bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of bridging locoregional therapies on survival in hepatocellular carcinoma patients undergoing orthotopic liver transplantation: UNOS population study.
Authors: Xing Minzhi , Kim Hyun Sik
Published: February 2017

346

Background: The effect of bridging locoregional therapies (LRT) on overall survival (OS) in pts with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) has not been investigated in large-scale population studies. Methods: TheUnited Network for Organ Sharing (UNOS) database was used to identify pts with HCC who received OLT between 2002 and 2010. Pts within Milan Criteria for whom an HCC Model for End-Stage Liver Disease (MELD) exception was approved were included. OS was compared between pts who received bridging LRT (including transarterial chemoembolization (TACE)) and those who did not. Kaplan-Meier estimation and Cox proportional hazard models were used for OS analysis. Results: Of 11,287 pts with HCC who received OLT, 9,876 pts had LRT data, mean age 56.6 yrs, 77% male; 5,103 received bridging LRT, including 3,676 who received TACE. Comparison groups were similar for age at OLT, waitlist duration, sex, race, BMI and MELD score (p>.05 for all). Significantly prolonged OS with bridging LRT vs. none was observed from both OLT (111.6 vs 106.4 mo, p<.001) and from Listing (176.1 vs 169.4 mo, p=.001). Similarly, significantly prolonged OS with bridging TACE vs. none was observed from both OLT (112.0 vs 107.2 mo, p<.001) and from Listing (177.7 vs 169.9 mo, p=.001). Conclusions: In HCC pts undergoing OLT, both bridging LRT and TACE correlated with prolonged survival from OLT and from Listing in a UNOS population-based study. [Table: see text]
Role of chemoradiation in locally advanced pancreatic cancer: A systematic review and meta-analysis.
Authors: Nagrial Adnan , Chin Venessa T. , O'Connor Chelsie , Sjoquist Katrin Marie , Chantrill Lorraine A. , Biankin Andrew Victor , Yip Desmond
Published: February 2017

348

Background: The role of combined modality therapy in the management of locally advanced pancreatic cancer (LAPC) is uncertain. Current guidelines recommend combined modality therapy for select patients. We sought to review the evidence for combined modality versus single modality therapy in LAPC. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) comparing chemoradiation versus chemotherapy alone as well as chemoradiation versus radiation alone in patients with LAPC. Methods: We searched MEDLINE, EMBASE and CENTRAL from inception to Oct 2013 for RCTs comparing chemotherapy alone versus chemotherapy plus radiation and radiation alone versus chemotherapy plus radiation. We also searched abstracts of major cancer meetings from 1990 to 2013. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), response rate and adverse events. Hazard ratios (HR), confidence intervals (CI) and p-values (p) were estimated with a random-effects model due to the heterogeneity of included studies using Revman 5.3. Results: We included 7 eligible trials including 753 patients. Induction chemotherapy was delivered prior to randomisation in one study. Chemoradiation versus chemotherapy (n= 5 studies) did not improve PFS (HR 1.02, 95% CI 0.87 - 1.20, p = 0.80) or OS (HR 0.91, 95% CI 0.64 - 1.31, p = 0.61). However, chemoradiation versus radiation (n=2 studies) improved PFS (HR 0.63, 95% CI 0.41 - 0.96, p = 0.03) and OS (HR 0.65, 95% CI 0.43 – 0.96, p = 0.03). There was significant statistical heterogeneity in the included studies and subsequently wide confidence intervals in the pooled results. This is most likely due to the small participant numbers in each study. Adverse events were more frequent in the chemoradiation arms. Response rates were assessed in only two studies. Conclusions: Chemoradiation is not superior to chemotherapy alone in LAPC, but may be superior to radiation alone. The studies were small with significant heterogeneity. Combined modality therapy results in increased adverse events. Our results do not provide evidence for a universal standard of care, thus more studies of combined modality therapy in LAPC are needed.
Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.
Authors: Spolverato Gaya , Kim Yuhree , Alexandrescu Sorin , Marques Hugo , Aldrighetti Luca , Gamblin T. Clark , Pulitano Carlo , Bauer Todd W. , Shen Feng , Sandroussi Charbel , Poultsides George A. , Maithel Shishir Kumar , Pawlik Timothy M.
Published: February 2017

349

Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P<0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P<0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.
DocOx (AIO-PK0106): A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas—Final results.
Authors: Ettrich Thomas Jens , Perkhofer Lukas , Kaechele Volker , Berger Andreas W. , Guethle Melanie , Muche Rainer , von Wichert Goetz , Gress Thomas M. , Michl Patrick , Geissler Michael , Hebart Holger Frithjof , Buechner-Steudel Petra , Seufferlein Thomas
Published: February 2017

352

Background: Pancreatic ductal adenocarcinoma still remains a major cause of cancer related deaths in the western world. The current study was conducted to confirm the activity and feasibility of docetaxel/ oxaliplatin combination in second line treatment of advanced pancreatic ductal adenocarcinoma. Methods: Prospective single arm, non-randomized, multi-center, Simon’s two stage phase II trial using docetaxel (75 mg/m2, 60 min, d 1) and oxaliplatin (80 mg/m2, 120 min, d 2) in 21-day cycles. Duration of the trial was scheduled up two 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit. Results: Data represents the intention to treat analysis of 44 patients included between 2008 and 2012. The majority of patients received a gemcitabine based first-line chemotherapy (95.5%). The primary endpoint of tumor response was achieved in 15.9% (7 partial remissions, no complete remission), with a disease control rate of 48% after the first two treatment cycles. Median progression free survival was 7 weeks (CI 6-15.9 weeks) and overall survival 40 weeks (CI 20.4-56.4 weeks). No unexpected adverse events occured. The recorded AEs were mainly hematologic (neutropenia grade 3/4 63.6%, febrile neutropenia 4.6%), gastrointestinal (29.6% grade 3/4 AEs) and infectious (18.2% grade 3/4 AEs). Conclusions: In this single-arm second line trial for the treatment of advanced PDAC, the combination of docetaxel and oxaliplatin shows promising results comparable with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin) or liposomal irinotecan (MM-398) plus 5-FU/leucovorin (NAPOLI 1-trial). Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding to a disease control rate of 18%. The toxicity profile was quite tolerable and comparable to other second line studies. Clinical trial information: NCT00690300.
Curative treatments and survival benefit in elderly patients with hepatocellular carcinoma: A SEER population-based analysis.
Authors: Makarova-Rusher Oxana V. , Ulahannan Susanna Varkey , Duffy Austin G. , Greten Tim F. , Altekruse Sean
Published: February 2017

355

Background: Transplant, resection, and ablation are potentially curative treatments for hepatocellular carcinoma (HCC) with limited outcome data in young-old (65-74) and older (≥75) patients. Methods: We evaluated curative treatment and relative survival (RS) outcomes in patients with HCC in 3 age groups (<65 years, 65-74 years, and ≥75 years). Patients with HCC diagnostic codes (histology 8,170-8,175, morphology C22) were identified in the SEER 18 database from 2000 to 2011. Treatments included curative (transplant, resection, radiofrequency ablation (RFA), and other ablations) and palliative therapies. Primary outcome was 5 year RS. Statistical analysis was performed using Kaplan-Meier and Chi-Square tests. Results: We identified 29,654 cases. The mean age was 62 years with almost 40% of HCC cases in patients over 65 years old. Potentially curable, localized stage rates were similar in all age groups, 46%, 48% and 46%, respectively. As a result of less resection and rare transplant use, fewer cases underwent curative treatments in the group 75 years and older in comparison to all other age groups (15% vs. 27%, p = 0.001). Five-year RS in all 3 age groups (<65 years, 65-74 years, and ≥75 years) was better after resection relative to RFA (47% vs. 35% p<0.0001, 44% vs. 37%, p=0.0093, and 43% vs. 28% p=0.0002). The highest survival was seen after liver transplant. Interestingly, among transplanted patients with HCC, 13% were 65-75 years old. Five-year RS was similar in transplanted patients 65-75 vs. those under 65 (76% vs 74% p=0.65). Conclusions: The use of curative treatments for HCC significantly decreases with age, yet there are clear survival benefits in elderly patients receiving such. Even when considering transplant, the data shows that outcome is as good in elderly patients as in younger patients. The benefit of hepatic resection appears to be superior compared to RFA in all age groups, in our analysis. [Table: see text]
Outcomes of liver-directed therapy for metastatic carcinoid tumors.
Authors: Hamner John Blair , White Michael , Iruarte Philip HG , Singh Gagandeep
Published: February 2017

356

Background: Patients with liver metastases from carcinoid tumors can have a variable and often indolent disease course. That said, left untreated, these tumors will often lead to the death of the patient secondary to the effects of tumor burden within the liver and the sequelae of carcinoid syndrome. In this study, we evaluate the effects of liver directed therapy on disease-specific survival in patients with liver metastases from carcinoid tumors. Methods: The California Cancer Registry was queried for patients with liver metastases from a primary carcinoid tumor. Demographic data was recorded. Patients were subdivided into six groups: those who received 1) no liver directed therapy, 2) surgical resection only, 3) trans-arterial chemoembolization (TACE) only, 4) radioembolization (RE) only, 5) surgical resection plus TACE, or 6) surgical resection plus RE. Kaplan-Meier curves were applied to estimate 10 year disease-specific survival. Results: 4,566 patients were identified with liver metastases from a primary carcinoid tumor, and 4,277 patients with complete clinical information included in the analysis. A slight majority of cases were male (51.4%), 183 (4%) were less than 40 years of age, 2,006 (44%) were between 40 and 65 years, and 2,363 (52%) were over 65. The 10 year median disease-specific survival was 66 months for those treated with TACE only, 80 months for those who received no liver directed therapy and 111 months for those who received liver resection plus TACE. The 10 year median survival has not yet been reached for the other groups. When compared directly, surgery plus RE had a trend toward better disease specific survival than surgery plus TACE, though statistical significance was not reached. Conclusions: While patients with liver metastases from carcinoid tumors often have an indolent disease course, liver directed therapy may help improve disease-specific survival. Surgical treatment, when completely resectable, remains the best treatment, although many patients will not have disease that is amenable to complete resection. In these cases, resection with the addition of RE appears to be more effective in improving disease-specific survival than other forms of liver directed therapy alone or in combination.
Next-generation sequencing (NGS) to identify potential therapeutic targets in advanced pancreatic cancer.
Authors: Kundranda Madappa N. , Braun Donald Peter , Kramer Kim , Ai Jizhou , Tan Bradford A. , Kilmant Eiko , River George L. , Markman Maurie
Published: February 2017

357

Background: Even with the advent of newer systemic therapies; long term survival in advanced PDAC is dismal. Hence there is an urgent need to use technologies such as NGS to identify potential therapeutic targets. Methods: A retrospective analysis was performed of all advanced PDAC patients (pts) evaluated with NGS through Foundation One (Foundation Medicine Inc., MA). DNA was extracted from biopsy specimens and sequencing was performed of 315 cancer-related genes plus select introns. Statistical analysis including Kaplan Meier survival analysis along with the log-rank test was used to compare the differences between groups. Results: 53pts were analyzed between Nov 2012 - Sep 2014; 25 (47%) were females; median age was 59 yrs (range: 33-77). 178 genomic alterations (GAs) were identified in 52 pts (average 3.43 GAs/pt). The GAs included mutations 140 (78%), amplifications 25 (14%), loss/deletions 13 (7%) and 1 pt had no GAs. Most frequent GAs and associated survival are listed in Table 1. There was no statistically significant difference in median overall survival (mOS) between the groups with or without KRAS (22.1 vs. 21 months; p=0.95) and with or without TP53 (21 vs. 23.4 months; p=0.76). 6/52 pts (12%) who had received at least 3 prior lines of therapy (range 3-4) and had an ECOG performance status <2; were treated off label with trametinib. The median PFS on the last therapy prior was 5 months (range 1.6-7). On trametinib, the median PFS was 1.9 months (range 1.1-7.1) with mOS of 5.1 months. Conclusions: Our data demonstrate that there are a range of GAs that are eligible for investigational targeted therapies. Secondly, the choice of agents (eg. Trametinib - targets downstream RAS effectors ) based on individual genomic profile can be considered when an appropriate clinical trial is not available or inaccessible even in heavily pretreated patients with a good performance status. Tumor profiling should be utilized in drug development to personalize treatment options in patients with advanced PDAC. [Table: see text]
Phase II trial of veliparib (V) in patients (pts) with previously treated BRCA or PALB2-mutated (mut) pancreas adenocarcinoma (PC).
Authors: Lowery Maeve Aine , Kelsen David Paul , Smith Sloane C. , Moore Malcolm , Kindler Hedy Lee , Golan Talia , Segal Amiel , Hollywood Ellen , Maynard Hannah , Capanu Marinela , Moynahan Mary Ellen , Fusco Anne , Stadler Zsofia Kinga , Do Kinh G , Chen Alice P. , Yu Kenneth H. , Tang Laura H. , O'Reilly Eileen Mary
Published: February 2017

358

Background: BRCA1, BRCA2, and PALB2 germline mutations are associated with an increased risk of PC. Other BRCA-associated cancers have demonstrated increased sensitivity to PARP inhibitors (PARPi) and early trials have shown activity of PARPi in untreated BRCAmut PC. We evaluated theactivity of V in patients with previously treated BRCA/PALB2mutPC. Methods: Eligibility: BRCA1/2, or PALB2mutPC, at least 1 and up to 2 prior treatment regimens, measurable stage III/IVPC; ECOG 0-1. Treatment Plan: V 300mg BID (N= 3 pts), then V 400mg BID day1- 28. Primary endpoint: RECIST 1.1 response rate (RR). Statistical plan: Single-arm, non-randomized, open-label, phase II, two-stage design, unacceptable RR 10%, promising 28%, type I, II error rates 10%. Secondary endpoints: progression-free survival (PFS), duration of response, overall survival, safety, tolerability and archival tumor analyses. Results: Between 05/12 and 12/13, N= 16 enrolled. Male= 8, Female= 8. Median age= 52 years (range 43- 77). BRCA1 mut=5. BRCA2 mut=11. N= 1AJCC stage III PC, N= 15 AJCC stage IV PC. N= 8 and N= 8 (50%) had 1 and 2 prior lines of therapy respectively. N= 13 (81%) received prior platinum therapy. Response: N= 1 unconfirmed PR (PR at 4 months (mo), POD at 6 mo), N= 4 stable disease (SD), N= 10 progressive disease (PD); N= 1 inevaluable (12 days of V only due to disease-related complications). Median PFS was 52 days (range 12 to 423). Three pts treated at 400mg V were dose-reduced for toxicity. Six pts had V related grade 3 toxicity including fatigue (N=3), hematologic (N=2) and nausea (N=1). No therapy-related grade 4-5 toxicities were observed. Conclusions: V was well tolerated. While no confirmed partial responses were observed, single-agent activity of V in previously treated PC was noted, and N= 4 (25%) remained on study with SD for ≥ 4mo (4, 6, 6, 9 mo). A randomized phase II trial evaluating cisplatin,gemcitabine +/- V is underway in untreated BRCA/PALB2mutPC (NCT01585805). Results of correlative studies will be presented. Acknowledgements: Lustgarten Foundation. NCI.AbbVie. Clinical trial information: NCT01585805.
Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma.
Authors: Mellon Eric Albert , Hoffe Sarah E. , Springett Gregory M. , Hodul Pamela Joy , Malafa Mokenge Peter , Frakes Jessica M. , Chuong Michael D. , Strom Tobin Joel Crill , Shridhar Ravi
Published: February 2017

360

Background: Limited data is available for neoadjuvant treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. We update our institutional outcomes with a neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) approach. Methods: We performed an IRB-approved analysis of all BRPC and LAPC patients treated with our departmental treatment protocol. After staging, medically fit patients underwent chemotherapy for 2-3 months, with regimen at the discretion of the treating medical oncologist (FOLFIRINOX, GTX, gem/abraxane, or gemcitabine alone). Patients then received SBRT delivered in 5 consecutive daily fractions with median radiation doses of 30 Gy to tumor and 40 Gy dose painted to tumor-vessel interfaces. This was followed by restaging imaging for possible resection. Overall survival (OS), event free survival (EFS), and locoregional control (LRC) rates were estimated and compared by Kaplan-Meier and log-rank methods. Results: We identified 159 patients, 110 BRPC and 49 LAPC, with 14.0 months median overall follow-up. The resection and margin negative (R0) rate for BRPC patients who completed neoadjuvant therapy was 50.9% and 96.4%, respectively. Estimated median OS was 14.4 months for BRPC patients and 11.3 months for LAPC patients (p=0.402). Median OS was 34.2 months for surgically resected patients vs 14.0 months for unresected patients (p<0.001). Five of 21 (23.8%) LAPC patients receiving FOLFIRINOX chemotherapy underwent R0 resection. In LAPC, FOLFIRINOX recipients underwent R0 resection more often than other chemotherapy recipients (5 of 21 vs. 0 of 28, p=0.011). There was a trend for improved survival in those resected LAPC patients (p=0.09). For those not undergoing resection, one year LRC was 78.4%. Grade ≥3 potentially radiation related toxicity rate was 6.9%. Conclusions: This data underscores the feasibility, safety, and effectiveness of neoadjuvant SBRT and chemotherapy for BRPC and LAPC. Compared with other chemotherapies, FOLFIRINOX induced greater tumor response in LAPC, permitting for R0 resection in a subset of LAPC patients and trend towards improved OS.
Change of skeletal muscle index during the chemotherapy as a prognostic factor of survival in pancreatic cancer patients receiving palliative chemotherapy.
Authors: Choi Younak , Kim Tae Yong , Lee Kyung-Hun , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue
Published: February 2017

363

Background: Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at the diagnosis and progressive loss of skeletal muscle were associated with survival in pancreatic cancer (PC) patients receiving palliative chemotherapy. Methods: We retrospectively reviewed PC patients receiving palliative chemotherapy between 2003 and 2010. Skeletal muscle cross-sectional area at L3 was measured by computed tomography. Sarcopenia was defined using the previously published sex-specific cutoff points for Korean people. Loss of skeletal muscle was classified by sex-specific cutoffs from ROC curve. Results: Among 484 patients, 260 (53.7%) patients were more than sixty years old and 295 (61.0%) patients were male. Overall, 187 (38.6%) patients were sarcopenic at the diagnosis (male, <49.2cm2/m2; female, <31.1 cm2/m2). Decreased skeletal muscle index (SMI) during the chemotherapy, which was defined as a reduction by more than 0.21 for male and by more than 2.19 for female, was observed in 198 (77.3%) male patients and 61 (38.1%) female patients. Decreased body mass index (BMI) by more than 1 was observed in 149 patients (37.3%) without difference between genders. Median overall survival (OS) of whole patients was 8.4 months [95%CI 7.6-9.2]. In the multivariate analysis, sarcopenia (p=0.001), decreased SMI (p=0.003), and decreased BMI (p=0.001) was significantly poor prognostic factors for OS. When we analyzed four groups by SMI and BMI changes (maintained SMI and BMI, maintained SMI and decreased BMI, decreased SMI and maintained BMI, decreased SMI and BMI), the groups with maintained SMI had longer survival than the groups with decreased SMI regardless of BMI changes. Median OS was 11.5 months with maintained SMI and 8.1 months with decreased SMI (HR 0.534 and 1, p=0.004) in decreased BMI groups and 9.9 months with maintained SMI and 8.6 months with decreased SMI (HR 1 and 1.490, p=0.002) in maintained BMI groups, respectively. The analyses separately done by gender showed similar results. Conclusions: Decrease of SMI during chemotherapy was a significantly poor prognostic factor for survival regardless of BMI changes.
FOLFIRNOX for advanced pancreatic cancer (aPDAC) according to schedule and dose modifications: Clinical feasibility and impact of supportive care.
Authors: Vaccaro Vanja , Sperduti Isabella , Melisi Davide , Bria Emilio , Vasile Enrico , Santoni Matteo , Giordano Guido , Bertocchi Paola , Lucchini Eleonora , Pino Maria Simona , Russano Marco , Garufi Carlo , Santini Daniele , Zaniboni Alberto , Febbraro Antonio , Cascinu Stefano , Falcone Alfredo , Tortora Giampaolo , Cognetti Francesco , Milella Michele
Published: February 2017

372

Background: Although FOLFIRINOX is considered one of the standards for aPDAC, concerns emerged with regard to the safety profile in clinical practice. Thus, we investigated the impact of dose/schedule modifications and additional supportive measures. Methods: The clinical charts of 292 aPDAC patients (pts) receiving classic (group 1) or modified (m)FOLFIRINOX (group 2) were retrieved at 8 Institutions. Results: Table summarizes pts’ characteristics;82/709 and 188/1127 pts/cycles were analyzed for groups 1 and 2, respectively. Overall toxicity was mild; significant differences in G2-4 toxicities between the two groups: asthenia (12.5% vs 6%, p<0.0001), anemia (6.1% vs 3.1%, p=0. 003), diarrhea (6.5% vs 4%, p=0.02), and thrombocytopenia (5.4% vs 0.5%, p<0.0001), favouring group 2, and neutropenia (4.7% vs 12.3%, p<0.0001), favouring group 1. G-CSF was used more frequently in group 1 (80% vs 36%, p<0.0001). Dose delays were comparable between the two groups; dose reductions were more common in group 2 (39% vs 28%, p<0.00001). No differences in the complete control of nausea/vomiting at cycle 1 (no N/V) with or without aprepitant were observed (50% vs 45%, respectively). The presence of a biliary stent did not appear to significantly worsen toxicity. Overall ORR and disease control rate (DCR: PR+SD) were 40% and 62%, respectively, without significant differences between the two groups. Median PFS was 7 mos for both groups. Median OS, however, was significantly longer in group 2 (12 vs 18 mos, respectively; p=0.01). Conclusions: Both schedulesare easily manageable and well tolerated and may be safely administered on an outpatient basis in pts carrying biliary stents as well. The minimal differences in toxicity and efficacy obtained with mFolfirinox require additional investigation. [Table: see text]
Intensity-modulated radiation therapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC).
Authors: Hajj Carla , Huguet Florence , Wu Abraham Jing-Ching , O'Reilly Eileen Mary , Winston Corinne , Reidy Diane Lauren , Allen Peter J. , Goodman Karyn A.
Published: February 2017

377

Background: To assess IMRT safety and evaluate local control and resectability among patients with LAPC treated with induction CT followed by IMRT. Methods: We reviewed records of 134 LAPC patients treated with CT (median duration 3.2 months) followed by IMRT (median dose 56 Gy) between 11/2006 and 11/2012. Patients had LAPC based on T4 disease or unreconstructable involvement of portal vein/hepatic artery on imaging (n=102) or were found to be unresectable after an attempted resection (n=32). Induction CT was gemcitabine-based (n=98) or FOLFIRINOX (n=32); concurrent CT was gemcitabine in 88 patients, continuous 5-FU or capecitabine in 37 patients. IMRT was given after induction CT in the absence of evidence of disease progression. After IMRT, 81 patients received maintenance CT. Results: Acute grade 3 GI and hematologic toxicity were seen in 4 (2.9%) and 33 (24.6%) patients, respectively. Acute grade 4 GI and hematologic toxicity were seen in 0 and 5 (3.7%) patients, respectively. Ten patients (7.4%) developed late grade 1 GI toxicity and 2 patients (0.7%) developed compression fractures. Twenty-six (19.4%) patients underwent resection 4.1 months (mean) after IMRT; 22 (84.6%) had negative margins, one of whom had a pathologic complete response and 4 had a microscopically positive margin. With 20.1 months median f-up, median local progression-free survival (LPFS) was 17.6 months. One- and 2-year LPFS were 90% and 55% respectively. Median distant metastasis free survival (DMFS) was 15.2 months. One- and 2-year DMFS were 69.5% and 30.7% respectively. Median OS was 19.7 months for the whole population (24.8 months for surgical patients and 19.7 months for the non-surgical patients). One- and 2-year OS for all patients were 85% and 47% respectively; one- and 2-year OS for the surgical patients were 96% and 72% respectively. Conclusions: In this large cohort of patients treated with IMRT for LAPC, acute and late toxicity was minimal. Patients with non-progressive LAPC after induction CT who received IMRT had high rates of local control which could translate into a better quality of life. In selected patients, induction CT followed by IMRT can downstage tumors allowing for R0 resections and improved overall survival.
Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary cancers.
Authors: Spolverato Gaya , Kim Yuhree , Margonis Georgios A , Makary Martin , Wolfgang Christopher Lee , Weiss Matthew J. , Hirose Kenzo , Cameron John L. , Pawlik Timothy M.
Published: February 2017

378

Background: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) may be indicative of the immune response around the time of surgery. We sought to determine whether NLR or PLR were associated with outcomes of patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy. Methods: Between 2010-2011, 289 patients who underwent an HPB procedure for a malignant indication were identified. Clinicopathological characteristics, NLR and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR were classified using a cut-off value of 3 and 150, respectively, based on ROC analysis. Results: Median patient age was 63 years and 52.3% were female. The majority of tumors were pancreatic in origin (67.2%), while a subset were primary (10.3%) or secondary (22.5%) liver tumors. Patients with low vs. high NLR and PLR had similar baseline characteristics with regard to performance status and tumor stage (all P>0.05). Operative interventions included pancreaticoduodenectomy (55.0%), ≤hemi-hepatectomy (29.1%), or extended hepatectomy (2.4%). Within 90-days of surgery, 143 patients experienced a complication for a morbidity of 49.5% (pancreas: 54.9% vs. liver: 40.0%). Patients with either an elevated NLR (OR=1.72) or PLR (OR=2.15) were at higher risk of a postoperative complication (both P<0.05). Among patients with a pancreatic, primary or secondary liver tumor, 3-year survival was 38.6%, 43.0%, and 65.0%, respectively. While elevated NLR was not associated with long-term outcome (HR=1.36)(P=0.14), patients with an elevated PLR had a higher risk of death (HR=2.14)(P=0.01). Conclusions: Patients with a high NLR or PLR had an increased risk of a perioperative complication. Elevated PLR was also a predictor of worse survival among patients with HPB malignancy undergoing resection.
Risk factors for severe weight loss after gastrectomy for gastric cancer.
Authors: Segami Kenki , Aoyama Toru , Kawabe Taiichi , Hayashi Shigeya , Makuuchi Yousuke , Sato Tsutomu , Yamada Takanobu , Hayashi Tsutomu , Fujikawa Hirohito , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki
Published: February 2017

38

Background: Body weight loss (BWL) is frequently observed in gastric cancer patients who underwent gastrectomy for gastric cancer. Recently, we reported that severe BWL after gastrectomy was a significant risk factor for continuation of S-1 adjuvant chemotherapy. However, risk factors of BWL after surgery remain unclear. Methods: The present study retrospectively examined the patients who electively underwent curative gastrectomy for gastric cancer between January of 2012 and June of 2014. All patients received peri-operative care of ERAS protocol. %BWL was calculated by percentile of body weight at one month after surgery to preoperative body weight. Severe BWL was defined as %BWL over 10%. Risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses. Results: Two-hundred seventy eight patients were examined. Median age (range) was 68 years (27-86). Median body mass index (range) was 22 (13.4-33.5). Thirty patients had received neoadjuvant chemotherapy. Operative procedure was total gastrectomy (TG) in 97 patients (Open in 61 and laparoscopic in 36) and distal gastrectomy (DG) in 181 patients (Open in 94 and laparoscopic in 87). Median operation time (range) was 268.5 minutes (95-554). Median blood loss (range) was 115 mL (0-1600). Morbidity of grade 2 or more defined by Clavien-Dindo classification was observed in 37 patients including pancreatic fistula in 8, anastomotic leakage in 5, and abdominal abscess in 3. No mortality was found. Completion of ERAS protocol without any variance was 95.3%. Median %BWL was 6% (-4.3% to 19.5%). Both univariate and multivariate logistic analyses demonstrated that morbidity (odds rate 3.56, p=0.001), blood loss over 300ml (odds rate 2.04, p=0.0356), and total gastrectomy (odds rate 2.1, p=0.0258) were significant risk factors for severe BWL. Conclusions: Nutritional intervention trial to inhibit BWL after gastrectomy should be focused on the patients who developed morbidity, showed blood loss over 300ml, or received total gastrectomy.
Association between equivalent uniform dose (EUD) and rates of local progression in liver tumors treated with stereotactic body radiation therapy (SBRT).
Authors: Lu Louis , Tao Yebin , Schipper Matthew J , Wahl Daniel , Stenmark Matthew H. , Lawrence Theodore Steven , Feng Mary Uan-Sian
Published: February 2017

380

Background: When tumors are near organs at risk such as bowel or heart, this results in partial underdosing relative to prescribed dose. We hypothesized that equivalent uniform dose (EUD) may better capture the biologic effect than other dose metrics. Methods: In this IRB-approved retrospective study, 257 primary and metastatic liver tumors from 168 patients treated with SBRT at the University of Michigan Health System between 2005 and 2014 were identified. Univariate analysis and multivariate Cox regression models were used to correlate patient, tumor, and treatment characteristics with rates of LC. Results: 1 and 2 year LC were 93% and 75% for all. Of the 156 primary liver tumors, 1 and 2 year LC were 94% and 76%, compared to 83% and 61%, for patients with colorectal metastases (CRM). 22 tumors locally progressed in 17 patients of which 9 were CRM, 5 hepatocellular carcinomas (HCC), and 3 other. Tumors that locally progressed received a median prescribed dose of 50 Gy (24 - 60), GTV EUD (a=-10) 49 Gy (23 - 72), and PTV EUD 46 Gy (17 - 69). Median gross tumor volume (GTV) was 21 cc (1-103). Tumors that did not locally progress received a median prescribed dose of 50 Gy (19 - 60), GTV EUD (a=-10) 52 Gy (17 - 86), and PTV EUD 47 Gy (7 - 76). Median GTV was 10 cc (0.2 - 2092). On univariate analysis, CRM (p = 0.005) was correlated with higher progression, while high GTV and PTV EUD (a=-10) (p = 0.01, 0.05) were correlated with lower progression. HCC (p = 0.06) was borderline for low progression. Age, gender, primary or metastatic, prescribed dose, biologically equivalent dose (BED), minimum GTV or PTV dose and GTV did not predict for progression. In a multivariable model including age, gender, histology, prescribed dose, BED, GTV EUD and GTV size, only GTV EUD predicted for LC, HR = 0.947, 95% CI = 0.901 - 0.996, p = 0.036. Every 1 Gy increase in EUD decreased the risk of local failure by 5%. Conclusions: EUD was predictive of local progression even when accounting for histology, size, and dose as measured by prescribed dose and BED. GTV EUD (a=-10) over 47.64 Gy yielded a >95% local control. EUD may be the preferred dose metric in future tumor control studies.
Tumor reduction in pancreatic versus metastatic sites in a randomized phase III study (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone.
Authors: Kunzmann Volker , Ramanathan Ramesh K. , Goldstein David , Penenberg Darryl Neil , Ferrara Stefano , Lu Brian , Von Hoff Daniel D.
Published: February 2017

382

Background: nab-P + Gem was superior to Gem alone in MPACT, a phase III metastatic pancreatic cancer (PC) trial, for all endpoints examined. An updated analysis verified the superior overall survival of nab-P + Gem vs Gem alone (median 8.7 vs 6.6 months; hazard ratio 0.72; P < 0.001). Whether antitumor agents may have differential activity on pancreatic vs metastatic lesions in PC has not been definitively addressed. This prespecified analysis examined the activity of nab-P + Gem vs Gem alone in reducing tumor size in pancreatic and metastatic lesions. Methods: Previously untreated metastatic PC pts (N = 861) were randomized 1:1 to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 days 1, 8, and 15 every 4 weeks or Gem alone 1000 mg/m2weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycles ≥ 2). Most pts (99%) underwent spiral CT imaging, allowing precise tumor measurement. Changes in the sum of target tumor diameter from baseline to postbaseline nadir were evaluated separately for pancreatic and metastatic lesions by independent radiological review. Results: Baseline sizes of pancreatic and metastatic tumors were comparable between treatment arms (Table). nab-P + Gem elicited an approximately 3-fold greater median percentage decrease vs Gem alone in pancreatic (−22.15% vs −7.02%) and metastatic (−24.27% vs −8.74%) tumor size, agreeing with the 3-fold higher overall response rate of target lesions by RECIST. Tumor shrinkage was similar between pancreatic and metastatic lesions. Conclusions: nab-P + Gem was associated with a greater reduction in tumor size of both primary and metastatic lesions compared with Gem alone. Clinical trial information: NCT00844649. [Table: see text]
Overall survival in intermediate-stage hepatocellular carcinoma (HCC) patients after first transarterial chemoembolization (TACE): Proposal of a new scoring system.
Authors: Sacco Rodolfo , Mismas Valeria , Romano Antonio , Ginanni Barbara , Marceglia Sara , Giacomelli Luca , Masi Gianluca , Falcone Alfredo , Bresci Giampaolo , Bartolozzi Carlo , Bargellini Irene
Published: February 2017

386

Background: TACE is the standard treatment for patients with intermediate-stage HCC (BCLC-B according to the Barcelona Clinic Liver Cancer [BCLC] classification). However, prognostic factors for survival after the first TACE cycle are unclear. We correlated pre-treatment characteristics and response to therapy with overall survival (OS) and time to tumor progression (TTP), in order to propose a scoring system aimed at facilitating clinical decision after the first TACE. Methods: We retrospectively analyzed 149 patients (125 males; mean age 65.1±9.2 years) with BCLC-B HCC who received ≥1 cycle of TACE (Lipidol TACE, n=106; drug-eluting beads TACE, n=43). Univariate and multivariate analysis were used to correlate pre-treatment characteristics and response to TACE with OS and TTP. Identified predictive factors were used to define a score for each patient. Results: Median OS was 23 (95% Confidence interval [CI] 11.5-27) months, and median TTP was 11 months (CI 7-11). Complete response (CR) was reported in 63 patients (42.3%) and partial response (PR) in 71 (47.7%). Age >65 years (Hazard Ratio [HR] 1.77; 95% CI: 1.18-2.67), ascites (HR 2.44; 95% CI 1.32-4.29), total diameter of nodules >61 mm (HR: 1.96; 95% CI 1.28-3.08) and response at 1 month (HR 1.70; 95% CI 1.30-2.20) were predictors of survival and were used to build the scoring system (Table). Three groups of patients with different OS and TTP were then identified. Patients with score 0-1 had a longer OS (57.8 months) and TTP (12.7 months) than those with score 2-3 (21.1 and 8.2 months) or score 4-6 (8.0 and 6.3 months) (p<0.001 for both comparisons). Conclusions: This scoring system may allow the identification of three groups of patients with different prognosis after a first cycle of TACE and may therefore be useful in guiding clinical decisions, in particular whether continuing TACE therapy after a first cycle or moving to different therapies. Validation of this scoring system on a larger population is ongoing. [Table: see text]
A multicenter, phase II trial of preoperative gemcitabine and nab-paclitaxel for resectable pancreas cancer: The AGITG GAP study.
Authors: Barbour Andrew , O'Rourke Nicholas , Samra Jaswinder S. , Haghighi Koroush S , Kench James , Mitchell Jenna , Pavlakis Nick , Burge Matthew E. , Fawcett Jonathan , Gananadha Sivikumar , Harris Marion , Aghmesheh Morteza , Chua Yu Jo , Joubert Warren Lance , Chan Matthew MK , Chandrasegaram Manju Dashini , Yip Sonia , Simes John , Gebski Val , Goldstein David
Published: February 2017

387

Background: Pancreatic cancer (PC) outcomes remain poor, recent series show approximately 37% of patients achieve R0 resection (all margins ≥ 1mm) for resectable disease. Recent data in metastatic disease shows that nab-paclitaxel (nab-PC) and gemcitabine (GEM) chemotherapy (CX) is an active regimen. We aimed to determine the feasibility and R0 resection rate with peri-operative nab-PC and GEM for resectable PC. Methods: A multicentre, single arm, phase 2 trial. Patients with operable PC received 2 cycles of neo-adjuvant GEM 1000mg/m2 and nab-PC 125mg/m2CX on days 1, 8 and 15 of a 28 day cycle followed by surgical resection and then 4 cycles of post-operative CX. The primary endpoint was R0 resection with the aim to assess if a rate of 85% could be achieved. Secondary endpoints included feasibility, toxicity, pathological response (College of American Pathologists Cancer Reporting Protocol for Exocrine Pancreatic Cancer, 2009), recurrence and survival. Results: Forty-one patients were enrolled from 2012-14. Median age was 65 (range 43-79), 41% male, 49% stage I and 51% stage II. Twenty nine (71%) patients underwent resection with evaluable cancer: 1 did not have proven cancer on central pathology review; 5 did not go to surgery (2 disease progression, 2 refused surgery, 1 due to cholangitis); and in 6 patients surgery was abandoned (unresectable disease). No deaths were surgery-related. Median tumor size was 27.5mm (IQR = 25-35). Pre-operative GEM and nab-PC produced an R0 rate of 52% (15/29) (95% CI 34-69%). 15/29 (52%) of resected tumors showed grade 0-2 tumor regression grade. Twenty-nine patients (71%) experienced >1 grade 3/4 toxicities (total 52 events) during pre-operative CX, neutropenia (46%) being most frequent with 8% febrile neutropenia. 39/41 (95%) patients received 2 cycles of pre-operative CX. Conclusions: Peri-operative GEM and nab-PC CX is feasible and well tolerated. The pre-operative regimen was associated with an R0 resection rate comparable or higher than surgical series without pre-operative therapy, although the primary endpoint of 85% could not be met. The value of this regimen will also depend on longer term outcomes related to recurrence and survival. Clinical trial information: 12611000848909.
The efficacy and risk of prophylactic entecavir for hepatitis B virus-related hepatocellular carcinonma receiving transcatheter arterial chemoembolization.
Authors: Li Xing , Zhong Xiang , Chen Zhan-Hong , Xing Yan-Fang , Ma Xiao-kun , Lin Zhi-Huan , Lin Qu , Wu Xiang-yuan
Published: February 2017

388

Background: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusions: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.
Clinicopathologic characteristics of patients who underwent additional gastrectomy after incomplete endoscopic resection for early gastric cancer.
Authors: Hwang Jae Jin , Lee Dong Ho , Lee Ae-Ra , Yoon Hyuk , Shin Cheol Min , Park Young Soo , Kim Nayoung
Published: February 2017

39

Background: Endoscopic resection (ER) is widely accepted as standard treatment for early gastric cancer (EGC) without lymph node metastasis. However, surgery is sometimes needed after endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) due to incomplete resection. We analyzed the clinicopathological characteristics of patients who underwent additional gastrectomy after incomplete EMR/ESD. Methods: From 2003 to 2013, 80 patients received additional gastrectomy after EMR/ESD due to incomplete resection. The patients were grouped according to the presence of histologic residual tumor in specimens obtained by gastrectomy as residual tumor (RT, n = 47) or non-residual tumor (NRT, n = 33). We analyzed reasons for gastrectomy, tumor characteristics of RT and NRT group, risk factors associated with residual tumor, retrospectively from medical records. Results: After the gastrectomy, the positive residual tumor rate and lymph node metastasis rate were 58.7% (47/80) and 7.5% (6/80). RT group showed significantly higher rate of lateral and vertical margin involvement compared to NRT group (59.5 vs. 15.1%).Multivariate analysis demonstrated that endoscopic piecemeal resection, H. pylori infection, depressed or mixed type, large tumor size (> 2cm), histologic diagnosis (signet ring cell carcinoma or mixed carcinoma) were significantly independent predictive factors associated with positive residual tumor of patients who underwent additional gastrectomy after incomplete EMR/ESD (p < 0.05). Conclusions: For complete and curative ER, endoscopists should try to determine the depth of invasion, histologic diagnosis accurately and to eradicate the H. pylori infection before ER. During ER, wide marking and En bloc resection could be considered to avoid the risk of incomplete resection.