tbuckley/cabot-search huggingface dataset:
Multiplexed tissue protein assay to predict patient response to targeted therapy in advanced renal cell carcinoma.
Authors: Ulka N. Vaishampayan, Seema Sethi, Wei Chen, Alexandrine Derrien-Colemyn, John Williams Gillespie, Brenda Dickow, Daryn W. Smith, Vladimir Rait, Peter Tunon
Journal: Journal of Clinical Oncology (2013)

382 Background: Although a number of prognostic biomarkers have been explored in advanced renal cancer, to date none have been useful in therapeutic outcome prediction. Methods: Following regulatory approval, formalin-fixed paraffin embedded pre-therapy (sunitinib and/or mTOR inhibitors) tissue samples and clinical data on kidney cancer patients (pts) were obtained. The samples were analyzed using layered immunohistochemistry which allows analysis of multiple biomarkers using a single tissue section. Two panels of 9 protein biomarkers each were used to probe tissue sections for proteins along the mTOR and/or the VEGFR/PDGFR signaling pathways. Biomarker expression in regions of cancer were scored and levels correlated with the patient’s clinical outcome status. Results: Tissue samples of 30 pts treated with sunitinib were analyzed and scored in a blinded fashion using 4 biomarkers. If the sum of the scores assigned to VEGFA, VEGF2 and HIF2alpha was above 19, pt was predicted to be a responder. If initial score &lt; 19 and the sum of VEGFR2 and VEGFB was 2 or more, the pt was predicted to have an objective response (OR)/stable disease (SD). If score &lt; 2 the pt was predicted to have no benefit from sunitinib. 14 of 15 OR/SD pts and 11 of 15 with progressive disease (PD) were accurately predicted. 35 cases treated with mTOR inhibitor were analyzed. 6 biomarkers in the mTOR pathway were used to create a composite score. 11/14 OR/SD pts (sensitivity 79%) and 18/21 PD pts (specificity 86%) were accurately predicted using a score cutoff of 10. Median time to treatment failure (TTF) was 2 months in the PD pts, as compared to 11 months in the OR/SD group. A subgroup analysis of patients followed for 18 months or less showed linear correlation between the biomarkers and the TTF (Spearman correlation coefficient 0.43 with p value 0.04). Statistical modeling, results of ongoing validation testing, and score correlation with TTF will be presented. Conclusions: These results indicate that an assay based on multiplexed protein analysis of tumor tissue is capable of providing clinically applicable information, to help guide therapy. Funding source: Supported in part by NCI BRIDGE Grant 5R44CA123994-06 and by 20/20 gene systems.
Is screening enough? Implications of a pilot utilizing standard screening criteria for early palliative referral.
Authors: Kavitha Ramchandran, Marcy Winget, Erika L Tribett, Bev Anderson, Alison Morris, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2015)

119 Background: Early integration of palliative medicine (PM) into cancer care improves outcomes including quality of life, care coordination and survival. Despite broad endorsement and established guidelines for integration of PM into cancer care, patients are not routinely or comprehensively screened for PM needs. Misconceptions and biases about PM impede screening, uptake and access. A set protocol or triggers for PM may be able to overcome these barriers. This study evaluated the feasibility of using a basic screening protocol using NCCN criteria for automatic PM referral with nurse navigators in gynecologic oncology at one academic medical center. Methods: All patients attending the gynecologic oncology clinic at Stanford Cancer Institute between June 2014 and February 2015 with an assigned nurse navigator (n = 120) were screened for palliative medicine needs using the NCCN guidelines at their new patient visit. A one-page screening tool was developed and nurses were trained to make referrals to PM based on positive screen results. Chart reviews were conducted to identify the percent of new patients screened, the percent of patients who screened positive based on NCCN criteria, and the percent of patients referred to PM. Results: 50% of the cohort of patients were screened using the protocol. Less than 5% percent were referred to PM. However, chart review revealed that forty percent of all patients met NCCN criteria for referral to PM. Referrals to other support services based on screening included oncology social work and survivorship. Conclusions: Implementation of a standard screening tool is not sufficient to ensure that palliative care needs are assessed, and that appropriate referrals are made. Automated mechanisms to make screening facile, as well as algorithms for assessment and intervention are critical to ensure that patients unmet physical and psychosocial palliative needs are identified and treated. Additionally addressing barriers such as branding of palliative medicine, and education of staff on primary palliative care skills such as pain management and therapeutic communication may be strategies to incorporate going forward.
Founder mutation versus full sequencing of MYH for increasing clinical sensitivity.
Authors: Sophia Ceulemans, Christopher Arnell, Lynn Anne Burbidge, Brian Abbott, Rajesh R. Kaldate, Michelle Landon
Journal: Journal of Clinical Oncology (2013)

343 Background: MYH-associated polyposis is an autosomal recessive syndrome caused by biallelic mutations in the base excision repair gene MYH. Initial reports indicated that a majority of European biallelic individuals carried two founder mutations, Y165C and G382D. A common MYH analysis strategy involves evaluation of the two founder mutations (FMs) with subsequent full sequencing only if one of the FMs is identified. This study aimed to determine the sensitivity of full MYH sequencing over the strategy described above in a cohort of individuals that has undergone genetic testing by a commercial laboratory. Methods: A retrospective analysis was performed on 1,522 individuals who had clinical MYH testing ordered either independently or in conjunction with APC gene analysis. All patients underwent MYH analysis for Y165C and G382D. Subsequent full gene sequencing was performed for all patients, except for those biallellic for the two FMs. Demographic, personal, and family cancer histories were collected on the test request form. Results: 86 biallelic individuals were identified, with 47 carrying two FMs, 18 carrying one FM and one mutation identified on sequencing, and 21 carrying biallelic mutations identified only on full sequencing. 21/86 (24.4%) biallelic MYH mutation carriers would have been missed by FM analysis only. The mutation spectrum is distributed among different ethnicities (Table). The majority of individuals met clinical criteria for a polyposis syndrome, with 21 individuals reporting more than 99 adenomas (24.4%) and 50 individuals reporting 20-99 adenomas (58.1%). Conclusions: Analysis of only the two MYH FMs would miss 24% of biallelic individuals in our cohort. Due to the ethnicity distribution of mutations, it is difficult to predict who would be missed by this strategy. Consideration of MYH full sequencing is warranted to achieve highest clinical sensitivity. [Table: see text]
Emibetuzumab plus ramucirumab: Simultaneous targeting of MET and VEGFR-2 in patients with advanced hepatocellular cancer in a phase 1b/2 study.
Authors: James J. Harding, Johanna C. Bendell, Charles S. Fuchs, Xuejing Wang, Volker Wacheck, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2016)

300 Background: The mesenchymal-epithelial transition factor (MET) pathway is upregulated by anti-vascular endothelial growth factor (VEGF) therapies in vivo. Emibetuzumab (E) is a bivalent monoclonal anti-MET antibody that inhibits ligand-dependent and ligand-independent MET signaling. Here we report safety and initial anti-tumor activity for the combination of E plus ramucirumab (R), a human VEGFR-2 antibody in patients (pts) with advanced hepatocellular cancer (HCC) as part of a Phase 1b/2 study (NCT02082210). Methods: Pts with Child Pugh A advanced or metastatic HCC and no further standard therapy available received E (750 mg flat dose) and R (8mg/kg) intravenously every 2 weeks (Q2W) on a 28 day cycle. The primary objective was to evaluate safety and tolerability of the E+R dose and schedule in this patient population. As a co-primary objective, preliminary antitumor activity by RECIST v1.1 was studied. Exploratory objectives included evaluation of biomarkers for MET/HGF and VEGF pathways from fresh pre-treatment tumor biopsies. Results: As of July 2015, 15 pts were treated with E + R in the HCC expansion cohort. Most of the pts had ECOG PS of &lt; 2, and prior sorafenib therapy. Ten pts (67%) experienced ≥ 1 drug-related adverse events (AEs). Commonly related AEs included fatigue (33%), peripheral edema (33%), hypertension (27%), and hypophosphatemia (27%). Most of these events were mild or moderate in severity and the only ≥ grade 3 related events reported included 1 case each of grade 3 fatigue, hypertension, neutropenia, leukopenia, and lymphopenia. In the 9 pts evaluable for response, there were 2 partial responses (PR; 1 unconfirmed, pt still ongoing) and 5 additional pts had stable disease for a disease control rate of 47% (7/15). Six pts were not evaluable and 5 pts remained on treatment at the time of data cut-off. Five pts received 4 or more cycles of therapy, including 1 pt ongoing in cycle 10. Both patients with PR were positive for MET expression. Updated results will be presented at the meeting. Conclusions: The combination of 750 mg E plus 8mg/kg R at Q2W demonstrated an acceptable safety profile and early evidence of antitumor activity in pts with advanced HCC. Clinical trial information: NCT02082210.
Stage at presentation for medically underserved gastric cancer patients.
Authors: M. Alattar, K. Hahn, C. J. Wray
Journal: Journal of Clinical Oncology (2011)

26 Background: Survival disparities in the United States exist for nearly all malignancies. The relationship between stage at presentation and outcome is not well understood. Our hypothesis is that medically un- and underinsured gastric cancer (GC) patients present at advanced stage leading to worse outcomes. Methods: Institutional review board approved review of the departmental gastrointestinal cancer database from 04/08/2000 to 11/18/2008. All patients diagnosed with gastric adenocarcinoma were included; clinicopathologic, treatment and outcome data was recorded. Statistical analysis was performed using STATA 10. Results: A total of 185 patients (108 male, 77 female) were included in this study. Mean age at diagnosis for all patients was 55.3 yrs. The mean age at diagnosis was lower for Hispanics (52.4 years) when compared to other races (ANOVA p = 0.00). The majority of Hispanic patients presented with stage IV disease (55%, chi square p = 0.01). The age range and minimum age at diagnosis was different for Hispanics. Median survival for the entire cohort was 12.3 mo. Although not significant (log rank p = NS), median survival was lowest for African Americans (AA) and Asians. Cox proportional hazards model demonstrated surgical resection and adjuvant therapy (chemoradiation) to be independent predictors of survival. Conclusions: Hispanic patients in medically un- and underinsured populations showed significantly younger age at presentation and more advanced stage of GC. However, median survival for Hispanic GC patients was not significantly shortened compared to other races in this cohort. Survival for AA and Asian patients in a public safety net hospital remains poor and investigation into factors contributing to such disparities is ongoing. [Table: see text] No significant financial relationships to disclose.
A retrospective, multicenter analysis of the clinicopathologic features of extra-gastrointestinal stromal tumor (EGIST).
Authors: Jun Ho Yi, In Gyu Hwang, Hee Kyung Ahn, Sung Hee Lim, Byeong-Bae Park, Young-Woong Won, Se Hoon Park
Journal: Journal of Clinical Oncology (2014)

36 Background: GIST is the most common mesenchymal tumor of the gastrointestinal tract although it constitutes only 1 percent of primary GI malignancy. Some GIST develops outside the alimentary canal such as omentum, mesentery, and retroperitoneum. These types are called extra-gastrointestinal stromal tumors (EGISTs). In this study, we retrospectively analyzed the clinicopathologic features of EGIST patients from 4 institutes in Korea Methods: From 2004 to 2012, a total of 43 patients with EGIST were identified. The clinicopathologic features including gender, age, location, tumor size, hisology, mitotic rate, IHC features, and genetic status were collected along with survival analysis. Results: The median age was 55 (range 29-80) and M:F ratio was 20:23. The most common sites were mesentery (11) and retroperitoneum (11) followed by omentum (7) and vagina (3). Other primary sites were liver (2), ovary (2), pancreas (2), perianal area (2), chest wall (1), pleura (1) and prostate (1). The median tumor size was 8.0 cm (range 2.6 – 30) and median mitotic rate was 5.0/50HPF (0 – 185) 4 cases were negative for c-Kit IHC, which were all confirmed by either IHC for DOG1 or mutational analysis. KIT analysis was performed in 10 cases with 6 wild-types and 4 exon 11 mutation were found. As for PDGFRα, 4 cases were analyzed which were all exon 18 mutation. Among 43 patients, 26 patients had undergone curative resection and 8 patients had unresectable disease and had taken palliative imatinib. Among 26 patients who had undergone curative resection, 12 patients had taken adjuvant imatinib and 14 patients had been observed without imatinib. The median tumor size of two groups were 11.0 (3.0 – 19.0) vs. 5.85 (2.6 – 18.9) and the median mitotic rate was 7.0 (2 – 18.5) vs. 1.0 (0 – 45). Regarding the 9 patients taken palliative imatinib, median tumor size was 20.9 (16.5 – 30.0), median mitotic rate was 15.0 (3 – 60) and median PFS was 22.7 months (95% CI 7.7 – 37.7). Conclusions: As the biologic behavior of GISTs is different by location, a more stratified strategy is needed for managing EGISTs including incorporation of molecular features. We are planning to perform further mutation analysis in this cohort.
The role of concurrent chemoradiation in the treatment of locally advanced nasopharyngeal carcinoma among endemic area: A meta-analysis of the phase III randomized trial
Authors: L. Zhang, C. Zhao, B. R. Ghimire, Y. Guo, Z. Z. Guan
Journal: Journal of Clinical Oncology (2008)

6032 Background: The main objective of this meta-analysis was to determine the clinical benefit of concurrent chemoradiation (CCRT) compared with radiation alone (RT) in treatment of nasopharyngeal carcinoma (NPC) patients in endemic geographic area. Methods: Using a prospective meta-analysis protocol, two independent investigators reviewed the publications and extracted the data. Fully published randomized controlled trials (RCTs) done in endemic area for which patients with NPC were randomly assigned to receive CCRT or RT alone was included. The criteria inclusion of the RCTs also required adequate doses of RT in both arms (≥64Gy), with conventional fractionation. Risk ratios (RRs) for the 2, 3, 5-year overall survival (OS), the locoregional recurrence rate (LRR) and distant metastasis rate (DMR) were calculated. Results: Six RCTs (1,483 patients total) were eligible. Risk ratio (RR) of 0.65 (95% CI, 0.51 to 0.83), 0.72 (95% CI, 0.59 to 0.87) and 0.72 (95% CI, 0.54 to 0.95) were observed for 2, 3 and 5 years overall survival, respectively, in favor of the CCRT group. The RR is larger than that detected in the previously reported meta-analysis [Lagendijk JCO 2004, Bertrand Int J Radiat Oncol Biol Phys, 2006] which indicated that the relative benefit of survival is smaller than what considered before. However, the relative benefit of CCRT is associated with both improvement of LRR (RR=0.57, 95% CI, 0.43 to 0.74) and DMR (RR=0.71, 95% CI, 0.59 to 0.85) and is similar with the previously reported results. Conclusions: This is the first meta-analysis of CCRT vs RT alone in NPC treatment which included studies only done in endemic area. The results confirmed CCRT is more beneficial compared with RT alone. However the relative benefit of CCRT in endemic population might be overestimated by previous meta-analysis especially concerning the cost of higher toxicities in CCRT arm. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, Lilly, Roche Bayer, Novatis
Multicenter phase II study of gemcitabine, capecitabine, and bevacizumab in patients with advanced pancreatic cancer (APC): Final analysis of clinical and quality of life endpoints
Authors: R. V. Iyer, J. Yu, C. R. Garrett, A. Litwin, N. Khushalani, M. Tarquini, N. Webb, J. Phelan, M. M. Javle
Journal: Journal of Clinical Oncology (2008)

4616 Background: Gemcitabine + capecitabine improves survival as compared with gemcitabine monotherapy for patients (pts) with APC and good performance status. We hypothesized that addition of the antiagiogenic agent, bevacizumab (BV) would improve clinical outcomes. Endpoints were primary-progression-free survival (PFS), Secondary- response rates, overall survival (OS), toxicity assessment and quality of life (QOL) using the EORTC-PAN-26. Methods: Pts with APC (inoperable stage III or IV), ECOG PS 0–1, normal organ and marrow function. Schema: BV 15 mg/ kg q 21 days; capecitabine 650 mg/m2 bid x 14 days, both starting day 1; gemcitabine 1,000 mg/m2 days 1 & 8; cycles repeated q 21 days. Statistics: Power of 0.8 at 0.05 significance level to determine if PFS is > 4.1 months with study regimen (2.5 months with gemcitabine). Results: Fifty pts were enrolled; 46 are evaluable for response (4 had clinical progression). Median age 64 (range 38–83 years), 28 male, 5 stage III, 45 stage IV. Cycles: median 6 (range 1–18)/ pt, total 348. Responses (RECIST): 1 CR (2%), 10 PR (20%), 30 SD (60%), 5 PD (10%) and 4 (8%) clinical progression. For evaluable pts: Response rate (CR+PR) =11/44=0.25 (95% CI: 0.13–0.40). Median PFS: 5.8 months (95% CI: 4.2–7.8). Median OS: 9.8 months (95% CI: 8.3- 11.9). QOL: 24 improvement (48%) defined as a greater than 5% decrease in two consecutive scores compared to baseline score, 16 stable (32%), 10 not-evaluable (20%). One year survival rate was 0.28. Grade 3/4 toxicities: neutropenia 38%, thrombocytopenia 16%, thromboembolic events 14%, hypertension 8%, nausea 14%, and GI bleeding 8% were other most frequent side effects. Other significant events (<5%) were coronary events and proteinuria. One treatment related death occurred (hemorrhage). Reasons for treatment discontinuation were: toxicity (37%), progression (47%), death (8%), normal completion (2%) or other reasons (6%). Conclusion: The primary study goal of PFS improvement over historical controls was met. QOL stabilized or improved in the majority. Toxicity profile is acceptable. Study is supported by a grant from NCCN and by Genentech. No significant financial relationships to disclose.
Mechanistic studies of BRN-SJS.
Authors: Z. G. Wang, W. Zhang, T. Jaw, D. Na, S. Ning
Journal: Journal of Clinical Oncology (2011)

e13501 Background: To evaluate the antitumor effect of BRM-SJS and its mechanism. Methods: Tumor inhibition was tested in vivo on mice with subcutaneous transplanted tumor cells in vitro with and MTT method and tumor cell apoptosis test including cell electric morphology, agarose gel electrophoresis and flow cytometry. Results: It was found that BRM-SJS could the resistance to the attack of 5′106 of mouse pancreascarcinoma (MPC-83), Ehrlich ascite tumor (EAC), mouse sarcoma (S-180), and mouse glioblastoma (G422) cells, with the inhibition rate of tumor weight of 66.2%, 50.9%, 47.3%, and 38.7% respectively. The inhibition rate of Suzhou human glioma (SHG-44), human breast carcinoma (MCF-7), and human pancreas carcinoma (PANC1) in vitro were 92.2% (BRM 1:10), 85.1% (BRM 1:10), 48.3% (BRM 1:10), respectively. Meanwhile, BRM-SJS was able to induce apoptosis in several human tumor cell lines such as SHG-44 and MCF-7 cells. Morphological changes including cell shrinkage and condensation of chromosomes were observed with electric microscope. Agarose gel electrophoresis of DNA from SHG-44 and MCF-7 cells treated with BRM-SJS extracts (1:80 to 1:20) for 24 h, 40 h revealed typical DNA “Ladder” pattern. The early stage and middle-late stage apoptos is increased in SHG-44 and MCF-7 cells treated with BRM-SJS extracts (BRM 1:160 to 1:40) from 14 h to 48 h by Annexin-V/PI flow cytometry one analysis. Conclusions: BRM-SJS has obvious antitumor bioactivity in vivo to MPC-83, EAC, S-180, and G422 mouse cell strains, and in vitro to SHG-44, MCF-7 human cell lines. Water extracts of BRM-SJS could induce apoptosis.
Inpatient care at the end of life: A closer look.
Authors: Alison Wiesenthal, Anabella Lucca Bianchi, Vinnidhy Dave, Robert Sidlow, Susan Seo, Deborah Korenstein
Journal: Journal of Clinical Oncology (2015)

43 Background: Goals of care discussions in the inpatient setting often focus on the limitation of cardiopulmonary resuscitation and Allow Natural Death (AND) directives; decisions regarding medication administration and further diagnostic studies may be missing from the conversation. De-prescribing at the end of life (EOL) can be emotionally complex for patients and their families, though data is emerging that quality of life may be enhanced by limiting unnecessary medications. Our study assessed care in the last 3 days of life for cancer patients who die in hospital. Methods: Retrospective chart review of all inpatient deaths at a tertiary cancer center between 12/1/2012 and 11/30/2014. The frequency of lab draws, administered medications, and subspecialty consultations during the last 3 days of life were recorded. Results: Of the 1,311 inpatient deaths during the two year study period, 44% had Palliative Medicine consultation. On average, Palliative Medicine was consulted 6.5 days before death, with a median consultation time of 3 days before death. Do not resuscitate (DNR) orders were active for over 80% of patients at the time of death, with an average DNR enacted 4.6 days prior to death (range 0-60 days). Medications most often provided at the end of life were analgesics, fluids, and antibiotics (See Table 1). Consistent with Quality Oncology Practice Initiative (QOPI) Measures, &lt;1% of patients were treated with chemotherapy in the last 3 days of life. Most patients (85%) had laboratory tests in their final 3 days of life, with a mean of 21 orders per patient. Conclusions: Non-palliative services are often provided to hospitalized patients at the end of life. Careful consideration must be given to the potential benefits and harms of medical interventions at the EOL to improve quality of life for the dying patient. Further research is needed to understand the drivers behind the care provided at EOL to inform educational tools for clinicians. [Table: see text]