tbuckley/cabot-search huggingface dataset:
Assessment of genomic alterations in adenosquamous carcinoma of the pancreas (ASCOP).
Authors: Emmet Jordan, Olca Basturk, Steven D Leach, David S. Klimstra, Peter J. Allen, Michael F. Berger, Gokce Askan, Kenneth H. Yu, Eileen Mary O'Reilly, Maeve Aine Lowery
Journal: Journal of Clinical Oncology (2016)

261 Background: ASCOP represents a rare subtype (1-4%) of exocrine pancreatic cancer for which the clinical and molecular features are not well defined. We reviewed clinical characteristics and performed comprehensive molecular profiling in a cohort of patients with ASCOP treated at MSKCC. Methods: Patients (pts) with ASCOP diagnosed from January 2000-July 2015 were identified from a prospectively maintained database, following IRB approval. Clinicopathological data including time to progression (TTP), recurrence-free interval (RFI) and overall survival (OS) were recorded. Samples were reviewed by a pancreas pathologist to optimally select the squamous component for molecular profiling using MSK-IMPACT platform. This is a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of 410 key cancer genes. Tumor and matched normal libraries (where available; n=9) were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline to detect single nucleotide variants, short indels, copy number aberrations and structural rearrangements. Results: We identified 84 pts with ASCOP of whom 15 had sufficient tissue/consent for analysis. Median OS for resected pts was 17 months (mo) and 6 mo respectively. Median PFS on 1st line therapy (FLT) for stage IV disease was 3 mo. 53 pts underwent surgical resection, of whom 11 remain disease free at median follow up of 24 mo. 15/15 (100%) had KRAS mutations (mut). 11/15 (73%) had TP53 mut. 6/15 (40%) had SMAD4 mut [4 point mutations (PM), 2 frameshift deletions]. 6/15 (40%) had CDKN2A mut (4 deletions, 2 PM). Mut were also found in FAT 1 (3/15), JAK3 3 (3/15), TBX 3 (2/15) and FGFR amplification was found in 1 pt sample. Conclusions: ASCOP like conventional ductal adenocarcinoma has a poor prognosis with a comparable molecular signature in the most common alterations. Potential targets e.g., FGFR1 may allow novel agents in select pts. [Table: see text]
Cetuximab plus chemotherapy in patients with liver-limited or non-liver-limited <i>KRAS</i> wild-type colorectal metastases: A pooled analysis of the CRYSTAL and OPUS studies.
Authors: Claus-Henning Kohne, Carsten Bokemeyer, Ute Sartorius, Michael Schlichting, Philippe Rougier, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2012)

96 Background: In the CRYSTAL and OPUS studies, adding cetuximab (cet) to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer. In a pooled analysis of these trials the benefit of treatment according to whether pts had liver-limited disease (LLD) or non-LLD was investigated. Methods: Cox‘s proportional hazards model for overall survival (OS) and progression-free survival (PFS) or logistic regression model for objective response rates (ORR) and R0 resection were used on individual pt data, stratified by study. Likelihood ratio tests were used to statistically explore interactions. Results: Adding cet to CT significantly improved PFS and ORR in LLD pts, and OS, PFS and ORR in non-LLD pts ( table ), and increased R0 resection rates: LLD 11.8% vs 5.3%, odds ratio=2.38, p=0.11 and non-LLD, 3.3% vs 1.7%, odds ratio=1.97, p=0.19. No treatment-by-study interactions were noted. Treatment effects did not vary significantly by LLD status (PFS, p=0.60, OS, p=0.68, ORR p=0.074). However LLD vs non-LLD pts had improved outcome in each treatment arm: PFS, CT HR=0.74, p=0.091; CT + cet HR=0.66, p=0.031; OS, CT HR=0.70, p=0.009; CT + cet HR=0.74, p=0.039; ORR, CT odds ratio=1.20, p=0.47, CT + cet odds ratio=2.32, p=0.002; R0 resection, CT odds ratio=3.15, p=0.050, CT + cet odds ratio=3.82, p=0.0018. Conclusions: The OS benefit from adding cet to CT is mainly seen in pts with non-LLD, thus strengthening the value of cet in palliative treatment. LLD status appears to be predictive for response in pts receiving CT + cet, facilitating potential resection. A larger number of pts (with R0 resection and longer follow-up) may be needed to confirm an OS benefit from CT + cet in LLD pts. [Table: see text]
A phase I study of etirinotecan pegol in combination with 5-fluorouracil and leucovorin in patients with advanced cancer.
Authors: Smitha S. Krishnamurthi, Manpreet Chadha, Mary Beth Rodal, Glen J. Weiss, Joseph A. Bokar, Gayle S. Jameson, Catherine Patricia Mast, Carol Zhao, Bridget Waluch, Ute Hoch, Alison Hannah, Afshin Dowlati, Neal J. Meropol, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2014)

550 Background: Etirinotecan pegol (EP; NKTR-102) is the first long-acting topoisomerase I inhibitor designed to concentrate and provide continuous tumor exposure. This study was designed to identify the recommended dose of EP in combination with 5-fluorouracil (5FU; 400/2400 mg/m 2 by bolus, then 46-hour infusion) and leucovorin (LV; 400 mg/m 2 ). Methods: Patients (pts) were enrolled in a standard 3+3 design. Initially, pts received all 3 agents every 2 weeks (schedule A). Due to higher SN38 exposure with the triplet compared to single-agent EP in the 25 mg/m 2 dose cohort, the schedule was modified to deliver all 3 agents for the first 4 doses at 2-week intervals; 5FU/LV continued at 2-week and EP at 4-week intervals thereafter (Schedule B). The protocol enrolled adults with an advanced malignancy; pts had ECOG 0 or 1 with adequate organ function. Results: 26 pts were enrolled in 5 cohorts: median age 63 (44-80); male:female 12:14; median prior regimens 3.5 (1-9). Schedule A: 25 mg/m 2 (n=8, 6 evaluable for toxicity) and 50 mg/m 2 (n=3). Schedule B: 50 mg/m 2 (n=3), 75 mg/m 2 (n=6) and 100 mg/m 2 (n=6). DLTs: Grade (G) 3 abdominal pain following the infusion (1 pt; 25 mg/m 2 ); G3 nausea/dehydration and G4 neutropenia (NTP) &gt;3 days (2 pts; 100 mg/m 2 ). 5 pts at a dose of 75 mg/m 2 had a dose delay due to NTP or diarrhea in the first 2 months. Common G3+ toxicity at 75 mg/m 2 : NTP (50%), diarrhea and lymphopenia (both 33%). At &gt;50 mg/m 2 EP, SN38 exposure was comparable to that previously observed after single-agent EP. 5-FU exposure: comparable to prior reports. Two pts (ovarian, gall bladder) had a PR; 11 additional pts had stable disease &gt;6months (3 NSCL 6M-9M; 3 CRC 6-8M; esophageal 7M, desmoplastic round cell sarcoma and pheochromocytoma 6M) or tumor marker response (pancreatic pt who had received prior irinotecan 93%, 9M; breast 82%, 5M). ORR or SD&gt;6M was observed in 8 of the 12 patients in the two highest dose levels. Conclusions: 75 mg/m 2 EP with 5FU/LV (Schedule B) shows promising clinical activity with an acceptable safety profile. The combination warrants further clinical testing. Single-agent EP is currently being studied in a phase 3 trial in breast cancer compared to physician’s choice (n=852).
Final results from PROGRESS trial of sargramostim (GM-CSF) in combination with irinotecan (I), 5-fluorouracil (F), and leucovorin (L) for metastatic colorectal cancer (CRC)
Authors: M. Kleinman, E. Mohandoss, M. Gilbert, G. Jones
Journal: Journal of Clinical Oncology (2005)

3717 Background: Weekly/biweekly I-based regimens improve survival in CRC patients but are associated with significant toxicity. Sargramostim (Leukine) was added to two commonly used regimens to determine if it could reduce toxicities and permit increased chemotherapy delivery, thereby delaying disease progression. Methods: Weekly: Day 1: 125 mg/m2 I, 500 mg/m2 F, 20 mg/m2 L. Leukine 250 μg/m2 on Days 2–6. Cycles consisted of 4 weekly courses + 2 weeks rest for up to 48 weeks. Biweekly: Day 1: 180 mg/m2 I, 1000 mg/m2 F, 200 mg/m2 L. Day 2: 400 mg/m2 F bolus, followed by 600 mg/m2 F infusion over 22 hr; 200 mg/m2 L. Leukine 250 μg/m2 on Days 4–13. The primary endpoint was progression-free survival (PFS) at 24 weeks (using null hypothesis that PFS ≤ 55%). Results: The study terminated early due to slow accrual: 200 patients were planned, 88 enrolled, and 88 evaluable for PFS. Of these, 66 (75%) had liver involvement, 32 (36%) had lung involvement, and 35 (40%) had prior F therapy. At 24 weeks, 39 patients (44%) had no disease progression (45–66% CI), 26 (44%) had progressed, and 13 (15%) had died. Median time to progression was 202 days. Mean dose intensity was 83% of the planned I and F doses. Grade 3/4 events included diarrhea (27%), neutropenia (23%), deep vein thrombophlebitis (13%), dehydration (9%), asthenia (8%), and anorexia (7%). There were two Grade 3/4 events of pneumonia, two of fever, and one of infection. Conclusions: Leukine combined with weekly/biweekly I-based regimens was well tolerated and decreased associated side effects. Final results suggest the addition of Leukine supports increased chemotherapy delivery and progression-free survival while decreasing neutropenia, GI toxicity, and severe infections. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Berlex Berlex
Risk of Burkitt Lymphoma Correlates with Breadth and Strength of Antibody Response to Plasmodium Falciparum Malaria Stage-Specific Antigens
Authors: Peter Aka, Maria Vila, Amar Jariwala, Francis Nkrumah, Benjamin Emmanuel, Masanory Yagi, Nirianne Palacpac, Maria Periago, Janet Neequaye, Christine Kiruthu, Takahiro Tougan, Paul Levine, Robert Biggar, Ruth M Pfeiffer, Toshihiro Horii, Kishor Bhatia, Jeffrey Bethony, Sam Mbulaiteye
Journal: Blood (2012)
Over-Expression of RANKL In Invariant NKT Cells Is Characteristic of Active Myeloma but Not of MGUS or Asymptomatic Myeloma
Authors: Emmanouil Spanoudakis, Menelaos Papoutselis, Ioannis Kotsianidis, Evangelos Terpos, Meletios A. Dimopoulos, Ming Hu, Amin Rahemtulla, Dimitrios Margaritis, Georgios Bourikas, Konstantinos Tsatalas, Anastasios Karadimitris
Journal: Blood (2010)
Secondary Malignancies after Autologous Stem Cell Transplantation for Hodgkin’s Lymphoma: Incidence and Analysis of Risk Factors.
Authors: Mireia Constans, Anna Sureda, Reyes Arranz, Maria Dolores Caballero, Juan Jose Lahuerta, Juan Carlos Hernandez-Boluda, Maria Jesus Vidal, Jose Garcia-Laraña, Jose Rifon, Josep Maria Ribera, Pascual Fernandez-Abellan, Jose Maria Moraleda, Maria Teresa Bernal, Maria Victoria Mateos, Maria Martin-Mateos, Rafael Cordoba, Javier Garcia-Conde, Jorge Sierra, Eulogio Conde
Journal: Blood (2004)
Identification of the correlation between drug activity and sensitivity of HSP90 inhibitors in breast cancer cells using a multivariate gene expression assay
Authors: Q. Xu, P. Pezzoli, J. Monforte, G. Vansant
Journal: Journal of Clinical Oncology (2008)

22214 Background: Heat shock protein 90 (HSP90) is a ubiquitously expressed molecular chaperon which has become a well defined drug target for a variety types of cancer. In a previous study, we had developed a 31-gene, multivariate gene expression assay to monitor multiple pathways of pharmacodynamic activity of HSP90 inhibitors in cancer cells. This study evaluated the dose and time-dependent expression responses but did not explore compound specificity (AACR 2007). We have broadened these studies to elucidate the differential activities of a pair of chemically different HSP90 inhibitors in multiple cell lines. Methods: To understand the relationship between the expression profiles and drug sensitivities, the gene expression levels for the 31 genes were measured following the treatment of two HSP90 inhibitors, 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) and Ridicicol. Using our multivariate assay their GI50s were measured in 4 human breast cancer cell lines, 2 HSP90 sensitive and 2 HSP90 insensitive. Unsupervised clustering analysis was performed to assess the relationships between compound activities and their sensitivities in these cancer cells. Results: We have observed that the cancer cells showed different expression profiles based upon the HSP90 inhibitor treatment and the cell line used. In addition, the clustering results on the expression profiles of untreated cells clearly separate sensitive from insensitive breast cancer cell lines. Conclusions: Our multivariate gene expression assay for the HSP90 inhibitors shows strong correlation between drug activity and drug sensitivity in cancer cells. This assay also showed potential to be used as a stratification biomarker to identify breast tumors that might respond well to HSP90 inhibitors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Althea Technologies Inc.
Association of <i>KRAS</i> and <i>EGFR</i> mutations with survival in patients with advanced lung adenocarcinoma.
Authors: M. L. Johnson, C. Sima, P. K. Paik, Y. Y. Janjigian, W. Pao, M. G. Kris, M. Ladanyi, G. J. Riely
Journal: Journal of Clinical Oncology (2010)

7541 Background: Lung adenocarcinoma can be molecularly distinguished by mutated oncogenes. EGFR and KRAS mutations occur in mutually exclusive subsets of patients. The prognostic and predictive properties of EGFR mutations have been appreciated; however the prognostic relevance of KRAS mutations has not been established. We hypothesized that EGFR and KRAS mutations identified patients with distinct outcomes. To test this hypothesis, we examined the association of EGFR and KRAS mutation status with survival after diagnosis in patients with stage IIIB/IV non-small cell lung cancer. Methods: With Institutional Review Board approval, we collected clinical information for patients with advanced lung adenocarcinoma and known EGFR and KRAS mutation status evaluated at MSKCC between 2004 and 2009. Age, gender, Karnofsky performance status (KPS), smoking history, and survival from diagnosis of stage IIIB/IV disease were obtained. Overall survival (OS) was analyzed using the Kaplan-Meier and Cox proportional hazard methods. Results: A total of 1,081 patients were evaluable, including 638 women (59%) and 354 never smokers (33%). Patients had a median age of 65 (range 25-92) and 82% had a KPS ≥ 80%. Gender, KPS, smoking history, and age were univariately associated with OS in this population. In multivariate analysis, EGFR and KRAS mutations were independent prognostic factors. Conclusions: In this population of patients with stage IIIB/IV lung adenocarcinoma, those with KRAS mutations had a shorter survival than those patients with EGFR mutations or EGFR/KRAS wild-type tumors. This is the largest reported analysis of outcomes for patients with stage IIIB/IV lung adenocarcinoma including KRAS and EGFR mutation status. Genotype No. of patients Median OS 95% confidence interval p value* KRAS mutant n=253 15 mo 13-22 mo 0.049 KRAS/EGFR wild type n=541 23 mo 21-28 mo ref EGFR mutant n=287 37 mo 32-42 mo 0.0002 * Adjusted for EGFR, KRAS, KPS, and gender in multivariate analysis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, MolecularMD AstraZeneca, Boehringer Ingelheim
Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial.
Authors: Eric P van der Stok, Cornelis Verhoef, Dirk J. Grunhagen
Journal: Journal of Clinical Oncology (2016)

TPS790 Background: Colorectal carcinoma is a leading cause of cancer death worldwide, mostly as a consequence of metastatic disease. If metastases are confined to the liver, surgical resection is the only therapy providing potential for cure. Efforts to improve the outcome of hepatectomy for colorectal liver metastases (CRLM) by combining surgery with chemotherapy have failed to demonstrate overall survival (OS) benefit. This may partly be explained by the fact that previous trials on this subject involved strict inclusion criteria. Consequently, patients with a high oncological risk profile - who might benefit the most from chemotherapy – might have been underrepresented in previous trials. Several Clinical Risk Scores (CRS) have been developed predicting patients’ prognosis after resection of CRLM. The most widely used and validated CRS was described by Fong et al., which characterizes 2 risk groups (high versus low) based on 5 independent clinicopathologic prognostic variables. Each variable is assigned 1 point. Multiple retrospective observations showed that neo-/adjuvant chemotherapy induced significant OS benefit in patients with a high-risk profile (CRS of 3 to 5 points). The CHARISMA trial evaluates the impact of neo-adjuvant chemotherapy in patients with high-risk, primarily resectable liver-only colorectal metastases. We hypothesize that adding neo-adjuvant chemotherapy to surgery improves OS in this high-risk patient group. Methods: The CHARISMA trial is a randomized (1:1) phase III trial. Patients receive either surgery only for CRLM (arm A) or 6 cycles of neo-adjuvant Oxaliplatin + Capecitabine, followed by surgery (arm B). The primary endpoint is OS. On basis of retrospective data, the expected hazard ratio for arm B is 0.60. With an expected 5-year OS of 25% in arm A, a two-sided significance level α = 0.05 and power 1 - β = 0.8, 224 patients have to be recruited. Major eligibility criteria are: liver-only metastases, primarily resectable CRLM, high-risk patients (CRS 3-5). The trial is currently accruing in 10 Dutch liver centers and is registered in the “Dutch Trial Register”: NTR4893 ( www.trialregister.nl ). Clinical trial information: NTR4893.
Influence of age on symptoms and survival of hospitalized advanced cancer patients
Authors: S. Teunissen, A. de Graeff, E. de Nijs, H. de Haes, E. Voest
Journal: Journal of Clinical Oncology (2005)

8234 Background: Symptoms of hospitalized elderly advanced cancer patients have been reported to be underassessed. However, limited data about symptom prevalence in these patients are available. Aim of the study: To analyze the differences in symptom prevalence and survival of hospitalized advanced cancer patients ≤70 and >70 years. Patients and Methods: An analysis was performed in 181 advanced cancer patients (44% male; 77% ≤70, 23% >70) admitted to the University Medical Centre Utrecht and referred to the palliative care team during 1998–2003. The diagnosis was (≤70/>70): breast 14/13%; gynaecological 11/15%; gastrointestinal 18/25%; head & neck 11/13%; lung 13/5%; prostate 4/18%; other 29/13%. Clinical nurse specialists using a standardized symptom checklist interviewed patients. Survival was measured from the date of first consultation until death from all causes. Results: The median number of symptoms per patient was 4 in both age groups. WHO performance status: 1: 2/3%; 2: 26/29%; 3: 50/47%; 4: 21/17%; unknown 3/3% (p=.961). For most symptoms, there were no differences in prevalence. Significant differences were only found for constipation (34/55%, p=.016), urinary tract problems (6/20%, p=.009), depression (21/48%, p=.001). Symptom cluster analysis did not reveal “troubles of old age” patterns as published in geriatric literature. All except three patients have died. Median survival: 66 days for younger patients, 43 days for elderly (p=.194). Remarkably, elderly patients who reported depression, lived longer than elderly who did not (median survival respectively 49 days versus 24 days, p=.002). Conclusions: Hospitalized advanced cancer patients >70 years have, in general, the same symptoms as their younger counterparts. Performance and survival do not differ between the two groups. Data indicating underassessment and undertreatment of symptoms in elderly patients highlight the importance of comprehensive symptom assessment in these patients. No significant financial relationships to disclose.
Gliosarcoma - clinical study
Authors: P. S. Sridhar, R. Prabhakar, M. B. Pandey, D. N. Sharma, P. K. Julka, G. K. Rath
Journal: Journal of Clinical Oncology (2005)

1582 Background: Gliosarcomas are rare neoplasm of central nervous system. Consisting gliomatous and sarcomatous components. No clear data is available regarding its cell of origin and behavior. This study examines clinical features, treatment and survival. Methods: 14 patients of Gliosarcomas treated between Jan 1993 to June 2004 were analyzed retrospectively.10 were male, 4 female, with median age of 50 years (range 12–70 yrs). All were situated in supratentorium, 8 were left side, 6 right side.7 in temporal region, 4 in temporoparietal and 3 in parietal region. All patients underwent surgery and 12 patients received postoperative radiotherapy to dose of 60 Gy/30 fractions in 6 weeks.10 patients received platinum based chemotherapy.2 patient received concurrent taxane and radiotherapy. Results: Median survival was 9.3 months, 10 patients died of disease, 2 patients stable disease, and 1 patient is in PR and 1 in CR. Conclusions: Gliosarcoma is aggressive neoplasm; Clinically indistinguishable from GBM.Chemoradiotherapy is beneficial No significant financial relationships to disclose.
Implementing provider and patient initiated survivorship care planning: Lessons from baseline.
Authors: Katherine Clegg Smith, Stephen C Greco, Susan Hannum, Archana Radhakrishnan, Karen L. Smith, Elliott Tolbert, Claire Frances Snyder
Journal: Journal of Clinical Oncology (2016)

65 Background: It is recommended that cancer patients completing treatment receive a Survivorship Care Plan (SCP). Most SCP templates are designed for provider initiation and completion. Barriers to SCP provision include time and resource restrictions in the oncology clinic. Patient-initiated SCPs are one alternative. We conducted a pilot trial describing and comparing implementation of a provider-initiated versus patient-initiated tool. We present clinician and patient baseline data. Methods: We recruited oncologists from two community-based academically affiliated hospitals and conducted qualitative interviews exploring perceptions of patients’ needs and SCP value. To determine feasibility of oncologists identifying patients for an SCP, participating oncologists were to refer adult patients completing active treatment for non-metastatic cancer to the study team. Enrolled patients completed the Cancer Survivors’ Unmet Needs (CaSUN) and Preparing for Life as a New Survivor (PLANS) surveys. Results: Of 58 invited clinicians, 13 agreed to participate, 5 referred patients. Participating clinicians were not currently providing SCPs. Opinions were mixed about SCP value for improving care; most saw value for communication and care coordination. The study team worked with nurses to identify eligible patients, given challenges with identification as part of routine practice. We recruited 41 patients (aged 44-90 years, 68% female, 81% White, 53% reporting excellent or very good health) from 71 approached. At baseline, patients reported an average of 13.8 informational and support needs; 9.3 of which were met and 4.5 were unmet. The most common unmet needs were recurrence concerns (37%), case management to identify services (30%), adjusting to changes in quality of life (22%), and coordination among providers (21%). In terms of understanding follow-up care, 24% reported not feeling prepared for what to expect and not knowing about follow-up tests; 22% reported providers not communicating well with each other. Conclusions: Need exists for robust systems to identify eligible patients. Enrolled patients’ needs were relatively modest, with recurrence concerns and inter-professional coordination being key. Clinical trial information: NCT02405819.