tbuckley/cabot-search huggingface dataset:
Incorporation of HIPEC into a high volume ovarian cancer program: Initial results and outcomes.
Authors: Aliza L. Leiser, Eugenia Girda, Ruth D. Stephenson, Mihae Song, Alexandre Buckley de Meritens, Lorna Rodriguez-Rodriguez
Journal: Journal of Clinical Oncology (2019)

e17040 Background: HIPEC showed a progression free survival when incorporated into interval cytoreductive surgery for ovarian cancer patients in a recent phase lll trial. This has led to a paradigm shift at many institutions and the consideration of HIPEC. The goal of this study is to report on the initiation of this program and change in practice at a high volume cancer center over a period of 1 year. Methods: Reviewed surgical cases from 1/2018 through 1/2019 where patients were thought to have a primary ovarian or fallopian tube cancer. Variables included age, stage, histology, primary or interval debulking surgery, number of neoadjuvant (NAJ) chemotherapy cycles. HIPEC patients were selected out and variables examined included intraoperative procedures, optimal cytoreduction, type of chemotherapy administered, postoperative complications, and ability to receive consolidation chemotherapy. Results: 35 cases where ovarian cancer known or suspected preoperatively. 23 patients had primary surgery consisting of tah/bso/surgical staging/tumor debulking. 0/23 of these patients were offered HIPEC chemotherapy as an upfront strategy. 12 patients received neoadjuvant chemotherapy for recurrent (2) or advanced (10) disease. 11/12 of these patients proceeded to an interval surgery. 6/11 (54%) were planned for HIPEC. This was aborted in 1/6 because of thrombocytopenia. 5/6 patients went on to receive HIPEC. They received 3-6 cycles of NAJ chemotherapy, platinum and taxane. 3/5 also received preoperative Avastin. All had R0 resection. 1 patient had a bowel resection. Either carboplatin or cisplatin was used for HIPEC over 90 minutes. 2/5 patients had postoperative G2-3 cytopenias. 3/5 patients were able to receive consolidation chemotherapy, 2 of them within six weeks of surgery and with Avastin containing regimens. Conclusions: In a large volume center initiating a HIPEC ovarian cancer program in less than one years’ time, HIPEC was offered to 50% of patients undergoing interval debulking for Stage III or IV serous ovarian cancer after NAJ chemotherapy and in rare cases for patients with recurrent cancer planned for cytoreduction. Patients may go on to receive postoperative chemotherapy but may have prolonged cytopenias and consolidation therapy delays. HIPEC was not incorporated into an upfront surgical strategy.[Table: see text]
Case 29-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, M.J. Barza, R.T. Schooley
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 38-year-old woman was admitted to the hospital because of a question of sepsis.She was in a stable state of health until two days earlier, when she received an unprovoked dog bite on the right lower leg while camping with her husband on Martha's Vineyard, Massachusetts, in mid-September. Minimal bleeding occurred, and with the help of the dog's owner the wound was cleansed. Twenty-four hours later the patient experienced increased pain, swelling, and purplish discoloration about the area of the bite, with a frank chill; scanty, blood-tinged vaginal discharge occurred. On the following day weakness, diarrhea, . . .
Abstract 17213: CD34+ Cell Therapy is Associated With Decreased Hospital Readmission in Patients With Chronic Heart Failure
Authors: Gregor Poglajen, Gregor Zemljic, Andraž Cerar, Sabina Frljak, Vesna Androcec, Renata Okrajšek, Martina Jaklic, Miran Šebeštjen, Bojan Vrtovec
Journal: Circulation (2017)

Introduction: Hospital readmissions due to worsening heart failure have been associated with adverse prognosis in chronic heart failure patients. Hypothesis: We sought to investigate the effects of...
Discordant treatment response in primary tumors and lymph node metastases after four weeks of preoperative PD-1 blockade in head and neck squamous cell carcinoma (HNSCC).
Authors: Adam Luginbuhl, Jennifer Maria Johnson, Madalina Tuluc, Stacey Mardekian, Larry Harshyne, Benjamin Leiby, Ralph Zinner, Joseph M. Curry, David M. Cognetti, Ulrich Rodeck, Athanassios Argiris
Journal: Journal of Clinical Oncology (2019)

6016 Background: Discordant radiographic responses are described in other tumor types in response to immunotherapy with response at some anatomic sites and progression in others. Here we determined the frequency of discordant treatment effects (TE) in HNSCC patients treated with immunotherapy in the context of a neoadjuvant trial. Methods: 23 Patients with resectable primary HNSCC were 1:1 randomized to receive nivolumab (240 mg IV Q 2 weeks x 2) or nivolumab and tadalafil 10 mg daily. Surgery was performed 4 weeks after the first nivolumab infusion. Resection specimens were graded histopathologically by two pathologists. Areas exhibiting TE (defined by fibrosis with chronic inflammation, foamy macrophage reaction and multinucleated giant cells) were expressed relative to the total tumor area. This was assessed in the primary tumor and all lymph nodes (LN). Each primary lesion and individual LN was defined as a) no response 0%TE, b) minimal response 1-19%TE, c) response 20-99% or d) complete response 100%. Concordance was defined if primary lesion and LNs were in the same ordinal data set. Results: 11/23 (48%) of subjects experienced concordant ΤΕ in the primary tumor and LNs. Within this cohort, 3 patients had a complete pathologic response both at the primary site and LNs. In contrast, 12/23 patients (52%) revealed discordant ΤΕ between the primary tumor sites (average of 17% TE) and involved LNs (average of 62% TE), (p= 0.018; signed rank test). Interestingly, in the discordant group, TE effects in LNs were invariably greater than in primary lesions. In 5 of 11 patients with multiple involved LN, the TE varied between nodes. This included patients with adjacent LNs demonstrating 0% and 100% TE in the same level. Systemic and local immune parameters as they relate to concordant and discordant TEs in individual patients will be presented including a type 1 immune bias. Conclusions: Early histologic evaluation of TE in patients with HNSCC receiving immunotherapy demonstrate a wide variety of response between the primary tumor and LNs. Further investigations will lend insight into complex interactions of cancer cells with the microenvironment. Clinical trial information: NCT03238365.
DDP4 inhibitors as novel agents in improving survival in diabetic patients with CRC and lung cancer: A SEER-Medicare study.
Authors: Rohit Bishnoi, Young-Rock Hong, Chintan Shah, azka ali, William Paul Skelton, Jinhai Huo, Nam H. Dang, Long H. Dang
Journal: Journal of Clinical Oncology (2019)

e14633 Background: DPP4 is a cell surface protein that is widely expressed on different tissues and can play important role in tumor biology by acting as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are a class of drug used in the clinical setting to treat diabetes mellitus type II (DM-II) while recent research has suggested that they play a role in regulating tumor growth. Methods: We conducted this large population database Surveillance Epidemiology and Endpoint Research (SEER-Medicare) study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of patients with colorectal and lung cancers. Results: Our results showed that diabetic patients with colorectal cancer (CRC) or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (HR of 0.89; 95% CI: 0.82-0.97, p = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin, which is already known to improve OS in many cancers, the survival advantage was even more pronounced (HR of 0.83; 95% CI: 0.77-0.90, p &lt; 0.0001). When results were analyzed for CRC-only cohort, the use of DPP4 inhibitors alone had a very positive survival advantage trend (HR of 0.87; 95% CI: 0.75-1.00, p = 0.055) whereas the combined use of DPP4 inhibitors and metformin was associated with statistically significant survival advantage (HR of 0.77; 95% CI: 0.67-0.89, p = 0.003). Similarly, in the lung cancer cohort, the DPP4 inhibitor group exhibited a potential survival advantage (HR of 0.93; 95% CI: 0.83-1.03, p = 0.153), while lung cancer patients treated with the combination of DPP4 inhibitors and metformin showed statistically significant survival advantage (HR of 0.88; 95% CI: 0.80-0.97, p = 0.010). Conclusions: These results again establish that DPP4 inhibition in CRC and lung cancer is associated with the suppression of tumor growth and improved OS. The beneficial effects of DPP4 inhibitor treatment are additionally improved when DPP4 inhibitors are used in combination with metformin. While the exact mechanism involved in the observed benefit of DPP4 inhibitor treatment in cancer remains to be elucidated, one possibility may be due to the effect of DPP4 inhibition on immunoregulation of cancer.
Three-year survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma (CM).
Authors: Eddy C. Hsueh, James R. DeBloom, Robert W. Cook, Kelly McMasters
Journal: Journal of Clinical Oncology (2019)

9519 Background: A 31-GEP test is a validated prognostic tool for predicting the risk of metastasis in CM, classifying patients (pts) as Class 1 (low risk) or Class 2 (high risk). Here we report updated survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in patients for whom the GEP test was part of their clinical care. Methods: Eleven US dermatologic and surgical centers participated using IRB-approved protocols. Participants were CM pts ≥16 years old who had successful 31-GEP test results. Recurrence-free (RFS), distant metastasis-free (DMFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox regression analysis. Results: At data censoring, 340 pts were accrued who had completed at least one follow-up visit. Median age was 58 years (range 18-87), 53.5% were male, median Breslow thickness was 1.2mm (range 0.2-12mm), 18.2% (62/340) were ulcerated, and 11.2% (38/340) had a positive sentinel lymph node (SLN). Median follow-up was 3.2 years for pts without an event. Six percent (16/265) of Class 1 pts had a recurrence compared to 33% (25/75) of Class 2 pts (p &lt; 0.001). Three-year RFS was 96%, 91%, 80%, and 62% for Class 1A, 1B, 2A, and 2B, respectively (p &lt; 0.001). Three-year DMFS was 97%, 93%, 84%, and 80% for Class 1A, 1B, 2A, and 2B, respectively (p &lt; 0.001). Three-year OS was 98%, 90%, 96%, and 74% for Class 1A, 1B, 2A, and 2B, respectively (p &lt; 0.001). Class 2 was an independent predictor of RFS and OS in multivariate analysis (respective HRs: 2.28 and 3.70, p &lt; 0.05). Conclusions: Consistent with results from previous studies, this analysis demonstrates that the GEP test complements conventional staging and improves the ability to identify high-risk CM pts. These results support use of the test for guiding decisions related to follow-up, surveillance, and treatment in CM pts. Clinical trial information: NCT02355574/NCT02355587.
Caveat medicus: Harrowing experiences of clinicians who identify and publish near-fatal oncology associated adverse drug reactions.
Authors: Ashley Caitlin Godwin, Charles L. Bennett
Journal: Journal of Clinical Oncology (2019)

6584 Background: Less than 1-10% of adverse drug reactions are reported. It is even more rare to find clinicians who choose to publish these reports in the literature. We identified clinicians who had treated a patient for an oncology-associated serious adverse drug reaction and published these findings. This is the first study that has investigated personal experiences of clinicians choosing to publish information about serious oncology-associated drug reactions they see in their patients. Methods: Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Results: 18 clinicians met inclusion criteria and 14 interviewees are included. Toxicities included central nervous system infections, arterial/venous thromboembolism, gastrointestinal toxicity, cardiac arrhythmias, and cancer development/progression. These investigations were frequently followed by label warnings and/or convening of Food and Drug Administration (FDA) Advisory Committee reviews of safety findings. Five studies were disseminated in four high-impact factor medical journals (JAMA, Lancet, Annals of Internal Medicine, and New England Journal of Medicine). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. Responses from FDA employees were characterized as negative by six clinicians. Three clinicians recommended that pharmacovigilance should include simplified clinician reporting systems. Conclusions: Our study finds that clinicians who published reports of serious oncology-associated drug reactions experienced negative feedback from pharmaceutical manufacturers. Feedback from FDA employees and academic clinicians were viewed as supportive by some and negative by others. Most clinicians recommended that future pharmacovigilance involve big data analyses.
Pretreatment eosinophil counts (PEC) in metastatic urothelial carcinoma (mUC) treated with anti-PD1/PD-L1 checkpoint inhibitors (CPI).
Authors: Jose Mauricio Mota, Min Yuen Teo, Karissa Whiting, Irina Ostrovnaya, Han Li, Chung-Han Lee, Samuel Aaron Funt, Margaret K. Callahan, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2019)

e16035 Background: Eosinophils may influence anti-tumor immunity, having been associated with outcomes in CPI-treated melanoma. We sought to examine the association between PEC and outcomes of CPI-treated mUC. Methods: Independent CPI-treated cohorts were identified: discovery (n = 60, Teo et al JCO 2018) and validation (n = 111, non-overlapping CPI-treated mUC patients [pts] from 2014-19). Uni- and multivariate analyses were performed using Cox proportional hazard models to evaluate prognostic value of PEC on (i) overall survival (OS) and (ii) time on treatment (ToT). A platinum-treated metastatic cohort (n = 81, Teo et al, CCR 2017) was used as non-CPI comparator. Results: The cohorts showed comparable OS and pts characteristics, except higher proportion of females and lower neutrophil at baseline (Neut) in the validation cohort. In the discovery cohort, PEC as a continuous variable showed a significant positive association with OS (HR 0.01, 95% CI 0.00-0.29, P = .009). PEC of 100 cells/µL was set as the optimal cut-off point (Eos-L: &lt; 100 cells/µL, n = 9; Eos-H: ≥100 cells/µL, n = 51). Eos-L showed inferior outcomes (OS: HR 3.98, 95%CI 1.85-8.56, P &lt; .001; ToT: HR 2.45, 95%CI 1.17-5.10, P = .017). Similar association was seen in the validation cohort (Eos-L, n = 17; Eos-H, n = 94; OS: HR 2.51, 95%CI 1.31-4.80, P = .006; ToT: HR 2.22, 95%CI 1.29 - 3.80, P = .004). A multivariate model adjusting for other prognostic variables was created (table). In the chemotherapy cohort, continuous Eos or Eos-L was not associated with OS/ToT, with or without adjusting for known prognostic factors (P &gt; 0.5). Conclusions: The association between Eos-L and shorter OS in CPI- but not chemotherapy-treated cohorts might represent a potential negative predictive biomarker for CPI in mUC. [Table: see text]
Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1.
Authors: Amod Sarnaik, Nikhil I. Khushalani, Jason Alan Chesney, Harriet M. Kluger, Brendan D. Curti, Karl D. Lewis, Sajeve Samuel Thomas, Eric D. Whitman, Omid Hamid, Jose Lutzky, Anna C. Pavlick, Jeffrey S. Weber, James M.G. Larkin, Debora Barton, Lotus Yung, Sam Suzuki, Maria Fardis, John M. Kirkwood
Journal: Journal of Clinical Oncology (2019)

2518 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable long-term responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel (LN-144), a centrally manufactured autologous TIL therapy are presented. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of the efficacy and safety of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 55) patients who received cryopreserved lifileucel. Tumors resected at local institutions were processed in central GMP facilities for TIL production in a 22-day process. Final TIL infusion product was cryopreserved and shipped to sites. Patients received one week of cyclophosphamide/fludarabine preconditioning lymphodepletion, a single lifileucel infusion, followed by up to 6 doses of IL-2. Results: In 55 patients with Stage IIIC/IV unresectable melanoma, 3.1 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 24%), high baseline tumor burden (110 mm mean target lesion sum of diameters), ORR was 38% (2 CR, 18 PR, 1 uPR). Of 21 responders, 4 have progressed to date with median follow up of 7.4 months. Overall disease control was 76%. Improved responses in some patients were observed with longer follow up. Most (54) patients progressed on prior anti-PD1 and those with PD-L1 negative status (TPS &lt; 5%) were among responders. Mean cells infused was 28 x10 9 . Median IL-2 doses administered was 6.0. Adverse events resolved to baseline, 2 weeks post TIL infusion, a potentially important benefit of one-time TIL therapy. Conclusions: Lifileucel treatment results in 38% ORR in heavily pretreated metastatic melanoma patients with high baseline disease burden who received prior anti-PD1 and BRAF/MEK inhibitor if BRAF mutated. Based on these data, a new Cohort 4 in C-144-01 has been initiated to support lifileucel registration. Clinical trial information: NCT02360579.
Assessment of ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients (pts) with advanced HER2-negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial.
Authors: Federica Morano, Monica Niger, Salvatore Corallo, Sara Lonardi, Stefano Tamberi, Samantha Di Donato, Elisa Giommoni, Francesco Giuliani, Giovanni Luca Frassineti, Gianluca Tomasello, Ferdinando De Vita, Giovanni Gerardo Cardellino, Graziella Pinotti, Maria Pia Brizzi, Lorenza Rimassa, Mario Scartozzi, Rossana Berardi, Filippo G. De Braud, Filippo Pietrantonio, Maria Di Bartolomeo
Journal: Journal of Clinical Oncology (2019)

TPS4151 Background: Platinum/fluoropyrimidine regimens are the backbone of first-line therapy for advanced gastric cancer (AGC). The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only 40% of AGC pts are eligible for second-line treatment. This study aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after a first-line with a platinum/fluoropyrimidine regimen. The hypothesis is that the early administration of an active, non-cross resistant regimen may delay disease progression and, consequently, improve pts’ quality of life. This strategy may also rescue all those subjects that become ineligible for a second-line therapy due to the rapid clinical deterioration. Methods: This is a randomized, open-label, multicenter, phase III trial. Eligibility criteria are: unresectable/metastatic HER-2 negative AGC or gastroesophageal junction (GEJ) cancer; ECOG PS 0-1; measurable and/or evaluable disease by RECIST v1.1; no progression after 3 months of therapy with either FOLFOX4, mFOLFOX6 or XELOX . The primary endpoint is to compare PFS of pts in ARM A (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine) versus ARM B (switch maintenance to ramucirumab and placlitaxel). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of pts receiving a second-line therapy per treatment arm, safety and quality of life. Exploratory analyses to identify primary resistance and prognosis biomarkers are planned, including Next-Generation Sequencing (NGS) on archival tumor tissues. The ARMANI study is sponsored by the Fondazione IRCCS Istituto Nazionale dei Tumori and it is ongoing at 29 Italian centers with a planned population of 280 pts. Clinical trial information: NCT02934464.