bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic arterial infusion chemotherapy after sorafenib treatment in patients with advanced hepatocellular carcinoma who are unfit for regorafenib.
Authors: Terashima Takeshi , Yamashita Tatsuya , Takata Noboru , Arai Kuniaki , Mizukoshi Eishiro , Kaneko Shuichi
Published: January 2019

355

Background: The RESORCE trial proved survival benefit of regorafenib on advanced hepatocellular carcinoma (aHCC) in the limiting cohort. This study aimed to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) as second-line treatment in patients with aHCC who are unfit for regorafenib. Methods: We studied consecutive 159 patients with aHCC treated with sorafenib in our institution from June 2009 to March 2018. We divided them into two groups according to the eligibility for RESORCE trial (Rego or non-Rego group) and investigated the efficacy of HAIC as post-sorafenib treatment. Moreover, we also analyzed the prognostic factors in each group. Results: When sorafenib treatment failed, 63 patients (39.6%) fulfilled key inclusion criteria of the RESORCE trial and were considered as fit for regorafenib treatment (Rego group). Among 96 remaining patients (non-Rego group), 34 patients (35.4%) were treated with HAIC after sorafenib. The objective response and the median progression-free survival of HAIC were 38.2% and 3.9 months, which were independent of the efficacy or treatment duration of sorafenib. The median survival of HAIC after sorafenib was 11.3 months which was significantly longer than that of 62 patients without HAIC (4.7 months; P = 0.023). Four factors, HAIC (HR 0.516), Child-Pugh A (HR 0.362), tumor size ≥35mm (HR 1.959), and AFP ≥200 (HR 1.728), were identified as independent prognostic factors after sorafenib in multivariate analysis. In Rego group, 14 patients were actually treated with regorafenib and their survival after sorafenib was longer than that of the patients without regorafenib and with HAIC (P < 0.01 and P < 0.01, respectively). In Rego group, regorafenib (HR 0.152), extrahepatic lesions (HR 2.160), and ≥10 intra-hepatic lesions (HR 2.099) were identified as prognostic factors after sorafenib in multivariate analysis. Conclusions: HAIC showed promising tumor response and patients’ outcome for the patients who are unfit for regorafenib. Further investigation is needed to compare HAIC with ramucirumab, cabozantinib or nivolumab.
Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.
Authors: Ikeda Naoya , Akahori Takahiro , Satoi Sohei , Yanagimoto Hiroaki , Nagai Minako , Nakagawa Kenji , Nishiwada Satoshi , Nakamura Kota , Takagi Tadataka , Hirooka Satoshi , Yamamoto Tomohisa , Yamaki So , Sho Masayuki
Published: January 2019

366

Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.
The Esophageal Online Patient Reported Outcomes (EsO-PRO) Questionnaire: Formal implementation and assessment of a combined clinical and research data collection tool.
Authors: Jiang Shirley Xue , Shah Shubhangi , Smith Elliot Charles , Baek Justine , Liang Mindy , Brown M. Catherine , Mayo Allyson , Liu Geoffrey , Yeung Jonathan , Wong Rebecca , Elimova Elena , Darling Gail Elizabeth
Published: January 2019

37

Background: Systematic symptom monitoring improves quality of life, and possibly overall survival in cancer outpatients receiving chemotherapy. To reduce patient, staff, and resource burden, combining research surveys with electronic PRO assessments in a multidisciplinary academic esophageal cancer clinic may allow dual clinical-research goals to be met. Methods: EsO-PRO is a data collection tool directed at esophageal cancer outpatients created through expert feedback. Using the Canadian Institutes of Health research (CIHR) Knowledge-to-Action (KTA) framework, clinic flow and stakeholder maps were constructed. Facilitators and barriers were then identified, and responses were generated to address implementation barriers. Multiple iterations of the questionnaire were implemented; patient and clinic staff feedback was collected through key informant interviews, and major themes were described. Results: Creation of EsO-PRO included multiple validated tools: the FACT-E, modified Cancer Research UK esophageal cancer risk questionnaire, EQ5D-5L, PRO-CTCAE for common esophageal symptoms, and baseline clinico-demographic data. Four iterations of the KTA cycle for pilot implementation identified specific key facilitators (clinician champions, staff engagement, resource-integration, and clinician-researcher synergy) and barriers (familiarity with technology, survey length, and communication barriers). Qualitative assessment also identified perceived importance of questions as key to patient completion, and role delegation, staff burden, clinic flow interruption as critical issues to address. Splitting EsO-PRO into two separate visits for completion, allowing completion at home, and changing fill-in-the-blanks to check-off boxes were identified as potential solutions. Conclusions: The CIHR-KTA framework identified concrete methods for improved integration of a combined clinical-research survey tool for routine use in a multidisciplinary esophageal cancer outpatient clinic. Our process serves as an effective model for integration of innovations in multidisciplinary esophageal cancer clinics.
Impact of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) on R0 resection rate for borderline resectable and locally advanced pancreas cancer.
Authors: Zakem Sara Jean , Mueller Adam Christopher , Meguid Cheryl Lauren , Torphy Robert J. , Schefter Tracey E. , Davis S. Lindsey , Leal Alexis Diane , Leong Stephen , Lieu Christopher Hanyoung , Messersmith Wells A. , Purcell William T. , Ahrendt Steven Arthur , McCarter Martin , Del Chiaro Marco , Schulick Richard D. , Goodman Karyn A.
Published: January 2019

370

Background: Management for borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) is controversial. Multiagent chemotherapy (CT) followed by SBRT may allow for tumor downstaging and the ability to perform an R0 resection. Methods: We retrospectively evaluated BRPC and LAPC patients (pts) treated on our multidisciplinary treatment pathway. Pts underwent 2-3 months of CT. Pts without systemic progression received five fractions of SBRT, delivered every other day, to a dose of 30-33 Gy. After restaging, pts underwent surgery if resectable. Overall survival (OS), distant metastasis free survival (DMFS) and local progression free survival (LPFS) were estimated and compared by Kaplan-Meier and log-rank methods. Results: We identified 80 pts with BRPC (65) or LAPC (15) treated with neoadjuvant CT + SBRT between 2011-2017. Median follow up was 20 months. CT primarily included FOLFIRINOX (65%) and gemcitabine/nab-paclitaxel (30%). Of pts completing CT + SBRT, 67 (84%) went to surgery and 53 (79%) of those pts underwent definitive surgery including seven LAPC patients. The remaining 14 pts underwent palliative or exploratory surgery due to intraoperative metastases (43%) or vascular involvement (57%). Of pts undergoing definitive surgery, 51 had R0 resection (96%) and 5 (9%) had a complete pathologic response (PR) to CT + SBRT. The R0 resection rate of the cohort was 64%. OS was 24.5 months. Pts with a complete or marked (14%) PR had significantly better OS than those with a moderate (40%) PR (41.3 vs 30 months, p = 0.04) and pts unable to undergo definitive surgery (18.2 months, p < 0.001). Zero of 11 pts who had a marked or complete PR had local progression, significant compared to those with moderate PR (p = 0.012). DMFS between these two groups was not statistically significantly different. Conclusions: Neoadjuvant CT + SBRT are associated with favorable PR rates and R0 resection rates. Marked or complete PR was associated with improved LPFS and OS compared to moderate PR and pts who did not undergo definitive surgery. DMFS was not significantly different between complete and marked PR compared to those with moderate PR.
Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity?
Authors: Lee Rachel M , DePalo Danielle K , Lopez-Aguiar Alexandra G , Zaidi Mohammad Yahya , Rocha Flavio G. , Kanji Zaheer S. , Poultsides George A. , Makris Eleftherios , Dillhoff Mary , Beal Eliza W , Fields Ryan , Panni Roheena Z. , Idrees Kamran , Marincola Smith Paula , Nathan Hari , Beems Megan , Abbott Daniel , Rendell Victoria , Maithel Shishir K. , Russell Maria C.
Published: January 2019

376

Background: The prognostic value of pathologic variables is not consistent for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We previously demonstrated a limited prognostic role of lymph node (LN) positivity in small bowel NETs (SBNET) compared to pancreatic NETs (panNET). Although minority race is often associated with worse cancer outcomes, the interaction of race with pathologic and oncologic outcomes of pts with GEP-NETS is not known. Methods: Pts with GEP-NETs who underwent curative intent resection at eight institutions of the US NET Study Group from 2000-16 were included. Given few pts of other races, only Black and White race pts were analyzed. Results: Of 2,182 pts, 1,143 met inclusion criteria. Median age was 58 yrs, median follow up was 3 yrs, 48% were male, 14% (n = 157) were Black, and 86% (n = 986) were White. Black pts were more likely uninsured (7 vs 2%, p = 0.005), had symptomatic bleeding (13 vs 7%, p = 0.006), required emergency surgery (7 vs 3%, p = 0.003), and had LN positive disease (47 vs 36%, p = 0.016). Despite this, Black pts had improved 5 yr recurrence free survival (RFS) compared to White pts (90 vs 80%, p = 0.008). The quality of care received was comparable between both groups, demonstrated by similar LN yield at surgery, neg margin resection rate, post-op complications, and need for reoperation or readmission (all p > 0.05). Black pts were more likely to have SBNET (22 vs 13%) and less likely to have panNET (43 vs 68%) compared to White pts (p < 0.001). Consistent with prior data, pts with LN pos panNET had decreased 5yr RFS (67 vs 83%, p = 0.001); however, for SBNET, LN involvement was not prognostic (77 vs 96%, p = 0.08). The prognostic value of LN pos disease was similar between Black and White pts in both SBNET (p = 0.34) and panNET (p = 0.95). Conclusions: Black pts with GEP-NET present with more advanced disease, including higher LN positivity. Despite this, Black pts have improved RFS compared to White pts. Although there may be delays in seeking or reaching care, Black pts received similar quality of care compared to White pts. The improved RFS seen in Black pts may be attributed to the epidemiologic differences in the site of presentation of GEP-NETs and variable prognostic value of LN pos disease.
Comparison of concurrent chemoradiation with stereotactic body radiation therapy versus conventionally fractionated radiation therapy following induction chemotherapy for unresected locally advanced pancreatic cancer.
Authors: Ma Sung Jun , Iovoli Austin J , Prezzano Kavitha M , Hermann Gregory , Serra Lucas M , Singh Anurag K
Published: January 2019

378

Background: Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). A recent National Cancer Data Base (NCDB) analysis has also shown improved OS with the use of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT). This NCDB analysis evaluated outcomes of concurrent chemoradiation with SBRT compared to CFRT, following iC. Methods: The NCDB was queried for primary stage III, cT4N0-1M0 unresected pancreatic adenocarcinoma treated with concurrent chemoradiation following iC (2004-2015). CFRT was defined as 1.8-2.5 Gy per fraction up to a total dose of 45-70 Gy, whereas SBRT was defined as > 4.0 Gy per fraction up to a total dose of 20-60 Gy. Baseline patient, tumor, and treatment characteristics were examined. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, Cox proportional hazards method, logistic regression, and propensity score matching were used. Results: Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24.3 months and 22.9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in the multivariable analysis compared to CFRT (HR 0.78, p = 0.025). Using 1:1 propensity score matching, a total of 240 patients were matched, with 120 patients in each cohort. The receipt of SBRT remained statistically significant for improved OS, including median OS (18.1 months vs 15.9 months) and 2-year OS (37.3% vs 25.5%) compared to the CFRT (p = 0.0040). Conclusions: This NCDB analysis shows a significant survival benefit with the use of SBRT versus CFRT, in the setting of definitive management for LAPC following iC. Further prospective studies evaluating the use of SBRT in the definitive treatment of this challenging population are warranted.
Prospective comparative study of endoscopic ultrasonography-guided fine-needle biopsy and unroofing biopsy.
Authors: Shin Sung Kwan , Park Jun Chul , Kim Eun Hye , Lee Sang Kil , Lee Yong Chan
Published: January 2019

38

Background: Adequate tissue acquisition is important in making treatment decisions for patients with upper gastrointestinal subepithelial tumors (SETs). This study aimed to compare the outcomes of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) with those of the unroofing biopsy technique. Methods: This study was a single-center, prospective comparative study conducted at Severance Hospital, Yonsei University College of Medicine. A total of 39 patients with SETs ≥15 mm were enrolled between January 2016 and August 2017. Results: Of the 39 patients, 28 underwent biopsy with both techniques (4 underwent only unroofing and 7 underwent only EUS-FNB). The mean tumor size was 21.0 mm (median, 19.0 mm; 15.0–45.0 mm). Histological diagnosis was made with EUS-FNB in 64.3% and with unroofing biopsy in 78.6% (p = 0.344), and immunohistochemical diagnosis was made with EUS-FNB in 46.4% and unroofing biopsy in 67.9% (p = 0.180). In the subgroup analysis (28 patients), there was no significant difference in diagnostic yield between the 2 methods. The mean procedural time with EUS-FNB was shorter than that with unroofing biopsy (p < 0.001). The larger SET (≥ 20 mm) (p = 0.035) and satisfaction of procedure (p = 0.019) were positively associated with successful histological diagnosis by EUS-FNB. No complications were reported with both methods. Conclusions: There was no significant difference in the histological diagnostic yield for SETs between the EUS-FNB and unroofing biopsy techniques. Further study is needed to confirm the efficacy of EUS-FNB and unroofing biopsy in a larger study population. Clinical trial information: NCT02646241.
Efficacy of liposomal-irinotecan (nal-IRI) plus 5-fluorouracil/folinic acid (5-FU/LV) versus oxaliplatin plus fluoropyrimidines in previous gemcitabine treated pancreatic adenocarcinoma (PAC) patients (pts).
Authors: Kieler Markus , Unseld Matthias , Bianconi Daniela , Scheithauer Werner , Prager Gerald W.
Published: January 2019

383

Background: The chemotherapy regimens nal-IRI plus 5-FU/LV as well as oxaliplatin plus fluoropyrimidines are used after previous gemcitabine based chemotherapy in the 2nd line treatment of metastatic PAC. We aimed to compare the clinical efficacy of these two treatment options. Methods: In this single institutional retrospective cohort analysis all pts with advanced PAC that were treated between 01/2012-08/2018 with nal-IRI plus 5-FU/LV or oxaliplatin plus fluoropyrimidines after previous 1st line gemcitabine based chemotherapy were analysed for clinical parameters, median progression free survival (mPFS) and overall survival (mOS). Survival analyses were performed by Kaplan-Meier method. Results: Characteristics of pts were well matched (Table). mPFS in pts (n=30) that received nal-IRI plus 5-FU/LV in the 2nd line treatment after gemcitabine based chemotherapy was 4.49 months while treatment with oxaliplatin plus fluoropyrimidines (n=31) resulted in a mPFS of 3.44 months (p=0.007, HR 0.47, 95% CI 0.27-0.81). Furthermore, pts with a CA 19-9 level >1000 kU/l at the beginning of 2nd line treatment had a significantly improved mPFS and mOS, when treated with nal-IRI plus 5-FU/LV compared to oxaliplatin plus fluoropyrimidines (mPFS 4.94 months versus 3.44 months, p=0.0186, HR 0.42, 95% CI 0.18-0.98; mOS 9.31 months versus 6.16 months, p=0.0386, HR 0.43, 95% CI 0.18-1.02). Conclusions: The efficacy of nal-IRI plus 5-FU/LV in our study is encouraging and outperforms oxaliplatin-based chemotherapy in the 2nd line treatment setting for PAC pts pretreated with gemcitabine. Prospective randomized trials are urged to validate our observation. [Table: see text]
Symptom burden of patients with advanced pancreas cancer (APC): A provincial cancer institute observational study.
Authors: Ward Julie , Kim Christina , Lambert Pascal J
Published: January 2019

384

Background: Patients (pts) with advanced pancreatic cancer (APC) experience many disease-related symptoms. The Edmonton Symptom Assessment System (ESAS) measures the severity of 9 separate domains, and is completed by pts at each visit at our provincial cancer institute. The aim of this study was to describe symptom burden at baseline and over time for chemotherapy (CT) treated pts with APC, using ESAS. Methods: Pts diagnosed with APC between 2012-2016 and treated with at least 1 cycle of CT were identified. ESAS scores were extracted from the electronic medical record. Descriptive statistics were used to report the most common symptoms of pts with APC. A joint model was used to describe the trajectory of ESAS during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Results: Of 123 pts identified, 61% had metastatic disease, 82.1% had a baseline ECOG of 0-1, with an average age of 64.8. 1608 clinic visits had an ESAS score documented and 87% of pts completed ≥ 2 ESAS assessments. Median overall survival was 10.2 months. Median progression free survival was 6.7 months. At baseline, the 10th percentile, median and 90th percentile for total symptom distress (TSD) score were 6.2, 24 and 53 respectively. 86% of pts had at least one ESAS score of ≥ 4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Using a joint model, average TSD scores for the cohort improved for the first 4 to 5 months after starting CT and started to rise after 6 months. Average TSD scores at 15 to 18 months were similar to scores at baseline. Controlling for metastatic disease and CT type, for every increase of 10 in baseline TSD score, there was a 5% increased risk of death. Conclusions: The ESAS tool reflects the heavy burden of cancer-associated symptoms in APC. Symptoms improve months after starting CT and eventually worsen. The impact of early intervention to address symptom management is an important area of investigation in APC.
Pooled safety analysis of high-specific-activity I-131 MIBG in iobenguane scan positive cancer patients.
Authors: Jimenez Camilo , Grewal Ravinder K. , Ravizzini Gregory , Chin Bennett B , Pampaloni Miguel H , Matthay Katherine K. , Jensen Jessica Donato , Lin Tess , Apfel Stuart , White Theresa , Stambler Nancy , DiPippo Vincent A. , Mahmood Syed , Wong Vivien , Pryma Daniel
Published: January 2019

388

Background: Iobenguane scan positive cancers include pheochromocytoma and paraganglioma (PPGL), neuroblastoma, and gastroenteropancreatic neuroendocrine tumors. A pooled analysis was conducted to assess the safety profile of high-specific-activity I-131 metaiodobenzylguanidine (HSA I-131 MIBG [AZEDRA]) in PPGL and neuroblastoma. Methods: Safety data were pooled from four clinical studies with 118 subjects who received HSA I-131 MIBG. Adverse events (AEs) were described by age, gender, race, number of HSA I-131 MIBG doses, temporal association of AEs within 12 weeks after therapeutic dose 1, vital signs, laboratory values, hematological events of Grade 3/4 or serious AEs, and changes in mean hematology values over a period of 12 months. Results: Out of 118 subjects, mean age was 47.0 ± 18.9 years (range 3-76); 57.6% were males and 74.6% were white. A total of 102 (86.4%) subjects had at least one AE assessed as treatment-related. The incidences of most AEs were similar among both genders and all racial groups. The most common toxicities associated with HSA I-131 MIBG were gastrointestinal disorders, with nausea the most prevalent. The incidences of nausea and salivary gland pain showed decreasing trends with age while dyspnea, asthenia, and peripheral edema showed increasing trends. The second most common toxicities were hematologic. Following each therapeutic dose, mean hemoglobin, leukocytes, neutrophils, and platelets decreased. Most hematological AEs resolved within 12 weeks, and recovery to pre-therapeutic dose values was apparent 6 months after each therapeutic dose. After therapeutic dose 1, higher percentages of subjects experienced AEs in the first 2 weeks, and the incidence decreased beyond 6 weeks. No notable changes were observed in clinical chemistry tests. The incidence of Grade 3/4 AEs was similar following each therapeutic dose. Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between baseline characteristics and AEs. Hematology results reflected toxicity profile expected in a population of subjects administered a radiopharmaceutical. Clinical trial information: Pooled Safety.
Combination chemotherapy for pancreatic cancer in older adults: Efficacy and safety analysis of patients at a majority-Hispanic NCI-designated cancer center.
Authors: Henkel Emily , Hernandez Brian , Michalek Joel , Mahalingam Devalingam , Arora Sukeshi Patel
Published: January 2019

389

Background: Pancreatic cancer (PCa) is more frequent in older adults, but older patients are underrepresented in large clinical trials. There is limited data on efficacy and safety of regimens such as FOLFIRINOX or nab-paclitaxel/gemcitabine (nab-gem) in older adults, especially Hispanics. Therefore, we compared the efficacy and safety of first-line PCa regimens in older adults. Methods: Retrospective analysis of stage IV PCa at our Hispanic-majority NCI-designated cancer center from 2000-2017. mPFS and mOS estimated from KM curves and groups were statistically compared with the log-rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: Forty-eight pts, mean age 71.7 years, median 69.2 (range 65-90). 31% Hispanic; 50% Male. First-line treatment: FOLFIRINOX (n=9), nab-gem (n=11), gem (n=11), other (n=9), supportive care (n=2). Baseline ECOG 0-1: 100%, 94%, 45%, 100%, 1% (p=0.004). Baseline albumin: 3.4, 3.4, 3.1, 3.5, 2.25 (p=0.06). mOS 7.1 months (95% CI 5.9-10.1). mPFS 5.6 months (95% CI: 5.3-NR). mOS by group: 8.6 mo, 7.1 mo, 3.2 mo, 2.9 mo, not available (p=0.95). Most patients had grade 0-2 toxicities (See table). Grade 3-4: fatigue n=2, neutropenia n=1, neuropathy n=1, mucositis n=1. Conclusions: Combination systemic chemotherapy are tolerated in older adults with PCa; however, in our cohort, survival was lower than historic phase 3 clinical trials with these regimens. Patients receive 2+ drugs had higher ECOG and albumin at baseline. Prospective studies with geriatric assessments are needed to determine patients who benefit from combination chemotherapy. [Table: see text]
Preoperative factors predictive of pathologic upstaging in clinical stage I gastric cancer patients.
Authors: Thuppal Hayavadhan , Friedmann Patricia , McAuliffe John Christopher , Muscarella Peter , In Haejin
Published: January 2019

39

Background: In patients with stage 1 gastric cancer, surgical resection without neoadjuvant therapy is offered as the first line treatment. However, some of these patients are found to have higher stage after resection and miss the opportunity for neoadjuvant therapy. Preoperative patient and tumor characteristics may be predictive of the likelihood of pathological upstaging in stage 1 gastric cancer patients who have not received neo-adjuvant therapy. Methods: The National Cancer Database was queried for patients diagnosed from 2004-2015 with clinical stage 1 gastric adenocarcinoma who had undergone surgical resection without neoadjuvant therapy. Univariate analysis and multivariable logistic regression were conducted to determine pre-operative factors associated with pathological upstaging. Candidate variables examined included age, sex, race, tumor size, histology, grade, tumor location, days to surgery, and lymphovascular invasion. Results: Analysis was conducted on 8,015 clinical stage 1 patients. Overall 1,981 (25%) patients were upstaged. On multivariable logistic regression analysis, significant predictors of upstaging included increasing tumor size [ref : size < 1 cm, 1-2 cm aOR=3.8 (95% CI 2.3-6.1); 2-4 cm aOR=12.4 (7.9-19.5); > = 4cm aOR=25.9 (22.9-56.4)], younger age [ref: > = 75, < 50 aOR=1.7 (1.4-2.1), 50-65 aOR=1.4 (1.2-1.6), 65-75 aOR=1.2 (1.1-1.5)], male gender [aOR=1.16 (1.0-1.3)], presence of diffuse type gastric cancer [aOR=2.3 (1.7-3.2)], mucinous type [aOR=1.7 (1.1-2.5)], or signet ring cell histology [aOR=1.6 (1.3-2.0)] compared to intestinal histology, presence of lymphovascular invasion [aOR=6.0 (5.0-7.1)], and increasing grade [ref: grade 1, grade 2 aOR=2.30 (1.7-3.5); grade 3 aOR=4.9 (3.6- 6.7)]. Conclusions: A quarter of all patients thought to have stage 1 gastric cancer prior to surgery had higher pathologic stage at time of resection. Patients with the above risk factors may be understaged with currently available diagnostic tools. The addition of neoadjuvant therapy should be considered when the above risk factors are present in clinical stage 1 patients.
Outcomes after cessation of therapy with alkylating agents (AA) for pancreatic neuroendocrine tumors (panNETs).
Authors: Wu Linda , Reidy Diane Lauren , Bielska Agata , Kelly Virginia , Raj Nitya Prabhakar
Published: January 2019

394

Background: There are several therapies now available for panNETs, raising concern that treatment-related toxicity, namely myelosuppression, may preclude use of all treatments. AA are an effective therapy in panNETs, but can cause irreversible bone marrow suppression. For this reason, our institutional approach is to treat patients (pts) with AA for a defined time period of up to 12 months prior to a treatment holiday; anecdotally, we observed continued disease shrinkage or stability after drug cessation. We aimed to identify and characterize these exceptional responders (ER). Methods: We retrospectively identified pts with well differentiated panNETs treated at MSKCC with AA from 2007 to present, and identified those that were placed on a treatment holiday after response to therapy. Pts with continued disease response by radiographic report (tumor shrinkage or stable disease) for greater than 9 months while on a treatment holiday were considered exceptional responders (ER). Results: 124 patients were evaluable, with 104 pts (84%) receiving temozolomide and 18 pts (15%) receiving dacarbazine. 40 (32%), 57 (46%), and 22 (18%) pts had low, intermediate and high-grade tumors, respectively. 80 pts (65%) achieved a response to AA and 21 pts (17%) responded to therapy initially with subsequent disease progression. In total, 58 pts (47%) entered a treatment holiday; 39/58 pts (67%) were ER and 16/58 pts (28%) had disease growth in < 9 months. No significant differences in tumor grade ( P = 0.85) were seen between ER and those who had disease growth in < 9 months. Next generation sequencing results were available in 17 tumors of pts classified as ER; 14/17 (82%) with alterations in chromatin remodeling genes ( MEN1/DAXX/ATRX). Upon disease progression, 11 ER were reintroduced to alkylating agents; 9/11 (82%) had progressive disease or death after reintroduction of drug, and 2/11 (18%) responded and went on a second treatment holiday. Conclusions: We observed durable responses to AA after cessation of therapy. Many of the ER tumors harbored alterations in chromatin remodeling genes. Reintroduction of alkylating agents upon disease progression was generally ineffective.
The correlation between the proportion of patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and overall survival between 2004 and 2015.
Authors: Molina George , Chawla Akhil , Clancy Thomas E. , Wang Jiping
Published: January 2019

395

Background: Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is associated with improved overall survival (OS), and this has led to its rising use. The aim of this study was to evaluate the correlation between use of NAT and OS among patients with PDAC. Methods: This population-level study evaluated the Spearman correlation between the annual proportion of patients receiving NAT and the annual 1-year and 5-year OS, respectively, using the 2004-2015 National Cancer Database. Annual 1-year and 5-year OS was calculated from year of diagnosis using Kaplan-Meier survival analysis. All patients with a confirmed diagnosis of PDAC (histology code 8500), without any metastasis, and who underwent an R0 or R1 resection were included. Results: A total of 18,852 patients (median age 67 (IQR 60–74); 49.4% female) with PDAC underwent an R0/R1 resection from 2004 to 2015. Among these patients, there was a significantly positive correlation between the proportion of patients who received NAT (12.1%; n = 2,133) and 1-year OS (Spearman’s rho = 0.9091; P = 0.0001) and 5-year OS (Spearman’s rho = 0.7833; P = 0.01), respectively. Patients who underwent R0 resection (n = 14,547; median age 67 (IQR 60-74); 49.9% female) had a significantly positive correlation between those who received NAT (13.1%; n = 1,773) and 1-year OS (Spearman’s rho = 0.8818; P = 0.0003) and 5-year OS (Spearman’s rho = 0.7333; P = 0.02), respectively. Among 9,142 patients who had upfront resectable disease with R0 resection margin status (median age 68 (IQR 60–75); 49.8% female), there was a significantly positive correlation between proportion of patients who received NAT (9.1%; n = 781) and 1-year OS (Spearman’s rho = 0.7273; P = 0.01) and 5-year OS (Spearman’s rho = 0.8000; P = 0.0096), respectively. Conclusions: Between 2004 and 2015 there has been an increase in the use of NAT for patients with PDAC. Concurrently, the OS has also increased during this time period. This study demonstrates that there is a statistically significant and positive correlation between the proportion of patients with R0/R1 resected PDAC who received NAT and 1-year OS and 5-year OS, respectively.
Impact of direct-acting antivirals and 12-week sustained viral response on clinical outcomes in patients with hepatitis C and hepatocellular carcinoma.
Authors: Kamp William M , Sellers Cortlandt , Stein Stacey , Lim Joseph K , Kevin Kim Hyun S.
Published: January 2019

397

Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C viral infections (HCV). Methods: Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Results: Nine hundred ninety-six patients met inclusion criteria (mean age 62.8±10.2 yrs, 79% male). Four hundred seventy-eight (50%) patients received interventional oncology (catheter-based therapies, ablation and combination locoregional therapies), 141 (15%) received supportive care (palliative or no treatment), 125 (13%) received a transplant, 112 (14%) had tumor resection and 94 (12%) received chemotherapy or radiation as their primary treatment. Median overall survival (OS) of the entire cohort was 24.2 months (95% CI: 20.9-27.9). Transplant patients were excluded from further analysis. Four hundred seventy patients had HCV (56%). One hundred twenty-three patients received one or more DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCC occurrence and recurrence were reported in 29 (26%) and 38 (45%) patients, respectively, after DAA therapy. HCV-positive and HCV-negative patients had similar survival (OS 20.7 mo vs 17.4 mo, p=0.22). Patients receiving DAA therapy had a higher OS of 71.8 mo (CI: 39.5-not reached) vs 11.6 mo (CI: 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had a higher OS of 75.6 mo (CI: 49.2-not reached) vs the non-SVR12 group (26.7 mo, CI: 13.7-31.1, p<0.0001). Multivariable analysis (MVA) showed that AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment allocation had independent influence on survival for the cohort (p<0.05). In HCV patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p<0.05). In patients receiving DAA, only MELD score and SVR12 remained significant factors (p<0.05). Conclusions: DAA therapy and achieving SVR12 is associated with increased overall survival in HCC patients with HCV. This analysis supports the importance of treating HCV to SVR12 as part of HCC management.
Incidence of and risk factors (RFs) for development of non-alcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) for pancreatic cancer: A single institutional review.
Authors: McGhee-Jez Amy , Ahuja Amisha , Nahar Ritu , Shah Samik , Loh Rebecca , Houtmann Sarah , Shah Rashesh , Chervoneva Inna , Lavu Harish , Cohen Steven J. , Halegoua-De Marzio Dina , Basu Mallick Atrayee
Published: January 2019

398

Background: PD may increase the risk of development of NAFLD, a precursor for non-alcoholic steatohepatitis and cirrhosis. Studies have not clearly identified consistent RFs for NAFLD, but patients with post-PD NAFLD do not appear to have the traditional RFs for NAFLD such as metabolic syndrome. The primary objective of this study was to identify the incidence of and RFs for post-PD NAFLD. Methods: Retrospective chart review was done on 425 patients who underwent PD for a cancer diagnosis at our institution from 2007 to 2017 and had at least 6 months of postoperative follow up. Cox proportional hazards model was used to examine multiple potential pre-operative RFs for NAFLD including body mass index (BMI), estimated surgical blood loss, LFTs, hemoglobin, albumin, age, sex, comorbidities, and tobacco use as predictors of time to develop post-PD NAFLD. Patients without post-PD NAFLD were considered censored at the time of last follow-up. The proportional hazard assumptions were validated. Post-PD NAFLD was identified by review of radiology reports. Results: Sixty (14.1%) of the 425 patients had post-PD NAFLD. The male to female ratio was 236:189 and median follow up time was 1 year. Median age was 65 years with median time to NAFLD development of 7 months. Multivariate Cox Proportional Hazard model identified higher BMI and female sex as RFs for the development of post-PD NAFLD. Each 1-point increase in BMI implied an 8.43% increase in the hazard of fatty liver (HR = 1.083, 95% CI: 1.032-1.136; p=0.001). Females had 89.7% higher hazard of fatty liver compared to males (HR = 1.897, 95% CI: 1.084 - 3.319; p=0.025). There was no statistically significant association between post-PD NAFLD and other pre-operative characteristics studied. Conclusions: Female sex and higher BMI may be RFs for the development of NAFLD post-PD. No other pre-operative RFs were identified. In conclusion, patients with higher BMI and female gender may need closer monitoring for earlier detection and management of NAFLD. [Table: see text]
Impact of new chemotherapy regimens on the treatment landscape and survival of advanced pancreatic cancer (PAC) patients (pts).
Authors: Kieler Markus , Unseld Matthias , Bianconi Daniela , Scheithauer Werner , Prager Gerald W.
Published: January 2019

403

Background: The clinical phase III first-line trials MPACT and PRODIGE4/ACCORD11 in metastatic PAC pts have changed the treatment paradigm. We aimed to analyse the impact of these regimens on the treatment landscape and survival of advanced PAC pts. Methods: In this single institutional retrospective cohort analysis patient characteristics and overall survival (OS) from all pts with advanced PAC treated between 01/2011-12/2017 were analysed. Survival analyses were performed by Kaplan-Meier method. Results: A total of 301 pts started a systemic treatment in the observation period. Concerning the first-line treatment, there was a clear shift from four different main regimens (gemcitabine/nab-paclitaxel (G+nab-P), FOLFIRINOX, gemcitabine/oxaliplatin +/- erlotinib, gemcitabine mono) to only two (G+Nab-P, FOLFIRINOX), that made up more than 80% of the administered first-line treatments in each of the groups (2011-2013 vs. 2014-2017). The rate for first-line FOLFIRINOX treatment was balanced between the two groups (19% and 15%). G+nab-P treated pts had a median age of 66 years, 41.3% had an ECOG 1-2, the FOLFIRINOX treated pts were younger and fitter (57 years and 24.5 % ECOG 1, 0% ECOG 2). 60.7% of pts treated with G+nab-P received a second-line and 30.7% pts received a third-line treatment, while for the FOLFIRINOX pts these rates were 69.8% and 41.5%. Median OS of pts that started first-line treatment between 2011 and 2013 was 8.77 months (95% CI 6.98-10.57) and for those that started first-line treatment between 2014 and 2017 median OS was 11.07 months (95% CI 8.94 13.20) (p = 0.038, Log-Rank-Test). Conclusions: There is a clear impact of new chemotherapy regimens on the treatment landscape. Furthermore, we provide real-world evidence that since the introduction of these new treatment options, the survival of pts with advanced PAC has significantly improved.
Plasma hyaluronan is a predictive marker for pegvorhyaluronidase alfa (PEGPH20; PVHA) response in a phase II study of pancreatic ductal adenocarcinoma (PDAC).
Authors: Taverna Darin , Printz Marie , LaBarre Michael J. , Sekulovich Rose E.
Published: January 2019

404

Background: Hyaluronan (HA) can be a constituent of the tumor microenvironment (TME). Accumulation of HA in the TME may result in elevated interstitial pressure, vascular compression, hypoxia, and reduced drug delivery and immune cell access. Pegvorhyaluronidase alfa (PEGPH20; PVHA) enzymatically degrades HA, potentially increasing access and antitumor efficacy of cytotoxic and immuno-therapies. Liquid biopsies may provide a non-invasive approach to predict therapeutic efficacy of PVHA. Methods: Total plasma HA was analyzed as a pharmacodynamic biomarker for PVHA activity in HALO 109-202 (NCT01839487), a Phase 2, open-label, two-stage randomized study of PVHA + nab-paclitaxel + gemcitabine (PAG) vs AG only, in previously untreated patients with Stage IV metastatic PDAC. HA was measured with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) disaccharide assay using baseline plasma samples from Stage 1 (n = 132) and Stage 2 (n = 128) of the study. Results: Lower baseline plasma HA values were significantly correlated with survival outcomes, predicting progression-free survival (PFS) benefit in PVHA-treated patients in Stages 1 and 2, and overall survival (OS) benefit in PVHA-treated patients in Stage 2 (Table). Conclusions: These results support further exploration of a liquid biopsy-based companion diagnostic (CDx) for predicting the therapeutic efficacy of PVHA. [Table: see text]
Dynamical changes of treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice.
Authors: Nagai Kazuki , Terashima Takeshi , Yamashita Tatsuya , Kido Hidenori , Hayashi Kotaro , Sunagozaka Hajime , Nakai Ryotaro , Mizuno Hideki , Hayakawa Hikaru , Nomura Yoshimoto , Takata Yoshiko , Orita Noriaki , Takabatake Hisashi , Kanno Masataka , Nishitani Masaki , Omura Hitoshi , Shugo Haruhiko , Ooishi Naoki , Mizukoshi Eishiro , Kaneko Shuichi
Published: January 2019

407

Background: Several new combination therapies, including GEM plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) has been developed for treating pancreatic ductal adenocarcinoma (PDAC) in these ten years. We investigated trends in characteristics, treatment patterns, and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. Methods: We retrospectively reviewed the medical records of 1917 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in our local area between January 2009 and April 2018. Results: The median age was 74, and 53.1% were men; 27.2% had locally advanced and 67.2% metastatic disease, and 5.6% had recurrences. Oncological therapy was administered to 1295 patients (67.6%): chemotherapy (n = 1161), chemo-radiotherapy (n = 117), or radiotherapy (n = 17); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 56.8% of the 266 patients diagnosed in 2017 or 2018 received GnP, 20.3% GEM, and 15.4% FFX. The objective response rates of patients treated with GnP, FFX and GEM were 16.8%, 17.6%, and 5.1%, respectively. The median time to treatment failures were 3.9, 3.6, and 2.8 months, and the overall survivals were 11.5, 11.7, and 6.5 months after GnP, FFX, and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 53.7%, 64.7%, and 34.6% of the patients treated with GnP, FFX, and GEM, respectively. The treatment discontinuation rates due to adverse events were 17.2%, 14.9% and 22.9% in the patients treated with GnP, FFX and GEM, respectively. Conclusions: Chemotherapeutic protocols changed dramatically between 2009 and 2018 in Japan. Both GnP and FFX are well-tolerable and effective in real-life practice despite high frequent adverse events.
Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).
Authors: Oh Do-Youn , Muhsin Mann , Bullock Andrea J. , Abou-Alfa Ghassan K. , Shroff Rachna T. , Sigal Darren , Chung Vincent , Hecht J. Randolph , Wu Wilson , Borad Mitesh J.
Published: January 2019

408

Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access, is high (67%) in CCA/GBC tumors. PEGPH20 enzymatically degrades HA. HALO 110-101 (NCT03267940) evaluates safety and activity of PEG-C-G-ATZ or PEG-C-G versus C-G in CCA/GBC pts. Methods: This study comprises two parts. In Run-In (RI) six pts were enrolled in PEG-C-G arm, then six pts in PEG-C-G-ATZ arm. Eight additional pts may be enrolled for tolerability. In Expansion (EX), up to 50 pts will be enrolled for efficacy. Treatment (Tx) cycle is 21 days (d). PEGPH20 dose is 3 μg/kg on d1, eight and 15 and ATZ dose is 1200 mg (one–three hours after PEGPH20) on d1 (PEG-C-G-ATZ only). C-G is dosed at 25 mg/m2 C and 1000 mg/m2 G on d2 and nine. In C-G arm (EX only), C-G is dosed on d1 and 8. Primary endpoints are ORR (RECIST v1.1), AEs (NCI CTCAE v4.03), laboratory/safety (RI only); secondary endpoints are PK; DOR, DCR, PFS; OS, OS by PD-L1 expression; ORR and DOR (imRECIST). Results: Eighteen pts have been enrolled (nine in each arm). The mean (SD) age is 57 (12.2) yrs in PEG-C-G and 69 (8.8) yrs in PEG-C-G-ATZ. 56% were men. All pts experienced ≥ 1 AE. The most common AEs are nausea, fatigue (50% each); decreased appetite (44%); anemia, constipation (39% each); thrombocytopenia, oedema peripheral, AST increased, myalgia (33% each). To date, there has been one dose-limiting toxicity (febrile neutropenia) in the PEG-C-G arm. There have been no deaths due to AEs. Conclusions: The overall safety profile of PEGPH20 + C + G ± ATZ is acceptable and consistent with safety observed for the individual components. There were no DLTs resulting in a dose reduction of PEGPH20, which is being dosed at 3 μg/kg in the EX phase. Clinical trial information: NCT03267940. [Table: see text]