bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of extending the original eligibility criteria for the “CROSS” neoadjuvant chemoradiotherapy on toxicity and survival in esophageal cancer.
Authors: Hulshoff Jan-Binne , de Heer Ellen C. , Klerk Daphne H. , De Groot Derk Jan , Plukker John Theodorus , Hospers Geke
Published: March 2017

187

Background: Patients with curable esophageal cancer (EC) which proceed beyond the original CROSS eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect of extending the CROSS eligibility criteria for nCRT on treatment related toxicity and overall survival (OS) in EC. Methods: Included were 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0), treated with the CROSS schedule followed by esophagectomy. Group 1 (N = 90) consisted of patients which met the CROSS criteria and patients in group 2 (N = 71) met the extended eligibility criteria, i.e. including a tumor length of > 8 cm (N = 23), > 10% weight loss (N = 35), > 2 – 4 cm extension in the stomach (N = 21), celiac lymph node metastasis (N = 13), and/or age > 75 years (N = 2). We assessed the differences in hematologic toxicity (≥ grade 3) and 90-day postoperative mortality. Moreover, we assessed the prognostic value on OS with multivariate Cox regression analysis. Results: No difference was found in hematologic toxicity and 90-day mortality. The OS differed significantly (P = 0.003), with a median of 37.3 (95% CI 10.56 – 64.0) and 17.2 (95% CI 13.8 – 20.6) months in group I and II, respectively. Pathological N-stage (P = 0.024), ypT-stage (P = 0.044), and group II (P = 0.006) were independent prognostic factors for OS. Conclusions: Extension of the CROSS study eligibility criteria for nCRT did not affect hematologic toxicity and postoperative mortality, but was prognostic for OS.
Outcomes for patients ≥75 years with localized gastroesophageal cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Natori Akina , Chan Bryan , Sim Hao-Wen , Chen Eric Xueyu , Liu Geoffrey , Darling Gail Elizabeth , Swallow Carol Jane , Brar Savtaj Singh , Brierley James D. , Ringash Jolie , Wong Rebecca , Kim Joon-Hyung J. , Rogalla Patrik , Hafezi-Bakhtiari Sara , Conner James , Knox Jennifer J. , Elimova Elena , Jang Raymond Woo-Jun
Published: March 2017

189

Background: The optimal treatment and outcome for elderly patients (pts) with localized gastroesophageal (GE) cancer remains unclear as they are underrepresented in clinical trials. We aimed to assess survival in pts ≥ 75 years according to treatment received. Methods: A retrospective analysis was performed for all pts aged ≥ 75 years with GE cancer treated in 2012 and 2013. Frailty was measured using the Charlson comorbidity index (CCI) and ECOG performance status (PS). Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors impacting treatment choices. Results: Of 70 pts, median age was 82 years (range: 75-98), primary sites were esophageal (40%, with 61% squamous histology), GE junction (24%) and gastric (36%). Baseline characteristics included: PS: 0 (40%), 1 (39%), 2 (14%), 3 (7%); and CCI: 0 (36%), 1 (20%), 2 (21%), ≥ 3 (23%). Treatment received included surgery (33%), radiotherapy (RT) (31%); surgery plus adjuvant chemotherapy (chemo) and/or RT (9%); chemoradiation alone (7%) and 20% had no active treatment. In univariable analysis; age < 85 (p = 0.007) and surgery (p = 0.022) were associated with improved OS. Chemo and RT, either alone or in combination, did not significantly improve OS. In multivariable analysis; age < 85 (HR 0.46, 95% CI: 0.23-0.94, p = 0.034), surgery (HR 0.32, 95% CI: 0.14-0.74, p = 0.008) and CCI < 2 (HR 0.52, 95% CI: 0.27-0.99, p = 0.048) were identified as independent predictors for improved OS. Age ≥ 85 was significantly associated with omission of surgery (OR 3.61, 95% CI: 1.13-14.01, p = 0.041) but in contrast, PS ≥ 2 (p = 0.475) and CCI ≥ 2 (p = 0.939) were not predictive. Conclusions: At our institution, very few pts ≥ 75 years received multimodality therapy for localized GE cancers. Surgery was the only treatment modality associated with a significant survival advantage, and additional chemo and/or RT did not further improve OS. The only predictor for having surgery was age. Consequently, future studies should consider comprehensive assessment for surgery so that eligible elderly pts can benefit.
Outcomes of ERCC1 high locally advanced esophageal cancer patients treated with non-platinum vs platinum based CRT.
Authors: Yogarajah Meera , Stroud Chipman Robert Geoffrey , Hegde Aparna Madhukeshwar , Walker Paul R.
Published: March 2017

192

Background: ERCC1 is a DNA excision repair enzyme which repairs the DNA adduct damage caused by platinum and hence high levels of ERCC1 has been associated with platinum resistance. Thus utility of platinum as a first line chemotherapy in esophageal cancers with high ERCC1 levels is controversial. SWOG S0356 trial noted a significantly low 2 year overall survival of 37% for platinum based CRT in ERCC1 high esophageal carcinomas, yet no studies have identified the alternative first line chemotherapy. Our Program utilized combined irinotecan 65mg/m2 on D1 and D8 and nab-paclitaxel 100mg/m2with concurrent radiation therapy of 50.4Gy for ERCC1 high esophageal cancers at the treating physician’s discretion. We compared the differences in survival with non-platinum versus platinum CRT. Methods: Retrospective analysis from 2011 to 2016 identified 25 locally advanced esophageal cancer patients in whom ERCC1 levels were checked. Out of this 25 patients 23 had high ERCC1 levels and 2 had low ERCC1 levels. Patients with low ERCC1 were excluded. Patients with high ERCC1 levels received either non-platinum or platinum CRT as neo-adjuvant, adjuvant or definitive chemotherapy. Results: Patient characteristics: Male 69.5%, female 30.5%, squamous 43.4%, adenocarcinoma 52.1%, other 4.5%, operable 39%, non-operable 61%. Non-platinum therapy was utilized for 69.5% and platinum based therapy for 30.5% of the patients. Kaplan-Meier analysis for survival showed clear separation of the curves around 2 years. Median overall survival of non-platinum doublet was not reached during a median follow up of 22 months. Overall survival at 2 years was 57%. The median overall survival for the platinum doublet was 22 months and the 2 year overall survival was 42%. (p = 0.22). Hazard ratio (HR) 0.48(95% CI 0.14-1.58 p = 0.23) .This statistical non significance was due to small sample size. Conclusions: Abraxane and irinotecan showed improved overall survival in the ERCC1 high group when compared with platinum based therapy demonstrated both in our population and the SWOG 0356 trial. [Table: see text]
Impact of race on gastric adenocarcinoma outcomes in a multiracial population.
Authors: Acoba Jared David , Simon Nicholas E
Published: March 2017

196

Background: Gastric adenocarcinoma continues to be a major health issue, with a high prevalence among Asian and Pacific Islander populations. We performed a comprehensive analysis to evaluate outcomes and prognostic factors in a multiracial population with a focus on Whites, Asians (Chinese, Japanese, Koreans, Filipinos), and Pacific Islanders (Native Hawaiians, Samoans). Methods: We collected data from 615 consecutive patients with gastric or gastroesophageal adenocarcinoma diagnosed between 2000 and 2015. Multivariable Cox proportional hazards regression models for survival were built adjusting for race, age at diagnosis, stage, number of lymph nodes resected, histologic grade, HER2 status, systemic treatment, and insurance status for the entire study population and for those with resectable cancer. Results: Pacific Islanders presented at a younger age, higher stage, and more often were underinsured. White patients were more often diagnosed with proximal tumors. Analysis of the entire population demonstrated that older age, underinsured status, higher tumor grade, and advanced stage but not race were poor prognostic factors. Among patients with resectable cancers, the Filipino and Samoan racial sub-groups were adversely associated with survival even after adjusting for other prognostic factors. Furthermore, among Asians, Filipinos had worse outcomes compared with other Asian sub-groups. Overall, 9.5% of the 118 tumors tested for HER2 were deemed HER2(+), however the rate varied by race being as high as 43% among Samoans. Conclusions: No racial survival disparity was detected for gastric and gastroesophageal adenocarcinoma, however among resectable and potentially curable patients, Filipinos and Samoans fared worse. This could be in part due to differences in tumor biology such as HER2 expression. Further study in this area should be pursued. Within the Asian race, Filipinos demonstrated poorer survival than other sub-groups. Given the differences in survival within the Asian race, studies exploring the relationship between race and cancer should consider analysis by sub-group.
Long-term survival in 101 metastatic gastroesophageal cancer (mGEAC) patients eventually treated with consolidative local therapy.
Authors: Mizrak Kaya Dilsa , Wang Xuemei , Harada Kazuto , Blum Murphy Mariela A. , Das Prajnan , Minsky Bruce D. , Estrella Jeannelyn , Lin Quan , Ghazanfari Amlashi Fatemeh , Lee Jeffrey H , Weston Brian , Bhutani Manoop S. , Matamoros Aurelio , Sagebiel Tara L. , Skinner Heath Devin , Wu Carol C , Hofstetter Wayne Lewis , Badgwell Brian D. , Ajani Jaffer A.
Published: March 2017

197

Background: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation and/or surgery) for selected mGEAC patients. We present results in a large cohort. Methods: From our database, we identified a 101 such patients. We analyzed the association of various clinical variables (location of primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose {≥50.4 Gy vs. <50.4 Gy}) with overall survival (OS). Results: There were 71 patients with proximal primary (esophageal, Siewert types I/II) and 30 patients with distal primary (Siewert type III and gastric). The median OS was 25.7 months (95% CI: 22.3-32.8 months). The OS rates at 2-years and 5-years from diagnosis were 53.8% (95% CI: 44.7%-64.8%) and 20.7% (95% CI: 13.4%-31.9%), respectively. The median OS was highly associated with the location of primary (22.8 months for proximal GEACs vs. 41.5 months for distal GEACs, p=0.03). Duration of initial chemotherapy was highly associated with OS (21.8 months for <3 months vs. 32.5 months for ≥3 months, p=0.004). Association between OS and tumor/treatment characteristics. Conclusions: Selected patients with mGEAC (who have favorable clinical course) can have up to 20% 5-year survival with this strategy. Patients with distal GEAC and those who receive initial chemotherapy for longer time are the maximum beneficiaries. [Table: see text]
Comparison of neoadjuvant chemoradiation versus peri-operative chemotherapy for adenocarcinoma of the distal esophagus and gastroesophageal junction.
Authors: Bertke Matthew , Gurka Marie Kate , Sharma Vivek R. , Redman Rebecca A. , Scoggins Charles Raben , Martin Robert C. G.
Published: March 2017

198

Background: Both neoadjuvant chemoradiation (NACRT) and peri-operative chemotherapy (PCTX) are viable treatment options when combined with surgical resection for locally advanced distal esophageal and gastroesophageal junction (GEJ) cancers. There is a paucity of data comparing these treatment regimens; therefore, the goal of this study was to compare the outcome of these two approaches at our institution. Methods: This is a retrospective review of a prospectively managed database, in which 66 patients with adenocarcinoma of the distal esophagus or GEJ who received either NACRT or PCTX from 2006 to 2015 were identified. Groups were balanced in regards to age, sex, subsite, T stage, and N stage. Patients treated with NACRT received either carboplatin/taxol or 5FU-based chemotherapy. PCTX regimens included ECF, EOX, DCF, or 5-FU based chemotherapy. Survival was calculated by the Kaplan–Meier method with a log‐rank test used for comparison between groups. Differences between subgroups were compared with Fisher’s Exact test. Results: A total of 47 patients were treated with NACRT and 19 with PCTX with a median follow-up of 14 months. All but three patients underwent definitive resection. No patients died within 90 days of surgery and the rate of operative complications was similar between the two groups (p = 0.77). The pathological complete response rate was 12.1% overall, with 14.9% in NACRT and 5.3% in PCTX. Median overall survival was 16.6 months and was not different between treatment subgroups (p = 0.77). Fewer treatment failures were seen with NACRT compared to PCTX (29.8% vs. 57.9%, p = 0.050), probably driven by improved local control in the NACRT arm (95.7% vs. 73.6%, p = 0.017). Distant failure was not significantly different between NACRT and PCTX (27.7% vs. 42.1%, p = 0.38). Conclusions: Pre-operative chemoradiation provided better overall disease control compared to peri-operative chemotherapy. However, improved survival could not be demonstrated, possibly due to the similar rates of distant failure and the study being underpowered due to small number of patients.
Neoadjuvant chemoradiotherapy (NCRT) compared with chemotherapy (NCT) in locally advanced squamous-cell cancer of the esophagus.
Authors: Li Xue , Hao Daxuan , Yang Yuanyuan , Cheng Xinyu , Zhang Yougai , Wu Xiaoyuan , He Chunyu , Liu Jinsong , Wang Jianhua
Published: March 2017

202

Background: Neoadjuvant chemotherapy with or without radiotherapy are the common treatments for locally advanced squamous-cell esophageal cancer(ESCC). There is no sufficient data to choose between these two effective therapies. The aim of our retrospective study was to compare the clinical efficacy between these two strategies of complete pathological response (pCR), postoperative morbidity, mortality, and overall and disease-free survival in patients with locally advanced ESCC. Methods: Patients with stage T2-4N0-1M0 squamous-cell esophageal cancer at our institution were recruited, including patients who underwent NCRT (1 cycle of cisplatin and 5-fluorouracil with concurrent radiotherapy) or NCT (2 cycles of cisplatin and 5-fluorouracil only ) before esophagectomy. Results: From January 2009 to October 2015, a total of 177 patients were analyzed, with 72 received NCRT and the remaining 105 received NCT. The pathological complete response (pCR) rate was 22.2% (n = 16) in NCRT group and 9.5% (n = 10) in NCT group ( P= 0.019). The postoperative mortality was 1.4% in NCRT group, versus 4.8% in NCT group. The postoperative morbidity was 20.8% in NCRT group, versus 27.6% in NCT group. There was no significant difference in recurrence between the two groups ( P= 0.397). 1-,2-,3-year overall survival rates in NCRT and NCT group were 87%, 74%, 51% and 81%, 64%, 51%, respectively ( P= 0.527), and 1-,2-,3-year DFS rates were 77%, 54%, 50% and 65%, 54%, 46%, respectively( P= 0.379). Conclusions: For patients with locally advanced squamous-cell esophageal cancer, the addition of radiotherapy to neoadjuvant chemotherapy may result in higher complete pathological response with acceptable postoperative mortality and morbidity, while the long-term survival benefit is not significant.
Clinicopathologic differences and survival of Hispanics (H) versus Non-Hispanic Whites (NHW) with gastric cancer (GC) at a Majority Minority Cancer Center in South Texas.
Authors: Barron Cesar Ivan , Hernandez Brian , Mahalingam Devalingam , Michalek Joel , Patel Sukeshi R.
Published: March 2017

208

Background: Incidence rates for GC have shown to be increased in H vs NHW in studies. With a higher incidence of GC in South Texas compared to the rest of US, South Texas H have more than twice the incidence of GC than NHW with possibly worse survivals. However, these patients are not included in the SEER database, and the etiology of worse survival is unclear. To date, evaluation of a South Texas population with a more homogeneous H population has not been undertaken. Therefore, we chose to evaluate differences in clinical and histopathologic features in H vs NHW with GC at our South Texas NCI-designated cancer center where the homogenous H population is the majority. Methods: Retrospective analysis of GC patients from 2000-2016 at the Cancer Therapy and Research Center, San Antonio, TX. Median overall survival (mOS) was estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. Results: 168 patients with H 64% (n = 108), NHW 36% (n = 60). Median age 59 years (26-94): H 59.6 vs NHW 58.8 years. Females: H 48% vs NHW 37%. ECOG 0-1: H 48% vs NHW 53% (p = 0.46). Common Locations: H (Antrum 30%, Body 30%, GEJ 16%, Cardia 7%, Fundus 3%) vs NHW (Antrum 23%, Body 40%, GEJ 18%, Cardia 2%, Fundus 2%) (see table). Poorly differentiated: H 58.3% vs NHW 48.3% (P = 1). Stage IV at diagnosis: H 42% vs NHW 23% (P = 0.22). Diffuse-type: H 38% vs NHW 30% (P = 0.41); Intestinal-type: H 9% vs NHW 10% (P = 0.78). No significant difference in regards to Her2, H pylori, location of metastases. mOS: H 11 months (95% CI: 7-14) vs NHW 9.5 months (95% CI 6-n/a), p = 0.66. Conclusions: Despite historical worse prognosis of GC in H, at our majority minority cancer center in South Texas,H did not have a worse prognosis than NHW, and significant differences were not observed in clinicopathologic features. Prospective studies of H patients with GC should investigate differences in epidemiology, pathogenesis, and molecular signatures of GC between both groups to identify variables that correlate with survival and predict efficacy to cancer treatments. [Table: see text]
Entral feeding tube insertion after esophagectomy: Technique via transgastric conduit or transduodenal.
Authors: Ogata Takashi , Nakajima Tetsushi , Kano Kazuki , Maezawa Yukio , Ikeda Kousuke , Yamada Takanobu , Cho Haruhiko , Yoshikawa Takaki
Published: March 2017

210

Background: We always used early enteral feeding after esophagectomy as perioperative management. The common procedure for feeding tube insertion is jejunostomy, but sometimes complication such as internal hernia was occurred. In case of retrosternal gastric tube reconstruction, we usually inserted feeding tube through gastric conduit. But in case of posterior mediastinal gastric tube reconstruction, this procedure was not available because of the distance between abdominal wall and gastric tube. So we have developed the new procedure for feeding tube insertion using the mobilized round ligament of liver. Methods: The aims of the study is to clarify the safety of these procedures. In case of retrosternal reconstruction, we usually inserted feeding tube from prepylorus of gastric conduit, and feeding tube was delivered through pyloric ring to 3rd portion of duodenum(Procedure A). Insertion point of the tube was always close to abdominal wall, and easy to be guided to extra-abdomen. On the other hand, in case of posterior reconstruction, we used the new procedure as below(Procedure B). At first, the round ligament of liver was cut at the liver edge. Next, feeding tube was inserted 15~20cm from anterior wall of 2nd portion of duodenum with Witzel suture fixation. After that, feeding tube was led to outside of the abdominal wall through in the mobilized round ligament. The cut edge of round ligament was fixed to the duodenum wall with 4-point suture at tube insertion point, and finally feeding tube completely surrounded by round ligament without direct exposure to the abdominal cavity. And to prevent internal hernia, the space between abdominal wall and mobilized round ligament was covered by omental fat. Results: From January 2012 to December 2014, 126 cases were inserted by procedure A, and from June 2015 to February 2016, 35 cases were done by procedure B. There was no trouble derived from the feeding tube insertion such as intra-operative bleeding, leakage of digestive juice, infectious complication, ileus, and there was no trouble in removal at outpatients in both procedures. Conclusions: Both procedures were safe, so we can manage the feeding tube insertion route by the reconstruction route after esophagectomy.
Phase II trial of cabozantinib in patients with carcinoid and pancreatic neuroendocrine tumors (pNET).
Authors: Chan Jennifer A. , Faris Jason Edward , Murphy Janet E. , Blaszkowsky Lawrence Scott , Kwak Eunice Lee , McCleary Nadine Jackson , Fuchs Charles S. , Meyerhardt Jeffrey A. , Ng Kimmie , Zhu Andrew X. , Abrams Thomas Adam , Wolpin Brian M. , Zhang Sui , Reardon Amanda , Fitzpatrick Bridget , Kulke Matthew H. , Ryan David P.
Published: March 2017

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Background: Activation of VEGFR2 and c-MET has been implicated in driving growth of neuroendocrine tumors (NET); additionally, expression of c-MET has been associated with shorter survival. Cabozantinib inhibits VEGFR2 and c-MET. We performed a two-cohort phase II study to evaluate the efficacy of cabozantinib in patients (pts) with advanced carcinoid or pNET (NCT01466036). Methods: Pts with progressive, well differentiated, grade 1-2 carcinoid or pNET were enrolled in parallel cohorts and treated with cabozantinib 60 mg po qd . There was no limit to prior therapy. Pts were restaged every 2 mos for the first 6 mos, then every 3 mos. The primary endpoint was objective response rate as measured by RECIST 1.1. Enrollment of approximately 35 patients of each tumor type was planned. Results: 41 pts with carcinoid (median age 63 yrs, 44% male, % ECOG PS 0/1 = 51/49) were accrued. Accrual to the pNET cohort was halted due to investigator/sponsor decision after 20 pts (median age 55 yrs, 60% male, % ECOG PS 0/1 = 40/60). Carcinoid pts completed a median of 8 (range 0-44) 28-day treatment cycles; pNET pts completed a median of 10 (0-35) cycles. 14 pts remain on treatment. Reasons for discontinuation were progression or death (51%), withdrawal of consent or investigator decision (28%), adverse events (AE, 21%). 3/20 pts with pNET achieved PR (ORR 15%, 95% CI 5-36%); 15/20 had SD. 6/41 pts with carcinoid achieved PR (ORR 15%, 95% CI 7-28%); 26/41 had SD . Median PFS was 21.8 mo (95% CI, 8.5-32.0 mo) in pts with pNET and 31.4 mo (95% CI, 8.5 mo-NR) in pts with carcinoid. Gr 3/4 toxicity in ≥ 1 pt included hypertension (13%), hypophosphatemia (11%), diarrhea (10%), lymphopenia (7%), thrombocytopenia (5%), fatigue (5%), increased lipase or amylase (8%). Unexpected Gr 3/4 AEs included heart failure and autoimmune hemolytic anemia, each in 1 pt. 81% of 53 pts completing more than 1 cycle of treatment required dose reduction from the initial 60 mg dose. Conclusions: Treatment with cabozantinib was associated with objective tumor responses and encouraging PFS durations in patients with advanced carcinoid and advanced pNET. While dose reduction was common, treatment was tolerable. Further evaluation of cabozantinib is warranted in both NET subgroups. Clinical trial information: NCT01466036.
Oesophageal cancer: Commonly familial, possibly heritable.
Authors: Peters Niamh , King Sinead , O'Donovan Emily , Gallagher David James , Reynolds John V
Published: March 2017

23

Background: Oesophageal cancer (OC) accounts for 400 deaths in Ireland per year. Prognosis remains poor, and improved prevention is needed. Familial clustering has been described however, The Nordic Twin Study of Cancer does not support a strong hereditability. We investigated familial OC over a decade in Ireland. Methods: The independent records of two national referral services were reviewed: an oesophageal surgery database and a hereditary cancer genetics database. Demographic Factors including family history of OC were recorded from the surgical database. Families containing a single OC diagnosis were identified in the genetics database. Age at diagnosis and additional cancer diagnoses in the family were recorded. Results: 1238 patients with OC were seen at St. James’s Hospital from 2005 to 2015. Demographic characteristics are shown in Table. 641 patients (51%) had a family history of malignancy. Seventy eight (6.3%) reported a family history of OC, 6 (7.6%) of whom had two or more first degree relatives with OC and 10 (13%) had both a first degree and second degree relative with OC. More male relatives were diagnosed with OC than female (59% vs 41%).The majority (24%) with a family history were diagnosed at Stage III, the majority (29%) without a family history were diagnosed at Stage II. 1840 pedigrees from the genetic database were reviewed. No pedigree contained a Proband with OC.4.5%(n = 84) included at least one family member with OC. The median age at diagnosis was 64. Breast, colorectal and gastric were the most commonly associated cancers with median ages of 50,59 and 64 respectively. Conclusions: More than half of patients presenting with OC report a family history of cancer, with likely hereditary and environmental components. OC patients are rarely referred for genetic assessment, possibly due to treatment related morbidity and poor clinical outcome. [Table: see text]
HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for novel therapeutic targets.
Authors: Ethun Cecilia Grace , Postlewait Lauren McLendon , Lopez-Aguiar Alexandra Grace , Zhelnin Kristen , Krasinskas Alyssa , El-Rayes Bassel F. , Russell Maria C. , Kooby David A. , Staley Charles A. , Cardona Kenneth , Maithel Shishir Kumar
Published: March 2017

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Background: Heat shock protein (HSP) 90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known. Methods: HSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray (TMA) blocks created in triplicate for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution from 2000-2013. Primary outcome was recurrence-free survival (RFS). Results: Of 278 tumors reviewed, 194 (68%) were primary GEP NETs, and 31 (11%) were NET liver metastases. Of the primary GEP NETs, mean age was 56yrs, 42% were male; 103 (53%) were pancreas and 44 (23%) were small bowel. HSP90 expression was high in 66 (34%) and low in 128 (66%). Compared to low expression, high HSP90 was associated with lymphovascular invasion (70vs42%; p = 0.049) and advanced T-stage (T3/T4: 48vs27%; p = 0.01). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 147), high HSP90 was associated with decreased 1-, 3-, and 5-yr RFS (80%, 72%, 62%) compared to low (89%, 86%, 83%; p = 0.03), which persisted on multivariable analysis (HR 5.2, 95%CI 1.7-16.0; p = 0.004), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67 index. When assessing NET liver metastases, high HSP90 expression was seen in 4 (13%) patients and low in 27 (87%). Similar to primary GEP NETs, patients with liver metastases that exhibited high HSP90 expression had decreased 1-, 3-, and 5-yr progression-free survival (25%, 25%, 0%) compared to those with low HSP90 (69%, 49%, 33%; p = 0.052). Conclusions: Heat shock protein 90 exhibits differential expression in resected GEP NETs and liver metastases. High cytoplasmic expression is associated with early recurrence of disease, even after accounting for other adverse pathologic factors, including Ki-67 index. HSP90 inhibition is a potential target for novel therapeutic strategies for neuroendocrine tumors.
Second cancer risk after diagnostic and monitoring radiation exposure with computed tomography in patients with hepatocellular carcinoma.
Authors: Park Joong-Won , Ki Moran , Choi Hwa Young , Cho Hyunsoon , Lee Ju Hee , Koh Young Hwan
Published: March 2017

238

Background: Contrast-enhanced dynamic computed tomography (CT) is preferred for initial diagnosis and post-treatment monitoring of hepatocellular carcinoma (HCC). The risk of a second cancer with diagnostic and monitoring CT radiation exposure in HCC patients is unclear. Methods: We analyzed cumulative radiation dose (CRD) for diagnostic and monitoring CT with/without transarterial chemoembolization (TACE) in patients with HCC alone (HA group) and HCC patients with a second cancer (SC group), using the big dataset of the National Health Insurance of South Korea. We performed survival analysis, with death treated as a competing risk. Results: A total of 20,073 patients with HCC were enrolled. With a median follow-up of 5.7 years, the SC group comprised 2,005 patients, resulting in a standardized incidence ratio of 1.5 (95% confidence interval [CI], 1.4-1.6) in men and 1.7 (95% CI, 1.6-1.9) in women, as compared with the general population. Use of CT/positron emission tomography (PET) was significantly higher in the SC group (p<0.001). However, the CRD of CT/PET was not significantly different between the SC group and the alive HA group (median effective dose [ED], 93 mSv for the SC group and alive HA group, respectively, p=0.510). After including TACE (n= 9,004 [44.9%], median frequency 2), total CRD was not significantly different between the SC group and the alive HA group. CRD >300 mSv significantly increased the risk of second malignant neoplasms in the subgroup with >7 years of follow-up (YFU) (hazard ratio [HR] 2.01, 95% CI 1.38-2.92, p<0.001). Second cancers in digestive organs and respiratory-intrathoracic organs were significantly increased by CRD in the subgroup with >300 mSv and over 7 YFU (HR 2.41, 95% CI 1.26-4.62; HR 5.69, 95% CI 1.62-20.04, respectively, p<0.01). TACE did not affect the increased risk of second cancers in digestive and respiratory organs in the subgroup >300 mSv and over 7 YFU. Conclusions: The risk of second cancers increased in HCC patients who survived over 7 years with CRD >300 mSv. Consideration of alternative monitoring tests and guidelines for reducing radiation exposure is crucial for long-term HCC survivors.
Long-term quality of life comparison after endoscopic submucosal dissection versus surgery in early gastric cancer patients.
Authors: Kim Young-Il , Kim Young Ae , Kim Chan Gyoo , Ryu Keun Won , Kim Young Woo , Sim Jin Ah , Yun Young Ho , Choi Il Ju
Published: March 2017

24

Background: The aim of this study was to compare the serial changes of health-related quality of life (HRQOL) after Endoscopic submucosal dissection (ESD) with those after surgery in patients with early gastric cancer (EGC). Methods: Gastric cancer patients were prospectively enrolled from 2004 through 2007. HRQOLs of 161 EGC patients were prospectively assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) and the stomach cancer-specific module EORTC-QLQ-STO22 at the baseline, 1, 6, 12, 18 and 24 months after treatments. Analysis was done using the generalized linear model and paired- ttests. Results: Of 161 patients, 48 (29.8%) underwent ESD (ESD group) and 113 (70.2%) underwent surgery (surgery group). The median age of stomach cancer patients was 57 years. Surgery group had poorer scores compared with those of ESD group in the most HRQOL factors one month after treatments ( P< 0.05), except for emotional and cognitive functioning, financial problems, anxiety, and hair loss. However, most of the functional and symptom scales after surgery subsequently improved and became insignificant until 24 months of follow up. Only 3 parameters including physical functioning, diarrhea and body image in ESD group still remained better until 24 months after treatment ( P< 0.05). Conclusions: Because poorer HRQOLs after surgery in the early post-treatment periods become insignificant during long-term follow-up, surgical treatment should not be discouraged in EGC treatment solely based on the QOL aspects.
Clinical features and tumor mutational profile of younger versus older patients with cholangiocarcinoma (CCA).
Authors: Goyal Lipika , Reyes Stephanie , Jain Apurva , Shroff Rachna T. , Le Tri Minh , Rahma Osama E. , Kelley Robin Kate , Bocobo Andrea Grace , Kanakamedala Advaita , Boyhen Kylie , VanCott Christine , Lindsey Stacie , Zheng Hui , Zhu Andrew X. , Javle Milind M.
Published: March 2017

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Background: As seen in lung cancer, young patients with cancer can have different risk factors, presentation, and tumor genotype than older patients with the same disease. The clinical and molecular features of young patients with CCA have yet to be well characterized. Methods: Retrospective chart review was performed on patients with intrahepatic (ICC) or extrahepatic cholangiocarcinoma (ECC) across 5 institutions. Data on demographics, risk factors, treatments, pathology, and overall survival (OS) were collected. Tumor genotyping results from MGH SNaPShot and Foundation Medicine were analyzed. Log-rank tests and Kaplan-Meier survival curves were used for statistical analysis. Results: Of 567 patients analyzed, 134 (23.6%) were < 50 years old (yo) and 455 (80.2%) had ICC. When assessed for risk factors, younger patients ( < 50yo) were more likely to have primary sclerosing cholangitis (PSC) (p < 0.001) and less likely to have diabetes (p = 0.05), compared to older patients ( ≥ 50yo). Surgical resection rates were similar in younger vs older patients (41.9 vs 42.6%, p = 0.890), but younger patients had larger tumors (median size 7.1 vs 5.3cm p = 0.012). Younger patients were also more likely to receive palliative systemic chemotherapy (p < 0.001) and more lines of therapy (median, 2 vs 1 line, p < 0.001). Frequency of treatment with liver directed therapy did not differ between the two groups. Molecular testing was performed on 222/567 (39.1%) patients of which 84/134 (62.7%) were younger patients and 138/433 (31.9%) were older patients. FGFR aberrations were more common in younger patients versus older patients (17.6 vs. 5.7%, p = 0.002). Targeted therapy was given to 15/84 (17.9%) younger and 28/138 (20.3%) older patients based on results of mutational profiling. Finally, no significant difference was seen in OS between younger and older patients (22.9 vs 22.7 months, p = 0.89). Conclusions: Younger patients with CCA may have different risk factors, tumor biology, and tolerance of systemic therapy compared to older patients. Further study is needed as referral patterns to tertiary care centers and motivation of younger patients to seek tertiary care may impact these results.
Real-world evidence (RWE) to show improved time to progression among resected pancreatic cancer (RPC) patients receiving adjuvant chemotherapy (adjch).
Authors: Kish Jonathan , Feinberg Bruce A. , Maida Tracy , Biggs Craig , Mujumdar Urvi , Chopra Dhruv , Laney Jalyna R. , Kennedy Eugene
Published: March 2017

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Background: Two recent clinical trials (IMPRESS and APACT) suggest the overall survival (OS) of patients with resected pancreatic cancer (RPC) is far longer than previously believed. Improvements in patient selection, intra/post-operative surgical care adjch are suggested as explanations for the improved OS. RWE of time to progression (TTP) from surgery were calculated to assess if the results of these trials are generalizable. Methods: RPC patients (ICD-9=157.x, excluding 157.4; CPT=48140, 48146, 48150, 48152-5) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 administrative claims database. Adjch was defined as initiating chemotherapy within 90 days of surgery. TTP was the time from surgery until the first claim for metastatic disease (ICD-9 =196.0-.3, .5-.6, 197.0-.8, 198.0-.8) using the Kaplan-Meier method. Patients without a metastatic diagnosis during their follow-up were censored at 12 months to adjust for underreporting of metastatic disease codes in claims. Results: 1,014 RPC patients selected. Mean follow-up time was 12.9 months (SD = 10.8). Mean age at diagnosis was 62.7 years (SD = 13.0) and 39.7% (n=403) had commercial insurance, 40.9% (n=415) Medicare and 18.5% (n=188) Medicaid. Of all RPC patients, 54.4% (n=552) received any chemotherapy of which 59.8% (n=330) was adjch; 37.4% (n=379) were diagnosed with metastatic disease at the time of or following resection. The rate of progression events was 40.5% (n=277) without adjch and 30.9% (n=102) with adjch (p<0.01). Among all resected patients, median TTP was 15.7 months (95% CI: 13.8-26.0) with 93.7% (n=355) of progression events by 12 months. Median TTP was 20.4 months (95% CI: 15.5-NR) in patients receiving adjch vs 17.7 months (95% CI: 17.7-31.5) without adjch (p=<0.0001). Conclusions: This analysis demonstrated a 2.7 month longer TTP for patients who received adjch compared to those who did not (p<0.0001). The median TTP in both adjch and non-adjch groups was longer than the observed in the ESPAC-1 trial for adjch patients TTP (15.3 months) and OS (20.1 months). These data support a new baseline for efficacy in adjch trials and are in line with more recent RCT estimates.
Incidentally discovered pancreatic ductal adenocarcinoma: Is detection of asymptomatic cancer associated with better outcomes than symptomatic cancer?
Authors: Takeda Yoshinori , Saiura Akio , Mise Yoshihiro , Ishizawa Takeaki , Inoue Yosuke , Takahashi Yu , Ito Hiromichi
Published: March 2017

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Background: The number of incidentally discovered asymptomatic pancreatic ductal adenocarcinoma (APDAC) has been increasing along with recent wide spread use of imaging studies in general practice. However, the clinical implication in early detection of asymptomatic pancreatic cancer remains yet to be determined. In this study, we reviewed our experience of patients with PDAC in high volume cancer center and compared the characteristics and long-term outcomes between those with APDAC and symptomatic PDAC (SPDAC). Methods: This retrospective study included 569 consecutive patients with PDAC initially treated in our institution from January 2007 to December 2012. Median follow-up period was 29 months for the survivors. Two hundred and fifty patients underwent surgical resection and 319 patients were deemed unresectable. The patient’s demographics, tumor locations, pathologic stages, and treatment type received, and the overall survival (OS) were compared between the patients with APDAC and those with SPDAC. Results: One hundred and sixty-three patients (29%) presented without any subjective symptoms. When compared with SPDAC, APDAC was associated with early stage (stage I, 6% vs. 1%, p<0.01). Among 163 patients with APDAC, 104 patients (64%) underwent surgical resection, while only 146 patients (36%) out of 406 SPDAC underwent resection ( p<0.01). The 5-year OS rate of the patients with APDAC was 18%, comparing with 7% for those with SPDAC ( p<0.01). Among the patients who underwent resection, the presence of symptoms did not affect the chance of incomplete resection (R1, 12% vs. 22% for patients with APDAC and SPDAC, respectively, p=0.06) and the 5-year OS rate (23% vs. 22%, p=0.09). However, the patients with SPDAC required complex operation (concomitant vascular resection and reconstruction 56% vs. 29% for those with APDAC, p<0.01). Conclusions: Asymptomatic PDAC is associated with better long-term outcomes than symptomatic PDAC due to early stage at presentation and higher chance of resectability. Our findings highlight the potential implication of screening program for early detection of PDAC for selected high-risk patient population.
Multigene hereditary cancer panel testing for patients with pancreatic cancer.
Authors: McGill Anna K , Solomon Sheila R , Marshall Megan L , Susswein Lisa , Fillman Corrine , Skora Katherine A , Vogel Postula Kristen J , Klein Rachel , Hruska Kathleen S. , Xu Zhixiong
Published: March 2017

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Background: Pancreatic ductal adenocarcinoma (PC) is associated with multiple hereditary cancer syndromes. Genes implicated in hereditary PC include ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2 and PMS2. The advent of multi-gene hereditary cancer panel testing streamlines diagnoses and medical management for clinicians and patients. Our objective was to assess the yield of pathogenic/likely pathogenic variants (PV/LPV) in individuals with PC undergoing panel testing as an initial test at GeneDx. Methods: We retrospectively reviewed panel test results of 605 individuals reporting a personal history of PC. Panel testing evaluated up to 32 genes associated with hereditary cancer. Individuals reporting neuroendocrine pathology or previous BRCA1/BRCA2 testing were excluded. Results: In this cohort, 61 PV/LPV were detected in 57 individuals in the following genes: ATM (17), BRCA2 (14), BRCA1 (5), CDKN2A (5), PALB2 (5), CHEK2 (4), MLH1 (2), MUTYH (2), PMS2 (2), BARD1 (1), FANCC (1), MSH2 (1), RAD51D (1) and TP53 (1), corresponding to a positive yield of 9.4% (57/605). Fifty-one of 61 PV/LPV were detected in genes associated with PC (84%) while 10 PV/LPV (16%) were identified in other genes including BARD1, CHEK2, FANCC, MUTYH, and RAD51D. The diagnostic yield among those reporting a family history of PC (33/294, 11.2%) was not statistically different from those without a reported family history (24/311, 7.7%). However, PV/LPV in ATM were detected more often in individuals reporting a family history of PC compared to those without a family history (4.1% vs. 1.6%, p=0.018). Conclusions: In total, 9.4% of patients with PC tested positive for PV/LPV in 14 different genes by panel testing. Although the majority of PV/LPV were identified in known PC genes, 16% of positive findings occurred in genes not typically associated with PC. ATM was most commonly implicated and more frequently reported in patients reporting family histories of PC. Assessing whether these genes are indeed causally related to PC and/or are possibly associated with other cancer types requires further investigation. Based on our results we conclude multi-gene panel testing may be considered as a first option for patients with PC regardless of their family history.
A population-based study of biliary tract cancers (BTCs) in Alberta, Canada: How do our patients fare?
Authors: Lui Arthur Gregory Ang , Yusuf Dimas , Randolph Brock , Tam Vincent C. , Bathe Oliver F. , Ghosh Sunita , Spratlin Jennifer L.
Published: March 2017

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Background: BTCs are poorly studied due to their rarity and heterogeneity. We explored demographics and outcomes of BTC pts over a 15 year period. Methods: All patients (pts) with biopsy-proven BTC (intrahepatic [IC] and extrahepatic [EC] cholangiocarcinomas, gallbladder cancers [GB], and ampulla of vater cancers [AV]) in Alberta were reviewed from January 1, 2000, to December 31, 2015. Demographic, pathologic, and survival data were extracted from electronic charts. Descriptive statistics were utilized. Overall survival (OS) was defined as the time from pathologic diagnosis to death date. Results: A total of 1,718 pts with BTCs were identified. Median age was 68 with 52% being male. The Table demonstrates OS breakdown based on tumour location and stage. Regardless of location of primary tumour, grade impacted survival (median OS in with well differentiated tumours vs undifferentiated tumors 26.6 vs 3.9 months). Pts who received standard of care palliative cisplatin/gemcitabine (Cis/Gem) chemotherapy (n = 123) had a median OS of 15.4 months. Conclusions: Patients with AV and IC have the best and worst prognosis, respectively. Shorter survival is observed with higher stage, grade, and unresectable disease. Pts who received palliative Cis/Gem had better OS than reported in the pivotal phase III trial. Further analysis of prognostic factors will be presented. [Table: see text]
Racial and ethnic disparities among young patients with gastric cancer.
Authors: Nassour Ibrahim , Mokdad Ali , Khan Madiha , Mansour John C. , Yopp Adam Charles , Minter Rebecca M , Polanco Patricio , Augustine Mathew M , Choti Michael A. , Wang Sam C. , Porembka Matthew
Published: March 2017

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Background: Although up to 15% of patients with gastric cancer present at young age, the characteristics of these patients are not well described. We sought to determine if there are different clinical and pathologic characteristics associated with race and ethnicity in young gastric cancer patients. Methods: We identified all gastric adenocarcinoma patients who were younger than 45 years in the National Cancer Data Base between 2006 and 2013. We analyzed patient, tumor, and treatment-related factors as well as overall survival using standard statistical methods. Results: 5,869 patients were identified with 40.6% being Non-Hispanic Whites (NHW), 27.7% Hispanics (HS), 16.9% African Americans (AA), and 9.0% Asians (AS). HS patients presented at a younger age compared to the other groups (p < 0.01). HS presented most often with metastatic disease (59.2%) followed by AA (50.2%), NHW (49.6%), and AS (49.8%; p < 0.01). NHW presented more often with tumors in the cardia (45.7%) compared to AA (12.7%), HS (12.5%), and AS (9.6%, p < 0.01). HS (28.4%) and AA (14.2%) were more likely to be uninsured compared to AS (12.0%) and NHW (7.1%; p < 0.01). AA (60.5%) and HS (49.1%) were more likely to have below median income compared to NHW (35.8%) and AS (24.2%, p < 0.01). AS had better overall outcome, with median overall survival of 22.7 months compared to 15.2 months for NHW, 14.0 months for HS and 13.6 months for AA (p < 0.01). Independent variables associated with favorable survival included being AS or HS, cardia tumor, treatment at an academic center, higher income, and low Charlson Comorbidity Index. Conclusions: There is racial/ethnic variability in disease presentation, treatment delivery, and outcomes in young gastric cancer patients. Further studies are warranted to determine whether these variations are due to disparity in health care access and/or inherent difference in biology.
Impact of BRCAness on the efficacy of oxaliplatin-based chemotherapy in patients with unresectable pancreatic cancer.
Authors: Kondo Tomohiro , Kanai Masashi , Kou Tadayuki , Sakuma Tomohiro , Mochizuki Hiroaki , Kamada Mayumi , Nakatsui Masahiko , Uza Norimitsu , Kodama Yuzo , Masui Toshihiko , Takaori Kyoichi , Matsumoto Shigemi , Miyake Hidehiko , Okuno Yasushi , Muto Manabu
Published: March 2017

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Background: Defects in individual genes that are involved in homologous recombination repair (HRR) is called “BRCAness” and several studies suggested that patients with BRCAness are more sensitive to platinum-based chemotherapy (Golan et al, 2014; Lowery et al, 2011; Vollebergh et al, 2014). We introduced the multiplex gene panel test into daily clinical practice since April 2015 at Kyoto University Hospital, in which we can monitor the entire coding region of 215 cancer-related genes and the rearrangement of 17 frequently rearranged genes. The purpose of this study was to evaluate the association between BRCAness status monitored by multiplex gene panel test and clinical outcome of patients with unresectable pancreatic ductal adenocarcinoma (PDAC) who received oxaliplatin-based chemotherapy. Methods: A total of consecutive 17 patients with histologically confirmed PDAC who underwent multiplex gene panel test were eligible. BRCAness status was determined according to the results of multiplex gene panel test. Oxaliplatin-based chemotherapy included FOLFIRINOX, GEMOX and SOX. We assessed the time to treatment failure (TTF) to evaluate the efficacy of oxaliplatin-based chemotherapy by log-rank test. Results: BRCAness-related mutations were detected in BRCA2 (n = 6), ATM (n = 4), ATR (n = 2), BRCA1 (n = 2), and PALB2 (n = 1). Based on these results, 11 patients were classified into non-BRCAness group and six patients were into BRCAness group. Seven and five patients received oxaliplatin-based chemotherapy in non-BRCAness and BRCAness group, respectively. Median TTF of oxaliplatin-based chemotherapy was 52 days (95% confidence interval [CI], 40–90 days) in non-BRCAness group and 294 days (95% CI, 56 days–NA) in BRCAness group. The difference was statistically significant (P = 0.027). Of note, two patients with BRCAness showed good response to FOLFIRINOX without disease progression > 500 days. Conclusions: BRCAness-related mutations could be a promising predictive marker of the efficacy of oxaliplatin-based chemotherapy.