bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose remote afterloading intraluminal brachytherapy in the treatment of unresectable hilar or upper bile duct carcinoma.
Authors: Andoh H. , Shindo Y. 
Published: February 2017

273 Background: To evaluate intraluminal brachytherapy (ILBT) for the treatment of unresectable hilar or upper bile duct carcinoma. Methods: Between 1992 and 2005, 48 patients were identified who were not indicated for surgical resections. Among them, 22 patients received only biliary drainage (group I) and 26 patients received ILBT (group II). Expandable metallic stents (EMSs) were used in 17 patients and ILBT was delivered using the Varisource 200 remote afterloading unit with a 10 Ci 192Ir or 60Co. Each treatment of ILBT delivered 6 Gy at a 1-cm depth, and was repeated weekly for 5 weeks. A total of 30 Gy was administered to each patient. Survival rates between the groups were compared using Kaplan-Meier survival curves. Results: In group I, survival rates at 6 and 12 months were 9% and 0%, respectively. Median survival was only 2 months. In contrast, group II survival rates at 6, 12, and 24 months were 77%, 54%, and 9%, respectively, and the median survival of this group was 13 months. Improved survival with the use of ILBT was significant, particularly in clinical stages III, IVa (p<0.01), and IVb (p<0.05). ILBT helped keep the bile duct lumen patent for a long period, but was not effective for the treatment of patients with positive lymph node metastasis. Conclusions: Although randomized controlled studies will be necessary, the results of the present study are encouraging for using high-dose ILBT in the treatment of unresectable hilar or upper bile duct carcinoma without lymph node metastasis. No significant financial relationships to disclose.
Clinical update on the SHELTER study: A phase I/II trial of the HDAC inhibitor resminostat in patients with sorafenib-resistant hepatocellular carcinoma (HCC).
Authors: Bitzer M. , Horger M. , Ganten T. , Ebert M. P. , Woerns M. A. , Dollinger M. M. , Mais A. , Hauns B. , Hentsch B. , Lauer U. ,   Shelter Study Group
Published: February 2017

275 Background: Resminostat (4SC-201) is a novel oral pan-HDAC inhibitor in clinical development in a variety of cancer indications. The aim of the SHELTER study is to evaluate safety, tolerability, and efficacy in patients (pts) with HCC exhibiting progressive disease under sorafenib first-line therapy. Methods: Sorafenib-refractory pts with advanced HCC, BCLC B or C are included in a multicenter, open-label, two-arm parallel group trial. Resminostat is administered orally on three dose levels of 200 (DL1), 400 (DL2), and 600 mg (DL3) once daily, in combination with 400 mg sorafenib (arm A) or as mono therapy (600 mg, arm B). For arm A, a precedent dose escalation of resminostat and sorafenib is performed to determine the MTD. Resminostat is administered in a “5+9” dosing schedule, consisting of 5 consecutive treatment days (D1-5) followed by a 9-day rest period resulting in 14 day cycles. In arm A sorafenib is given twice daily throughout the treatment period. Primary objective is to determine progression-free survival rate after 12 weeks (6 cycles). Secondary objectives include safety and tolerability, tumor response, estimation of TTP, OS, assessment of PK, and biomarkers. Results: To date, 14 pts were treated either with 600 mg resminostat alone or on DL1-3 in combination with 400 mg sorafenib. The majority of AE observed so far include gastrointestinal disorders such as nausea and vomiting. Plasma exposure to resminostat increased dose-dependently on D1 (cycle 1) with mean AUC 0-6 h values of 10.5 h*mg/L (600 mg mono) and 9.01 h*mg/L (DL3). No major changes in PK characteristics of resminostat were found with or without co-administration of sorafenib. A considerable portion of patients showed stabilization of their disease (SD): 9 out of 12 pts and 4 out of 5 pts examined after 6 and 12 weeks, respectively, displayed SD. In one patient treated on DL2, SD persisted for 36 weeks along with good long-term tolerability. Conclusions: Preliminary clinical data confirmed the favorable oral drug profile of resminostat either in mono or in combination treatment with sorafenib. Initial data on therapeutic activity to overcome resistance to sorafenib are promising. [Table: see text]
Neoadjuvant therapy for adenocarcinomas of the duodenum and ampulla of Vater.
Authors: Manoukian G. , Lal A. , Wen S. , Jiang Z. , Shroff R. T. , Wolff R. A. , Overman M. J. 
Published: February 2017

279 Background: Adenocarcinomas of the ampulla of Vater and duodenum are both rare periampullary tumors with limited data regarding the use of neoadjuvant therapy. We sought to better define the role of neoadjuvant therapy as compared to adjuvant therapy in patients with high-risk disease. Methods: Retrospective review of the M. D. Anderson Cancer Center (MDACC) tumor registry from 5/1990 to 1/2009 identified 66 cases of ampullary (26 neoadjuvant, 40 adjuvant) and 41 cases of duodenal adenocarcinoma (18 neoadjuvant, 23 adjuvant). Only patients who received adjuvant or neoadjuvant therapy and underwent surgical resection at MDACC where included. High-risk factors were defined as T3 or T4, poor differentiation, or lymph node involvement. Relapse-free survival (RFS) and overall survival (OS) were calculated from the start of surgical resection. Results: Median age was 61 yrs (range 30-82) and 39% were female. Neoadjuvant (n=44) and adjuvant therapy (n=63) consisted of 5-FU chemoradiation in 93% and 65%, systemic 5-FU based chemotherapy only in 5% and 24%, and gemcitabine or irinotecan based therapy in 2% and 11%, respectively. Pathological high-risk factors were seen in 77% and 95% of neoadjuvant and adjuvant patients, respectively. Indications for neoadjuvant therapy were high risk disease (70%), poor surgical candidate (16%), and concern for possible metastatic disease (14%). In the neoadjuvant group T and N downstaging were observed in 25% and 32% of patients, respectively; 3 patients (7%) had a pathological complete response. Neoadjuvant as compared to adjuvant therapy had similar 5-year OS (66% vs. 59%, p =0.8) and 5-year RFS (54% vs. 59%, p=0.4). Variables significant (p <0.05) in the multivariate analysis for OS were age >60 yrs, lymph node involvement, and margin positivity; and for RFS were lymph node involvement and margin positivity. Neither tumor type (duodenal vs. ampullary; OS HR: 1.6, p =0.2; RFS HR: 0.9, p=0.8) nor treatment type (neoadjuvant vs. adjuvant; OS HR: 1.2, p =0.6; RFS HR: 1.1, p=0.7) were significant for OS or RFS in the multivariate model. Conclusions: Neoadjuvant therapy appears to be a viable approach for high-risk duodenal and ampullary adenocarcinomas. Further investigation of this treatment approach is needed. [Table: see text]
Early gastric cancer: The importance of early diagnosis on prognosis of gastric carcinoma.
Authors: Bouca-Machado T. , Santos Sousa H. , Lima-da-costa E. , Pinto-de-Sousa J. , Preto J. , Sousa-Rodrigues J. , Costa-Maia J. 
Published: February 2017

29 Background: The aim of this study was to evaluate the characteristics of early gastric cancer (EGC) in comparison to advanced tumors and its role in patient's prognosis. Methods: This study was related to 1,272 patients admitted with gastric or gastroesophageal junction carcinoma in our department, between January 1988 and December 2008. During this period the incidence of EGC was 12.68% (3.62% T0, 42.75% T1a and 53.62% T1b). Several clinical, pathological and staging parameters were evaluated according to classification in EGC and advanced tumors. Results: Significant differences were observed in location (p<0.001); type of resection surgery (p<0.001) and of lymphadenectomy (p=0.008 for Siewert and p<0.001 for Japanese classifications) with less radical surgery in EGC patients. This type of tumors presented characteristics associated with a better prognosis in the following pathological parameters: tumor dimensions (p<0.001), macroscopic form (p<0.001), Ming's classification (p<0.001), venous invasion (p<0.001) and lymphatic permeation (p<0.001). The 5-year survival rate of this series was 33.7%. There were significant differences in survival curves according to classification in EGC and advanced tumors (73% at 5 years and 26% at 5 years, respectively). Cox-regression analysis identified age, T and lymph node ratio as independent prognostic factors. There was no significant differences in age (cut-off 45 years), but there was significant differences in lymph node metastasis (p<0.001). In 23.87% of EGC there was lymph node involvement, with significant differences (p=0.002) according to the depth wall invasion [T0 (100% N0), T1a (91.5% N0, 8.5% N1), T1b (60.8% N0, 21.6% N1, 13.5% N2, 4.1% N3a)]. Conclusions: The EGC percentage in our series was lower in comparison with other countries with high incidence of gastric cancer. The prognosis of the patients with gastric carcinoma continues to be gloomy mainly due to the late diagnosis and, given that the surgical treatment doesn't seem plausible of achieving a margin of significant additional progression, the need for an early diagnosis emerges if an improvement in patient survival is desired. No significant financial relationships to disclose.
Biliary tract cancer (BTC) in the older adult: Complex decisions for complex patients.
Authors: Horgan A. M. , McKeever E. , Knox J. J. 
Published: February 2017

295 Background: BTC is an uncommon malignancy. Complex patient (pt) factors potentially determine treatment choices in older pts and may independently impact outcomes. Methods: Between 2000 and 2010, 133 pts aged ≥ 75 years with BTC were evaluated at Princess Margaret Hospital. Clinical and histopathological characteristics, geriatric-specific factors, and survival outcomes were studied in a retrospective analysis. Results: Median age was 79 years (range 75-93). Predominant histology was adenocarcinoma (95%). 31 pts (23%) had curative surgery, 4 (13%) had additional (neo)adjuvant chemotherapy (CT) ± radiation therapy (RT). Pathological staging included: I/II: 20 (65%); III: 6 (19%); IV: 5 (16%). 25 pts (19%) received CT ± RT alone, 4 (15%) had stage I/II and 21(84%) stage III/IV disease. 77 pts (58%) received best supportive care (BSC) alone. Radiological complete or partial response was noted for 33% of pts treated with CT [gemcitabine (gem) alone 48%; gem doublet 52%]. 24% pts discontinued CT with toxicity. Untreated pts had greater degrees of functional dependence and poorer social supports. Of those untreated, the risk of treatment was felt to outweigh potential benefit given age ± comorbidities in 17%. In 22%, the pt opted not to receive treatment. Median overall survival was 19.7 months for the surgical group, 12.3 mths for the CT ± RT group and 4.37 mths for the BSC group. Conclusions: Untreated BTC has a poor prognosis. Factors other than clinicopathological features may impact treatment decisions. Integrating geriatric assessements into the evaluation of this vulnerable patient group may help better guide treatment choices. [Table: see text] No significant financial relationships to disclose.
Primary pancreatic lymphoma: A population-based analysis using the Surveillance, Epidemiology and End Results database.
Authors: Mishra M. V. , Keith S. W. , Shen X. , Biswas T. 
Published: February 2017

303 Background: Primary pancreatic lymphoma (PPL) is a rare disease, accounting for only 0.5% of all pancreatic masses. The clinical presentation of PPL is similar to that of pancreatic adenocarcinoma and the two are difficult to distinguish radiographically. A paucity of literature exists on the epidemiology and outcomes of PPL. Given the limited case reports published on PPL, a comparison of the different treatment modalities has previously not been possible. Here, we present a series of 523 cases of PPL obtained from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the tumor characteristics and compare the different treatment modalities. Methods: Patients diagnosed with a primary pancreatic lymphoma from 1973-2007 were identified. Data on patient and tumor characteristics as well as initial treatment with surgery or radiation was extracted. Chemotherapy information is not available through SEER. Overall survival was calculated using the Kaplan-Meier method. A multivariate analysis was performed to determine independent prognostic factors predicting for survival using a Cox proportional hazards model. Results: Fifty-eight percent of patients identified were male. The median age range at diagnosis was 65-69 years (range, 10-14 years – greater than 85 years). The most common histologic subtype in the present series was diffuse large B-cell lymphoma (DLBCL), which accounted for 71% of all patients. The 5-year overall survival for the group was 47%. Multivariate analysis indicates that age >60 and a marital status of single were predictive of a decreased cause-specific and overall-survival specific survival (p<0.05). Radiation therapy, but not surgery, was predictive of an improved overall survival (p<0.05). Conclusions: PPL is a rare form of extra-nodal NHLs of the GI tract. Adjuvant radiation therapy for patients with a PPL should be strongly considered and a surgical treatment should be avoided if an early diagnosis is established. A prospective study evaluating this patient population will be difficult given the rarity PPL. We hope that this case series will provide a context in evaluating and treating patients with PPL. No significant financial relationships to disclose.
Gemcitabine (G) fixed-dose-rate infusion (FDR) plus erlotinib (E) in patients with advanced pancreatic cancer (APC).
Authors: Munoz Llarena A. , Mane J. , Lopez-Vivanco G. , de Lobera A. Ruiz , Sancho A. , Iruarrizaga E. , Arruti M. , Marrodan I. , Fuente N. , Ballesteros D. 
Published: February 2017

304 Background: G (30-minute infusion) plus E improves survival in patients with APC compared with G alone. In a recent phase III trial, G-FDR showed a trend to better OS compared with standard G (6.2 vs. 4.9 months, HR 0.83, p=0.04), although the study was underpowered to detect great difference in OS. Based on our previous experience with G-FDR, we decided to evaluate the combination of G-FDR plus E, after E approval for APC. Methods: Patients with previously untreated pathologically confirmed APC, locally advanced (LAPC) or metastatic (MPC), and ECOG PS 0-2 were included. G 1500 mg/m2 was given by 150-min infusion (10 mg/m2/min) on days 1, 8, and 15 every 28 days combined with E 100 mg/day orally. Treatment modifications for G-FDR were planned according with previously Tempero's phase II trial, and as described in prescribing information for E. Results: 62 pts were included (36M/26F), with a median age of 63 y-o (range 37-78). ECOG PS 0/1/2: 19/40/3. LAPC/MPC: 16/46. All except one had measurable disease. ORR was 13% (8 PR), 95% CI: 4.7-21.3, and there were 34 (55%) SD. Mean relative dose intensity for G was 0.76 and 0.90 for E. Main hematologic toxicities 3/4 per pt: anaemia 12/0, thrombocytopenia 7/4, neutropenia 18/7. Acneiform rash 1/2/3 occurred in 16/16/3 pts. Other relevant adverse events were (grade 2/3/4): diarrhoea 18/3/0, mucositis 5/1/0, infection 9/8/1, thrombosis 1/4/1 and vomiting 6/4/0. There were three treatment-related deaths (septic shock, cholangitis, and bilateral pulmonary embolism). Ten pts (all LAPC) received RT after ≤ 6 cycles, all with concomitant capecitabine 825 mg/m2 bid. In 4 pts salvage surgery were performed: 2 R0, 1 R1 and 1 R2. Median PFS was 4.9 months (95% CI: 3-6.7), 7.9 m for LAPC and 2.5 m for MPC (p = 0.004). Median OS was 10 months (95% CI: 7.1-12.9), 17.5 m for LAPC and 7 m for MPC (p = 0.019). OS was significantly shorter in males (p = 0.01) and in pts taking major opioids (p = 0.027). There was a trend to better OS in pts who developed skin rash grade ≥ 2 (p = 0.078). Conclusions: In this noncomparative study, G-FDR plus E is a feasible regimen in APC with an acceptable toxicity and notable activity. G-FDR seems to increase hematologic toxicity compared with standard infusion. No significant financial relationships to disclose.
Effect of blood transfusion on early outcome of liver resection for colorectal hepatic metastases.
Authors: Gruttadauria S. , Saint Georges Chaumet M. , Pagano D. , Marsh J. W. , Bartoccelli C. , Gridelli B. G. 
Published: February 2017

314 Background: The useof intraoperative blood transfusions (IBT) has been associated with worse surgical outcome in patients undergoing liver resection for malignancy. However, detailed analyses are required to define clinical findings impacting short-term outcome in this scenario.The aim of this study is to evaluate whether IBT are associated with a worse short-term outcome of liver resection in patients with colorectal hepatic metastases, and to assess whether certain patient characteristics and/or surgical variables affect the need for IBT. Methods: In a series of 127 consecutive patients who underwent partial liver resection for colorectal metastases, between July 1999 and March 2010, we studied postoperative 90 days surgical outcome relative to IBT, and the effect of a variety of factors, including type of resection, surgical technique used, concomitant colo-rectal resection, non-tumoral hepatic histological findings, site of primary tumor, and comorbidities, on the incidence of IBT. Results: Patients who received IBT during their liver resection were more likely to have a longer postoperative length of stay (p = 0.02), to experience complications (p = 0.0003), and to experience a Clavien Grade IIIa or worse complication (p = 0.003). Furthermore, undergoing a major resection, and the presence of portal fibrosis in the non-tumoral liver were both correlated with an increase in IBT (respectively, p = 0.003 and p = 0.049), while the surgical technique used (Kellyclasia or TissueLink), the presence of steatosis, undergoing a concomitant major colonic or rectal resection, and having a major comorbidity had no effect on the incidence of IBT (p ≥ 0.05). Conclusions: This study confirmed that receiving IBT during partial liver resection for colorectal hepatic metastases is associated with a worse short-term surgical outcome. These clinical findings suggest that although several significant factors (surgical technique chosen, comorbidities present, etc.) do not seem to influence the short-term outcome of surgery, it is important to be aware of the deleterious effects of the type of resection performed and the presence of portal fibrosis on blood loss during partial liver resection. No significant financial relationships to disclose.
Mixed photon and neutron radiotherapy given concurrently with chemotherapy in unresectable pancreatic cancer.
Authors: Christensen M. E. , Paximadis P. , Shields A. F. , Philip P. A. , Weaver D. W. , Konski A. A. 
Published: February 2017

328 Background: Unresectable tumors of the pancreas remain difficult to treat despite the advent of targeted radiotherapy and modern chemotherapy. Randomized trials exploring the efficacy of chemotherapy and radiation have demonstrated median survival of 9 to 11 months. These survival times have not improved appreciably in the modern era. The purpose of this study was to retrospectively review our institutional experience with unresectable pancreatic cancer treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Methods: Thirteen patients with unresectable tumors of the pancreas were treated between 1993 and 2001. All patients were treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Median photon dose was 39.6 Gy (30.6-45Gy) and median neutron dose was 8 nGy (7-9 nGy). 12 of 13 patients were treated with neoadjuvant chemotherapy, followed by 5-FU given concurrently with radiotherapy. Median survival, overall survival, and local control were calculated for all patients. Results: The median age of all patients was 65 years (46-75 years). Twelve patients had histologic diagnosis of adenocarcinoma, with the other having an islet cell carcinoma. All patients are now deceased. Median survival for all patients was 11.5 months (3.0-25.6 months). The 1 and 2- year overall survival was 46.2% and 7.7%, respectively. Local control of the primary tumor was excellent at 92.3%. The rate of distant metastasis was 76.9%. One patient experienced decline without documented recurrence. No grade ≥3 acute toxicities were reported. However, there were 2 grade 5 late toxicities, both caused by gastrointestinal bleeding. Conclusions: Our experience demonstrates that treatment of unresectable pancreatic tumors with mixed photon-neutron radiotherapy given concurrently with chemotherapy results in excellent local control, with survival time equivalent to or exceeding that demonstrated in previous series. With the added capability of intensity modulated neutron radiation therapy (IMNRT), the incidence of treatment-related morbidity may be improved while taking advantage of the superior tumor control that high-LET radiation may impart. No significant financial relationships to disclose.
Sorafenib for the treatment of patients with advanced hepatocellular carcinoma and alcoholic cirrhosis.
Authors: Giovanis P. , Vincenzi V. , Manuppelli C. , Berletti R. , Marcante M. , Ricagna F. , Pinto F. , Giusto M. 
Published: February 2017

352 Background: Hepatocellular carcinoma (HCC) from alcoholic cirrhosis, associated or not with chronic hepatitis C virus (HCV) infection, is a particularly severe liver disease. Scanty and inconsistent data concerning the efficacy of sorafenib in patients (pts) with this disease are available. Methods: Since February 2009 we screened 26 Child-Pugh liver function class A pts bearing the above characteristics. Sixteen of them (61.5%), 15 males and 1 female with median age of 69 years (range 54-79), received 400 mg sorafenib b.i.d. Predominant cause of HCC was alcohol consumption in 13 pts (81.2%), associated with chronic HCV infection in 2 pts (12.5%), and hemosiderosis in 1 pt (6.2%). All pts suffered from multiple comorbidities, and 3 had been previously treated for Burkitt lymphoma, bladder and breast cancer. One pt with prostate cancer was on treatment with androgen blockade. Median number of concomitant medications was 4 (range 2-9). Four pts never received locoregional treatment, and none had received previous antineoplastic therapy. Results: Twelve pts (73%) discontinued sorafenib after a median time of 2 months (range 2-6). The reasons for treatment discontinuation were disease progression (4 pts), liver function deterioration (5 pts), and mild gastrointestinal adverse events (2 pts): 1 pt refused sorafenib treatment after 15 days. 2/4 patients still on treatment with sorafenib at 7, 8, 11, and 18 months showed partial response (RECIST criteria). Seven pts (40%) died because of disease progression at a median time of 5.5 months (range 2-9) and at a median overall survival time of 36 months from diagnosis (range 2-84). Conclusions: Treatment with sorafenib in pts affected by HCC and alcoholic cirrhosis seems effective and well tolerated with high-level compliance. The most common cause of discontinuation was progression of disease and liver function deterioration. No significant financial relationships to disclose.