bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nab-paclitaxel (Nab-P) and gemcitabine (G) first-line chemotherapy (CT) in patients (pts) with metastatic pancreatic cancer (mPC) who relapsed after adjuvant treatment (ADJ T): A “REAL LIFE” study.
Authors: Giordano Guido , Milella Michele , Lo Re Giovanni , Di Marco Mariacristina , Melisi Davide , Passardi Alessandro , Febbraro Antonio , Iop Aldo , Vaccaro Vanja , Foltran Luisa , Bertocchi Paola , Bergamo Francesca , Vecchiarelli Silvia , Giommoni Elisa , Ricci Vincenzo , Aloi Maria Bernardetta , Vasile Enrico , Zaniboni Alberto , Zagonel Vittorina , De Vita Ferdinando 
Published: March 2017

396 Background: Nab-P and G represents a standard of care in first line mPC treatment. Only 5% of pts in Nab-P + G arm received ADJ T in the MPACT phase III trial. Accordingly, there is a lack of information about Nab-P + G benefit in this population. Aim of this analysis was to evaluate outcomes in mPC “real life” pts receiving first-line Nab-P + G after relapsing from ADJ T. Methods: Clinical records of 330 mPC pts receiving Nab-P + G with standard schedule as first line CT were retrospectively reviewed, investigating, efficacy (Progression Free Survival, PFS and Overall Survival, OS defined as time elapsed from the start of Nab-P + G to progression or death respectively) in pts treated with prior ADJ T. Analysis was then performed in ADJ T subgroup according disease free survival (DFS) cut-off ( ≤ 6 vs 6-12 vs ≥ 12 months). OS and PFS were estimated with Kaplan-Meyer method with 95% CI. Cox-regression model was applied to the data with univariate and multivariate approach. Results: At time of data analysis in the entire cohort median (m) OS was 11.3 months (95% CI 9.157-13.443); mPFS 7 months (95% CI 5.827-8.173). 90 out of 330 pts (27.3%) had received G-based ADJ T with mDFS of 29.2 months (95% CI 25.62-32.78). In the overall population at multivariate analysis, ADJ treatment was an independent prognostic factor related to better OS (HR 0.53, 95% CI 0.40-0.66; p < 0.001) and PFS (HR 0.69, 95% CI 0.49-0.89; p = 0.024). Median OS in ADJ T pts was significantly higher than pts who had not received ADJ T (15.0 vs 10.8 months respectively; p = 0.012). A similar trend in mPFS was observed in ADJ T versus non ADJ T pts (8.6 vs 6.9 months; p = 0.06). Pts with longer DFS after ADJ T showed major benefit in mOS (16.3 vs 13.1 vs 8.7 months in ≥ 12 vs 6-12 vs ≤ 6 months DFS respectively; p < 0.001). No significant differences in mPFS were observed in the three subgroups (p = 0.271). Conclusions: Nab-P + G is a standard of care also in pts treated with ADJ T. ADJ treatment is an independent prognostic factor related to better survival, maybe reflecting the effect of prior radical surgery. Pts who received G-based ADJ T may benefit of Nab-P+G combination with an increased survival in pts with longer DFS.
Safety and tolerability of lanreotide autogel/depot (LAN) in patients (pts) with neuroendocrine tumors (NETs): Pooled analysis of clinical studies.
Authors: Phan Alexandria T. , Wolin Edward M. , Fisher George A. , Ruszniewski Philippe B. , Pavel Marianne E. , Liyanage Nilani , Strutt Kristina , Braun Stephan , Caplin Martyn E. , Vinik Aaron 
Published: March 2017

398 Background: Two international randomized double blind (DB) phase 3 trials provided evidence on LAN 120mg/4wks vs placebo in NETs: CLARINET reported on PFS improvements in metastatic intestinal/pancreatic NETs; ELECT on reduced use of short-acting rescue medication for carcinoid syndrome (CS) symptoms. ELECT and CLARINET open-label (OL) extensions recently provided further long-term (LT) data. Here, we pool all current data from LAN trials, to provide an overview of safety in functioning and nonfunctioning NETs. Methods: Data were pooled from CLARINET (96wk DB, ≤6yr LTOL), ELECT (16wk DB, 32wk initial OL, ≥2yr LTOL) and three other OL studies: 6mo study for CS symptom relief; 7–8mo study of self-administered LAN; and 92wk study of tumor-growth control. Occurrence of AEs was examined in all studies (except for diarrhea/flushing, an efficacy measure in ELECT DB + initial OL). Results: Of all 378 pts, 90% received LAN 120 mg (10% ≤90 mg). AE profiles were similar across DB, OL and all studies. GI events were most frequent AEs: 56% of pts reported GI events, excluding diarrhea, across all studies; 28% reported diarrhea in all studies excluding ELECT DB + initial OL. No study withdrawals occurred due to diarrhea or other GI AE. No deaths were considered treatment related. Long-term (>12mo) treatment produced no additional safety signals vs ≤6mo. Conclusions: This comprehensive safety analysis supports the positive benefit–risk profile of LAN both for CS control in symptomatic NET and for tumor control in metastatic intestinal/pancreatic NET. Clinical trial information: NCT00353496, NCT00842348, NCT00774930, NCT00681187, NCT00326469. [Table: see text]
Phase 1b study with PEGylated human IL-10 (AM0010) with 5-FU and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC).
Authors: Hecht J. Randolph , Naing Aung , Falchook Gerald , Patel Manish R. , Infante Jeffrey R. , Aljumaily Raid , Wong Deborah Jean Lee , Autio Karen A. , Wainberg Zev A. , Javle Milind M. , Bendell Johanna C. , Pant Shubham , Van Vlasselaer Peter , Brown Gail Linda , Oft Martin , Papadopoulos Kyriakos P. 
Published: March 2017

399 Background: The benefit of adding nal-irinotecan or oxaliplatin to 5-FU in second-line therapy for PDAC is relatively small and it has been refractory to immune therapies. The success and the durability of immunotherapy is thought to depend on the activation and expansion of intratumoral, tumor specific cytotoxic CD8+ T cells which are absent in most PDACs. AM0010 stimulates the survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune stimulation and prolonged stable disease in PDAC patients (pts) with single agent AM0010 was recently presented. Irinotecan may eliminate cytotoxic T cells. Treatment with platinum or 5-FU may activate immune responses to cancer and AM0010 has synergistic anti-tumor function with both in preclinical models. In this phase 1b clinical study, the efficacy of AM0010 with FOLFOX was explored in patients with PDAC. Methods: PDAC pts progressing on a median of 1 prior therapy (range 1-3) were treated daily with AM0010 in combination with FOLFOX (n=20). Tumor responses were monitored using irRC. Immune responses were monitored using analysis of serum cytokines, activation of blood derived T cells and peripheral T cell clonality. Pretreatment samples were analyzed by IHC for tumor infiltration by CD8+ T cells. Results: G3/4 TrAEs included thrombocytopenia (55%), anemia (45%) and neutropenia (25%). There was no significant bleeding or febrile neutropenia. 16 pts had a objective tumor response assessment; 2 had an irCR, 1 an irPR, 10 had irSD. Eight remain on treatment, 2 for > 1 year. ORR was 15%, the DCR was 65%. The mPFS was 3.9 months. AM0010 increased serum Th1 cytokines and reduced mediators of chronic inflammation IL-23 and IL-17 and the immunosuppressive cytokine TGFb. AM0010 increased the number and proliferation of PD1+ activated CD8+ T cells and induced de-novo oligoclonal expansion of T cell clones without affecting total lymphocyte counts. Conclusions: AM0010 with FOLFOX is well tolerated with moderate hematological toxicity in patients with PDAC. The observed immune activation including CD8+ T cell activation and prolonged objective responses are encouraging and will be explored in a phase 3 trial starting in 2016.
Long-term survival of gastrointestinal cancer diagnosed in Hodgkin lymphoma survivors.
Authors: Rigter Lisanne Sara , Schaapveld Michael , Aleman Berthe M.P. , Janus Cecile P.M. , van Eggermond Anna M. , Krol Augustinus D.G. , Van Der Maazen Richard , Roesink Judith M. , Zijlstra Josee M , Van Imhoff Gustaaf Willem , Poortmans Philip M. , Beijert Max , Lugtenburg Pieternella J. , Visser Otto , Snaebjornsson Petur , Van Leeuwen Flora , van Leerdam Monique Esther 
Published: March 2017

40 Background: The risk of developing gastrointestinal (GI) cancer is increased in Hodgkin lymphoma survivors. This study aims to compare overall survival of GI cancer in Hodgkin lymphoma survivors with survival of first primary GI cancer patients. Methods: This cohort study compared overall survival of GI cancer patients in a Hodgkin lymphoma survivor population (HL-GI (n = 92) including esophageal (n = 25), gastric (n = 31), small intestinal (n = 2), colorectal cancer (n = 34)) with survival of a population-based cohort of first primary GI cancer patients (GI-1, n = 911) which was generated by individual matching of the 92 cases, based on tumor location, gender, age and year at diagnosis. Clinical characteristics were compared by Chi square tests. Cox regression was used for multivariable survival analysis (corrected for age, gender, and clinicopathological characteristics related to the GI tumor). Results: When comparing HL-GI and GI-1 patients, no differences in tumor stage, grade of differentiation or frequency of surgery were found. HL-GI patients were less frequently treated for their GI tumor with radiation therapy (7% vs. 24% in GI-1 patients, p < 0.001) or chemotherapy (28% vs. 41%, p = 0.02). Overall 5-year and 20-year survival of HL-GI patients and GI-1 patients was non-significantly lower (28% vs. 38%, p = 0.13 and 19% vs. 29%, p = 0.06, respectively). This result was confirmed multivariably (5-year survival, p = 0.33, 20-year survival, p = 0.14). Also, for esophageal, gastric and colorectal cancer separately, no differences in overall survival were found between HL-GI patients and GI-1 patients. Conclusions: Long-term overall survival of GI cancer patients is similar in Hodgkin lymphoma survivors and first primary GI cancer patients. HL-GI patients did however receive less treatment with radiation therapy or chemotherapy. These treatments may not have been recommended due to prior Hodgkin lymphoma treatment or comorbidity. As risks of other causes of mortality are also increased in Hodgkin lymphoma survivors, the relatively good survival in this population is remarkable.
Sorafenib for hepatocellular carcinoma managed by non-oncologists: Impact on drug exposure and survival.
Authors: Kaplan David Edward , Taddei Tamar H. , Mehta Rajni , D'Addeo Kathryn , Aytaman Ayse , Hunt Kristel , Fox Rena , Baytarian Michelle , Valdarrama Adriana ,   VOCAL Study Group
Published: March 2017

404 Background: Few data exist on practitioner type, initial dosing regimens, and survival for patients with HCC treated with sorafenib in a real-world setting. Methods: HCC patients exposed to sorafenib were identified from the VA CDW using ICD9 codes and pharmacy records. ICD9 codes, CPT codes, AUDIT-C surveys and laboratory tests were utilized to characterize underlying liver disease, calculate Child-Turcotte-Pugh (CTP) and MELD scores. Two abstractors achieved 100% chart verification of tumor number, size, macrovascular invasion and extrahepatic spread on imaging immediately proximate to sorafenib initiation to quantify Barcelona Clinic Liver Cancer (BCLC) stage and to determine the provider specialty initiating sorafenib. Results: 4838 patients prescribed sorafenib for HCC between 2008 and 2015 were included in this interim analysis. Median age was 62; 98.8% were male, 61.8% white/26.0% black; 44% EtOH/54% HCV/5% HBV/29% other; CTP A 58%/B 37%/C 4%; median MELD 11; 96% ECOG < 2; and pre-sorafenib BCLC 0-0%/A-5%/B-37%/C-49%/D-8%. Sorafenib was prescribed by oncologists (92%), GI/hepatologists (7.6%) and other practitioners (0.4%). Patients treated by GI/hepatologists rather than oncologists had similar BCLC distributions, similar treatment durations (median 90 vs. 90 days), received more pills (median 360 vs. 240, p = 0.0016), but had identical survival (median 234 vs. 239 days, p = NS). Hepatologists were more likely than oncologists to uptitrate during the first month (25% vs. 14%, p < 0.0001) whereas oncologists were more likely to uptitrate later (8.9% vs. 3.8%, p < 0.001). Oncologists were more likely to stop sorafenib due to progression (29 vs. 18%), while hepatologists were more likely to continue sorafenib until death (28 v. 18%) with no difference in discontinuation for AEs or functional decline. In multivariable models including CTP, BCLC, and ECOG PS, prescriber specialty had no impact on OS. Conclusions: In the VA, 8% of sorafenib is prescribed by GI/hepatologists. Despite modest differences in prescribing practices, hepatologists and oncologists achieve similar sorafenib exposure and overall median survival rates of 7.8 months in real-world practices.
Clinical and molecular determinants of treatment benefit with phase I trials in patients (pts) with advanced pancreatic cancer (PC).
Authors: Verdaguer Helena , Sauri Tamara , Zeron-Medina Jorge , Villacampa Guillermo , Capdevila Jaume , Elez Elena , Alsina Maria , Argiles Guillem , Hierro Cinta , Grasselli Julieta , Matos Ignacio , Rodón Jordi , Tabernero Josep , Dienstmann Rodrigo , Sanz-Garcia Enrique , Macarulla Teresa Mercade 
Published: March 2017

409 Background: PC is the 4th leading cause of cancer-related death, with limited efficacy of systemic treatment (tx) beyond first-line chemotherapy (chemo). We aimed to assess the potential benefit of phase 1 trials in this setting. Methods: From 2011 to 2016, 49 pts were enrolled in 54 phase 1 trials at our institution. Clinical and molecular data were retrospectively extracted from medical records. Time to progression (TTP) was calculated from time of tx start to discontinuation due to progressive disease, and clinical benefit rate (CBr) was defined as partial response or stable disease > 4 months. Results: Median age was 58 (41-75), 69% were male, 60% had metastases in liver. Most pts received gemcitabine-based regimens (47%) or Folforinox (32%) as first-line tx (median TTP of 5.63 months [CI 95% 4.0-8.1]). Median tx line of Phase 1 trial was 3 (range 2-5). Regimens included chemo or immunotherapies (chemo-imm group) in 16 cases (12 and 4, respectively), small molecule inhibitor (SMI) as single-agent in 19 cases (SMI.1 group), and SMI in combinations in 19 cases (SMI.2 group). In 17 cases, tx was matched to genomic profile; most frequent matches were PI3K + MEK SMI or RAF SMI ( KRAS mut in 7 pts), PI3K SMI ( PTEN loss/ PIK3CA mut in 3 pts) and PD1 blockade (PDL1 high in 4 pts). There were 3 (6%) partial responses (PI3K SMI unmatched, RAF SMI matched and anti-PD1 agent matched) and 12 (24%) disease stabilizations. Median TTP in phase 1 trial was 1.9 months [CI 95% 1.6-2.5], without significant differences if matched/unmatched agent (p = 0.5) or tx given as second-line/later regimen (p = 0.5). Median TTP was 2.7 months [CI95% 1.6-10.7] with chemo-imm (control arm), 2.0 months [CI95% 1.8-5.6] with SMI.2 (HR = 1.8, p = 0.13) and 1.4 months [CI95% 1.3-2.8] with SMI.1 (HR = 3.0, p = 0.004). This difference was maintained in a multivariable model (HR = 2.9, p = 0.005). CBr with chemo-imm (38%) or SMI.2 (21%) was higher as compared with SMI.1 (5%; p = 0.06). Conclusions: Selected PC pts are eligible to phase 1 trials and up to one-third derive substantial benefit from the intervention. In our experience, chemo-imm agents or targeted SMI given as combination regimens associate with longer TTP and CBr when compared with single-agent SMI.
Prognostic factors of trastuzumab-based chemotherapy in patients with advanced HER2 positive gastric cancer.
Authors: Marshall Shoko , Wakatsuki Takeru , Matsushima Tomohiro , Osumi Hiroki , Ogura Mariko , Ichimura Takashi , Takahari Daisuke , Shinozaki Eiji , Chin Keisho , Yamaguchi Kensei 
Published: March 2017

41 Background: Prognostic factor in patients with HER2 positive gastric cancer who received trastuzumab (T-mab) based chemotherapy remains unclear. The aim of this study is to reveal the clinical factors which predict prognosis in T-mab based chemotherapy. Methods: We retrospectively reviewed HER2 positive gastric cancer patients treated with T-mab based chemotherapy in our institute from March 2011 to June 2016. Patients’ demographics according to the ToGA study and laboratory data were examined. Results: Total of 143 patients were enrolled. Median follow-up period was 14.9 months, and median progression-free survival (PFS) and overall survival (OS) were 11.2 months (95% CI: 8.6-13.9) and 20.9 months (95% CI: 16.6-25.2), respectively. In univariate analysis, performance status (0 vs. 1-2), present of measurable lesion, presence of visceral metastases, No. of metastatic lesion (1-4 vs. > 4), LDH, ALP, Alb, median CEA (≧ 13.6 mg/ml vs. < 13.6mg/ml), and median Neutrophil/Lymphocyte (N/L) ratio (≧ 3.11 vs. < 3.11) were significantly associated with PFS. Regarding OS, extension of disease (locally advanced vs. metastatic), presence of visceral metastases, No. of metastatic lesions, Hb, ALP, Alb, CRP, median CEA and median N/L ratio were significant. In multivariate analysis, CEA levels (HR 0.54: 95%CI 0.34-0.86, p = 0.010) and ALP (HR 0.57: 95%CI 0.33-0.99, p = 0.046) retained to be significant in regard to PFS. Patients with < median CEA level had a median PFS of 13.1 months vs. 7.2 months with ≧ median CEA level. Patients with normal level of ALP showed a median PFS of 12.8 months vs. 5.9 months with abnormal ALP level. With respect to OS, CEA levels (HR 0.59: 95%CI 0.34-1.03, p = 0.061) and N/L ratio (HR 0.55: 95%CI 0.29-1.06, p = 0.074) were marginally significant. Patients with < median CEA level had a median OS of 27.6 months vs. 17.6 months with ≧ median CEA level. Patients with > median N/L had a median OS of 24.5 months vs. 16.5 month with ≧ median N/L. Conclusions: Lower CEA levels and normal ALP levels were associated with favorable PFS, and lower CEA and N/L ratio were marginally associated with favorable OS.
Survival difference among patients with hepatocelluar carcinoma (HCC) based on stage of disease: The pre- and post-sorafenib era.
Authors: Shah Chintan , Chhatrala Hardik Satish , Vora Kinjal , Bishnoi Rohit , Bejjanki Harini , Chandana Sreenivas 
Published: March 2017

411 Background: Sorafenib was approved for unresectable and metastatic HCC in 2007. We conducted this retrospective study using U.S. Surveillance, Epidemiology and End results (SEER) database to evaluate the relative survival rates of HCC patients before and after the approval of sorafenib. Methods: We analyzed SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival at 12,24,36,48 and 60 months interval was measured for patients diagnosed with HCC between 2001 and 2013. Relative survival rates were compared between pre sorafenib (2001-2007) and post sorafenib (2008-2013) eras. Results: A total of 54,901 patients (23,963 in pre sorafenib era and 30,938 in post-sorafenib era) were reported with HCC in SEER database. Relative survival at 5-years significantly improved for HCC patients diagnosed after 2007 (16.00±0.30% vs 18.90±0.30% for pre and post sorafenib era respectively; P-value < 0.001). Relative survival for HCC patients with the solitary tumor was significantly improved (33.10±0.80% vs 35.40±0.90% survival at 5 years for pre and post sorafenib era respectively; P-value < 0.001). Similarly, survival was found to be significantly improved for patients with multiple tumors without vascular invasion (17.10±0.70% vs 19.40±0.80% survival at 5 years for pre and post sorafenib era respectively; p-value < 0.001). Relative survival continued to be poor with no statistically significant difference at any intervals for patients with tumor with vascular invasion (P-value 0.748) or distant metastasis (P-value 0.055). Survival difference was not significant among different age groups and gender between pre and post sorafenib eras. Conclusions: While relative survival significantly improved in post sorafenib era, it is largely limited to patients with the localized disease with the solitary tumor or multiple tumors without any vascular invasion or metastasis. Survival in patients with advanced stage HCC remains poor and has not shown significant improvement since the approval of sorafenib. The study shows better alternatives are needed for advanced-stage unresectable HCC patients.
Usefulness of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy to predict prognosis of advanced biliary tract cancer.
Authors: Cho Kyoung Min , Park Hyunkyung , Oh Do-Youn , Kim Tae Yong , Lee Kyung-Hun , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue 
Published: March 2017

416 Background: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. Methods: We reviewed 554 patients with advanced BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. Results: Higher systemic inflammation status also had relation with a primary tumor site ( p = 0.044) and higher levels of CEA ( p = 0.041). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (7.10 vs. 10.23 months, p < 0.001; 8.43 vs. 11.87 months, p = 0.001, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) ( p = 0.014, p= 0.020 respectively). Results are similar for PLR. Conclusions: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.