tbuckley/cabot-search huggingface dataset:
Quality of life following laparoscopic distal gastrectomy with modified billroth II reconstruction.
Authors: Maithao N. Le, Jacob Ellenhorn, Joseph Kim, Vijay Trisal, Joshua D. I. Ellenhorn
Journal: Journal of Clinical Oncology (2012)

140 Background: Laparoscopic gastrectomy has been proposed as a procedure to reduce the morbidity of gastric cancer surgery. Modified Billroth II (BII) reconstruction with a side to side loop gastrojejunostomy is technically straightforward to accomplish laparoscopically. To determine the long term morbidity of this reconstruction technique, we performed a quality of life (QOL) analysis of patients undergoing laparoscopic distal gastrectomy with modified BII reconstruction. Methods: Between June 2005 and May 2011, 64 patients underwent laparoscopic distal gastrectomy with modified BII reconstruction at City of Hope Medical Center (COH). Patients alive with no evidence of disease were recruited to participate in the QOL study. The study was approved by the Institutional Research Board of COH. Research subjects completed the EORTC QOL-STO22 instrument which queried patients for post gastrectomy symptoms. Comparison between groups was done using the Student-t test. Results: 33 of 64 patients met the criteria for participation in our QOL study. Of these, 23 patients consented to participate and completed the EORTC QOL-STO22 instrument. Overall, 81% categorized symptoms as occurring “not-at-all” or “a-little” while 19% reported symptoms occurring “quite-a-bit” or “very-much”. Since symptoms could be worse in patients with small gastric pouches, we divided our cohort into two groups, one having at least 70% of the stomach resected (12 patients) and the other having less than 70% of the stomach resected (11 patients). The two groups were compared with respect to symptoms. There was no difference between the groups with respect to dysphasia (p=0.80), pain (p=0.98), reflux (p=0.93), and eating restriction (p=0.33). Overall 78% of patients with a small gastric pouch and 83% of patients with a larger gastric pouch reported these symptoms as occurring “not-at-all” or “a-little”. Conclusions: Laparoscopic distal gastrectomy with modified BII reconstruction resulted in an acceptable morbidity rate with few patients experiencing severe symptoms. Gastric pouch size did not predict symptoms and most patients with a small gastric pouch report excellent QOL.
Loss of SMAD4 and effect on overall survival in resected gastrointestinal neuroendocrine tumors.
Authors: Christina Lynn Roland, Ya'an Kang, Deyali Chatterjee, Jeannelyn Estrella, Asif Rashid, Jeffrey Edwin Lee, James C. Yao, Jason B. Fleming
Journal: Journal of Clinical Oncology (2014)

250 Background: Studies by comparative genomic hybridization have demonstrated that the 18q chromosomal region is frequently lost in gastrointestinal neuroendocrine tumors (GI-NET). However, the impact of DPC/SMAD4 loss, which is located 18q21, in the pathogenesis of GI-NET remains controversial. In this study, we sought to determine the protein expression of SMAD4 in GI-NET and the impact on oncologic outcomes. Methods: To investigate the role of SMAD4 in GI-NET, a tissue microarray consisting of 33 GI-NET was constructed and analyzed by immunohistochemistry for SMAD4 expression. SMAD4 expression was classified as negative, SMAD4-low (≤10% cells +) or SMAD4-high (&gt;10% cells+). Staining results were correlated clinicopathologic features and overall survival. Results: Of the 33 tumors examined, 93% were low- or intermediate-grade and 7% high-grade. 35% of GI-NET were negative for SMAD4, 45% were SMAD4-low and 15% SMAD4-high. Expression of Chromogranin was observed in 91% of all tumors, synaptophysin in 94%, CDX2 in 64%, and CK19 in 55%. We were unable to identify any association between loss of SMAD4 and stage or tumor grade. There was an inverse correlation between loss of SMAD4 and CK19 expression, whereby 75% of SMAD4-neg tumors expressed CK19 and only 32% of SMAD4+ expressed CK19 (p=0.01). At a median follow-up of 123 months, median overall survival was 203 months. Survival differences related to SMAD4 status resulted in clinically meaningful, although statistically non-significant, differences in overall survival (SMAD4-low: 132 months vs. SMAD4-high: 203 months, p=0.058). Conclusions: Differences in SMAD4 expression result in clinically important differences in overall survival, although this cohort may be underpowered to detect a statistically-significant difference. Future studies with larger patient populations may be critical to evaluate the importance of SMAD4 in the pathogenesis of GI-NET.
Association between genetic variations involved in tumor dormancy related genes and clinical outcomes in Japanese patients with gastric cancer.
Authors: Takeru Wakatsuki, David Páez, Wu Zhang, Melissa Janae Labonte, Dongyun Yang, Mizutomo Azuma, Yan Ning, Nico Volz, Sebastian Stintzing, Pierre Oliver Bohanes, Rita El-Khoueiry, Wasaburo Koizumi, Masahiko Watanabe, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2013)

43 Background: The major cause of cancer-related death is metastatic growth of disseminated tumor cells (DTCs) from the primary tumor despite approximate resection and adjuvant chemotherapy. Tumor dormancy is a stage in cancer progression in which micrometastases or residual tumor remains occult and asymptomatic until clinical appearance. The regulation of whether DTCs keep to a quiescent state or transit into a proliferative state can be explained through the interaction of the DTCs with the microenvironment, blood supply, and immunosurveillance. This suggests that host genetic background may impact this process. We tested our hypothesis whether polymorphisms involved in tumor dormancy related genes could predict clinical outcomes in gastric cancer (GC). Methods: One-hundred and sixty-nine Japanese patients with histolopathologically confirmed localized GC (stage Ib to IV; AJCC-6 th ) were enrolled from Kitasato East University Hospital and Fukushima Red Cross Hospital between 2002 and 2010. Twenty-four polymorphisms were selected from VEGF pathway genes, microenvironment related genes, and metastasis suppressor genes. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Results: The median age was 68 (31-88) years-old, and 64% of patients were males in this cohort. Pathological stages were 17% in stage Ib, 31% in stage II, 36% in stage III, and 17% in stage IV,. Almost all patients received D2 lymphadectomy based surgery and 65% patients received S-1 based adjuvant chemotherapy. The median follow-up periods were 4.0 years. NME1 rs2302254 was associated with significantly shorter disease-free survival (HR 1.555; 95%CI, 1.026-2.359; p=0.032). NME1 rs34214448 (HR 1.732; 95%CI, 1.082-2.770; p=0.036), PAI1 rs1799889 (HR 1.855; 95%CI, 1.032-3.333; p=0.02), and VEGF-A rs699946 (HR 1.678; 95%CI, 1.014-2.778; P=0.042) were associated with significantly shorter overall survival. Conclusions: NME1 rs2302254 may predict early recurrence of Japanese patients with GC. Additionally, survival after recurrence could be influenced by angiogenic factors in a synergic manner.
Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997–2013
Authors: S Lehmann, S Deneberg, P Antunovic, Å Rangert-Derolf, H Garelius, V Lazarevic, K Myhr-Eriksson, L Möllgård, B Uggla, A Wahlin, L Wennström, M Höglund, G Juliusson
Journal: Leukemia (2017)
Measuring alignment with evidence-informed practice in Ontario’s systemic treatment funding model.
Authors: Leonard Kaizer, Vicky Simanovski, Irene Blais, Carlin Lalonde, Huma Tariq, Jennifer Lam, William K. Evans
Journal: Journal of Clinical Oncology (2014)

15 Background: A new systemic treatment funding model (STFM) was implemented in Ontario on April 1, 2014, transitioning from life-time per case funding to reimbursement based on evidence-informed episodes of care. The effectiveness of the model will be evaluated against key indicators including the percent of patients on evidence-informed regimens (PPEIR). Methods: Provincial Disease Site Group (DSG) experts reviewed all chemotherapy regimens administered in Ontario over the two years prior to implementation. Each DSG identified the treatment regimens to be STFM reimbursed, based on evidence of clinical benefit according to treatment intent (curative/adjuvant vs. palliative or both). A year of pre-implementation data will serve as a baseline to assess the impact of transition to the new funding model. Clinical and administrative stakeholders have received their baseline facility-level data and will receive monthly reports, including the PPEIR, to aid in identifying and resolving clinical practice and/or data quality issues post-implementation. Results: Of approximately 1,000 regimens reviewed by the DSGs, ~100 were deemed to be evidence informed for adjuvant/curative intent, ~325 for palliative intent, and ~90 for both intents. Overall, the 2013/14 baseline provincial PPEIR was 91.6% for 16,200 treatment courses given with adjuvant/curative intent while 93.2% of 56,800 patient-months of treatment with palliative intent were aligned with the proposed evidence informed definition. Significant variation in baseline PPEIR was seen for the 29 level 1-3 provincial treatment facilities (range = 71-99%) and for the 10 different disease sites. Conclusions: Knowledge of the PPEIR utilized increases understanding of practice at the system (provincial), regional, facility and disease site level and will provide opportunities for benchmarking and ongoing improvement in quality of care.
Comprehensive multiplatform biomarker analysis of 313 hepatocellular carcinoma to identify potential therapeutic options.
Authors: Ghassan K. Abou-Alfa, John Thomas Miura, T. Clark Gamblin, Joanne Xiu, Sherri Z. Millis, Zoran Gatalica, Sandeep K. Reddy, Celina Ang, Nelson S. Yee
Journal: Journal of Clinical Oncology (2015)

283 Background: Effective treatment strategies for hepatocellular carcinoma (HCC) remain limited. Identification of additional therapies remains paramount as currently available agents have resulted in marginal improvements in overall survival. Methods: 313 HCC sampleswere evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing (Sanger, NGS [N=79]), protein expression (IHC) and gene amplification (ISH). Results: Biomarker changes of interest are shown. See Table. TP53 was mutated in 28%, CTNNB1 in 23%, and BRCA2 in 20%; other gene mutation rates were &lt; 5%.TP53-mutated tumors show significantly higher TOPO2A (89% vs. 39%, p&lt;0.0001), TS (70% vs. 32%, p=0.0067) and RRM1 expression (40% vs. 12%, p=0.017), implying high rates of proliferation and DNA synthesis. CTNNB1-mutated tumors showed significantly higher SPARC (67% vs. 21%, p=0.0013) and AR expression (53% vs. 22%, p=0.025). Primary HCC (N=209) exhibited significantly higher PD-1 (89% vs. 33%, p=0.01) and TS expression (35% vs. 13%, p&lt;0.0001) than metastatic (N=105). Patient history/outcomes relative to biomarker status are being evaluated. Conclusions: These data suggest potential therapeutic targets, such as tyrosine kinase inhibitors, anti-PD1 agents, or PI3 kinase pathway inhibitors. Although no evidence shows that cytotoxics are effective in patients with HCC, irinotecan, alkylating agents, fluoropyrimidines, anthracyclines, nab-paclitaxel, gemcitabine, or taxanes may be therapeutically relevant. The protein changes associated with CTNNB1-mutated tumors suggest potential benefit of targeting WNT pathway in combination with nab-paclitaxel or anti-androgens. Immuno-modulatory agents may be a therapeutic option in primary HCC, based on the higher levels of PD-1. Multiplatform tumor profiling reveals molecular heterogeneity HCC, similar overall to previous reports, and identifies different potential treatment options for molecular subtypes. [Table: see text]
The clinical significance of S100A10 in pancreatic cancer.
Authors: Naoto Yamamoto, Yoshiyasu Nakamura, Soichiro Morinaga, Koji Numata, Sho Sawazaki, Takuo Watanabe, Masakatsu Numata, Hiroshi Tamagawa, Teni Godai, Manabu Shiozawa, Makoto Akaike, Kameda Yoichi, Makoto Ueno, Shinichi Ohkawa, Takashi Oshima, Norio Yukawa, Yasushi Rino, Munetaka Masuda, Yohei Miyagi
Journal: Journal of Clinical Oncology (2013)

194 Background: S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. They regulate a number of cellular processes such as cell cycle progression and differentiation. The objective of this study is to clarify the clinical significance of S100A10 in patients with pancreatic cancer. Methods: A total of 48 pancreatic adenocarcinoma tissues from patients underwent curative surgery were enrolled. Double 2-mm core tissue microarrays were made from paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for S100A10 protein. The correlations of expression level and clinicopathological outcome including recurrence free survival (DFS) were analyzed. Results: Expression level of the S100A10 protein in cytoplasm was categorized as overexpressed or others according to the baseline expression level in normal pancreatic duct. Overexpression of S100A10 protein was found in 9 of 48 (16.7%) cases. Statistical analysis revealed that related factor was distant lymph node metastasis. Univariate and multivariate Cox proportional hazard analysis showed S100A10 overexpression was significant independent predictors of DFS in patients with R0/1 resected pancreatic cancer (p=0.003). Although univariate Cox analysis showed overall survival in patient with S100A10 overexpression was significantly shorter (p=0.04), it didn’t show significance in multivariate analysis. Conclusions: S100A10 overexpression is considered to be useful predictor of post-operative recurrences in patients with pancreatic cancer.
Hepatitis B reactivation in patients with lymphoma: A meta-analysis.
Authors: Lee Mozessohn, Kelvin K. Chan, Jordan J. Feld, Lisa K. Hicks
Journal: Journal of Clinical Oncology (2013)

228 Background: Patients with hepatitis B virus (HBV) who are HBsAg+ are at risk of HBV reactivation if rituximab is administered in the absence of antiviral treatment. Recently, it has been reported that patients with so-called “resolved HBV infection”(HBsAg-/cAb+) may also be at risk; however, the degree of risk is not known. Methods: We performed a systematic review of the English and Chinese language literature in Medline (1996 to June week 3 2013) and Embase (1996 to 2013 week 26) using the MeSH terms “lymphoma” and “hepatitis B”. Eligible studies were limited to those reporting primary data on HBV reactivation rates in HBsAg-/cAb+ patients receiving rituximab. We excluded case series with less than 5 patients. Pooled estimates were calculated for HBV reactivation and the impact of HBsAb status on HBV reactivation rate was explored. We also examined reactivation in HBsAg+ patients receiving rituximab by performing a systematic review of the English language literature in PubMed (1997 to June 21, 2013) using the terms “hepatitis B virus”, “reactivation” and “lymphoma”. Results: Data from 550 HBsAg-/cAb+ patients in 12 studies were included. Using a standardized definition of HBV reactivation, (increase in HBV DNA from baseline or HBsAg seroreversion +/- ALT &gt;3 x upper limit of normal), the pooled estimate for the risk of HBV reactivation in HBsAg-/cAb+ patients was 8.1% (I 2 = 55%, P = 0.007). Significant heterogeneity was apparent. Exploratory analyses suggested that patients were less likely to reactivate if they were HBsAb+ (OR = 0.32; 95% CI 0.12-0.85, P = 0.0285). In HBsAg+ patients we meta-analyzed prospective, controlled studies. Without antiviral prophylaxis, the reactivation rate for HBsAg+ lymphoma patients was 51.0% (I 2 = 0%, P = 0.93). Conclusions: Our meta-analyses confirm that there is a risk of HBV reactivation in HBsAg-/cAb+ patients exposed to rituximab. HBsAb+ patients may be at lower risk than those who are HBsAb-. However, heterogeneity in the risk estimates limits their generalizability. Without prophylaxis, significant reactivation in HBsAg+ patients exists. Large prospective studies are needed to clarify the risk of HBV reactivation in HBsAg-/cAb+ patients and to inform decisions about best practice.
Effectiveness of triplet chemotherapy plus bevacizumab intensive regimen (FIr-B/FOx) and secondary liver surgery according to KRAS genotype in metastatic colorectal cancer (MCRC).
Authors: G. Bruera, K. Cannita, D. Di Giacomo, G. Troncone, A. Marchetti, G. Coletti, J. Sabourin, M. Tosi, C. Ficorella, E. Ricevuto
Journal: Journal of Clinical Oncology (2011)

e14028 Background: FIr-B/FOx association, consisting of triplet chemotherapy plus bevacizumab, can increase activity, efficacy and resection rate of liver metastases in MCRC patients (Bruera G et al, BMC Cancer 2010). Even if Bevacizumab-containing chemotherapy is also active in KRAS mutant (m) patients, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) are lower compared to KRAS wild-type (wt) patients (Hurwitz et al, Oncologist 2009). Present data evaluates activity and efficacy of FIr-B/FOx according to KRAS genotype. Methods: FIr-B/FOx association consisted of 5fluorouracil associated to alternating irinotecan/bevacizumab or oxaliplatin according to previously reported weekly schedule. KRAS genotype was analyzed by direct sequencing or SNaPshot (Di Fiore et al, BJC 2007) for KRAS codon 12 and 13 mutations. Results: Forty-two tumoral samples of the 50 patients (84%) enrolled in FIr-B/FOx trial were available: 25 patients (59.5%) KRAS wt, 17 patients (40.5%) KRAS m. Clinical features were balanced, except for Male/Female ratio: 16/9 and 9/8, respectively. In KRAS evaluated patients, activity and efficacy were equivalent to that previously reported: ORR 86% (C.I. ± 11), median PFS 13 months (3-46+), median OS 28 months (8-47); liver metastasectomies (LM) 29% (12 patients), 46% of liver-MCRC patients and 58% of liver-only patients. In KRAS wt: ORR 88% (C.I. ± 14), median PFS 14 months (3-46+), median OS 31 months (8-47); LM 36% (9 patients), 56% of liver-MCRC patients and 73% of liver-only patients. In KRAS m: ORR 82% (C.I. ± 19), median PFS 12 months (4-37+), median OS 19 months (8-44); LM 18% (3 patients), 30% of liver-MCRC patients and 37.5% of liver-only patients. Median PFS and OS in liver-only patients, respectively: KRAS wt, 21 and 47 months; KRAS m, 17 and 44 months. KRAS m patients showed a trend toward worse median OS. Conclusions: High efficacy of FIr-B/FOx is equivalent in KRAS wt and m patients; ORR and PFS are particularly increased in KRAS m patients. Effectiveness of integrated intensive chemotherapy and secondary LM raises in liver-only MCRC patients, independently from KRAS genotype.
A phase Ib study of oral panobinostat (LBH589) in combination with cytarabine (ARA-C) and mitoxantrone (MT) as salvage therapy for refractory or relapsed acute myeloid leukemia (AML).
Authors: J. Krauter, O. G. Ottmann, R. F. Schlenk, M. Schaich, D. Bouscary, H. Dombret, F. Lüdicke, H. J. Weber, I. J. Winiger
Journal: Journal of Clinical Oncology (2010)

TPS276 Background: Panobinostat (PAN; LBH589) is a potent pan-deacetylase inhibitor (pan-DACi) targeting epigenetic and nonepigenetic oncogenic pathways. In preclinical studies with AML cell lines and patient (pt) blast cells, PAN potentiated the activity of ARA-C and fludarabine and was synergistic in combination with doxorubicin. Combining PAN with an active cytotoxic chemotherapy (CT) regimen can potentially improve therapeutic outcomes of and be safely administered to pts with AML who have relapsed or are refractory to prior induction therapy. This phase Ib, multicenter, open-label, dose-finding study comprises two phases: a dose-escalation phase to determine the maximum tolerated dose (MTD) of PAN in combination with ARA-C and MT (an active and representative regimen in the salvage setting of AML), and a subsequent dose-expansion phase to assess safety and preliminary anti-leukemic activity (FPFV Aug 9, 2009). Methods: Adult pts with AML (WHO criteria) relapsed after 1 prior induction regimen or refractory to not more than 1 prior combination CT induction are eligible (ECOG PS ≤2). Pts in the dose-escalation phase are evaluated for dose-limiting toxicity (DLT) using an adaptive Bayesian logistic regression model with overdose control. PAN is orally administered (20 mg starting dose) thrice weekly on Days (D) 1, 3, 5, 8, 10, and 12, combined with iv ARA-C (1 g/m2) D1–6, and iv MT (5 mg/m2) D1–5 of a 28-D cycle (C). At least 3 pts are required per dose cohort and ≥9 evaluable pts are required to declare MTD. An additional 11 pts will be enrolled at MTD for the 2nd phase. Treatment is continued until disease progression, unacceptable toxicity, or consent withdrawal. Pts achieving CR in C 1 or 2 can receive a maximum of 3 additional Cs for consolidation of remission status. Pts who respond to PAN in combination with ARA-C/MT and are not eligible for other treatments can continue on single-agent PAN (60 mg thrice weekly). The primary endpoint is DLT incidence. Secondary endpoints include type, duration, and frequency of adverse events. Exploratory endpoints includeCR, CR with residual neutropenia or thrombocytopenia, PR, and safety endpoints. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Celgene, Novartis Novartis Bristol-Myers Squibb, Celgene, Novartis Bristol-Myers Squibb, Novartis Novartis