tbuckley/cabot-search huggingface dataset:
Clinical outcomes of African-American patients with advanced or metastatic non-small cell lung cancer on nivolumab in a single community based cancer center.
Authors: Andrew Chua Tiu, Rashmika Potdar, Djeneba Audrey Djibo, Muhammad Masab, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2018)

e21131 Background: Lung cancer is the leading cause of cancer-related deaths in African-Americans (AA) with increased incidence and decreased survival rates in all stages of the disease. AA are diagnosed at an earlier age and have higher prevalence of smoking related lung cancer. PD-L1 inhibitor, Nivolumab, was approved as a second line agent after failure of platinum-based therapy for advanced or metastatic Non-Small Cell Lung Cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients. Methods: In this retrospective study, we reviewed the charts of 38 patients with advanced or metastatic NSCLC who received Nivolumab from March 1, 2015 until November 30, 2017 from a single community-based cancer center and compared our results with historical data by Borghaei et al. Results: Among 29 AA patients, Adenocarcinoma was the most common histology. Five (17%) continued to use Nivolumab while 15 (52%) discontinued the treatment mainly due to progression of the disease. The median overall survival was 17.6 months (95% CI, 11.5 to 27.6) compared to 12.2 months (95% CI, 9.7 to 15) reported in historical data. At 1 year, the overall survival rate was 66 % (95% CI, 40 to 82) versus 51% (95% CI, 45 to 56). The median progression-free survival was 6.0 months (95% CI, 2.3 to 8.0) versus 2.3 months (95% CI, 2.2 to 3.3), historically, while the 1-year progression-free survival rate was 28% (95% CI, 12 to 47) versus 19% (95% CI, 14 to 23), historically. Overall tumor response rate was 24 % (95% CI, 10 to 43) versus historically 19% (95% CI, 15 to 24), while the median time to response was 2.8 months and the median duration of response was 4 months. Treatment-related adverse events of grade 3 or 4 were reported in 10 % similar to the rate previously shown. Conclusions: AA patients with advanced or metastatic NSCLC on Nivolumab had increased overall survival and progression free survival. Higher benefit with immunotherapy in AA can be related to higher incidence of smoking related cancer and higher mutation burden.
MORPHEUS: A phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy (CIT) combinations in patients (pts) with gastric or pancreatic cancer.
Authors: Do-Youn Oh, Salah-Eddin Al-Batran, Hyun Cheol Chung, Antoine Hollebecque, Syma Iqbal, Kyu-Pyo Kim, Jill Lacy, Gulam Abbas Manji, Eileen Mary O'Reilly, Osama E. Rahma, Harry H. Yoon, Antonia Kwan, Xian He, Hila Barak, Pakeeza Zahra Sayyed, Xiaosong Zhang, Jun Wang, Edward Cha, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2018)

TPS4134 Background: Multiple cancers have been treated successfully with CIT; nonetheless, only subsets of pts experience durable response with CIT monotherapy. CIT combinations may therefore be needed to simultaneously address multiple mechanisms of cancer immune evasion. The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to investigate CIT combinations in pts with different tumor types. Using a randomized trial design, multiple CIT combination arms will be compared with a single control arm. Furthermore, the design of the trials will aid in the development of CIT combinations by identifying early signals and offers the flexibility to open new treatment arms with novel CIT combinations and to close arms that show minimal clinical activity or unacceptable toxicity. Various CIT combinations that simultaneously enhance immune cell priming and activation, tumor infiltration and/or recognition of tumor cells for elimination will be evaluated. Here, we describe MORPHEUS Phase Ib/II trials in pts with gastric or gastroesophageal junction cancer (GC) or metastatic pancreatic ductal adenocarcinoma (mPDAC), both representing major unmet medical needs. Methods: MORPHEUS-GC (NCT03281369) will enroll 2 cohorts, including pts with advanced unresectable or metastatic GC who are chemotherapy naive or have progressed on platinum- or fluoropyrimidine-based chemotherapy. MORPHEUS-PDAC (NCT03193190) will enroll pts with mPDAC who have progressed on 1 line of prior chemotherapy. Additional eligibility criteria include measurable disease per RECIST v1.1 and accessibility of the tumor for biopsy. Pts in both trials will be randomized to one of the CIT combination arms or a control arm (up to 8 arms across 2 cohorts in GC; 4 arms in PDAC). In the setting of unequivocal disease progression/toxicity, pts may be eligible to switch to a different CIT combination arm. Safety measures and investigator-assessed ORR per RECIST v1.1 are primary endpoints. PFS, OS, DCR and DOR are among the secondary endpoints. Exploratory biomarkers will also be examined. Clinical trial information: NCT03281369 and NCT03193190.
Effect of biglycan on melanoma invasiveness via increased tissue stiffness and integrin-β1 expression.
Authors: Hana Andrlova, Justin Mastroianni, Josef Madl, Johannes Steffen Kern, Wolfgang Melchinger, Marie Follo, Kristin Technau-Hafsi, Venugopal Rao Mittapali, Tilman Brummer, Paul Timpson, Hendrik Ungefroren, Justus Duyster, Frank Meiss, Winfried Römer, Robert Zeiser
Journal: Journal of Clinical Oncology (2016)

11526 Background: A better understanding of the biology of the melanoma microenvironment may help to develop new therapeutic strategies. The expression level of the extracellular matrix molecule biglycan (Bgn) has been linked to poor prognosis in several cancer entities, but its functional role in the tumor microenvironment remains unclear. Methods: Bgn-/- and Bgn+/+ mice were injected with two melanoma cell lines and tumor growth and survival were monitored. Contraction of collagen by fibroblasts derived from Bgn+/+ or Bgn-/- mice, as well as tumor cell migration in the Bgn+/+ or Bgn-/- collagen matrices were quantified. Analysis of the matrix stiffness was performed by atomic force microscopy and collagen bundle formation was evaluated using picrosirius red staining. Expression level of integrin-β1 (Itgb1) was measured in the cells isolated from Bgn-/- and Bgn+/+ matrices. Both Bgn-/- and Bgn+/+mice were injected with Itgb1 overexpressing B16 melanoma cells and survival was monitored. Immunohistochemistry staining of human melanoma samples was performed to analyze Bgn and Itgb1 expression. Results: We observed reduced melanoma growth and tumor-related death in Bgn-/- mice compared to Bgn+/+ mice in two melanoma models. Absence of biglycan in the collagen-derived matrices led to delayed contraction and diminished melanoma cell invasion into these matrices. Reduced tissue stiffnes, as measured by atomic force microscopy and diminished collagen bundle formation were observed in Bgn-/-matrices. Cell isolation from the stiffer Bgn+/+ collagen matrices revealed a higher Itgb1 expression compared to the Bgn-/- matrices. Overexpression of Itgb1 in B16-melanoma cells rescued the delayed tumor growth-phenotype of Bgn-/- mice leading to a survival comparable to that of Bgn+/+ mice. In humans, high Bgn expression correlated with poor prognosis and low overall and progression-free survival of the patients. In agreement with the mouse and in vitro studies, Bgn-expression in human melanoma samples positively correlated with the expression of Itgb1. Conclusions: This study describes a novel role of Bgn in the melanoma microenvironment, regulating the tissue stiffness and Itgb1 expression in both mice and humans.
Effect of metabolic syndrome on risk of recurrence and immune pathways in invasive lobular carcinoma disparately compared to ductal.
Authors: Patricia A. Robinson, Tina Treece, Clodia Osipo, Rubina Qamar, Robin Zon, Ellis Glenn Levine, Raye Budway, Blanche H. Mavromatis, Sarah Untch, Rene Bernards, M. William Audeh, Hatem Hussein Soliman
Journal: Journal of Clinical Oncology (2018)

e24229 Background: Compared with breast invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) has been shown to be more strongly associated with risk factors that modulate hormone levels, including lifestyle factors such as obesity. We evaluated the effect of metabolic syndrome (MS) in patients with ILC vs. IDC histopathological tumor types using transcriptome gene expression analysis (GEA) and pathway analyses. Methods: This subanalysis included 492 patients from the PROMIS and IMPACt studies for whom metabolic characteristics were captured with informed consent. To be classified as having MS, the patient had to exhibit any 3 of the 5 metabolic factors (obesity, HTN, hypercholesterolemia, hypertriglyceridemia, DM). Risk of recurrence was established using the 70-gene signature (70-GS). Results: A similar proportion of ILC (34%, 26/76) and IDC (38%, 160/416) patients had MS. Significantly more ILC patients with MS than without MS were 70-GS high risk (42% vs. 12%, respectively, [P = 0.007]). There was no significant difference in the incidence of 70-GS high risk results for IDC patients. GEA identified 509 significant differentially expressed transcripts between MS and non-MS ILC patients; 120 transcripts were identified in IDC patients; only 6 transcripts overlapped between the two groups. Pathway analysis indicated immune pathways were affected in ILC, whereas growth-regulating pathways were affected in IDC tumors. Within MS patients, 262 transcripts were differentially expressed between ILC and IDC. Conclusions: Although ILC is generally considered to have a lower risk of recurrence than IDC, we show that ILC patients with MS have a significantly higher 70-GS risk of recurrence than their non-metabolic counterparts. GEA analysis indicated the biology of disease engages disparately for ILC and IDC. Larger studies are needed to characterize differences in tumor biology stratified by histology as it relates to optimizing duration or adding novel targeted therapeutics. Clinical trial information: NCT02670577.Tumor Type MS 70-GS High Risk 70-GS Low Risk P-value Total ILC (n = 76) No 6 (12%) 44 (88%) 0.007 50 Yes 11 (42%) 15 (58%) 26 IDC (n = 416) No 120 (47%) 136 (53%) 0.165 256 Yes 87 (53%) 73 (46%) 160
Clinical relevance of mutations in patients with myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms with normal karyotype.
Authors: Guillermo Montalban-Bravo, Ana Alfonso Pierola, Koichi Takahashi, Marina Konopleva, Elias Jabbour, Gautam Borthakur, Naval Guastad Daver, Courtney Denton Dinardo, Zeev Estrov, Tapan M. Kadia, Naveen Pemmaraju, Farhad Ravandi, Carlos E. Bueso-Ramos, Hagop M. Kantarjian, Keyur Patel, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2017)

7053 Background: Clinical outcomes of patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are heterogeneous. Specific mutations and mutation patterns are known to define prognostic groups in normal karyotype acute myeloid leukemia. Whether this is the case in MDS and MDS/MPN remains unknown. Methods: We evaluated 325 previously untreated patients with MDS or MDS/MPN with normal karyotype evaluated from 2012 to 2016. Next generation sequencing (NGS) on whole bone marrow DNA analyzing a panel of 28 or 53 genes was performed at the time of diagnosis. Results: A total of 225 (69%) patients had MDS and 100 (31%) had MDS/MPN including 77 (24%) patients with chronic myelomonocytic leukemia (CMML). Median age was 69 years (31-92). Among patients with MDS, 189 (84%) had lower-risk and 36 (16%) had higher-risk based on IPSS. NGS data was obtained by 53-gene panel in 93 (29%) patients and by 28-gene panel in 232 (71%). A total of 202 (62%) patients had detectable mutations. Median number of mutations was 1 (range 0-6). Detected mutations are detailed in Table 1. A total of 111 (34%) patients, 70 with MDS and 41 with MDS/MPN, received therapy with hypomethylating agents. Median follow up was 12 months (0-167). By univariate analysis, NRAS (HR 3.28, CI 1.25-8.62, p=0.016) and TP53 (HR 4.9, CI 1.44-16.67, p=0.011) predicted for shorter overall survival (OS) among MDS patients. After multivariate analysis including IPSS-R, only TP53retained its impact in OS (HR 5.25, CI 1.44-19.13, p=0.012). Among MDS/MPN patients, no mutation was found to significantly impact OS. Conclusions: With the exception of TP53mutations, no other identified mutation seemed to independently define prognosis of patients with MDS or MDS/MPN with normal karyotype. In view of the high proportion of lower-risk patients, longer follow up is required to better define prognostic impact of mutations in this population. [Table: see text]
Analysis of chemotherapy selection for locally advanced squamous cell carcinoma of head and neck (SCCHN) in a commercially insured population in the United States.
Authors: Hyunseok Kang, Christine Gail Gourin, Ana Ponce Kiess, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2016)

6066 Background: Multiple standard of care options exist for locally advanced SCCHN. We analyzed treatment plans submitted for commercially insured patients by practicing medical oncologists for pre-authorization to look into patterns of practice. Methods: Consecutive chemotherapy treatment plans for a population of 2 million covered lives across the US for newly diagnosed oral cavity, oropharynx, larynx and hypopharynx cancers submitted to insurers using the eviti Connect portal for chemotherapy pre-authorization between June 1, 2011 and June 30, 2015 were analyzed. Results: A total of 393 treatment plans were submitted for 340 newly diagnosed patients; 68 (20%) patients were from academic centers (AC) and 272 (80%) patients were from community practices (CP). Plans for chemotherapy before and during radiotherapy were identified in 61 (18%) patients, plans for definitive concurrent chemoradiation were identified in 217 (64%) patients, and plans for adjuvant chemoradiation after surgery were identified in 62 (18%) patients; no significant difference in treatment approach was seen between AC and CP. Only 9 (15%) patients at AC submitted plans for clinical trials. CP proposed upfront concurrent chemoradiation in larynx SCC more frequently than AC (79% vs 56%, p = 0.06). Single agent cisplatin, single agent cetuximab and single agent carboplatin were the 3 most commonly proposed regimens concurrent with radiotherapy, and there was no significant difference between AC and CP, although CP tended to use cetuximab more often in non-oropharynx SCCs (24% vs 10%, p = 0.16). For oropharynx SCC, unknown HPV status was reported more frequently in CP compared to AC (51% vs 31%, p = 0.04). In logistic regression, there were tendencies for more cetuximab use in older patients (OR 1.05, p = 0.09) and following induction chemotherapy (OR 2.03, p = 0.11). Conclusions: Among commercially insured patients with locally advanced SCCHN, clinical trials are not commonly proposed even at AC. HPV status was not routinely reported in oropharynx SCC, especially in CP. Single agent cisplatin continues to be the most commonly used regimen for concurrent chemoradiation in both AC and CP.
Outcomes of intermediate-high grade retroperitoneal sarcomas.
Authors: Ruoyu Miao, Graham Boyd, Matthew C Dimaria, Haotong Wang, Genevieve M Maquilan, John Thomas Mullen, Alex Bernard Haynes, Thomas F. DeLaney, Edwin Choy, Gregory Michael Cote, Yen-Lin Chen
Journal: Journal of Clinical Oncology (2018)

e23562 Background: Retroperitoneal sarcomas (RPS) can cause local, intraperitoneal, and distant failures. Treatment requires a tailored, multidisciplinary strategy. Methods: In an IRB approved protocol, we analyzed clinicopathologic characteristics, treatment and outcomes of patients with non-metastatic grade 2-3 RPS treated at our institution between 1975-2016. Results: We found 267 grade 2-3 RPS: 39% had liposarcoma, 24% leiomyosarcoma, 6% MPNST, and others. Patients presented as M0 (85%), positive lymph node (LN, 6%), peritoneal extension (9%), or distant metastasis (15%; liver most common). Rate of M1 was no significantly different by histology (leiomyosarcoma 17%, liposarcoma 10%, and MPNST 6%). Of 227 M0 patients (median age 59 years), 41% had liposarcomas, 23% leiomyosarcomas, 13% UPSs, 7% MPNSTs and 7% others. Surgical extent was 41% R0, 31% R1, and 22% R2. Radiotherapy (RT) was given preoperatively in 48%, postoperatively 29%, 11% both and 12% alone without resection. Chemotherapy was given in 19% using single/combined doxorubicin (84%), ifosfamide (37%), dacarbazine (21%), or others (44%). 11% did not undergo surgery for unresectable disease or rapid metastases preoperatively. At median follow-up of 44 months (range 1-326), 5-year overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were 52%, 52% and 49%. The risk of subsequent peritoneal or distant metastasis differed by histology: 5-year MFS was 61% in liposarcoma, 46% in leiomyosarcoma, and 27% in MPNST (p = 0.03). On univariate analysis, chemotherapy was associated with better OS (P = 0.05). On multivariate analysis, increased age (HR 1.02), MPNST (HR 2.68) and positive LN (HR 2.43) were associated with worse OS. No resection was associated with poor OS (HR 7.09), LC (HR 4.61) and MFS (HR 3.81), while RT (HR 0.56) reduced local and peritoneal failures. Conclusions: Although chemotherapy may have benefit in intermediate-high grade RPS, surgical resection remains the most significant predictor of survival. More trials are warranted to assess the optimal treatment for RPS histologies at high risk for local and distant failure.
Clinical impact of using a deep genomic profile in carcinoma of unknown origin
Authors: A. Fernandez Díaz, V. Iranzo, S. Calabuig Fariñas, E. Jantus, A.J. Cunquero Tomas, C. Avila Andrade, S. Sauvage, G. Beniuga, C.J. Camps
Journal: Annals of Oncology (2018)

Background: Diagnosis and treatment of Cancer of Unknown Origin (CUP) continues to be a challenge. In the era of personalized medicine, genomic profile by Next-Generation-Sequencing (NGS) in addition to immunohistochemistry (IHC) tests may complement clinical features improving diagnosis and detecting targetable mutations. In the present study we have analysed the clinical utility of the OncoDEEP® CUP platform for tissue of origin assessment and genotyping in a cohort of CUP patients. Methods: We conducted this multicentric prospective exploratory study across 22 institutions (September 2017- March 2018). The cohort included 60 patients with histologically diagnosed metastatic CUP and available FFPE tumor samples. The molecular analysis was performed using the OncoDEEP® CUP platform, which includes a deep genomic tumor characterization as well as a panel of IHC tests. Results: Patient's median age was 60 years [24-80], 61.7% were females. At time of diagnosis,48% presented a single metastatic site whereas 52% has multimetastatic locations. In 10% of the cases, the analysis could not be completed due to insufficient tumor samples. In the remaining 54 samples, a probable primary origin was assessed in 43 patients (80%). Potentially actionable mutations were found in 36 cases (61%). Follow-up information has been obtained so far for 46 of the 60 patients (76%). Interestingly, in 37 patients (80%) the treatment was changed after performing the genomic study. From these, in 33 cases (72%) the therapeutical decisions were based in the results obtained from the study: one patient was included in a clinical trial (3%); 2 patients received immunotherapy (6%); and the rest (91%) received chemotherapy based on the results of the immunohistochemistry tests (not on the NGS results). 43% of the oncologists who participated in the study had not previously considered the therapy given. The evaluation of response is ongoing. Conclusions: The genomic study OncoDEEP® CUP has identified new therapeutical options, both standard and innovative. The fact that no analysed patient has received targeted therapy based on NGS results for the moment shows the current barriers to accessing these treatments also in this kind of patients with limited options and bad prognosis. Legal entity responsible for the study: Hospital General Universitario de Valencia. Funding: Spanish Institute for Foreign Trade (ICEX). Disclosure: S. Sauvage: Employee of OncoDNA. All other authors have declared no conflicts of interest.
Analysis of survival and prognostic factors in metastatic colorectal cancer patients treated with first line bevacizumab.
Authors: Nazim Demircan, Faysal Dane, Mehmet Akif Ozturk, Mehmet Besiroglu, Nalan Babacan, Serap Kaya, Ozlem Ercelep, Eda Tanrikulu Simsek, Suleyman Halil, Sinan Koca, Ozkan Alan, Rahib Hasanov, Perran Fulden Yumuk
Journal: Journal of Clinical Oncology (2017)

e15009 Background: Colorectal cancer is a major cause of mortality worldwide. Survival has been improved by usage of bevacizumab. Our study aimed to analyze survival and prognostic factors in metastatic colorectal cancer patients treated with first-line bevacizumab. Methods: Files of patients were examined retrospectively and 360 patients treated with first-line bevacizumab were included. Data regarding age, gender, family history, location of the primary, histopathology, KRAS status, surgery and chemotherapy were acquired from the files. Overall response rates (ORR) to chemotherapy, progression and exitus dates or dates of last examination were recorded. Median progression-free and overall survival (PFS and OS) were calculated. Survival was analyzed with Kaplan-Meier method. Log-rank test and Cox regression model were used for univariate and multivariate analysis, respectively. Results: 201 (%55,8) of the patients were male and 159 (%44,2) were female. Median age at the time of the diagnosis was 59.5. 260 patients (%72,2) had initially stage IV disease. KRAS was mutant in 125 patients (%34,7). Median PFS was 8.5 months, median OS was 25.3 months and ORR was %51,4. Median PFS was 8.2 and 9.5 months, median OS was 30.4 and 28.1 months, ORR was %62,6 and %58.4 in KRAS wild type and mutant groups, respectively. In patients with left colon cancer median PFS and OS (9.6 and 27.1 months) were superior compared to patients with right colon cancer (7.3 and 19.4 months) (p = 0.005 and 0.016, respectively). Location of the primary, histopathologic grade, primary surgery, metastasectomy and KRAS status affected overall survival significantly (p &lt; 0.05) in univariate analysis. In multivariate analysis, histopathologic grade (p = 0.034) and metastasectomy (p = 0.001) were independent prognostic factors. Conclusions: In our study, response rates and survival of metastatic colorectal cancer patients treated with first-line bevacizumab were similar to previous studies. Left colon cancer patients had superior median PFS and OS compared to right colon cancer patients as shown in recent studies. Histopathologic grade and metastasectomy were independent prognostic factors in correlation with literature.