tbuckley/cabot-search huggingface dataset:
A phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in patients with recurrent, metastatic, or persistent cervical carcinoma.
Authors: Amir A. Jazaeri, Robert P. Edwards, Robert Michael Wenham, KOJI MATSUO, Gini F. Fleming, David M. O'Malley, Brian M. Slomovitz, Bradley J. Monk, Robert James Brown, Samuel Suzuki, Igor Gorbatchevsky, Maria Fardis, Emese Zsiros
Journal: Journal of Clinical Oncology (2018)

TPS5604 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has demonstrated efficacy in the treatment of immunogenic tumors with high mutation loads, such as melanoma, and virally-associated tumors, such as HPV-mediated cervical cancer. As outcomes for patients with recurrent, metastatic or persistent cervical cancer remain extremely poor, there is an enormous need for the development of novel immunotherapeutic approaches with curative potential such as ACT with TIL. Methods: Clinical trial C-145-04 (NCT03108495) is a prospective, phase 2 multicenter, open-label study evaluating the efficacy of a single autologous TIL infusion (LN-145) followed by IL-2 after a non-myeloablative lymphodepletion (NMA-LD) regimen in patients with recurrent, metastatic, or persistent cervical cancer who have failed at least one prior systemic therapy. Patients undergo surgical resection of a tumor from which TIL are extracted and expanded at a central GMP manufacturing facility that prepares a cryo-preserved TIL (LN-145) product for infusion. One week prior to LN-145 infusion, patients undergo NMA-LD consisting of cyclophosphamide (60 mg/kg) daily x 2 days followed by fludarabine (25 mg/m2) daily x 5 days. LN-145 is infused 24 hours after NMA-LD and followed by up to 6 doses of IL-2 (600,000 IU/kg) every 8-12 hours. The primary endpoint is the objective response rate (ORR) per RECIST v1.1. Secondary endpoints include safety and efficacy parameters such as complete response, duration of response, disease control rate, progression free- and overall survival. In addition to the tumor resected, patients must have an additional measurable lesion for response assessment. Other major eligibility criteria include adequate bone marrow, liver, pulmonary, cardiac and renal function; ECOG performance status of 0 or 1. Clinical trial information: NCT03108495.
Is there a correlation between serum Epstein-Barr virus DNA level and tumor metabolic activity, TNM staging and tumor load in nasopharyngeal cancer patients?
Authors: Aysel Ahmedova, Kubra Ozkaya, Makbule Tambas, Ugur Gezer, Emre Ozgur, Dilek Sahin, Yasemin Sanli, Musa Altun
Journal: Journal of Clinical Oncology (2017)

e17543 Background: To investigate the relationship between pretreatment Epstein-Barr virus (EBV) DNA copy number and tumor metabolic activity, TNM stage and tumor volume in nasopharyngeal cancer (NPC) patients. Methods: Blood samples were collected 0-3 weeks before treatment and number of EBV DNA copies were determined by PCR . MRI and PET-CT were performed 0-4 weeks before treatment. The primary tumor volume (TVnp) and total volume of metastatic lymph nodes (TLV) were delineated separately on MRI by the same radiologist by the aid of program “Osirix” and recorded in cm 3 . Maximum SUV values of primary tumor (Tsuv) and metastatic lymph nodes (LNsuv) were determined with each PET-CT images. Kruskal Wallis test and Spearman's Correlation Analysis were used for the comparison of 3 or more groups with no normal distribution and the evaluation of the inter-parameter relations, respectively. Results: The study included 50 NPC patients treated between 2011 and 2015. There was no significant relation between serum EBV DNA copy number and the distribution of T stage (p = 0.81), N stage (p = 0.08), TVnp (r:0.009; p = 0.95), and Tsuv (r:-0.007, p = 0.96). However, a significant correlation was detected between EBV DNA copy number and both LNsuv (r:0.337; p = 0.017) and TLV (r:0.579; p = 0.001) (LNsuv and TLV increased as virus load increased). Conclusions: There is no significant relation between pretreatment EBV DNA load and T and N stages and TVnp in NPC patients. However, EBV DNA load has a significant correlation with TLV and LNsuv. These results may imply that TLV can be included in nodal staging and together with LNsuv be integrated in treatment planning.[Table: see text] [Table: see text]
Development of a digital patient navigation application: Results from subject interviews.
Authors: Thomas William LeBlanc, Kris Herring, Jack Chilcott, Katherine Bletcher, Miya Osaki, Hugo Manassei, Trudy Pendergraft, Cheyenne Corbett, Yousuf Zafar, Adam Higgins, Steven R. Patierno
Journal: Journal of Clinical Oncology (2018)

e22146 Background: People living with cancer face challenges too numerous to attend to during brief clinic visits, and thus may benefit from additional help with supportive care needs. While patient navigators offer promise, they are a limited resource. Digital navigation offers a scalable solution, to extend navigators’ reach and connect patients with existing resources, thereby enhancing our ability to address unmet needs. Methods: Utilizing a “design thinking” approach, we developed and tested a digital navigation platform to enhance utilization of support resources in the Duke Cancer Institute (DCI). The alpha version of the application (app) was based upon insights gleaned from interactions with patients, caregivers, advisory board members, and staff. It was then tested among adult patients with advanced cancer and/or caregivers at the DCI. Subjects participated in qualitative interviews with design/content experts, to elicit supportive care needs and gauge interest in the app to improve their care. Detailed notes were taken, and emerging themes compiled. Results: 12 subjects were interviewed, including 7 patients and 5 caregivers. Subjects reported feeling overwhelmed by information, feeling that “they don’t know where to start when looking for support.” They also expressed uncertainty about what questions to ask, and said they are not always comfortable asking for help. All struggled to define “supportive care;” only one knew it refers to a set of services. Subjects felt a digital navigation app would enable them to explore and access services as needed, to help them “feel less alone,” and to know “someone or something was there for them.” They expressed dislike for being asked lots of questions, wanting to explore options on their own instead of being led somewhere. Digital navigation has the promise to increase their sense of control, with one subject noting: “I like to know what my options are and decide for myself…people try to assume they know what you need all the time.” Conclusions: Digital supportive care navigation may be an effective, scalable, and cost-efficient intervention to support patients and caregivers, and ultimately improve outcomes. Further refinement and testing is needed.
Use of PD-1 pathway inhibitors among patients with non-small cell lung cancer (NSCLC) and preexisting autoimmune disorders.
Authors: Giulia Costanza Leonardi, Justin F. Gainor, Roxana S. Azimi, Jonathan Riess, Hira Rizvi, Matthew David Hellmann, Mark M. Awad
Journal: Journal of Clinical Oncology (2017)

9081 Background: Since patients (pts) with NSCLC and autoimmune (AI) disease were largely excluded from immune checkpoint inhibitor clinical trials, we aimed to determine the safety of PD-1 inhibitors in NSCLC pts with a history of AI diseases. Methods: As part of a multi-center, retrospective study, we collected clinicopathologic data from pts with advanced stage IIIB or stage IV NSCLC with a history of AI disease and who received treatment with a PD-1 inhibitor as monotherapy. Qualifying AI disorders included but were not limited to: thyroiditis (excluding hypothyroidism without clear autoimmune etiology), inflammatory bowel disease, as well as rheumatologic, neurologic and dermatologic conditions. Results: We identified 46 pts with NSCLC treated with a PD-1 inhibitor who also had a history of AI disease. At the time of PD-1 inhibitor treatment initiation, 13% of pts had active AI symptoms and 19% were receiving immunomodulatory agents for their AI condition. The median period of follow up after initiation of anti-PD-1 therapy was 17.4 weeks (range 0.6-72.1 weeks). Exacerbation of the underlying AI condition occurred in 8 pts (17%). Two of these pts required steroid treatment (both for rheumatoid arthritis), and three of these pts required temporary interruption of treatment due AI disease flare. Overall, twelve (26%) pts developed at least one immune-related adverse event (irAE) unrelated to the underlying AI condition (8 grade 1-2, 4 grade 3); there were no cases of grade 4-5 irAEs. PD-1 therapy was permanently discontinued in 3 cases due to the development of an irAE (1 for grade 1 pneumonitis, 1 for grade 3 transaminitis, 1 for grade 3 diabetes insipidus). Conclusions: In pts with NSCLC and a history of AI conditions treated with PD-1 blockade, symptomatic flare of underlying AI disease was uncommon. The rate of immune-related toxicities in this population appears similar to published studies in pts without baseline AI conditions. Further analysis of pts with active AI conditions is needed to clarify the safety profile in this population.
Efficacy and safety of adjuvant intraperitoneal chemotherapy in carcinoma ovary: A prospective observational study.
Authors: Varun Goel, Prasanta DASH, Vineet Talwar, Sajjan Singh, Dinesh Doval, Nivedita Patnaik
Journal: Journal of Clinical Oncology (2016)

e17069 Background: It has been demonstrated in few trials, that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer. But it has been associated with high treatment related toxicities leading to very low acceptance of this modality among medical oncologists. So, various modifications in treatment schedules have been tried to reduce toxicities. In this study, we decided to study the response and tolerability of IP paclitaxel on day 8 with IV paclitaxel on day 1 and IV cisplatin day 2 in carcinoma ovary, in view of paucity of data with this modification. Methods: In this prospective observational study, from March 2013 to June 2015, the efficacy and tolerability of adjuvant IP/IV chemotherapy in optimally cytoreduced stage III epithelial ovarian cancer patients were assessed. Treatment consisted of 135 mg/m2 of IV paclitaxel over a 3-hours period on day 1 followed by AUC 5 carboplatin IV on day 2 and 60 mg/m2 of IP paclitaxel on day 8 every 3 weekly for six cycles. Results: Total 50 patients were enrolled. The median age of patients was 53 yrs (32yrs – 67yrs). Out of a total of 300 I/P cycles, 264 cycles (88%) were completed. 38 patients (76%) received all the 6 cycles by IP route. 6 out of those 38 patients had one or more adjustment including delay or dose reduction. After median follow up of 18 months, 7 patients (14%) had local or systemic recurrence, 2 patients (4%) had progression during treatment. Median progression free survival not reached yet. Catheter block was seen in 5 cases. Two cases had needle displacement and extravasations of drug around the port chamber. 6 patients had grade 3 abdominal pain and cramp. Grade 3/4 Leucopenia was experienced by 25 patients (50%) but Febrile Neutropenia occurred in only 5 (10%) patients. Renal complication present in 3 patients (6%) and transient transfusion reaction developed in 5 patients. Conclusions: In Indian patients, adjuvant chemotherapy with day 8 I/P paclitaxel in optimally cytoreduced epithelial ovarian cancer is associated with survival benefits comparable to western literature and better tolerated with very high treatment completion rate.
Abstract 17559: Norepinephrine Levels are Associated With the Magnitude of Vasoconstriction During Mental Stress
Authors: Ayman Alkhoder, Nino Isakadze, Malik Obideen, Viola Vaccarino, J. Douglas Bremner, Brad D Pearce, Danielle Chou, Paolo Raggi, Kobina Wilmot, Ibhar Al Mheid, Qi Long, Naser Abdelhadi, Michael Kutner, Arshed Quyyumi, Amit Shah
Journal: Circulation (2015)

Background: Patients with CAD develop varying degrees of microvascular vasoconstriction in response to mental stress, leading to myocardial ischemia. Catecholamine increases during mental stress may explain this effect. We hypothesized, in a cohort of stable CAD patients, that increased epinephrine and norepinephrine levels from rest to peak mental stress predict peripheral microvascular vasoconstriction. Methods: We analyzed data from 204 patients with CAD and high quality vascular data. Subjects underwent a standardized mental stress test using a public speaking task. Peripheral arterial tonometry (PAT) was used to assess peripheral microvascular function during rest and mental stress. The PAT response was calculated as a ratio of the minimum pulse wave amplitude during the speaking task to the mean amplitude during rest. Plasma epinephrine and norepinephrine levels were obtained 15 minutes before and at peak mental stress. Linear regression modeling was used to adjust for potential confounders. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Subjects in the quartile with the greatest vasoconstriction had the highest increase in norepinephrine levels (73.5 (31.4) ng/mL [mean (SEM]), while those in the quartile with the least vasoconstriction had decreased norepinephrine levels by 47.7 (32.5) ng/mL, p for trend&lt;0.001 (Figure). There was no significant association between PAT and epinephrine. After multivariable adjustment for sociodemographics, CAD risk factors, medical history, medication use, major depression, and PTSD, the association between the PAT ratio and norepinephrine remained significant (p=0.003). Conclusion: Changes in circulating norepinephrine, but not epinephrine levels predict peripheral microvascular vasoconstriction during mental stress.
TCT-703 Early Results Following Magnesium Bioresorbable Vascular Scaffold Implantation in Patients with Acute Myocardial Infarction
Authors: Alfonso Ielasi, Enrico Cerrato, Salvatore Geraci, Massimo Leoncini, Chiara Bernelli, Francesco Granata, Paolo Sganzerla, Nadia Garro, Mario Iannaccone, Gianluca Campo, Maurizio Tespili, None Ferdinando varbella
Journal: Journal of the American College of Cardiology (2018)
Longitudinal ctDNA analysis to enable early assessment of prognosis in lung adenocarcinoma in the absence of matched tissue biopsy.
Authors: Xiaoju Max Ma, Nalin Tikoo, Christine Ju, Aarthi Balasubramanyam, Liu Xi, Stephanie Yaung, Dan Klass, Alexander F. Lovejoy, Amrita Pati, Owen Solberg, Yuqiu Jiang, Hans-Peter Adams, Michael Thomas, Felix Lasitschka, Michael Meister, Marc Schneider, Felix Herth, Thomas Muley, Birgit Wehnl, John F. Palma
Journal: Journal of Clinical Oncology (2018)

12077 Background: Longitudinal ctDNA monitoring using variants identified in tissue biopsies is an emerging method for disease management. However, tissue biopsy is often inaccessible for many late stage lung cancer patients. We hypothesized that variants found in baseline plasma ctDNA can also be used for monitoring, and that an early response assessed by changes in the level of ctDNA could predict treatment effect. Methods: We employed a 197-gene NGS assay, the AVENIO ctDNA Surveillance Kit, which allowed us to perform longitudinal ctDNA analysis and measure changes in the allele frequency (AF) of the variants identified in baseline plasma. Using this tissue-independent method, we evaluated the association between change in ctDNA levels and survival of advanced lung adenocarcinoma subjects treated with first-line chemo or chemoradiation therapies. Post-treatment AF values were compared with the lowest AF value (nadir) of all previous timepoints, including baseline. New variants were included if the AF was above the mean AF at baseline (b0). The algorithm was tested in a training cohort (44 subjects) and validated in an independent cohort from a prospective, observational study (40 subjects, all stage IV lung adenocarcinoma). Results: At b0, we identified variants in all subjects to enable ctDNA monitoring. From the training cohort, we defined the post-second treatment cycle (p2) as 30 to 60 days post-start of first treatment and compared AF value of each variant with the nadir value. Good responders at p2 were defined as having no significant increase in AF from the nadir. Applying this algorithm to the validation cohort, good early responders with samples collected within p2, 24/40 (60%), were associated with better progression-free survival (PFS) (6.1 vs. 3.8 mo, P = 0.0145; HR 0.43; 95% CI 0.21, 0.86) and overall survival (OS) (15.0 vs. 6.8 mo, P = 0.0032; HR 0.31; 95% CI 0.14, 0.70). Conclusions: Longitudinal ctDNA analysis in the absence of matched tissue biopsy may be feasible. No significant increase in post-treatment ctDNA levels measured by NGS was associated with better prognosis in advanced lung adenocarcinoma treated with first-line chemo or chemoradiation therapy.
Histology of Rosai-Dorfman disease in a subset of patients with Erdheim-Chester disease: A distinct entity mainly driven by MAP2K1.
Authors: Jerome Razanamahery, Eli L. Diamond, Karlheinz Plate, Frédéric Charlotte, Zofia Hélias-Rodzewicz, Ahmet Dogan, Omar Ibrahim Abdel-Wahab, Benjamin Heath Durham, Neval Ozkaya, Zahir Amoura, Jean-François Emile, Julien Haroche
Journal: Journal of Clinical Oncology (2018)

e24180 Background: Diagnosis of Rosai-Dorfman disease (RDD) is based on histology which is characterized by infiltration by CD68+ CD1a- S100+ histiocytes with large nuclei and abundant lesions of emperipolesis. By contrast, diagnosis of Erdheim-Chester disease is based on characteristic imaging of bones, retroperitoneal and/or cardiovascular involvement . Biopsy is mandatory, but diagnosis also relies on clinic and imaging .Up to 70% of ECD histopathological lesions exhibit BRAF or MAP2K1 mutations, which are rare in RDD. Methods: We investigated patients harboring an ECD phenotype but RDD histology. We reviewed record of ECD patients from 2007 to 2018 followed in Pitié-Salpêtrière hospital (Paris, France) and Memorial Sloan Kettering Cancer Center (New-York, NY, USA). Mutation in gene of MAP kinase pathway was performed on biopsy samples of all patients. Results: Among 209 patients with ECD, we found 10 patients (4.7%) with RDD histology. All patients had typical ECD clinical and radiological presentation with bones (n = 7), vascular (n = 5), peritoneal (n = 6) and neurological (n = 6) involvements. Biopsies disclosing RDD histology were performed during the course of the disease involving testes (n = 5), stomach (n = 1), tibia (n = 2), cheek (n = 1) and omentum (n = 1). All tissues showed large histiocytes infiltration. Histiocytes were CD68+ CD1a- S100+ with large nuclei and abundant lesions of emperipolesis. Five patient harbored MAP2K1 mutation and one patient had PIK3CA mutation. None of the patients had BRAF mutation. Conclusions: Some patients with ECD may also present the iconic histological lesions described by Rosai and Dorfman. Overlap forms of such distinct histiocytoses between ECD and RDD is mainly driven by MAP2K1 but not by BRAF.
Overweight and breast cancer risk in the International Breast Cancer Intervention studies I and II.
Authors: Samuel G Smith, Ivana Sestak, Michelle A Morris, Anthony Howell, John F. Forbes, Jack M. Cuzick
Journal: Journal of Clinical Oncology (2018)

1560 Background: Overweight increases breast cancer risk in population risk postmenopausal women. Data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 and P2 chemoprevention trials indicate premenopausal overweight, but not postmenopausal overweight, increases breast cancer risk in high risk women. We estimated the relationship between overweight and breast cancer risk in the International Breast Cancer Intervention Studies (IBIS) I and II. Methods: The IBIS prevention trials compared tamoxifen (IBIS-I) and anastrozole (IBIS-II) vs. placebo in women at increased risk of breast cancer. Baseline body mass index (BMI) was calculated for premenopausal (n = 3138) and postmenopausal (n = 3733) women in IBIS-I and postmenopausal women in IBIS-II (n = 3783). BMI change ( < 5%, 5-9.9%, > 10%) was available for 2504 IBIS-I women. There were 542 (IBIS-I) and 168 (IBIS-II) invasive breast cancer events and median follow-up was 19.6 years (IQR 17.8–21.1) and 9.3 years (IQR 7.2–11.4), respectively. We used Cox proportional hazards regression to calculate Hazard Ratios (HRs) for invasive breast cancer risk after adjusting for previous trial participation (IBIS-II only), age, diabetes, hormone therapy use, smoking and menopausal status (IBIS-I only). Results: Higher BMI was associated with increased invasive breast cancer risk in IBIS-I (HR = 1.02, 95% CI = 1.00-1.03, p = 0.044) and IBIS-II (HR = 1.06, 95% CI = 1.03-1.09, p < 0.001). In IBIS-I, the association between BMI and breast cancer risk was restricted to postmenopausal women (HR = 1.03, 95% CI = 1.01-1.05, p = 0.004). Among IBIS-I postmenopausal women, compared with healthy weight, HRs were 1.20 (95% CI = 0.92-1.56) for overweight and 1.29 (95% CI = 0.97-1.72) for obese women. In IBIS-II HRs were 1.15 (95% CI = 0.75-1.75) for overweight and 1.90 (95% CI = 1.27-2.84) for obese women. There was no interaction between BMI and treatment group in either trial. Weight gain did not affect breast cancer risk. Conclusions: Contrary to NSABP P1 and P2 data, we found no evidence for increased breast cancer risk among overweight premenopausal women. IBIS-I and IBIS-II data suggest higher BMI increases breast cancer risk in postmenopausal women with elevated breast cancer risk. Clinical trial information: ISRCTN91879928 and ISRCTN31488319.
A randomized, double-blind, placebo-controlled, phase III study of crenolanib in advanced or metastatic GIST patients bearing a D842V mutation in <i>PDGFRA</i>: The CrenoGIST study.
Authors: Jean-Yves Blay, Michael C. Heinrich, Peter Hohenberger, Paolo Giovanni Casali, Piotr Rutkowski, Cesar Serrano-Garcia, Robin Lewis Jones, Kirsten Sundby Hall, John Randall Eckardt, Margaret von Mehren
Journal: Journal of Clinical Oncology (2017)

TPS11080 Background: Activating mutations in the kinase domain of PDGFRA account for 10-15% of GIST. The most common PDGFRA mutation reported is D842V, which is known to confer resistance to imatinib and sunitinib. Currently, there is no approved treatment for GIST patients carrying such mutation. Cassier PA et al. showed that patients with D842V mutated GIST had a short median progression free survival (PFS) of 2.8 months with first line imatinib and 2.1 months with second line (2012 Clin Cancer Res). Crenolanib is a highly selective PDGFRA and FLT3 inhibitor with nanomolar activity against PDGFRα D842V mutation. In a previous dose-finding study, crenolanib showed a 31% clinical benefit rate with 2 pts achieving PR and 3 pts maintaining SD (total evaluable: 16 pts) in heavily pretreated GIST patients harboring the PDGFRA D842V mutation. In this study, 35% patients stayed on study for at least 7 months despite 80% patients having progressed after prior imatinib (15 pts), sunitinib (7 pts), dasatinib (5 pts), sorafenib (4 pts), nilotinib (2 pts), and regorafenib (2 pts). Therefore, a phase III trial has been initiated to further confirm the clinical activity of crenolanib in patients with PDGFRA D842Vmutation. Methods: This randomized phase III study will enroll adult subjects with histologically or cytologically confirmed advanced or metastatic GIST with a PDGFRA D842V mutation. Prior treatment with TKI is allowed. Approximately 120 subjects will be randomized in a 2:1 ratio to receive either crenolanib 100 mg or matching placebo orally 3 times daily in combination with best supportive care. Randomization will be stratified by prior tyrosine kinase inhibitor exposure and ECOG performance status. The primary objective is PFS; key secondary objectives include OS. A formal interim analysis is planned after approximately 50 subjects have met the primary outcome. This study is already opened in the US, France, Norway, and Poland, and will soon be opened in Germany, Italy, Spain, UK and Asia. NCT02847429; EudraCT: 2015-000287-34 Clinical trial information: NCT02847429.