bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereotactic body radiation therapy following transarterial chemoembolization for Child-Pugh A and B hepatocellular carcinoma.
Authors: Baden Craig Joseph , Hinton Benjamin , Jacob Rojymon
Published: February 2017

321

Background: Hepatocellular carcinoma (HCC) incidence continues to increase, but recent improvements in treatment of localized tumors have contributed to modest gains in survival rates. Though transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) are increasingly used in the management of unresectable HCC, outcomes data regarding the combination of these treatments is limited. Here we report institutional outcomes for patients with Child-Pugh A (CPA) and B HCC treated with TACE followed by SBRT. Methods: We completed an institutional retrospective review of all patients treated with combination TACE and SBRT between 2009 and 2013. After compiling dosimetry, toxicity, and outcomes data for each patient we calculated descriptive statistics for the cohort and determined local control (LC), distant liver control (DLC), progression free survival (PFS), and overall survival (OS) utilizing the Kaplan-Meier method. We also compared these disease-related outcomes between CPA and CPB groups with the Mantel-Cox test for equality. Results: Thirty-one patients with HCC, median age 65, were treated with TACE and SBRT and followed for a median 16.6 months (range: 6.2-50.8). Twenty-two patients had CPA disease and 9 CPB at the time of initial treatment. Following TACE and a median interval of 10.5 days (range: 4.4-25.6) patients underwent SBRT, the majority (23) with 45 Gy in 3 fractions. All but 3 patients were treated with respiratory gating, and all had cone-beam CT for image guidance. One and 2 year disease-related outcomes were as follows: LC 92.0 and 82.8%, DLC 81.5 and 61.0%, PFS 73.6 and 61.8%, OS 96.8 and 64.2%. There were no statistically significant differences between CPA or CPB patients with respect to any of these disease-related outcome measures. Median survival times for class A and B patients were 34.2 months (95% CI 12.3-56.1) and 27.2 months (14.9-39.5) respectively. Conclusions: The combination of TACE and SBRT is generally well tolerated, and results in very good local control in both CPA and CPB patients. Distant liver failure remains a major problem in these patients and requires further study.
Use of staging and scoring systems in hepatocellular carcinoma (HCC): Lessons from U.S. regional analysis of the GIDEON registry.
Authors: Miksad Rebecca A. , Cohn Allen Lee , El-Khoueiry Anthony B. , Geschwind Jean-Francois , Gholam Pierre Michel , Goldenberg Alec , Mantry Parvez , Martin Robert C. G. , McGuire Brendan , Piperdi Bilal , Sanyal Arun J. , Imperial Joanne , Venook Alan Paul
Published: February 2017

323

Background: Because HCC usually occurs in the presence of liver disease, patient (pt) evaluation and treatment are complex and require multidisciplinary care. Tumor staging and liver function scoring systems facilitate HCC research and treatment. However, specialists have varied training in these systems. We evaluated specialty-specific reporting of HCC-related staging/scoring data. Methods: GIDEON is a global, prospective, non-interventional study to evaluate sorafenib (SOR) in HCC under real-life practice conditions. Pts with unresectable HCC who were candidates for systemic therapy and for whom a decision was made to treat with SOR were eligible. Frequency of recorded Child-Pugh (CP); Barcelona Clinic Liver Cancer (BCLC); Cancer of the Liver Italian Program (CLIP); Tumor, Nodes, Metastasis (TNM); and calculated Model for End-stage Liver Disease (MELD) data were analyzed by physician specialty. Results are descriptive. Results: In the safety population (n=563), 299 pts (41%) were enrolled by medical oncology (MO), 228 (40%) by hepatology/gastroenterology (H/G), and 39 (5%) by other (23 by surgeons; 7 by interventional radiologists). 89% were treated by a multidisciplinary team. MO pts were twice as likely as H/G pts to be not evaluable (NE) for CP (table). Unknown international normalized ratio (INR) was the primary reason CP was NE. MO and H/G pts had similar % NE for BCLC stage. H/G pts were more likely to have ECOG performance status (PS) not recorded. MO pts were less likely to have CLIP or MELD data, while H/G pts were less likely to have TNM data. Portal vein thrombosis (PVT) and alpha-fetoprotein (AFP) were unknown in 17% overall. Conclusions: The elements of HCC staging systems represent factors that may influence patient management. Lack of complete data in up to 44% of pts, despite registry enrollment requiring data collection, suggests clinicians may be missing important information and the prevalence of clinicians using comprehensive HCC staging systems is variable. Clinical trial information: NCT00812175. [Table: see text]
Clinicopathologic features of gastric cancer in the elderly population.
Authors: Lim Joo Hyun , Lee Dong Ho , Shin Cheol Min , Kim Na Yung , Park Young Soo , Jung Hyun Chae , Song In Sung
Published: February 2017

33

Background: Gastric cancer is one of the most common cancers, having great incidence among the elderly. However, little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Methods: We reviewed medical records of 1107 patients who had undergone radical gastrectomy for gastric cancer between June 2005 and December 2009 retrospectively. They were divided into young age group (<65, n = 676), middle age group (65 ≤ age < 75, n = 332) and old age group (≥75, n = 99). To find out potential risk factors, these following factors were reviewed; symptoms, comorbidities, tumor marker levels, stages, H. pylori status, locations, Lauren type, differentiation, complications, microsatellite instability and p53 overexpression. Results: Elevated levels of CA 19-9 (5.6%, 13.4% and 14.6%, P = 0.001), advanced diseases (42.5%, 47.0% and 57.6, P = 0.014), and node metastasis (37.6%, 38.9% and 51.5%, P = 0.029) were more frequently detected in the middle and old age groups. However, no significant differences in H. pylori status (63.6%, 56.7% and 61.2%, P = 0.324) were observed among the three groups. Elderly patients had a tendency to show intestinal type in Lauren’s classification (40.7%, 58.7%, and 56.6%, P < 0.001). The rate of surgery-related complications did not differ among the three groups (5.3%, 5.1%, and 8.1%, P = 0.497). Microsatellite instability (P < 0.001) and p53 overexpression (P < 0.001) were more frequently found among the elderly patients. Conclusions: Gastric cancer in elderly patients was related to features known for favorable prognosis except p53 overexpression, despite the more advanced stage. Surgery in the elderly was as tolerable as in young patients. We recommend looking favorably upon surgery for elderly patients with operable gastric cancers.
Adjuvant chemoradiation to improve survival compared to adjuvant chemotherapy in selected patients with pancreatic cancer.
Authors: Kumar Aryavarta M. S. , Falk Gavin , Stephans Kevin L. , Walsh Matthew , Pelley Robert James , Abdel-Wahab May
Published: February 2017

330

Background: While surgery remains the only potential curative option for resectable pancreatic cancer, adjuvant therapy improves outcomes over surgery alone; however, adjuvant recommendations of chemotherapy vs chemoradiation remain controversial. We present outcomes comparing the two adjuvant treatments. Methods: In our single institution review, 343 patients (2000-2012) had pancreatoduodenectomy for pancreatic cancer. Medical oncology made adjuvant recommendations. Chemotherapy was gemcitabine or 5-FU and radiotherapy prescription was 45-54 Gy. Locoregional recurrences (LRR) were operative bed or regional nodal failures. Results: Median follow up and median survival (MS) for all patients was 17.5 and 19.5 mo respectively. 130 patients had resection alone (A), 84 had adjuvant chemotherapy (B), and 129 had adjuvant chemoradiation (C). MS for groups A, B, and C were 13, 23 and 26 mo respectively. Locoregional recurrence (LRR) was 60%, 63%, and 38% and distant failure was 64%, 65%, and 66% for groups A, B, and C respectively. Group C had significantly lower LRR compared to group B (p=0.01) however, survival between groups B and C was not statistically significant (p=0.23). Angiolymphatic invasion (ALI) and perineural invasion were correlated with LRR (p<0.01). Multivariable analysis showed LRR, laparoscopy, ALI, and the interaction term of LRR with surgical margin were significant predictors of survival (p<0.05). MS of patients with lymph node ratio (LNR) > 0.2 and LNR ≤ 0.2 was 18 and 27 mo respectively. Subgroup analysis showed survival advantages to adjuvant chemoradiation compared with adjuvant chemotherapy. R1 resections in groups B and C were 37% and 39% (p=ns) with MS of 16 vs 27 mo respectively (p=0.01). For patients with ≥ 8 LN dissected and LNR ≤ 0.2, MS was 24 vs 32 mo for groups B and C respectively (p=0.04). Conclusions: Adjuvant chemoradiation significantly decreases LRR in resected pancreatic cancer patients. Compared to adjuvant chemotherapy alone, adjuvant chemoradiation improved survival for patients with a 1) positive surgical margin and/or 2) LNR ≤ 0.2 with ≥ 8 LNs dissected.
Prognostic role of C-reactive protein levels in patients with hepatocellular carcinoma undergoing sorafenib therapy.
Authors: Lee Jean Kyung , Harding James J. , Chou Joanne F. , Capanu Marinela , Saltz Leonard , Abou-Alfa Ghassan K.
Published: February 2017

340

Background: Markers of systemic inflammatory response including C-reactive protein (CRP) are associated with the prognosis of various malignancies including HCC. We investigated the significance of the serum CRP level as a prognostic factor in patients with advanced HCC on sorafenib therapy. Methods: The MSKCC institutional database was retrospectively queried for patients diagnosed with advanced HCC who received sorafenib therapy from 2002-2012 and had available serum CRP measurements. Patient demographics and outcomes were extracted under an IRB-approved waiver. Baseline CRP levels within 30 days of starting of sorafenib and while on sorafenib treatment were correlated with clinical outcomes. CRP levels after the initiation of sorafenib were analyzed as a time dependent covariate in a Cox regression model. Results: 51 patients had available CRP levels and received sorafenib: Median age 65 years (range 45-82); KPS 80 (70-90%); 9 females (17.6%); 32 AJCC stage IV disease (62.7%); 10 AJCC stage III (19.6%); 12 hepatitis C (23.5%), 10 hepatitis B (19.6%), 12 alcohol (23.5%), and 20 non-alcoholic steatohepatitis (39%); and 43 Child-Pugh A (84.3 %). The median time on sorafenib was 2.4 months (range 0.2-21.6). The median overall survival (OS) was 9.2 months [CI 5.8 – 13.6] and the median progression-free survival (PFS) was 2.1 months [CI 1.6 – 2.6]. 46 of 51 patients had baseline CRP levels available for analysis. Baseline CRP level was associated with OS [hazard ratio (HR) 1.2 (CI 0.996 – 1.4, p=0.056)] but not with PFS [HR 1.1 (CI 0.96-1.3, p=0.14)]. Time dependent covariate analysis demonstrated an association between CRP levels during sorafenib therapy and overall OS [HR 1.08 (CI 1.01-1.16, p=0.02)] as well as PFS [HR 1.09 (CI 1.02 – 1.16, p=0.009)]. Conclusions: Baseline CRP level prior to the start of sorafenib therapy showed a borderline significant association with OS but no association with PFS. Higher CRP levels showed a significant association with increased risk of disease progression and death for sorafenib treated HCC patients. Potential prognostic role of CRP in HCC patients undergoing sorafenib therapy is to be further studied prospectively.
Survival trends in chemorefractory unresectable intrahepatic cholangiocarcinoma (ICC) and the effect of yttrium-90 (Y90) radioembolization: SEER versus tertiary cancer center.
Authors: Xing Minzhi , Prajapati Hasmukh J. , Kokabi Nima , Camacho Juan C. , El-Rayes Bassel F. , Kim Hyun Sik
Published: February 2017

342

Background: Survival in patients with chemorefractory unresectable ICC treated with Y90 radioembolization vs. best supportive care has not been investigated in large-scale population studies. Methods: Under IRB approval, our institute’s cancer registry was queried for Y90-treated patients with chemorefractory unresectable ICC diagnosed from Jan 2002 to Nov 2011. Eighteen registries of U.S. Surveillance, Epidemiology and End Results (SEER) database were queried for patients with advanced ICC not amenable to surgery/radiation diagnosed in the same period. Baseline characteristics, median overall survival (OS) from ICC diagnosis and median OS from first Y90 were stratified by national/state cohorts. Survival analysis and 95% confidence intervals (CI) were calculated using Kaplan-Meier estimation. Results: A total of 24 patients who received Y90 therapy for chemorefractory unresectable ICC (Group A) and 2757 patients with unresectable ICC who received neither radiation nor cancer-directed surgery (Group B) were included. Both groups were similar for mean age at diagnosis, gender, race, bilobar disease, portal vein thrombosis and mean largest tumor size (p>0.05). Median OS from ICC diagnosis was 20.8 months (Group A; 95% CI, 11.2-30.5) and 3.0 months (Group B; 95% CI, 2.7-3.3), p<0.001. Median OS from first Y90 was 11.5 months (Group A; 95% CI, 4.8-18.2). Interval survival rates from ICC diagnosis for Group A vs. B were: 100% vs. 77% (1 month), 100% vs. 63% (3 months), 92% vs. 30% (6 months), 67% vs. 17% (1 year), 42% vs. 6% (2 years), and 17% vs. 3% (3 years). Conclusions: Y90 radioembolization in patients with chemorefractory unresectable ICC demonstrated significantly greater median OS and favorable long-term survival rates compared to best supportive care. [Table: see text]
Adherence to the BCLC guidelines and impact on overall survival.
Authors: Mathew Jesna , Slipak Sasha , Kotru Anil , Blansfield Joseph , Woll Nicole , Shabahang Mohsen
Published: February 2017

345

Background: Multiple studies exist that validate the prognostic value of the Barcelona Clinic Liver Cancer (BCLC) staging. However, none have established a survival benefit to the treatment recommendations. The aim of this study was to evaluate the adherence to the BCLC guidelines at a rural tertiary care center, and to determine the effect of following the treatment recommendations on overall survival. Methods: A retrospective chart review was conducted for 97 patients newly diagnosed with hepatocellular carcinoma (HCC) from 2000 to 2012. The treatment choice was compared with the BCLC guidelines and percentage adherence calculated. Overall survival was estimated using the Kaplan-Meier method and the log rank test was used to test the difference between the two groups. Cox regression tests were used to determine independent effects of stage, treatment aggressiveness, and guideline adherence on survival. A p-value <0.05 was considered statistically significant. Results: Of 97 patients, 75% (n=73) were male. Median overall survival was 12.9 months. In 59.8% (n=58) of the patients, treatment was adherent to stage specific guidelines proposed by the BCLC classification. There was no significant difference in overall survival between the adherent and non-adherent groups (11.2 vs 14.1 months, p<0.98). However on stage specific survival analysis, we noted a significant survival benefit for adherence to the guidelines for early stage HCC (27.9 vs 14.1 months, p<0.05), but a decrease in survival for adherence in the end stage (20 days vs 9.3 months, p<0.01). On univariate analysis, more aggressive treatment was associated with increased survival (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.22 to 0.87; p = 0.018). Multivariate analysis revealed that adherence did not independently affect survival when stage and aggressiveness of treatment were included in the model (HR, 1.3; 95% CI, 0.76 to 2.2, p = 0.34). Conclusions: Although the BCLC guidelines serve as a practical guide to the management of patients with HCC, they are not universally practiced. These results indicate that survival of patients with hepatocellular cancer is determined by stage and aggressiveness of treatment, not adherence to BCLC guidelines.
Phase I study of adjuvant chemotherapy with gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1004).
Authors: Toyoda Masanori , Ajiki Tetsuo , Fujiwara Yutaka , Nagano Hiroaki , Kobayashi Shogo , Sakai Daisuke , Hatano Etsuro , Kanai Masashi , Nakamori Shoji , Miyamoto Atsushi , Tsuji Akihito , Kaihara Satoshi , Ikoma Hisashi , Takemura Shigekazu , Toyokawa Hideyoshi , Terajima Hiroaki , Ioka Tatsuya ,   Kansai Hepatobiliary Oncology Group (KHBO)
Published: February 2017

347

Background: GC has become a standard chemotherapy for patients with locally advanced or metastatic BTC. The benefit of adjuvant therapy for BTC is unclear, however, it is used worldwide due to BTC’s dismal prognosis. We conducted a phase I study for adjuvant chemotherapy with GC in patients with BTC in order to determine the maximum-tolerated dose (MTD) and recommended dose (RD). Methods: Patients with BTC were eligible if they met the following criteria: Stage IB or higher; undergoing resection without major hepatectomy; over 20 years of age; ECOG PS 0-1; adequate organ functions. The starting dose (Level 1) of GC was the same as the standard dose of advanced disease and dose was planned to adjust, using a 3+3 design with cohorts of 3-6 patients and further cohort expansion took place. The Dose Limiting Toxicities (DLTs) were determined during the first six weeks and RD was determined through the entire treatment. Results: One DLT out of 6 patients, with grade 4 neutropenia, was observed at Level 1 and an expanded cohort was further examined. A total of eighteen patients were enrolled and one DLT was observed as described above. During the first six weeks, the most common grade 3 or 4 related adverse events were neutropenia (n=10: 56%) and leukopenia (n=6: 33%). Through the entire treatment, non-hematologic toxicities were manageable. Seven (39%) patients completed the protocol treatment, seven (39%) dropped off due to the need of second time dose reduction, two didn’t meet starting criteria of creatinin with grade 1 increase in CTCAE, one had rapid tumor progression died within 30 days after the last administration of GC and one withdrew after reporting dead case. Conclusions: A standard dose of GC might be feasible for adjuvant chemotherapy for BTC undergoing curative resection without major hepatectomy. We selected standard dose of GC as RD for a subsequent phase II study. Clinical trial information: NCT01297998.
The role of staging laparoscopy in type 4 gastric cancer.
Authors: Sugisawa Norihiko , Bando Etsuro , Miki Yuichiro , Makuuchi Rie , Goto Hironobu , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Terashima Masanori
Published: February 2017

35

Background: In type 4 gastric cancer, the incidence of peritoneal metastasis which was unexpectedly found during surgery was as high as 40 percent. It is very difficult to detect peritoneal metastasis in clinical imaging such as computed tomography or ultrasound before operation. Staging laparoscopy (SL) is considered to be an only minimal invasive procedure to detect peritoneal metastasis. However, the significance of SL had not yet been fully elucidated. The aim of this study is to assess the role of SL in type 4 gastric cancer. Methods: From September 2002 to March 2012, a total of 169 patients with type 4 gastric cancer who were diagnosed as not having distant metastasis in clinical imaging were enrolled in this study. SL was performed for 56 patients, and the other 113 patients underwent open laparotomy (OL) without SL. We retrospectively examined the incidence of peritoneal metastasis and positive peritoneal cytology and treatment courses in patients who underwent SL and OL. Results: In 56 patients undergoing SL, 23 (41%) had peritoneal metastasis and 40 (71%) had positive peritoneal cytology. Similarly, 54 (48%) had peritoneal metastasis and 86 (76%) had positive peritoneal cytology in 113 patients undergoing OL. There were no significant differences of the incidence of peritoneal metastasis and positive peritoneal cytology between the two groups. Subsequent treatments after SL or OL were diverse depends on patients condition and participating clinical trials, however, 17 (32%) in SL group and 13 (12%) in OL group were treated without surgical interventions. There was no morbidity and mortality in both SL group and OL group. In SL group, open surgery was performed soon afterword in 39 patients. Among them, 2 patients was failed to detect peritoneal metastasis by SL. Therefore the accuracy of detecting peritoneal metastasis in SL was 23/25 (92%). Conclusions: In type 4 gastric cancer, the incidence of peritoneal metastasis was around 40% and positive peritoneal lavage cytology was around 70% in both SL and OL. As SL is less invasive than OL, SL appears to be a useful way to detect peritoneal seeding and establish treatment strategy in patients with type 4 gastric cancer.
Comparison of concurrent chemoradiotherapy and chemotherapy alone for locally advanced pancreatic cancer.
Authors: Choi Younak , Kim Tae-Yong , Oh Do-Youn , Kim Kyubo , Chie Eui Kyu , Lee Kyung-Hun , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Ha Sung W. , Bang Yung-Jue
Published: February 2017

351

Background: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), especially the role of chemoradiotherapy (CCRT), is still in debate. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with LAPC. Methods: We consecutively enrolled LAPC patients treated between 2003 and 2010. AJCC 7th edition was followed for the diagnostic criteria of LAPC. We retrospectively evaluated the clinical outcomes according to treatment groups (CCRT vs CA). Results: A total of 86 patients were enrolled. Median age was 60 years. ECOG PS was 0-1 in 77 (89.5%) and 2 in 9 (10.5%). Forty five patients (52.3%) were treated with CCRT and 41 patients (47.7%) with CA. Baseline characteristics were not significantly different between CCRT and CA group. In the CCRT group, gemcitabine (n=7, 15.6%), 5-FU (n=10, 22.2%), and capecitabine (n=28, 62.2%) were concurrently used with radiation. Radiation was delivered with 55.8Gy/ 31fraction. All of the CA group patients were treated with gemcitabine-based chemotherapy. Median progression free survival (PFS) and overall survival (OS) of whole patients were 6.9 months [95%CI 4.8-9.0] and 12.7 months [95%CI 11.6-14.3]. PFS and OS of CCRT versus CA was 8.9 months [95%CI 6.8-11.0] vs 3.7 months [95%CI 2.9-4.5] (p<0.001) and 15.8 months [95%CI 13.5-18.1] vs 11.3 months [95%CI 9.3-13.3] (p=0.017). In multivariate analysis, tumor size (≥3cm), positive lymph node, elevated CA 19-9, decreased serum albumin and CCRT was significant for PFS and OS (adjusted hazard ratio of CCRT was 0.424 (p=0.002) in PFS and 0.472 (p=0.014) in OS). Grade 3-4 hematologic toxicity was less frequent during CCRT period (p=0.002). Conclusions: In LAPC, patients who received CCRT show better OS and PFS compared with patients who were treated with palliative chemotherapy alone. It’s worthy to further study the role of CCRT in LAPC.
Prognostic factors of pancreatic neck cancer.
Authors: Hirono Seiko , Tani Masaji , Kawai Manabu , Okada Ken-Ichi , Miyazawa Motoki , Shimizu Atsushi , Kitahata Yuji , Ueno Masaki , Hayami Shinya , Shigekawa Yoshiyasu , Yamaue Hiroki
Published: February 2017

355

Background: Pancreatic neck cancer is surrounded by common hepatic artery (CHA), gastroduodenal artery (GDA) and portal vein (PV), and easily invades nerve plexus around main arteries, such as CHA, celiac trunk, and superior mesenteric artery (SMA). Therefore, the resectablity of pancreatic neck cancer is low, and the biological behaviors have been unclear. In this study, we reviewed 59 resected pancreatic neck cancer cases to identify the prognostic factors. Methods: From 2000 to 2012, 305 patients with pancreatic cancer underwent surgical resection, and in 59 patients (19%) among them with pancreatic neck cancer, 49 patients underwent pancreatoduodenectomy, 5 subtotal pancreatectomy, 4 distal pancreatectomy with en-bloc celiac axis, and 1 total pancreatectomy. We defined borderline resectable pancreatic cancer as tumor abutted CHA, celiac trunk, or SMA, and classified radiographic types of PV invasion into A (normal), B (unilateral), C (bilateral), or D (complete obstruction) by CT imaging. We analyzed retrospectively clinicopathological characteristics and prognostic factors for pancreatic neck cancer. Results: Pancreatic neck cancer was smaller than other located pancreatic cancer (21.1±7.0 vs. 32.0±13.5 mm, P<0.01), and the rate of pathological PV invasion was higher in pancreatic neck cancer (36 vs. 20%, P=0.01). In patients with pancreatic neck cancer, pathological PV invasion was observed in 0% of type A (0/9), 14% of type B (3/22), 48% of type C (10/21), and 86% of type D (6/7), and 37 patients (63%) had lymph node metastasis. In 32 patients with borderline resectable pancreatic neck cancer, neoadjuvant chemo(radiation)therapy (NAC) reduced the R1 rates (P=0.04) Pathological PV invasion, tub2/3 and lymph node ratio >0.1 were independent poor prognostic factors for pancreatic neck cancer (P<0.01, P=0.03, and P=0.03, odds ratio; 7.1, 2.8, and 3.1, respectively). Conclusions: Pancreatic neck cancer often had PV invasion even if CT imaging showed unilateral abutment, indicating that combined PV resection may be necessary for R0 resection of pancreatic neck cancer with radiological PV abutment. NAC may improve R0 resection rates and postoperative survival for pancreatic neck cancer.
The biomarkers of gemcitabine and erlotinib treatment in advanced pancreatic cancer.
Authors: Irie Kuniyasu , Ueno Makoto , Kobayashi Satoshi , Gouda Yoshihiro , Ohkawa Shinichi , Manabu Morimoto
Published: February 2017

358

Background: A combination of gemcitabine+erlotinib is one of the standard chemotherapies in advanced pancreatic cancer (APC). Since APC patients often take antiulcer drugs to prevent gastritis (e.g., NSAIDs to reduce cancer pain), erlotinib concentration is generally decreased through the mechanism of CYP3A4. Furthermore, unlike lung cancer, the biomarkers for APC are not obvious except rash. Here, we examined biomarkers of gemcitabine+erlotinib treatment in APC patients including the presence of antiulcer drugs. Methods: The subjects were 59 advanced pancreatic cancer patients. They were treated with gemcitabine+erlotinib starting from Nov. 2011 to Apr. 2013. Gemcitabine was administered at 1000 mg/m2, on days 1, 8, and 15 for every 4 weeks, and erlotinib was taken 100 mg daily. The progression-free survival (PFS), UICC stage, sex, age, CRP concentration, performance status (PS), rash, and presence of antiulcer drugs were examined. The PFS curve was plotted according to the method of Kaplan and Meier. The difference in the PFS was calculated using the log-rank test, and a multivariate analysis was conducted using Cox hazard model. Results: UICC stages were as follows; i.e., stage II: 1, stage III: 8, and stage IV: 50. There were 36 males and 23 females, and their ages ranged from 41 to 82 years old (median: 65). The CRP concentrations ranged from 0.02 to 11.5 mg/dl (median: 0.57). 37 patients received antiulcer drugs, and 48 patients had rash. The univariate analysis revealed that the CRP concentration and rash were significant (p=0.009 and p=0.005, respectively). Low CRP (<0.57mg/dl) and presence of rash were related to good PFS. The multivariate analysis also revealed that the CRP concentration (HR, 0.34; 95%CI, 0.16-072; p=0.005) and rash (HR, 0.40; 95%CI, 0.16-0.96; p=0.04) were significant. The presence of antiulcer drugs on PFS was insignificant. Conclusions: The CRP concentration and rash were biomarkers of gemcitabine+erlotinib treatment in APC patients.
A retrospective, multicenter analysis of the clinicopathologic features of extra-gastrointestinal stromal tumor (EGIST).
Authors: Yi Jun Ho , Hwang In Gyu , Ahn Hee Kyung , Lim Sung Hee , Park Byeong-Bae , Won Young-Woong , Park Se Hoon
Published: February 2017

36

Background: GIST is the most common mesenchymal tumor of the gastrointestinal tract although it constitutes only 1 percent of primary GI malignancy. Some GIST develops outside the alimentary canal such as omentum, mesentery, and retroperitoneum. These types are called extra-gastrointestinal stromal tumors (EGISTs). In this study, we retrospectively analyzed the clinicopathologic features of EGIST patients from 4 institutes in Korea Methods: From 2004 to 2012, a total of 43 patients with EGIST were identified. The clinicopathologic features including gender, age, location, tumor size, hisology, mitotic rate, IHC features, and genetic status were collected along with survival analysis. Results: The median age was 55 (range 29-80) and M:F ratio was 20:23. The most common sites were mesentery (11) and retroperitoneum (11) followed by omentum (7) and vagina (3). Other primary sites were liver (2), ovary (2), pancreas (2), perianal area (2), chest wall (1), pleura (1) and prostate (1). The median tumor size was 8.0 cm (range 2.6 – 30) and median mitotic rate was 5.0/50HPF (0 – 185) 4 cases were negative for c-Kit IHC, which were all confirmed by either IHC for DOG1 or mutational analysis. KIT analysis was performed in 10 cases with 6 wild-types and 4 exon 11 mutation were found. As for PDGFRα, 4 cases were analyzed which were all exon 18 mutation. Among 43 patients, 26 patients had undergone curative resection and 8 patients had unresectable disease and had taken palliative imatinib. Among 26 patients who had undergone curative resection, 12 patients had taken adjuvant imatinib and 14 patients had been observed without imatinib. The median tumor size of two groups were 11.0 (3.0 – 19.0) vs. 5.85 (2.6 – 18.9) and the median mitotic rate was 7.0 (2 – 18.5) vs. 1.0 (0 – 45). Regarding the 9 patients taken palliative imatinib, median tumor size was 20.9 (16.5 – 30.0), median mitotic rate was 15.0 (3 – 60) and median PFS was 22.7 months (95% CI 7.7 – 37.7). Conclusions: As the biologic behavior of GISTs is different by location, a more stratified strategy is needed for managing EGISTs including incorporation of molecular features. We are planning to perform further mutation analysis in this cohort.
Impact of adjuvant therapies on survival in patients with cholangiocarcinoma.
Authors: Dover Laura , Jacob Rojymon , Wang Thomas , Oster Robert , Dubay Derek
Published: February 2017

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Background: Surgical resection is the only curative option for Cholangiocarcinoma (CC) and currently there are no clear guidelines for adjuvant therapy following resection. Given the high incidence of local and distant recurrences following resection, we evaluated the impact of adjuvant chemotherapy or chemoradiation (CRT) on median survival (OS). Methods: A retrospective review was performed identifying all patients with CC who underwent curative surgical resection at our institution between 2002 and 2012. Patients who underwent aborted or palliative procedures were excluded. Survival estimates were quantified using Kaplan Meier curves, and differences between groups were compared with the log-rank test and Cox regression models. Results: During the study period, 103 patients underwent curative resection for CC at our institution. Tumor location was intrahepatic, perihilar and distal in 37% (n=38), 23% (n=24) and 40% (n=41) respectively. A total of 49 (48%) patients received adjuvant chemotherapy (n= 28) or CRT (n=21). Observation with no additional therapy was employed in the remaining 54 (52%) patients. No patient was treated using radiation alone. OS was 21.4 and 41.4 months (m) for those receiving adjuvant therapy versus observation (p=0.08). OS for adjuvant therapy versus observation were 28.4 m and 19.4 m respectively, if surgical margins were positive (p=0.036); and 79.1 m and 26.3 m respectively (p=0.4) with negative resection margins. OS was 41.4 m and 38.0 m with adjuvant chemo versus CRT respectively (p=0.1). Tumor stage was the only statistically significant pathologic indicator of outcome (p=0.019). Conclusions: A trend towards significant improvement in OS was observed with the use of adjuvant therapy among all patients following resection of CC. Adjuvant therapy significantly improved OS among CC patients with positive margins of resection. The small number of patients with negative margins of resection also benefitted, though not significantly. These data suggest that while adjuvant therapy should be considered for all patients irrespective of margin status; patients with positive margins are likely to benefit the most.
Stereotactic body radiation therapy (SBRT) combined with chemotherapy for locally advanced pancreatic adenocarcinoma.
Authors: Gurka Marie Kate , Kim Christine M , Haddad Nadim G , Carroll John , Charabaty Aline C , Jackson Patrick G , Harter K. William , Hwang Jimmy J. , Weiner Louis M. , Marshall John , Collins Sean P. , Pishvaian Michael J. , Unger Keith Robert
Published: February 2017

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Background: The role of conventionally fractionated radiation therapy in the management of locally advanced pancreatic cancer (LAPC) is controversial. One concern about concurrent chemoradiation relates to the timing of systemic chemotherapy. In contrast to conventional radiation therapy, SBRT delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here we report our results of patients treated with SBRT and chemotherapy for LAPC. Methods: Twenty-seven patients treated with SBRT for LAPC at our institution from January 1, 2008 to December 31, 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction in one week. The PTV included the pancreatic mass plus adjacent vasculature in most patients. The majority of patients received concurrent chemotherapy. Median time from diagnosis to SBRT was 1.9 months. Toxicities were scored using the CTCAE v.3. Survival was calculated using the Kaplan-Meier method. Results: The median age was 63 (range 45 – 90). ECOG performance status ranged from 0 – 2 and median Charlson Comorbidity Index was 3, range 0 – 7. All patients completed radiation as prescribed except one, who is excluded from survival analysis. Twenty-five patients received concurrent chemotherapy: 18 received gemcitabine, 6 received mFOLFOX and 1 received capecitabine. Two other patients received sequential chemotherapy. At the time of this analysis, 25 patients had died and the median OS from diagnosis was 13 months. Median PFS was 8.7 months. The first site of radiographic failure was local in 2 patients, local and distant in 1, and distant in 17. Of the other 7 patients, most died after clinical deterioration with no evidence of progression at last imaging. Acute toxicity was minimal. Severe late SBRT-related toxicities included one grade 4 biliary stricture and a grade 5 gastric hemorrhage without prior radiographic tumor progression. Conclusions: SBRT combined with gemcitabine or 5-FU based chemotherapy for LAPC is convenient, feasible and generally well tolerated. The outcomes of SBRT combined with chemotherapy compare favorably to the results of treatment with chemotherapy and conventional RT.
Natural history of untreated patients who had metastatic biliary tract cancer (BTC) with good performance status (PS).
Authors: Kang Jung Hun , Park Se Hoon , Lee Su Jin , Ji Jun Ho , Lee Soon Il , Oh Sung Yong , Hwang In Gyu , Song Haa-na
Published: February 2017

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Background: Although chemotherapy is widely recommended to the patients with metastatic biliary tract cancer, the natural course of those group, especially with good PS who are indicated for chemotherapy was rarely known. Methods: We retrospectively reviewed metastatic or distant relapsed BTC patients seen between January 2005 and August 2011 at four cancer centers. Patients were eligible if they had good PS (ECOG 0-2), no history of surgery, chemotherapy, radiotherapy or any treatment for cancer. Results: A total of 1302 patient cohort was identified for metastatic or distantly relapsed BTC and 959 patients were categorized for non-treatment group, 343 patients for treatment group. Of 959 patients, 131 patients were eligible for inclusion criteria and 737 patients were excluded for referral to other hospitals or lost followup, 89 patients for poor PS. The patient demographics were median age of 71 (range:39-89) and male predominant (n=81, 61.8%). Extrahepatic cholangiocarcinoma (n=55, 42.0%) was the most common site of eligible BTC followed by intrahepatic cholangiocarcinoma (n=42,32.1%). Median overall survival was 6.0 months (95% confidence interval [CI];4.9-7.1 months). Univariate analysis showed significant difference of survival depending on the serum level of CA19-9 (CA19-9≥100; 8.2 months vs CA19-9<100;4.4 months, log-rank p-value<0.001). Another potential prognostic factors including age, sex, PS, leucocytosis, serum albumin, CEA level and bile drainage did not have statistical difference in survival. Multivariate analysis showed that elevated 19-9 level was an independent poor prognostic factor(p<0.001, odd ratio, 2.8; 95% CI;1.8-4.8). Conclusions: Metastatic BTC patients with good PS had modest survival. However, patients with normal CA19-9 level showed favorable survival. Further studies comparing chemotherapeutic effect with best supportive care in those group are warranted.
FOLFIRINOX in the real-world setting: The multicentric experience of six Canadian institutions.
Authors: Amireault Carl , Beaudet Julie , Gaudet Guylaine , Raymond Nicolas , Ayoub Jean-Pierre M. , Letourneau Richard , Loungnarath Rasmy , Tehfe Mustapha , Aubin Francine
Published: February 2017

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Background: FOLFIRINOX has emerged as a new standard for patients with performance status ECOG 0-1 in metastatic pancreatic cancer and non-randomized studies also support this regimen in locally advanced disease. This regimen is however associated with significant toxicity. The purpose of this study was to assess efficacy and toxicity outside of a clinical trial, including community hospitals. Methods: We conducted a retrospective study of patients with pancreatic adenocarcinoma who received FOLFIRINOX between January 2011 and June 2013 in six institutions in the province of Quebec, Canada. Patients' characteristics, objective response, survival and toxicities were collected. Results: Forty-six patients were included (23 metastatic and 23 locally advanced). Median age was 59 years. Tumor was localized at the head in 65% of patients and 41 % had a biliary stent. Median overall survival was 12,6 months and survival at one year was 61% for metastatic patients. Survival at one year was 95% for locally advanced pancreatic cancer patients and no one with locally advanced tumor became candidate for curative surgery after FOLFIRINOX. Hospitalization rate was 54% with sepsis being the leading cause. There were three treatment-related deaths (7%) and two of them occurred after the first cycle. Neutropenia grade ≥ 3 was observed in 33% of patients and four patients had febrile neutropenia (9 %) with 61% of patients receiving colony stimulating factors (CSFs) for primary prophylaxis. Three patients had cholangitis and diarrhea grade ≥ 3 occurred in 15% of patients. Five patients (11%) experienced transient dysarthria during Irinotecan administration. Conclusions: Survival in our cohort is comparable with data reported by previous studies. However, toxicities were significant and higher than reported. These data highlight the importance of patient selection and support the universal use of CSFs in this population.
A treatment planning evaluation of protons versus IMRT in pancreatic cancer: A comparative study.
Authors: Slater Jerry Monroe , Ling Ted Chen-Tai , Nookala Prashanth , Mifflin Rachel , Grove Roger , Ly Anh , Patyal Baldev , Slater Jerry D. , Yang Gary
Published: February 2017

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Background: The purpose of this study is to investigate dose distributions of proton and intensity-modulated radiation therapy (IMRT) photon treatment plans in patients with resected pancreatic adenocarcinoma, focusing specifically on dose reduction to the kidney, liver, and small bowel as organs at risk. Methods: Ten patients with pancreatic head adenocarcinoma underwent Whipple procedure between 2010 and 2013 were included in this study. Most of the patients had locally advanced disease (T3-4N1). All patients were simulated with contrast-enhanced CT imaging. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10 mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15 mm. A dose of 50.4 Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 95% isodose coverage of at least 95% of the PTV. Dose-volume histograms, conformity index (CI), uniformity index (UI), homogeneity index (HI), were calculated and analyzed in order to compare plans between the two modalities. The OAR being evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The proton plans resulted in a lower mean kidney dose (3.17 Gy vs. 9.59 Gy, p=0.039), a lower dose delivered to 1/3 of the liver, D1/3, (0.25 Gy vs. 4.56 Gy, p=0.003), and a lower mean liver dose (1.83 Gy vs. 5.24 Gy, p=0.021). See table for a summary of the results. Conclusions: For patients receiving postoperative radiotherapy for pancreatic cancer, the proton plans are technically feasible and dosimetrically appealing with superior organ at risk sparing compared to IMRT photon treatment plans.[Table: see text]
Impact of postoperative intra-abdominal infection on tumor recurrence and survival in hepatocellular carcinoma after curative liver resection.
Authors: Ruan Dan-yun , Li Yang , Lin Ze-Xiao , Wu Dong-Hao , Wang Tian-tian , Li Xing , Jiang Nan , Wu Xiang-Yuan
Published: February 2017

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Background: Postoperative intra-abdominal infection has been reported contributed to higher tumor recurrence rate and poor survival in cancer patients. The study aims to evaluate the impact of postoperative intra-abdominal infection on recurrence free survival (RFS) and overall survival (OS) in patients undergoing curative liver resection for hepatocellular carcinoma (HCC). Methods: ALL patients underwent liver resection from 2003 to 2010 were identified. The Clavien–Dindo (CD) classification was adopted to classify the complications and patients who died of postoperative complications within 30 days of surgery (grade V) were excluded form the study. Univariate and multivariate analyses were used to assess variables. Results: 215 patients were included, the overall 30-day postoperative complication rate was 36.74% (n=79), 13.95% (n=30) were intra-abdominal infectious complication. Patients with intra-abdominal infection had worse RFS (27.6% vs 50%, p<0.001) and OS (46.7% vs 82.2%, p<0.001) than those without it. In multivariate analyses, postoperative intra-abdominal infection was an independent prognostic factor of tumor recurrence (hazard ratio = 2.183; 95% confidence interval, 1.334-3.573) and overall survival (hazard ratio = 4.990; 95% confidence interval, 2.643-9.420). Hepatitis B surface antigen positive, tumor diameter (>5cm) and Child-Pugh class (B) were other three independent factors associated with poor prognosis. Conclusions: According to the study, postoperative intra-abdominal infection predicts tumor recurrence and poor survival after radical liver resection in HCC patients. These findings may have implications of the potential association between inflammatory response and cancer progression.
Pretreatment [18F] FDG-PET texture analysis to predict local response of pancreatic cancer to radiotherapy.
Authors: Tuli Richard , Fraass Benedick , Yang Wensha , Sandler Howard Mark , Hendifar Andrew , Nissen Nicholas N. , Yue Yong
Published: February 2017

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Background: Accurate assessment of radiographic response following radiotherapy (RT) for pancreatic adenocarcinoma is challenging. Morphologic and textural features of FDG-PET have been shown to correlate with pathologic response and clinical outcomes in other solid tumors (PMID 23204495). The goal of this study was to develop a predictive algorithm derived from textural features of PET scans to predict response to RT. Methods: With IRB approval, we reviewed 10 patients with locally advanced pancreatic cancer treated with stereotactic body radiation therapy (25-30 Gy in 5 daily fractions). 18FDG-PET/CT scans were obtained 2 weeks pre-RT and 6 weeks post-RT. Pre-RT PET/CT images were deformably registered to the RT planning CT. Tumor volumes of interest were divided into (4.8mm)^3 subvolumes and characterized by mean SUV uptake, RT dose and comprehensive texture analysis. These pre-RT variables were correlated to post-RT mean SUV to identify potential predictors of treatment response. Response prediction was modeled by logistic regression with the Lasso algorithm and validated by 10-fold cross-validation. Model performance was assessed using cross-validated area under the receiver operating characteristic curves (AUC). Results: Mean uptake, RT dose and 6 texture features (energy, correlation, variance, sum mean, cluster tendency, and inverse variance) on pre-RT PET scans were significant in predicting treatment response (AUC 0.85). Within this model, each of the above noted variables was predictive of post-RT response (p<.05). Conclusions: Subvolume-based metabolic and texture features of pre-treatment PET scans were predictive of response following RT. Studies are ongoing to further correlate these variables to RECIST and pathologic response. This should serve as a useful model to help direct response-driven adaptive radiotherapy in patients with locally advanced pancreatic cancer.