , Watts Corey D. , Steensma David P. , Stone Richard M. , DeAngelo Daniel J. , Owens Robert L. , Wadleigh Martha , Abel Gregory Alan
Published: February 2017

99

Background: The fatigue of MDS is typically attributed to anemia and inflammatory cytokines expressed by hematopoietic cells. In contrast, the burden and impact of sleep disturbance in MDS has not been well-described. Methods: Starting in January 2006, patients with MDS seen at least twice at the Dana-Farber Cancer Institute (DFCI) were enrolled in a clinical database and underwent baseline administration of the EORTC QLQ-C30. This measure includes a question about sleep disturbance (“have you had trouble sleeping”) as well as a three-item fatigue assessment. For this analysis, we first determined if there were differences in fatigue assessment score by self-reported sleep disturbance, hemoglobin (Hb) and other clinical characteristics (age, gender, cytogenetic category, and blasts) using ANOVA. Next, a multivariable logistic regression model was created to determine the independent contribution of each factor to fatigue score above or below the sample median. Results: 251 patients had complete clinical and QLQ-C30 data. Median age was 68 years; 68% were men. The IPSS distribution was 18% Low, 38% Int-1, 29% Int-2 and 15% High. Median fatigue score was 33 out of 100 (IQR 33-56; reference value for similar-aged cancer patients is 33 with IQR 11-56). The majority (53%) reported trouble sleeping, which was strongly associated with increased fatigue (p<0.001). Among clinical factors, only lower Hb was also associated with fatigue (p<0.001). Sleep disturbance did not vary with IPSS category (p=0.40), and was not strongly correlated with Hb (ρ= 0.10). On multivariable analysis adjusting for age, gender, cytogenetics and blasts, Hb < 10 g/dL and the two highest levels of sleep disturbance independently predicted fatigue score above the median (p=0.003). Conclusions: Poor sleep is prevalent among patients with MDS, and is an independent predictor of fatigue when controlling for Hb. These data suggest that in addition to anemia, sleep disturbance should be addressed to relieve MDS-related fatigue. [Table: see text]
Surgery for solitary pulmonary metastasis after curative gastrectomy for gastric cancer: Contribution to the long-term survival.
Authors: Hayashi Shigeya , Segami Kenki , Kawabe Taiichi , Aoyama Toru , Makuuchi Yousuke , Yamada Takanobu , Sato Tsutomu , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki
Published: February 2017

102

Background: Surgical resection is rarely indicated for pulmonary recurrence after curative gastrectomy for gastric cancer because most tumors recurred as multiple nodules or carcinomatous lymphangitis / pleuritis and prognosis is extremely poor. However, some investigators reported a sporadic case developing a solitary pulmonary metastasis which was surgically resected and resulted in a relatively favorable clinical outcome. The present study aimed to clarify contribution of surgery for solitary pulmonary recurrence to the long-term survival. Methods: We performed a systematic review of the literature by searching the words of “stomach”, “neoplasms”, “lung”, and “metastasis” in the Pubmed and Japanese ICHUSHI database, and analyzed the cases reporting on resection of solitary pulmonary metastasis after curative gastrectomy for gastric cancer together with our cases treated at our hospital. Overall survival was estimated by Kaplan-Meier method. Results: A total of 45 patients, 42 from a systematic review and 3 from our cases, were examined. Median age (range) was 67 years (31–84 years). Primary gastric cancer had the following characteristics; histologically differentiated type in 30 patients, undifferentiated type in 2, and unknown in 13 patients and tumor depth of T1 in 3, T2 in 6, T3 in 13, T4 in 9, and unknown in 6. Surgery for the primary gastric cancer was total gastrectomy in 30 patients and distal one in 15. The median (range) disease-free survival (DFS) between initial gastric resection and the detection of pulmonary metastasis was 28.0 months (5-128 months). Surgery for pulmonary tumor was lobectomies in 20 patients, segmentectomies in 3, wedge resections in 18, and unknown in 4. Only 4 patients received adjuvant chemotherapy after pulmonary resection. The median (range) follow-up period after pulmonary surgery was 20 months (3-98 months). The overall survival after pulmonary resection was 86% at 1-year, 62% at 3-year, and 56% at 5-year with the median (range) survival time of 67 months (3-98 months). Conclusions: Surgery for solitary pulmonary recurrence could contribute to the long-term survival.
Salvage surgery following chemoradiotherapy in management of esophageal cancer: Is it a viable therapeutic option? Results of a multicenter European study.
Authors: Markar Sheraz , Gronnier Caroline , Duhamel Alain , Mabrut Jean-Yves , Bail Jean-Pierre , Carrere Nicolas , Lefevre Jeremie H. , Meunier Bernard , Collet Denis , Mariette Christophe
Published: February 2017

109

Background: Salvage esophagectomy (SE) has traditionally conferred a high rate of mortality and morbidity in small, monocenter, and old publications. The aim of this large multicenter study was to assess the impact of SE following definitive chemoradiotherapy (SALV) on clinical outcomes. Methods: Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000–2010 were collected. Among this population, the first step was to compare SALV (n=308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS group, n=540) groups. The second step was to focus on the SALV group and to compare patients that benefited from SE for persistent (PERS group, n=234) versus recurrent (REC group, n=74) disease. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. Results: Comparison of SALV and NCRS groups: In-hospital mortality was similar in both groups (8.4% vs. 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% vs. 10.7%; P=0.007) and surgical site infection, which were both increased in the SALV group. At 3 years, the groups had similar overall (43.3% vs. 40.1%; P=0.542) and disease-free (39.2% vs. 32.8%; P=0.232) survivals, along-with similar overall (46.8% vs. 47.9%; P=0.829), locoregional (18.8% vs. 15.9%; P=0.544), distant (24.3% vs. 28.1%; P=0.949) and mixed (13.0% vs. 13.5%; P=0.888) tumor recurrence. Comparison of PERS and REC groups: There were no significant differences between the groups in the incidence of in-hospital mortality or major complications, apart from reoperation, which was increased in the PERS group (17.9% vs. 8.1%; P=0.042). Overall (23.4% vs 39.2%, p=0.054) and disease free survivals (21.1% vs37.8%, p=0.070) were lower in the PERS group. Conclusions: The results of this large multi-center study suggest that SE can offer acceptable short and long-term outcomes in experienced centers. Randomized controlled trials are required to validate the SE strategy as a viable option in complete esophageal cancer responders.
A randomized 2X2 phase II trial comparing two and four courses of S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) as neoadjuvant chemotherapy for locally resectable advanced gastric cancer: Survival results of COMPASS.
Authors: Yoshikawa Takaki , Tanabe Kazuaki , Nishikawa Kazuhiro , Fujitani Kazumasa , Ito Yuichi , Matsui Takanori , Hayashi Tsutomu , Aoyama Toru , Cho Haruhiko , Morita Satoshi , Miyashita Yumi , Tsuburaya Akira , Sakamoto Junichi
Published: February 2017

111

Background: The prognosis for stage III gastric cancer is not satisfactory even by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy is a promising approach but its optimal duration and regimen have not been established yet. Methods: We conducted a randomized phase II trial to compare two or four courses and regimen of SC or PC using a two-by-two factorial design.Key eligibility criteria was (i) T2-3/N+ or T4aN0 in case of schirrhous or junctional tumors, T2-3 with N+ to the major branched artery, T4aN+, T4b, para-aortic nodal metastases, or resectable minimal peritoneal metastases confirmed by laparoscopy and (ii) no other distant metastasis. Patients received S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8) or paclitaxel / cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. Then, patients received D2 gastrectomy with curative intent. The primary endpoint was 3-year overall survival. The planned sample size was 80 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by 10% increase was to be selected with a probability of 88% or higher. Results: Eighty-three patients were assigned to SC (n=41, two courses in 21 and four courses in 20) and PC (n=42, two courses in 21 and four courses in 21). Pathological response rate was 42% (17/41) in SC and 33% (14/42) in PC, and 36% (15/42) in the two courses and 39% (16/41) in the four courses. Pathological CR was 0% (0/42) in the two courses and 10% (4/41) in the four courses. Grade 3/4 adverse events by chemotherapy and grade 3/4 surgical morbidities defined by Clavien-Dindo classification were both less than 10% in each arm without treatment-related death. The 3-year OS was 60.9% (95% CI, 44.3-73.9%) in SC and 64.3% (95% CI, 47.9-76.7%) in PC, and 64.3% (95% CI, 47.9-76.7%) in the two courses and 61.0% (95% CI, 44.4-74.0%) in the four courses. Conclusions: Two courses of SC as neoadjuvant chemotherapy is recommended for a test arm of future phase III study for patients with locally resectable advanced gastric cancer. Clinical trial information: UMIN000002595.
A phase II study of systemic chemotherapy with docetaxel, cisplatin, and S-1 (DCS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection for gastric cancer with extensive lymph node metastasis (ELM): Japan Clinical Oncology Group Study JCOG1002.
Authors: Ito Seiji , Sano Takeshi , Katayama Hiroshi , Mizusawa Junki , Takahari Daisuke , Sasako Mitsuru , Katai Hitoshi , Tanaka Yoichi , Kinoshita Takahiro , Terashima Masanori , Nashimoto Atsushi , Yamaue Hiroki , Fukushima Norimasa , Yamada Makoto , Fujiwara Yoshiyuki , Kimura Yutaka , Azuma Takeshi , Yoshimura Tsunehiro
Published: February 2017

116

Background: Gastric cancer with ELM is commonly regarded as unresectable with poor prognosis. We previously reported the safety and efficacy of cisplatin and S-1 (CS) followed by D2 gastrectomy with PAN dissection for this target (JCOG0405, Br J Surg 2014). Methods: Eligibility criteria included histologically proven gastric adenocarcinoma; bulky nodal involvement around major branched arteries to the stomach (Bulky N) and/or PAN metastases; cM0 (except PANs); negative lavage cytology; neither Borrmann type 4 nor large (8cm or more) type 3; PS 0 or 1. Patients received two or three cycles of induction chemotherapy of docetaxel (40mg/m2 day1), cisplatin (60mg/m2 day1), and S-1 (80mg/m2from day 1 to 14) every 4 weeks, and then underwent D2 gastrectomy with PAN dissection. After R0 resection, postoperative chemotherapy with S-1 was given for one year. The primary endpoint is response rate (RR) of NAC by central peer review. The planned sample size was 50 patients, provided 80% power under the hypothesis of primary endpoint as the expected RR of 80% and threshold RR of 65% with a one-sided alpha of 10%. Results: Between 07/2011 and 05/2013, 53 patients were enrolled and 1 patient was ineligible: 30 had Bulky N, 14 had PAN metastases, and 9 had both. 51of 52 patients (98.1%) completed a planned NAC. The clinical RR was 57.7% (30/52) (80%CI [47.9%-67.1%], one-sided p=0.89). The R0 resection rate was 84.6% (45/52). During DCS chemotherapy, grade 3/4 neutropenia occurred in 39.6% and grade 3/4 non-haematological adverse events in 20.8%. The incidence of grade 3/4 adverse events related to surgery was 30.6%. There was no treatment-related death. The pathological finding revealed minor response (residual tumor <1/3) was achieved in 50.0% (26/52) and major response (residual tumor <2/3) in 34.6% (18/52). The long-term survival is still under follow-up. Conclusions: Preoperative DCS revealed feasible but could not show sufficient efficacy. Preoperative CS is still being considered a standard treatment for this population. Clinical trial information: UMIN000006069.
Is linitis plastica a contraindication for surgical resection? A 7-institution study of the U.S. Gastric Cancer Collaborative.
Authors: Blackham Aaron Udell , Swords Doug S. , Levine Edward Allen , Fitzgerald Nora , Squires Malcolm Hart , Poultsides George A. , Fields Ryan C. , Bloomston Mark , Weber Sharon M. , Pawlik Timothy M. , Jin Linda X. , Spolverato Gaya , Winslow Emily , Schmidt Carl Richard , Kooby David A. , Worhunsky David J. , Saunders Neil , Cho Clifford Suhyun , Maithel Shishir Kumar , Votanopoulos Konstantinos Ioannis
Published: February 2017

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Background: Linitis plastica (LP) describes a diffusively infiltrative gastric adenocarcinoma that portends poor prognosis. Current treatment guidelines do not differentiate between LP and non-LP cancers and it is not known if the same staging system should be applied to both situations. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 patients with gastric adenocarcinoma who underwent resection between 2000-2012 were identified. Clinicopathologic, perioperative and survival outcomes of the 58 patients with LP were compared to the 811 patients without LP. Results: Advanced disease (stage III/IV) at presentation was more common in patients with LP compared to non-LP patients (90 vs 44%, p<0.01). Despite the fact that most LP patients underwent total gastrectomy (88% vs 57%, p<0.01), positive margins were more common in LP patients (33 vs 7%, p<0.01). There was no difference in perioperative complications (48 vs 43%, p=0.45) or mortality (7 vs 3%, p=0.12) between LP and non-LP patients. While survival correlated with stage in non-LP patients, there was no difference in median overall survival (OS) of LP patients based on stage (I/II, 17.3 mos; III, 10.6 mos; IV, 12.0 mos; p=0.46). Median OS was significantly worse in patients with LP (11.6 vs 37.8 months, p<0.01) when margin status and extent of lymphadenectomy were not factored in the analysis. However, when analyzing only patients with optimal resections (R0, D2 lymphadenectomy), the median OS for stage III LP (n=22) and non-LP (n=185) patients was nearly identical (26.8 vs 25.3 mos, p=0.69). There were no independent prognostic factors identified to predict survival in LP patients undergoing curative resection. Conclusions: The poor prognosis of LP gastric cancer is due primarily to its advanced stage at diagnosis. However, LP patients who undergo optimal resections can expect similar long term survival compared to optimally resected non-LP patients with advanced stage disease. Patient selection and multidisciplinary management are paramount when considering surgical resection in patients with gastric LP.
An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven-institution analysis of 837 patients from the U.S. Gastric Cancer Collaborative.
Authors: Dann Gregory C. , Squires Malcolm Hart , Postlewait Lauren McLendon , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Ejaz Aslam , Acher Alexandra W. , Jin Linda X. , Cho Clifford Suhyun , Winslow Emily , Russell Maria C. , Cardona Kenneth , Staley Charles A. , Maithel Shishir Kumar
Published: February 2017

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Background: A recent single institutional study demonstrated that jejunostomy feeding tubes (J-tubes) placed during resection of gastric adenocarcinoma (GAC) are associated with increased complications and no change in receipt of adjuvant therapy. Our aim was to validate these findings in a large multi-institutional cohort. Methods: All patients who underwent resection for GAC at 7 institutions participating in the U.S. Gastric Cancer Collaborative from 2000-2012 were identified. Patients with metastatic disease were excluded. Univariate and multivariate logistic regression were performed to assess the association of J-tubes with postoperative complications and receipt of adjuvant therapy. Subset analysis of patients who underwent total vs subtotal gastrectomy was also performed. Results: Of 965 patients, 837 were included for analysis, of whom 265 (32%) received a J-tube. Patients receiving J-tubes demonstrated greater incidence of preoperative weight loss, lower BMI, greater extent of resection, and more advanced TNM stage. J-tube placement was associated with increased infectious complications (36% vs 19%;p<0.001), including surgical site infections (14% vs 6%;p<0.001) and deep intra-abdominal infections (11% vs 4%;p<0.001). On multivariate analysis, J-tubes remained independently associated with increased risk of infectious complications (HR=1.93;p=0.001), surgical site infections (HR=2.85;p=0.001), and deep intra-abdominal infections (HR=2.13;p=0.04). J-tubes were not associated with increased receipt of adjuvant therapy (HR=0.82;p=0.34). Subset analysis of patients undergoing total and subtotal gastrectomy similarly demonstrated an association of J-tubes with increased risk of infectious outcomes andno association with increased receipt of adjuvant therapy. Conclusions: J-tubes placed during resection of gastric adenocarcinoma are independently associated with increased postoperative infections and are not associated with increased receipt of adjuvant therapy, despite being placed in patients with advanced TNM stage tumors. Selective use of J-tubes is recommended.
A phase I/II study of definitive chemoradiotherapy with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R) for advanced esophageal cancer.
Authors: Sato Yasushi , Ohnuma Hiroyuki , Hirakawa Masahiro , Okagawa Yutaka , Osuga Takahiro , Murase Kazuyuki , Takada Kohichi , Kawano Yutaka , Iyama Satoshi , Hayashi Tsuyoshi , Sato Tsutomu , Miyanishi Koji , Takimoto Rishu , Kobune Masayoshi , Sagawa Tamotsu , Hori Masakazu , Someya Masanori , Sakata Koh-ichi , Takayama Tetsuji , Kato Junji
Published: February 2017

123

Background: Deﬁnitive chemoradiotherapy is one of the options for advanced esophageal cancer (AEC). However, AEC patient survival remains unsatisfactory. To investigate a regimen of definitive chemoradiotherapy that exerts good local control of AEC, we performed a phase I/II study to assess the safety and efficacy of triple-drug chemoradiotherapy with docetaxel, 5-fluorouracil, and nedaplatin (DNF-R) that has less adverse events than cisplatin. Methods: Eligible patients had stage II-IVA AEC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m2 for dose levels 1, 2, or 3) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5-fluorouracil (400 mg/m2/day) on days 1-5 and 8-12, with concurrent radiotherapy (on days 1-5, 8-12, and 15-19, total 60 Gy) every 5 weeks. After DNF-R, patients received at least 2 more cycles of DNF. The recommended dose (RD) was determined with a 3 + 3 design. Results: Thirty-one patients were enrolled from July 2010 to April 2013. In the phase I study, the dose-limiting toxicity (DLT) was grade 4 neutropenia, which was observed in all 3 patients at dose level 2.Thus, the RD schedule was level 1. In the phase II study, the 25 eligibles had a median age of 64 (range 56-78; male/female: 21/4), with PS0/1/2 of 13/10/2 and cStage II/III/IVA of 6/10/9. Grade 3/4 acute toxicity included neutropenia (46%), leukopenia (43%), febrile neutropenia (11%), thrombocytopenia (18%), esophagitis (18%), and nausea (11%) during CRT. Grade3/4 late radiotoxicity included 2 cases of esophagostenosis (7%), but they improved by dilatation. Of the 28 patients treated at the RD level 1, including 3 patients of the RD phase I portion, all of them showed response including 23 (82%) CR and 5 PR. The protocol completion rate was 96.4% (27/28). No treatment-related death was observed. The median PFS (1-year PFS: 67.6% and 3-year PFS: 44.8%) and OS were 21 months and 33.2 months, respectively. The 3-year survival rate was 62.5%. Conclusions: DNF-R showed good tolerability and achieved a high CR rate, suggesting that it is a potentially effective therapeutic regimen for AEC. Clinical trial information: UMIN000005446.
Comparison between neoadjuvant chemotherapy followed by surgery (NAC-S) and definitive chemoradiotherapy (CRT) in overall survival for patients with clinical stage II-III esophageal squamous cell carcinoma (ESCC) (JCOG1406-A).
Authors: Nomura Motoo , Kato Ken , Mizusawa Junki , Kataoka Kozo , Ando Nobutoshi , Muro Kei , Ohtsu Atsushi , Igaki Hiroyasu , Shinoda Masayuki , Takeuchi Hiroya , Shimizu Hideaki , Hayashi Kazuhiko , Daiko Hiroyuki , Goto Masahiro , Komatsu Yoshito , Konishi Kazuo , Miyata Yoshinori , Kitagawa Yuko
Published: February 2017

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Background: NAC-S is a standard treatment for patients (pts) with stage II/III (UICC-TNM 5th ed.) ESCC in Japan. CRT is also optionally performed for pts who refused or who are not tolerable to surgery. However, no randomized clinical trial has been conducted comparing NAC-S with CRT. The aim of this study is to explore subgroups in which survival outcome of pts undergoing CRT was potentially equivalent to NAC-S. Methods: The data of two trials for cStage II/III ESCC, JCOG9907 (accrual period: 2000-2006) and JCOG9906 (2000-2002) were used. J9907 demonstrated that NAC-S (2 course of cisplatin and 5-fluorouracil [CF] followed by surgery) showed superior OS compared with surgery followed by postoperative chemotherapy. J9906 was a single arm trial which explored the efficacy and safety of CRT (CF plus 60 Gy). Both two trials were conducted under similar eligible criteria. Subgroup analyses between two trials (serum Albmin (Alb), cT, cN, c-stage, and tumor location) using Cox proportional hazard model were performed for pts assigned to receive NAC-S in J9907 and pts in J9906. Results: All eligible pts for NAC-S group (n=164) in J9907 and all eligible pts in J9906 (CRT group: n=73) were analyzed. Pts backgrounds were similar between two groups. OS for NAC-S group was better than that for CRT group (adjusted HR 1.73; 95% CI 1.19-2.51). Subgroup analysis using Cox proportional hazard model demonstrated that all subgroups in NAC-S group showed shorter OS compared with those in CRT group (see Table). Conclusions: OS of NAC-S was favored over that of CRT. The subgroup in which OS of CRT was equivalent to that of NAC-S was not detected. For further improvement of CRT for this population, single arm trial (JCOG0909) is ongoing to evaluate the efficacy and safety of CRT modifying chemotherapy regimen and total radiation dose. [Table: see text]
Value of peritoneal drain placement after total gastrectomy for gastric adenocarcinoma: A multi-institutional analysis from the U.S. Gastric Cancer Collaborative.
Authors: Dann Gregory C. , Squires Malcolm Hart , Postlewait Lauren McLendon , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Saunders Neil , Cho Clifford Suhyun , Winslow Emily , Russell Maria C. , Staley Charles A. , Maithel Shishir Kumar , Cardona Kenneth
Published: February 2017

131

Background: A recent randomized trial of peritoneal drain (PD) placement after pancreaticoduodenectomy concluded that placement of PDs decreased the frequency and severity of complications. The role of PD placement after total gastrectomy for gastric adenocarcinoma (GAC) is not well-established. Methods: Patients who underwent total gastrectomy for GAC at 7 institutions from the U.S. Gastric Cancer Collaborative from 2000-2012 were identified. Univariate and multivariate analyses were performed to evaluate the association of PD placement with postoperative outcomes. Results: 344 patients were identified and anastomotic leak rate was 9%.253 (74%) patients received a PD. Those with PD placed had similar ASA class, tumor size, TNM stage, and need for additional organ resection when compared to their counterparts with no PD. No difference was observed in the rate of any complication (54% vs. 48%;p=0.45), major complication (25% vs. 24%;p=0.90), or 30-day mortality (7% vs. 4%;p=0.51) between the two groups. In addition, no difference in anastomotic leak (9% vs. 10%;p=0.90), need for secondary drainage (10% vs. 9%;p=0.92), or reoperation (13% vs. 8%;p=0.28) was identified. On multivariate analysis, PD placement was not associated with a decrease in frequency or severity of postoperative complications. Subset analysis of patients stratified by whether they underwent concomitant pancreatectomy similarly demonstrated no association of PD placement with reduced complications or mortality. In patients who experienced an anastomotic leak (n=31), placement of PD was similarly not associated with a decrease in complications, need for secondary drainage, or mortality. Conclusions: Peritoneal drain placement after total gastrectomy for adenocarcinoma, regardless of concomitant pancreatectomy, is not associated with a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, or decrease in the need for secondary drainage procedures or reoperation. Routine use of peritoneal drains is not warranted.
A phase I/II study of divided-dose docetaxel, cisplatin, and fluorouracil (DCF) for patients with recurrent or metastatic squamous cell carcinoma of the esophagus.
Authors: Ojima Toshiyasu , Nakamori Mikihito , Nakamura Masaki , Iwahashi Makoto , Katsuda Masahiro , Hayata Keiji , Matsumura Shuichi , Yamaue Hiroki
Published: February 2017

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Background: The aim of this phase I/II study was to evaluate the efficacy and safety of the combined use of docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (DCF) in patients with recurrent/metastatic squamous cell carcinoma of the esophagus (SCCE). This study adopted divided doses of docetaxel and CDDP in order to reduce the toxicities of the treatment. Methods: The dose of docetaxel was escalated using the following protocol in the phase I stage: level 1, 30; level 2, 35 and level 3, 40 mg/m2, which was intravenously infused for two hours on days 1 and 8. CDDP was administered at a dose of 12 mg/m2 infused for four hours on days 1-5. The 5-FU was administered at a dose of 600 mg/m2continuously infused from day 1 to 5. This regimen was repeated every four weeks. Results: The study subjects were nine patients (phase I) and 48 patients (phase II). The recommended dose was determined as level 3 in phase I. In the phase II stage, the overall response rate was 62.5%, with a complete response rate of 12.5%. The median progression-free survival was six months, and the median overall survival was 13 months. Grade 3/4 toxicities of leukopenia, neutropenia and febrile neutropenia occurred in 64.6, 68.8 and 14.6% of the patients, while grade 3/4 non-hematological toxicities were relatively rare. No treatment-related death was recorded. Conclusions: This modified DCF regimen can be a tolerable definitive chemotherapy for unresectable SCCE because of its high efficacy, although adequate care for severe neutropenia is needed. Clinical trial information: NCT00915850.
Survival trends in advanced gastrointestinal stromal tumor patients: A population-based study.
Authors: Shah Binay Kumar , Budhathoki Nibash
Published: February 2017

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Background: In February 2002, imatinib was approved by US FDA for treatment of patients with advanced gastrointestinal stromal tumor (GIST). This study was performed to evaluate survival trends in patients with advanced GIST in pre- (1992-2001) and post- (2002-2008) imatinib era in the United States. Methods: We selected adult patients (≥18 years) with advanced GIST (regional and distant metastasis based on SEER’s LRD staging) from the Surveillance, Epidemiology, and End Results 18 database diagnosed during 1992-2008. We excluded patients diagnosed at autopsy or from death certificate only, or those without survival date. We analyzed 1- and 3- year relative survival (RS) rates of the patients by age (all ages,18-64yrs,64+yrs), race [White, Black and Others (American Indian/AK Native, Asian/Pacific Islander)], and gender in pre-imatinib (1992-2001) and post-imatinib (2002-2008) eras. We used Z-test in SEER*Stat to compare RS rates. Results: There were total of 1,734 cases of advanced GIST (regional and distant metastasis) during the study duration. Of the total population, 744 were females and 990 were males. The 1- and 3- year RS rates were significantly higher for patients diagnosed in post-imatinib era compared to those in pre-imatinib era (83.8±1.1% vs 72.5±2.3%; Z 4.47 at one year and 68.8±1.4% vs 51.0± 2.6%; Z 6.25). The survival rates in younger patients (18-64 years) improved significantly in post-imatinib era compared to pre-imatinib era (88.60±1.2% vs 74.20±2.9%; Z 5.19 at 1 year and 75±1.6% vs 56.1±3.4%; Z 5.81 at 3 years). Among older patients, there was improvement in 3- year survival rate (76.90±2% vs 70.40±3.5%; Z 1.22 at 1 year and 59.80±2.5% vs 44.9±4%; Z 2.82 at 3 years). Survival rates improved for both sexes and for Whites and Blacks (1 year RS: 83.80±1.3% vs 73.40±vs2.6%; Z 3.45 for Whites and 85±2.4% vs 68.80±6%; Z 2.53 for Blacks; 3 year RS: 68.60±1.7% vs 51.20±3.1%; Z 5.02 for Whites and 69.10±3.3% vs 42.6±6.6%; Z 3.76 for Blacks). There was no improvement in survival rates for Others. Conclusions: Overall, survival rates of advanced GIST patients have improved significantly in post-imatinib era compared to pre-imatinib era. There was no improvement in survival rates of Others.
Impact of surgical care on survival in esophageal cancer.
Authors: Campbell Chase , Hill Joshua S. , Boselli Danielle , Salo Jonathan C.
Published: February 2017

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Background: Survival after multimodality treatment of localized esophageal cancer depends upon complex interactions between the patient, tumor biology, and treatment factors. The National Cancer Database (NCDB) was used to analyze prognostic factors to identify areas for treament optimization. Methods: 8,072 patients with localized esophageal cancer treated with neoadjuvant therapy undergoing surgical resection between 2004 and 2006 were identified from the NCDB. Covariates were analyzed for association with survival using univariate and multivariate Cox models. Results: A multiviariate Cox proportional hazards model was constructed, with the following significant factors predictive of survival. (See Table.) Survival varied markedly based upon the annual surgical volume of esophageal resection performed at the hospital. For hospitals performing 5 or fewer esophageal resections per year (15% of cases), 5-year survival was 40.0%, compared with 48.6% for hospitals performing 20 or greater (26% of cases). Hospital length of stay after surgery also profoundly affected survival. For patients with a post-operative length of stay of less than 14 days, 5-year survival was 40% and median survival 39.1 months. Median survival was 28 months, 19 months, and 15 months in patients with a hospital length of stay of 14-21 days, 21-28 days, and greater than 28 days, respectively. Conclusions: Data from the NCDB confirms the association between perioperative events and long-term survival after resection for esophageal cancer. Given the wide variance in outcomes based upon perioperative treatment factors, future improvements in outcomes are unlikely to be dramatically influenced by optimization of chemotherapy and radiation therapy. Improvement in outcomes of the treatment of esophageal cancer will likely require understanding how the perioperative period influences long-term survival, which should drive priorities for research and treatment improvement. [Table: see text]
First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5- fluorouracil (DCF) plus panitumumab (P) in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction (GEJ): A phase II multicenter trial.
Authors: Tomasello Gianluca , Liguigli Wanda , Toppo Laura , Mattioli Rodolfo , Negri Federica , Curti Alessandra , Ratti Margherita , Poli Rossana , Lazzarelli Silvia , Gerevini Fabiana , Colombi Chiara , Martinotti Mario , Rovatti Massimo , Olivetti Lucio , Passalacqua Rodolfo
Published: February 2017

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Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.
Prognostic value of the circumferential resection margin after neoadjuvant treatment in esophageal cancer patients.
Authors: Hulshoff Jan-Binne , Faiz Zohra , Smit Justin Kendrick , Kats-Ugurlu Gursah , Burgerhof Johannes , Plukker John Theodorus
Published: February 2017

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Background: Involvement of the circumferential margin (CRM) is an important factor in esophageal cancer (EC) patients. CRM definitions are commonly based on the College of American Pathologists (CAP) at 0 mm and the Royal College of Pathologists (RCP) at >1 mm. We evaluated which CRM definition is useful in current practice with neoadjuvant chemoradiotherapy (CRT) and whether the CRM cut-off value differs after CRT. Methods: We prospectively included 209 patients (104 with CRT) with locally advanced EC (stage II-III), who underwent radical transthoracic esophagectomy. Patients were followed for at least 2 years after surgery or until death. Patients with <1 mm longitudinal resection margins were excluded. Cancer related death was scored as event and death of other causes as end of follow-up (median 27: IQR 14.0 - 42.8 months). CRMs were measured in tenths of millimetres by experienced pathologists. Pathologic proven tumor regrowth, unequivocal radiologic suspicion or obvious clinical manifestations were marked as recurrence. Prognostic factors with a P<0.1 in univariate analyses were incorporated in multivariate Cox-regression analyses in which both CRM definitions were assessed separately. In an explorative analyses the CRM cut-off values in the surgery-only and CRT group for 2-year disease free survival (DFS) was assessed using CRM between 0-1.5 mm in the Cox-regression model. Results: Independent prognostic factors for 2-year DFS (P<0.05) in the study group were: tumor length (>5cm), >0.2 L/N+ ratio, angioinvasion and CAP R0. In the surgery group; tumor length, >4 N+, angioinvasion and CAP R0 were independent prognostic factors (P <0.05). In the CRT group only pN stage (P<0.01) was independent prognostic for 2-year DFS. The CRM cut-off value was significant at 0.2-0.3 mm for the surgery and CRT group, respectively. Conclusions: The CAP value was only independent prognostic for 2-year DFS in the surgery group. The CRM cut-off value was significant at 0.2 and 0.3 mm in the surgery and CRT group, respectively.
Identification of novel upregulated microRNAs in the pathogenesis of gastric cancer by the use of open access databases and bioinformatics tools.
Authors: Wichmann Ignacio Alberto , Artigas Rocio , Alarcon Alejandra , Olivares Wilda , Roldan Nicole , Fry Jacqueline , Cerda Paulina , Corvalan Alejandro
Published: February 2017

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Background: Gastric cancer (GC) is the third leading cause of cancer death worldwide. Chronic infection by H.pylori and EBV is related to the multistep cascade of GC. This cascade hypothesizes that a specific sequence of lesions leads to GC. Epigenetic processes, such as DNA methylation or miRNAs, are new players in the pathogenesis of GC. We aim to identify novel upregulated microRNAs associated with the multistep cascade through the use of open access databases and bioinformatics tools. Methods: We selected 3 GEO DataSets with human miRNA expression levels in paired tumor and non-tumor samples from gastric cancer patients. The largest library, GSE 23739 (40 matched T/N samples) was used as a "discovery dataset”. Only miRNAs upregulated >1.2 fold T over N were considered. Upregulated miRNAs were further validated in two independent datasets: i) GSE28700 (22 fresh-frozen paired T and N samples) and ii) GSE54397 (16 formalin-fixed T and N samples) and confirmed with TCGA Stomach Adenocarcinoma (STAD) data (doi:10.1038/nature13480). Finally, upregulated miRNAs were analyzed by Diana Tools miRPath, for associated oncogenic pathways and target genes. Results: From the discovery dataset GSE 23739 we identified 231 upregulated miRNAs between 40 matched T/N samples. Only 12 of these candidates were found in both validation datasets GSE28700 and GSE54397. Only three of these miRNAs were undescribed in GC: miRNAs-505, -552 and -592. TCGA STAD data confirmed our results. Analysis in miRPath revealed association with three oncogenic pathways PI3K-AKT, TGFβ and Erbβ; as well as genes relevant in oncogenesis: MAP2K1, RPS6KB1, TGFA, SMAD3, IGF1, LAMC1, IFNAR1, ITGB6, PIK3CA, PPP2R2D, EIF4E, BRCA1, FOXO3 and CREB3L3. Conclusions: The use of open access databases and bioinformatics tools enabled us to identify three novel upregulated microRNAs with oncogenic potential in GC. The analysis of these miRNAs revealed associated oncogenic pathways and target genes. These findings need to be further inquired in an experimental manner in order to assess the potential role of these miRNAs in the multistep cascade of GC.