tbuckley/cabot-search huggingface dataset:
Accuracy of AASLD guidelines for pre-operative diagnosis of hepatocellular carcinoma in a surgical population.
Authors: Edwin Yang, Hennedige Priyanti Tiffany, Miaoshan Lim, Choon Hua Thng, Pierce K. H. Chow
Journal: Journal of Clinical Oncology (2016)

198 Background: The diagnosis of Hepatocellular Carcinoma (HCC) is mainly by dynamic imaging techniques based on guidelines such as that of the American Association for Study of Liver Disease (AASLD). No biopsy is required if criteria in the guidelines are met due to high pre-test probability of disease, risk of tumor seeding and patient morbidity that occurs with invasive liver biopsy. The 2005 AASLD guidelines mandates that there be liver cirrhosis before an imaging diagnosis of HCC can be made. However, updates to the guidelines in 2010 have been expanded to patients with either cirrhosis and/or chronic Hepatitis B carriers. AIM: To compare the sensitivity and positive predictive values of the 2005 and 2010 guidelines in a Hepatitis-B endemic region. Secondary aim: To evaluate proportion of patients who avoided unnecessary biopsies. Methods: A retrospective study of 176 patients from 2006-2010 from a joint cancer service in our centre who had undergone surgical resection for presumptive diagnoses of HCC, were analysed. Their hepatitis status and imaging findings were also examined. Multiphasic CT Liver images were re-examined by 2 oncologic radiologists and the diagnosis of HCC and cirrhosis was only made when there was concordance in opinion. Results: Of all cases, 89.6% of patients were histologically proven HCCs. Sensitivity of detecting cirrhosis on CT was 83.2% with an accuracy of 81.5%. Sensitivity of diagnosis based on the 2010 and 2005 guidelines were 58.1% and 57.4% respectively. When the sensitivities of the previous vs revised guidelines were compared using Mcnemar’s Test, the 2010 guidelines showed a 24.6% increase in sensitivity (p &lt; 0.05). 4.65% more cases avoided unneeded biopsies when applying the 2010 criteria. Conclusions: Diagnosis of HCC under the 2005 AASLD guidelines were based on the pre-operative diagnosis of cirrhosis which in this centre, was of high sensitivity and accuracy. The increase in the sensitivity of diagnosing HCC in the 2010 criteria may reduce the need for invasive biopsy and likelihood for tumor seeding.
Real world treatment patterns of previously treated advanced gastric and gastroesophageal junction adenocarcinoma (GC) in Mexico.
Authors: Kyla Jones, JUAN ALEJANDRO SILVA, Diego Novick, Brenda S Botello, Bárbara Monroy Cruz, JM Iglesias-Chiesa, Miguel Quintana
Journal: Journal of Clinical Oncology (2016)

143 Background: Little evidence is available on the management of patients (pts) with advanced GC after 1 st -line treatment (tx). Until recently, no licensed therapies for 2 nd -line tx were available. This study presents real-world data on pts characteristics, tx patterns, and resource utilization for these pts in Mexico. Methods: Data from medical charts was collected from 3 centers (tertiary-level). Eligible pts were ≥ 18 years old, diagnosed Jan 2007 - Jan 2015 with advanced or metastatic GC, had received 1 st -line fluoropyrimidine+platinum, had ≥ 3 months of follow-up after 1 st -line discontinuation, and had not participated in a clinical trial. Data were summarized using descriptive statistics. Results: Data from 180 charts was collected; the majority from the Mexican Institute of Social Security (IMSS) (167; 92.8%). Pts' mean age was 57.2 (±12.4) years and 56.7% were male. ECOG performance status (PS) during 1 st -line tx was 78.3% PS = 1, 17.2% PS = 2, 0% PS = 0. A total of 16 unique 1 st -line regimes were identified, of which EOX (32.2%), XELOX (23.3%), and ECF (14.4%) were the most frequent. The most common reasons for discontinuation were completion of planned regimen (27.2%), toxicity (27.2%) and disease progression (16.7%). A total of 151 (83.9%) pts received 2 nd -line chemotherapy. Of these, 54.3% were PS = 1 and 33.1% PS = 2. A total of 19 regimes were identified; with the most frequent being capecitabine (34.4%), docetaxel (16.6%), and XELOX (13.9%). Among pts who received 2 nd -line chemotherapy, 50 (33.1%) received 3 rd -line chemotherapy. Resource use for patients receiving 2 nd -line chemotherapy was: pain interventions (7.3%), nutritional support (1.3%), radiotherapy (13.9%), transfusions (10.6%), inpatient care (15.2%), emergency room visits (2.0%) and outpatient visits (other than scheduled follow-up) (3.3%). Conclusions: This study shows considerable variation in chemotherapy regime in both 1 st - and 2 nd -line therapy of pts with advanced GC. Understanding GC tx patterns in Mexico will help address unmet needs. Limitations: Pts who did not receive 2 nd -line tx are likely underrepresented because these pts are typically managed at local clinics and not tertiary hospitals.
Preliminary safety and efficacy of perioperative COI-B (capecitabine, oxaliplatin, irinotecan, and bevacizumab) in patients with borderline resectable or high–recurrence risk colorectal cancer liver metastases (CLM).
Authors: Marta Caporale, Christian Cotsoglou, Rosa Berenato, Mauro Scotti, Maria Di Bartolomeo, Jorgelina Clara Coppa, Massimo Milione, Alessia Mennitto, Maria Flores Reyes, Ilaria Bossi, Paola Valentina Consonni, Federica Brunero, Filippo de Braud, Filippo Pietrantonio, Vincenzo Mazzaferro
Journal: Journal of Clinical Oncology (2016)

719 Background: FOLFOXIRI and bevacizumab achieves high objective response rate (ORR)/R0 resections in pts with unresectable CLM. Bevacizumab increases pathological response, a surrogate endpoint of survival after CLM resection. COI-B regimen is feasible in pts with advanced colorectal cancer. In this phase II study, we aimed at assessing safety and efficacy of perioperative COI-B for pts with borderline resectable or high recurrence risk CLM. Methods: Inclusion criteria: borderline resectability with portal embolization/2-stage hepatectomy, involvement of &gt; 1 hepatic vein or &gt; 4 segments; and/or at least one poor prognostic factor: &gt; 4 metastases; CEA &gt; 200; synchronicity. Limited resectable extraepatic disease and in situ primary allowed. Primary endpoint: TRG1-3 (Rubbia-Brandt et al) according to Simon 2-stage design (first step 22; target 46 pts); secondary endpoints: ORR; R0 resection; safety; progression-free and overall survival. Pts received bi-weekly irinotecan (180 mg/m 2 ) and bevacizumab (5 mg/Kg) day 1, oxaliplatin (85 mg/m 2 ) day 2 and capecitabine (1000 mg/m 2 /day b.i.d.) days 2–6; 5 cycles pre-operatively (the last without bevacizumab) and 4 post-operatively. Results: We present preliminary data on the first 25 pts. M/F: 13/12, median age 61 years, synchronous disease 19 (76%), multiple nodules 15 (60%), N+ primary tumour 14 (56%), CEA &gt; 200 4 (16%), extrahepatic disease 1, RAS mutation 15 (60%)/BRAF mutation 0. Involvement ≥ 4 hepatic segments 9 (36%) and involvement of &gt; 1 hepatic veins 4 (16%). ORR was 91% (21 out of 23 evaluable, 2 too early), while 1 SD and 1 PD. Surgery performed in 21 pts (4 awaiting) and R0 resection in 18 (86%). TRG1-2 was observed in 6 (29%), TRG3 in 9 (43%), i.e. pathological response 72% (first step reached). Grade ≥ 3 toxicities: neutropenia 2, diarrhea 2, thrombosis 2. Median follow up 13 months, with only 4 relapses and 1 death. Conclusions: COI-B regimen is a feasible neoadjuvant strategy for borderline resectable or high recurrence risk CLM. This is the first trial to select pathological response as primary surrogate endpoint with encouraging results. Clinical trial information: NCT02086656.
MicroRNA-27b as a prognostic marker in pancreatic neuroendocrine tumor.
Authors: Bong Kyun Kang, In kyeom Hwang, Yoon Suk Lee, Jaihwan Kim, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2014)

251 Background: Pancreatic neuroendocrine tumors (PNETs) are heterogeneous group of tumors with a wide spectrum of behavioral characteristics. PNET generally behaves in an indolent fashion. However, when metastasis occurs, it is difficult to be treated. Little is known about prognostic biomarker in PNET. The aim of this study was to elucidate prognostic biomarker in PNET using nanostring microRNA (miRNA) array technology. Methods: We had already selected several candidate miRNAs (miR-27b, miR-122, miR-142-5p, miR-196a, miR-223, miR-590-5p, miR-630 and miR-944), which indicated 3 folds expression differences between primary tumor and metastatic tumor on the basis of nanostring-based microarray in two PNET patients. Further 39 PNET patients were enrolled for clinical validation (recurrence group includes patients who had metastasis subsequently; no-recurrence group includes the others) of 8 miRNAs. Surrounding pancreas and tumor miRNA were isolated separately from formalin-fixed paraffin-embedded tissues. Expression of candidate miRNAs was measured by quantitative real-time PCR using U6 as an internal control. Mann-Whitney U test and Spearman rank correlation analysis were used for statistical evaluation at p &lt; 0.05 level. Results: miR-27b expression was elevated in recurrence group compared to no-recurrence group (p = 0.019). And also, miR-27b expression was statistically significant correlated positively with CA 19-9 level (p = 0.015). The Hierarchical cluster analysis of eight miRNAs showed miR-27b linked functionally to miR-142-5p and miR-196a. Furthermore, miR-196 expression was associated with Ki-67 index with a statistical significance (p = 0.035). Conclusions: The miR-27b would be a prognostic marker of recurrence in resected PNET and link to miR-142-5p and miR-196a, which correlated with Ki-67 index. Further experimental investigation would be required to demonstrate the role of these miRNAs in PNET.
Gene therapy with tumor-specific promoter mediated suicide gene plus interleukin-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma.
Authors: Y. Zhou, Y. Xu, H. Yu, W. Sun, Z. Liao, F. Zhou, C. Xie
Journal: Journal of Clinical Oncology (2011)

e13086 Background: Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study was to establish a more effective and less toxic gene therapy of cancer. Methods: Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated. Results: HRP and mIL-12 proteins were detected in LLC cells and subcutaneous tumors. The combination of AdhTERTHRP/IAA treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (mean tumor volume, 427.4 ± 48.7 mm3 vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (mean tumor volume, 362.2 ± 33.8 mm3 vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The expressed mIL-12 in tumor in combination group stimulated more CD4+ T helper cells and CD8+ cytotoxic T cells, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+ T cells and 1.2-fold increase for CD8+ T cells, P<0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+ T cells and 2.2-fold increase for CD8+ T cells, P <0.01). The apoptotic cells in combination group were significantly increased compared with AdCMVmIL-12 alone group (2.8-fold increase, P<0.01) or AdhTERTHRP alone group (1.6-fold increase, P<0.01). No significant systematic toxicities were observed. Conclusions: Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects.
RAINIER: A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (nab-P) combined with apatorsen (A) or placebo (Pl) in patients (pts) with metastatic pancreatic cancer (mPC).
Authors: Andrew H. Ko, Patrick B. Murphy, James D. Peyton, Dianna Shipley, Ahmed Al-Hazzouri, Frank A. Rodriguez, Mark S. Womack, Henry Q. Xiong, David M. Waterhouse, Margaret A. Tempero, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2016)

419 Background: Heat shock protein 27 (Hsp27) is over-expressed in PC, enabling tumor growth and metastasis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m 2 IV, nab-P 125mg/m 2 IV days 1, 8, and 15. Restaging was every 2 cycles. Serum Hsp27 levels were collected at baseline and on treatment. Primary endpoint compared overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Demographics were similar for both arms. 36% of pts on Arm A and 48% of pts Arm B discontinued due to progressive disease, and 24% and 14% due to adverse events (AEs). There was a higher incidence of ≥Grade (G) 4 and serious adverse events (SAEs) in Arm A. The most frequently reported G 3/4 treatment-related AEs were anemia (20%), neutropenia (17%), and fatigue (16%) on Arm A and anemia (27%), neutropenia (19%), and thrombocytopenia (13%) on Arm B. Overall RR was 18% on each arm. With a median f/u of 9.1 mos, median PFS and OS are 2.7 and 5.2 mos on Arm A and 3.8 and 6.9 mos on Arm B (p=NS). Correlative analyses between Hsp27 expression and clinical outcomes will be presented. In a statistical model using only Arm B data, 3 base attributes, ECOG &gt;0, liver mets, and neutrophil levels had a strong prognostic relationship to OS. Conclusions: This study showed no improvement in clinical outcomes adding A to gem plus nab-p. G 4 AEs and SAEs were increased with A. We await analysis for Hsp 27 and CA 19-9 levels and further analysis to identify any pt subgroup who might have benefited from the experimental treatment. Clinical trial information: NCT01844817.
Wood-smoke exposure (WSE) as a predictor of response and survival in erlotinib-treated advanced lung adenocarcinoma (ALA) patients (pts) (ONCOLGroup study)
Authors: C. Castro, A. F. Cardona, N. Reguart, E. Carrasco-Chaumel, J. M. Otero, H. Carranza, C. Vargas, L. Reveiz, D. Torres, G. Blumenschein
Journal: Journal of Clinical Oncology (2009)

e19052 Background: There is consistent information suggesting that long-term WSE constitutes a risk factor for lung cancer. More than 50 years of WSE was associated with non-small cell lung cancer (NSCLC). In Colombia the prevalence of WSE in areas having less economic development is approximately 24%. The aim of the study was to evaluate WSE as a predictor of response and survival in ALA pts. Methods: This study included 168 pts with ALA treated between 2002 and 2007 in four referring hospitals of Bogotá. Retrospectively, we estimated overall response rates (ORR), time to progression (TTP) and overall survival (OS) in a subgroup of pts with significant WSE (exposure &gt;5 years for at least 4 hours/day) treated with erlotinib, and compared them with the non-WSE population treated with the same compound. Results: Median age was 66 years (range, 29–96), 53% were female, 39% had never been smokers, 24% of all cohort pts had been considerably exposed to WS and 45 pts had received erlotinib during disease treatment (as 2nd or 3rd line). Sixteen of these pts (F11/M5, PS ≥70% 9 pts) had been exposed to WS and 29 not so (F17/M12, PS ≥70% 22 pts); 10 pts having WSE had been smoking for a mean of 14pk/yr history. ORR to erlotinib was 7% and 32% in pts with and without WSE respectively (p = 0.02). TTP was significantly higher in pts treated with erlotinib with no history of WSE (4.9 mo. vs 1.7 mo., p = 0.034). and in those who had received this compound as second-line (vs erlotinib used as third line, p = 0.044). Among pts with WSE history, OS was 6.6 mo. (range, 5.8–7.3) for those treated with Erlotinib and 12.7 mo. (range, 10.2–17) for those not treated with this compound (p = 0.04). Multivariate analysis was carried out for determining the factors influencing mortality between pts with WSE; only PS (HR: 4.6, 95%CI: 1.2–29, p = 0.050) and gender (HR: 3.6, 95%CI: 2.7–18, p = 0.036) were significant. Conclusions: WSE was associated with a poorer response and survival in ALA pts treated with erlotinib in Colombia. No significant financial relationships to disclose.
Long-term survivorship in gastric cancer.
Authors: P. L. Kunz, M. A. Gubens, G. A. Fisher, J. M. Ford, D. Lichtensztajn, C. A. Clarke
Journal: Journal of Clinical Oncology (2011)

14 Background: Gastric cancer is the fourth most prevalent malignancy and second leading cause of cancer death worldwide. For all stages, gastric cancer is rapidly fatal with a 5-year survival rate of 25%. Of those patients who survive, very little is known about their demographic and tumor characteristics. Methods: Cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed between 1998 and 2005 were identified within the California Cancer Registry, a SEER registry. Univariate and multivariate logistic regression models were constructed predicting the outcome of survival to 3, 5 and 8 years based on demographic, disease and treatment variables. Results: Of the 47,049 patients with gastric or GEJ cancer, 38,380 (82%) died within 3 years of diagnosis, 8,669 (18%) survived at least 3 years, 5,336 (11%) survived at least 5 years, and 3,002 (6%) survived at least 8 years. The 5-year survivors had a median age at diagnosis of 67 years with a male predominance (64%). The majority were non-Hispanic whites (64%), followed by Asian/Pacific Islanders (23%), and Hispanics (18%). Most had localized (48%) or regional (41%) disease. In the multivariate model, odds of surviving to 5 years were highest with localized stage (odds datio=27), surgery (7.8), regional stage (5.9), fundus/body/antrum site (1.7), Asian/Pacific Islander race (1.5), intestinal histology (1.5), high SES (1.4), and well/moderately differentiated tumors (1.4). Kaplan-Meier curves for cause-specific death were examined by anatomic site and histology. Persons with tumors originating in the fundus/body/antrum had longer median OS compared to patients with tumors originating in the esophagus/cardia (15 vs. 12 months). Intestinal histology had longer median OS (30 months) compared to other or diffuse (both approx 12 months). Conclusions: Long-term survivors of gastric and GEJ cancer have distinct demographic patterns when compared to patients who died within three years. The multivariate analyses demonstrated that earlier stage, surgery, anatomic site (fundus/body), Asian race, intestinal histology, high SES, well/moderately differentiated tumors, and radiation were the strongest independent predictors of survival. No significant financial relationships to disclose.
Implementing psychosocial distress screening across a health system: Herding cats or herding cats?
Authors: Heather Sheaffer
Journal: Journal of Clinical Oncology (2016)

113 Background: With the American College of Surgeons Commission on Cancer 2015 Standards in hand, Penn Medicine embarked on a project to formulate an entity-wide plan for the provision of psychosocial distress screening. Identifying psychosocial distress and providing resources to meet those needs is an essential component of quality cancer care. Penn Medicine and the Abramson Cancer Center provided more than 91,000 chemotherapy treatments, 121,000 radiation treatments, and 14,000 proton therapy treatments in FY 15 in urban, suburban and rural settings with wide variations in resources. Methods: The establishment of the Psychosocial Distress Task Force was the key to the success of the project. Participants from multiple disciplines were invited from each facility including identified stakeholders and those with experience screening patients. After reviewing the literature, the task force set the agenda for the project including what tool to utilize for screening, when to screen, who will respond and what metrics would be evaluated. Results: Penn Medicine successfully developed a process for psychosocial distress screening across the health system by the 2015 deadline. The process includes screening all first return medical oncology patients for distress using the PHQ-4 and documenting the results in either the EMR or in the paper chart depending on the facility. The screening results then trigger a consult to social work where the patients are assessed using a standardized social work assessment developed by the task force for use by all oncology social workers across the system to standardize care. Conclusions: Given the scope of Penn Medicine oncology and the diversity of locations and staff models, formulating a plan for the provision of psychosocial distress screening presented a major challenge to the organization. This challenge was met through the establishment of a system-wide task force who planned and implemented distress screening across entity in a cohesive, coordinated way meeting the 2015 Standard.
Randomized multicenter phase II study with docetaxel in combination with either cisplatin or oxaliplatin as first-line treatment in patients with advanced or metastatic non-small cell lung cancer.
Authors: A. Atmaca, S. Al-Batran, T. Güner, C. Pauligk, A. Koepke, H. Bernhard, T. Wenzel, A. G. Banat, P. Brueck, K. Caca, N. Prasnikar, F. Kullmann, E. Jäger
Journal: Journal of Clinical Oncology (2011)

e18024 Background: This study was designed to compare cisplatin and docetaxel (arm A) with oxaliplatin and docetaxel (arm B) in patients with advanced and metastatic non-small lung cancer as a first-line treatment. Methods: Patients with previously untreated metastatic non-small lung cancer were randomly assigned to receive either cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks or oxaliplatin 50mg/m2 and docetaxel 50 mg/m2 every 2 weeks. The primary end point was response rate, secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results: Eighty eight patients (median age: 64 [39-86] years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95%CI: 33%-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17%-43%) in the oxaliplatin/docetaxel arm (p= 0.118). There was no significant difference in progression-free survival (5.7 in arm A vs. 5.3 months in arm B, p=0.139) and median overall survival (11.6 in arm A vs. 6.7 months in arm B, p=0.127) between arms, although slight trends favoring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs. 14%), complete alopecia (72% vs. 10%), and grade 3/ 4 leukopenia (45% vs. 6%) and neutropenia (64% vs. 12%). Conclusions: Oxaliplatin/docetaxel is an active first line regimen in metastatic non-small cell lung cancer, but the use of oxaliplatin should be limited to patients unable to receive cisplatin.
Interim Results From a Phase Ib/IIa Clinical Trial with the Soluble Fc-Gamma IIb Receptor SM101 for the Treatment of Primary Immune Thrombocytopenia
Authors: Tatyana Semenovna Konstaninova, Ivanova Valentina Leonidovna, Andrzej Hellmann, Slawomira Kyrcz-Krzemien, Sascha Tillmanns, Peter Sondermann, Peter Buckel
Journal: Blood (2012)