tbuckley/cabot-search huggingface dataset:
Radiation therapy and low dose doxorubicin in thyroid cancer: A phase II study.
Authors: Eric Jeffrey Sherman, Paul Bernard Romesser, Alan Loh Ho, Shrujal S. Baxi, Nadeem Riaz, Sean Matthew McBride, Susie Chan, R. Michael Tuttle, David G. Pfister, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2016)

6100 Background: The role of external beam radiation therapy has remained controversial in the management of differentiated thyroid cancer (DTC). There is an absence of prospective studies in this area despite the importance of locoregional control (LRC) in the neck. We performed a prospective phase II study to better evaluated both LRC and toxicity with intensity modulated radiation therapy (IMRT). Methods: We enrolled 26 patients in a prospective single institution phase II study. The first 7 did not receive chemotherapy; the next 19 received weekly doxorubicin (10 mg/m2) concurrently with IMRT (70Gy). Inclusion criteria included non-anaplastic, non-medullary DTC that is either grossly recurrent after surgery or unresectable with a Karnofsky Performance status > 60%. The primary objective was 2-year LRC rate of 90% in the group receiving concurrent chemotherapy compared to a historical LRC rate of 40%. Swallow evaluation was collected every 6 months for 2 years (not reported). Results: The median age was 63 years (29-83); 65% were male and 50% had distant metastatic disease at time of study entry; histology was papillary (65%), poorly differentiated (27%) and Hurthle Cell (8%). The BRAF V600E mutation status was known in 9 patients, 6 of which were positive. All patients completed IMRT without delay. Patients received a median of 7 (5-9) doses of doxorubicin. Of the 26 patients, 5 have died (none related to treatment) of which 4 had metastases at time of IMRT initiation. Median followup is 420 days (59-864 days). Only one patient has had proven failure in the neck (RT alone group). No proven LR failure has been noted in the chemotherapy group. No patients required permanent PEG use. Conclusions: Concurrent doxorubicin and IMRT appears to be effective in controlling LR disease in patients with recurrent or resectable DTC. Longer term follow up and toxicity data (swallowing evaluations) does need to be collected and analyzed. Clinical trial information: NCT01882816.
Updated outcomes of previously irradiated non-small-cell lung cancer (NSCLC) patients (pts) receiving programmed death 1 (PD-1) inhibitors.
Authors: Maria Bassanelli, Diana Giannarelli, Biagio Ricciuti, Valentina Magri, Fabiana Letizia Cecere, Michela Roberto, Silvana Giacinti, Viola Barucca, Raffaele Cassese, Andrea De Giglio, Simone Scagnoli, Michele Milella, Mario Santarelli, Carmelo Bengala, Enzo Maria Ruggeri, Paolo Marchetti, Francesco Cognetti, Alain Gelibter, Rita Chiari, Anna Ceribelli
Journal: Journal of Clinical Oncology (2018)

e15158 Background: The combination of external-beam radiotherapy (EBRT) and PD-1 inhibitors may enhance antitumor immune responses. The aim of this study was to assess the outcome of NSCLC pts who had undergone EBRT before receiving PD-1 inhibitors. Methods: We conducted an observational, retrospective analysis of 95 consecutive pts with advanced NSCLC who received any EBRT within 10 months (mo) prior to PD-1 inhibitors at seven Italian institutions. Tumor response to treatment was defined according to RECIST version 1.1. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier age 66 years [range 41-82]; male: 63.2%) with advanced NSCLC (adenocarcinoma [adc]: 66.3%; squamous cells [sqc]: 33.7%) were treated with PD-1 inhibitors after EBRT. Median OS was 11.9 mo [95% CI, 6.6-17.2 (adc: 13.0 mo; sqc 10.5 mo). Median progression free survival (PFS) was 6.3 mo [95% CI, 4.6-8.0] (adc: 6.4 mo; sqc: 3.7 mo). ECOG performance status (PS) was significantly associated with OS (PS 0 [38 pts]: 17.9 mo [95% CI,12.3-23.5; p< 0.0001]; PS1 [50 pts]: 6.9 mo [95%CI, 3.2-10.6]; PS2 [7 pts]: 4.4 mo [95% CI, 3.9-4.9]). Median OS in 70 pts who received ≤ 1 previous systemic therapy was 13.0 mo [95% CI, 10.4-15.6] and in 25 pts who received ≥2 prior lines was 7.4 mo [95% CI, 1.8-12.9]. Median OS in 69 pts (72.6%) receiving extracranial EBRT was 12.0 mo [95%CI, 6.6-17.4] and in 26 (27.4%) pts with cranial EBRT was 11.7 mo [95%CI,NE]. Median OS in 68 pts aged < 70 years was 11.9 mo [95% CI,6.5-17.3] and in 27 elderly (≥ 70 years) was 12.0 mo [95% CI, 3.8-20.1]. 1 (1.0%) complete response, 25 (26.3%) partial response, 28 (29.5%) stable disease and 41 (43.2%) progressive disease were observed. Conclusions: This study shows that combining EBRT with PD-1 inhibitors for the treatment of advanced NSCLC leads to improving OS. Such potentially synergistic effects are observed regardless of age, ECOG PS, and type of EBRT received.
Abstract 15051: The Impact of Percutaneous Coronary Intervention in Native Coronary Arteries versus Bypass Grafts on Health Status Outcomes
Authors: Mohammed Qintar, Mohamed Omer, Fengming Tang, Suzanne V Arnold, John A Spertus, Adam C Salisbury
Journal: Circulation (2016)

Background: Patients undergoing percutaneous coronary intervention (PCI) of a bypass graft are less likely to achieve TIMI flow grade 3 post-stenting and have higher complication rates than PCI to a native coronary artery. However, no data exists on the impact of bypass graft vs. native coronary PCI on health status outcomes after PCI. Methods: In a 10-center US PCI registry, patients were assessed for angina frequency (AF), angina-related physical limitation (PL) and quality of life (QoL) at baseline and at 6 and 12 months after PCI using the Seattle Angina Questionnaire (SAQ). Patients with graft PCI were propensity score matched in a 1:2 ratio to patient with native coronary artery PCI, and then health status recovery was compared between groups using repeated measures analysis. Results: Of 3267 PCI patients (71% male, 20% NSTEMI), 207 (6.3%) underwent bypass graft PCI of whom 200 were propensity matched to 396 similar patients with native coronary PCI. While patients with graft PCI had worse health st...
Clonal evolution and drug resistance in the blood of patients with metastatic solid tumors responding to targeted therapies: The CORNUCOPIA study.
Authors: Alberto Bardelli, Filippo Montemurro, Giulia Siravegna, Benedetta Mussolin, Andrea Milani, Francesco Leone, Donatella Marino, Mario Spione, Simona Corso, Filippo G. De Braud, Patrizia Racca, Filippo Pietrantonio, Agostino Ponzetti, Carmen Cristiano, Giuseppe Tonini, Andrea Ardizzoni, Vittorina Zagonel, Giuseppe Curigliano, Salvatore Siena, Silvia Marsoni
Journal: Journal of Clinical Oncology (2016)

TPS11615 Background: When metastatic cancers are challenged with targeted drugs a subset of resistant cells invariably emerges. As a result, targeted therapies are only transiently effective. Strategies to overcome resistance are essential and require a deeper understanding of the evolutive nature of cancer. There is no currently effective way to monitor the emergence of resistant clones in solid tumors patients (PTS). Trials often include exploratory biopsies at progression (PD) to identify the molecular determinants of resistance. However, single-lesion biopsies vastly underrepresent molecular heterogeneity and might fail to detect resistant alleles impacting on further treatment responses. Contrariwise, molecular profiles of circulating tumor DNA (liquid biopsies, LB) allow for a longitudinal tracking of the tumor dynamics and real time monitoring of secondary resistance. How serial LBs and lesion-specific radiographic responses can be integrated to delineate mechanisms of drug resistance and guide further rounds of therapies, is presently unknown. To address this question we designed CORNUCOPIA. Methods: CORNUCOPIA is a translational study in PTS with metastatic colorectal, gastric, and breast cancer, responding to targeted therapy against known actionable oncogenes. PTS are LB-sampled at baseline, longitudinally and at PD using a purposely designed next generation sequencing panel for DNA aberrations in > 200 loci associated with sensitivity and resistance to targeted agents. Concomitantly, the original paraffin diagnostic sample, serial CT scans and on therapy bioptic tissue specimens are collected. Clonal evolution maps for individual patients will be generated by integrating molecular profiles from LB with lesion-specific radiographic responses. A sample size of 250 PTS will allow detecting a representative sample of low prevalence ( < 10%) biomarkers of resistance in each subgroup. Based on these findings, a joined clinical-molecular review board will propose further lines of therapies. Funded by Grants AIRC 5x1000 9970; Italian Ministry of Health (IMH) NET-2011-02352137; FPRC-Candiolo 5x1000 IMH 2011. EudraCT 2016-000491-16. Clinical trial information: 2016-00491-16.
A phase 3 randomized study of pembrolizumab (pembro) plus lenalidomide (len) and low-dose dexamethasone (Rd) versus Rd for newly diagnosed and treatment-naive multiple myeloma (MM): KEYNOTE-185.
Authors: Saad Zafar Usmani, Fredrik Schjesvold, Albert Oriol Rocafiguera, Lionel Karlin, Robert M. Rifkin, Habte Aragaw Yimer, Richard LeBlanc, Naoki Takezako, Robert Donald McCroskey, Kenshi Suzuki, Michele Cavo, Thierry Facon, Sundar Jagannath, Sagar Lonial, Razi Ghori, Mohammed Z.H. Farooqui, Jason Liao, Patricia Marinello, Jesus San-Miguel
Journal: Journal of Clinical Oncology (2018)

8010 Background: KEYNOTE-185 (NCT02579863) evaluated Rd ± pembro in patients (pts) with newly diagnosed, ASCT-ineligible MM. Methods: Pts were randomized 1:1 to pembro (200 mg Q3W) + Rd (len 25 mg [days (d) 1-21] + 40 mg dex [weekly] every 28d) vs Rd until progression (PD), unacceptable toxicity, or withdrawal. Randomization stratified by age ( < 75 vs ≥75 y), and disease stage (ISS I or II vs III). Primary end point was PFS per 2011 IMWG; secondary end points included OS and safety. On July 3, 2017, based on interim data presented to the DMC, the FDA halted KEYNOTE-185. Results: 301/640 pts enrolled (151, pembro-Rd; 150, Rd), with median (range) age: 74 y (53-89) vs 74 y (57-91); 24 (16%) pts in pembro-Rd am vs 10 (7%) pts in Rd arm had high-risk cytogenetics. Median (range) drug exposure was 131.0 d (1-485) in pembro-Rd arm vs 162 d (1-467) in Rd arm; median 6.0 cycles. AEs with ≥5% difference between arms: constipation, pyrexia, rash, vomiting, decreased appetite, pneumonia, oral candidiasis, pruritus, hypo-/hyperthyroidism. No SAEs with ≥5% difference between arms. In pembro + Rd arm, immune-mediated AEs (≥2%): hypothyroidism (7%), hyperthyroidism (6%), colitis (2%), and skin reactions (13%). 19 (13%) pts died in the pembro-Rd arm (6 from PD, 13 from AEs); 5/19 deaths were high risk. 9 (6%) pts died in the Rd arm (1 from PD, 8 from AE); 0/9 were high-risk. 6 (4%) treatment related deaths occurred; 4 (3%) [1 cardiac arrest, 1 pneumonia; 1 myocarditis, 1 cardiac failure]) were related to pembro. Median duration of follow-up was 6.4 mo vs 6.9 mo. Median TTP was not reached in either arm. Median PFS was not reached in either arm; HR, 1.22 (95% CI, 0.67-2.22); P= 0.75. Median OS was not reached in either arm; HR, 2.06 (95% CI, 0.93-4.55); P= 0.97. A retrospective random forest analysis and a subsequent multivariable Cox regression analysis led to no conclusive results due to the small number of death events ( < 10%) at time of analysis. Conclusions: Benefit-risk profile for combination of pembro-Rd is unfavorable for newly diagnosed MM. Evaluation of T-cell subsets and cytokines along with long-term safety and survival follow-up is ongoing. Clinical trial information: NCT02579863.
Feasibility of cancer vaccine therapy using dendritic cells generated from induced pluripotent stem cells expressing carcinoembryonic antigen.
Authors: Toshiyasu Ojima, Junya Kitadani, Hiromitsu Iwamoto, Mikihito Nakamori, Masaki Nakamura, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2017)

e14538 Background: We investigated whether genetically modified human dendritic cells (DCs) derived from induced induced pluripotent stem cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce the CEA specific cytotoxic T lymphcytes (CTLs) against cancer cell lines endogenously expressing CEA in vitro model using healthy volunteers. Furthermore, we established in vivo tumor model using the CEA transgenic mice (TGM) as a preclinical experiment. Methods: Human model; we differentiated hiPSDCs from iPSCs of three healthy donors and transduced the CEA cDNA into DCs. Mouse model; we differentiated miPSDCs in CEA TGM and transduced the CEA cDNA into DCs. Results: Human model; the surface marker expression, cytokine secretion, and migratory capacity of hiPSDCs were equivalent to human monocytes derived-DCs (hMoDCs). After 3 cycles of stimulation to autologous peripheral blood mononuclear cells (PBMCs) by genetically modified hiPSDCs, the cytotoxic assay was performed using a 51Cr release assay. The CTLs induced by hiPSDCs-CEA exhibited CEA specific cytotoxic activity against the target cells expressing. Mouse model; in the CEA transgenic mice model, the CTLs generated in mice immunized with miPSDCs-CEA showed CEA specific cytotoxic activity against MC38-CEA. Moreover, in the subcutaneous tumor model, vaccination with miPSDCs-CEA achieved significantly high growth inhibitory effect for the MC38-CEA. No adverse events were observed. Conclusions: This vaccine therapy using genetically modified iPSDCs is promising for clinical application for patients with gastrointestinal cancer patients.
More effective systemic therapies are needed for chondrosarcoma: A National Cancer Data Base (NCDB) analysis.
Authors: Karen M Xu, Jeffrey M. Switchenko, Sibo Tian, Chase Edward Escott, Neil T Pfister, Theresa Wicklin Gillespie, Walter John Curran, Mohammad Khurram Khan
Journal: Journal of Clinical Oncology (2018)

e23508 Background: Chondrosarcoma is a rare malignant tumor of bones. Reports of its outcomes and prognostic factors are scarce. Methods: The NCDB was queried for patients diagnosed 2004-2013 with chondrosarcoma. Descriptive statistics were generated for categorical variables. Means and standard deviations were generated for numeric variables. Distributions for overall survival (OS) were estimated using Kaplan-Meier method. Univariate Cox proportional hazards models for OS were applied. Results: 865 patients were included, with 548 males (63.4%) and 317 females (36.6%). Median age at diagnosis was 56 (range: 18-90). 702 were Caucasian (81.2%) and 120 were African American (13.9%). 720 (83.5%) received surgery. 159 (19.4%) received chemotherapy, among whom 103 (64.8%) also underwent surgery. Tumor sites included lower extremity (52.1%), upper extremity (12%), pelvis (14.5%) and thorax (8.1%). Private insurance vs. Medicaid/Medicare (HR 0.52, p < 0.001), grade 1 tumor vs. unknown differentiation (HR 0.43, p < 0.001), and receipt of surgery (HR 0.20, p < 0.001) were associated with better OS. Charlson-Deyo score 1+ vs. 0 (HR 1.5, p = 0.008), grade 3 vs. unknown differentiation (HR 1.98, p < 0.001), larger than 15 cm tumor size vs. less than 5 cm (HR 3.13, p < 0.001), older than 60 vs. less than 50 (HR 1.66, p < 0.001), stage IV vs. stage I (HR 4.11, p < 0.001) and receipt of chemotherapy (HR 2.25, p < 0.001) were associated with worse OS. Of patients who received chemotherapy, 19.6% were stage III and 71.7% were stage IV. The majority were younger than 60 (73.6%), with Charlson-Deyo score of 0 (86.8%) and privately insured (66%). Chemotherapy did not appear to have OS benefit. 5-year OS for stage III patients was 60.6% with chemotherapy and 58.6% without chemotherapy (p = 0.709). 5-year OS for stage IV patients was 28.2% with chemotherapy and 31.2% without chemotherapy (p = 0.366). 2 patients received immunotherapy. Conclusions: Surgery remains the mainstay treatment for chondrosarcoma, associated with better OS. In contrast, chemotherapy appears to be of limited benefit. More effective systemic therapies are needed. In addition, potential worse survival in un-insured patients is concerning.
Ambulatory cancer care electronic symptom self-reporting (ACCESS) for surgical patients: A randomized controlled trial.
Authors: Cara Stabile, Larissa K. F. Temple, Brett A Simon, Peter D. Stetson, Daniel Stein, Andrew J. Vickers, Andrea Pusic
Journal: Journal of Clinical Oncology (2018)

TPS6622 Background: An increasing proportion of cancer surgeries are ambulatory (≤ 1 day in hospital) procedures. Providing patients and their caregivers with ongoing, real-time support after discharge is imperative to delivering high-quality postoperative care in this new health care environment. Despite abundant evidence that patient self-reporting of symptoms improves quality of care, Reference: 1. Kotronoulas G, Kearney N, Maguire R, et al. What is the value of the routine use of patient-reported outcome measures toward improvement of patient outcomes, processes of care, and health service outcomes in cancer care? A systematic review of controlled trials. Journal of Clinical Oncology. 2014;32(14):1480-1501. the most effective way to monitor and manage such data remains unknown. Methods: This is a two-armed, prospective randomized controlled trial evaluating two approaches to the management of patient-reported data: (1) Team Monitoring—symptom monitoring by the clinical team, with nursing outreach if symptoms exceed normal limits; and (2) Enhanced Feedback—real-time feedback to patients about expected symptom severity, with patient-activated care as needed. It is hypothesized that Enhanced Feedback about expected symptom severity would be more effective than Team Monitoring in improving patient-centered outcomes and the patient/caregiver experience. Breast, prostate, gynecologic, and head and neck cancer patients undergoing ambulatory cancer surgery (n = 1,700) will complete an electronic survey about their symptoms for up to 30 days after surgery. Information provided to patients in the Enhanced Feedback group is procedure-specific and based on continuously updated survey data from previous patients. Qualitative interviews will also be performed. Accrual began in August 2017. Primary outcomes will evaluate unplanned emergency department visits within 30 days. Secondary outcomes will assess the patient/caregiver experience (i.e., patient engagement, patient anxiety, and caregiver burden). Findings will be relevant in designing future coordinated care models targeting improved health care quality and patient experience. Clinical trial information: NCT03178045.
Safety and usefulness of patient-centered shared survivorship care after chemotherapy for testicular cancer.
Authors: Hink Boer, Sjoukje Lubberts, Sophie Bunskoek, Janine Nuver, Joop D. Lefrandt, Gerrie Steursma, Wim J. Sluiter, Sabine Siesling, Annette J. Berendsen, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2017)

4561 Background: Testicular cancer (TC) survivors are at risk to develop early cardiovascular morbidity. Close collaboration between oncologists and primary care physicians (PCPs) is mandatory for optimal cardiovascular risk management. We designed a simple shared survivorship care program in which TC patients regularly visit their PCP instead of their oncologist. The primary aim of this study was to test safety and feasibility of shared-care follow-up after chemotherapy for metastatic TC. Methods: TC patients with complete remission after chemotherapy and age ≥18 years were eligible. Participants received a personalized survivorship care plan with scheduled visits to the oncologist and PCP, which was available both on paper and as a mobile application. During PCP visits, signals indicating cancer recurrence, cardiovascular risk and psychosocial issues were assessed. Safety boundaries were defined for the occurrence of failed response to signals indicating cancer recurrence. Patient data were monitored real-time to check if the shared-care follow-up was carried out within these boundaries. Secondary outcomes were satisfaction among TC patients and PCPs, measured with an evaluation questionnaire, and anxiety levels, measured with the Hospital Anxiety and Depression Scale. Results: 64% of eligible TC patients and 99% of the approached PCPs were willing to participate; 162 patients were enrolled in the shared-care program and 241 primary care visits took place. No failures occurred in the detection of relapsed TC. Therefore, the safety boundary was crossed, indicating that shared-care follow-up is a safe alternative to hospital-only follow-up. Four primary care visits were deemed as failed visits because of logistic issues.Anxiety levels did not increase during shared-care follow-up (3.6 vs 3.3 (p = 0.38). Patients were satisfied with the knowledge of PCPs and appreciated this regular contact. 78% of the PCPs would like to extend their role in shared-care follow-up. Conclusions: This easy to use shared survivorship care program is safe and feasible in the follow-up of TC patients. Communication within this patient-centered follow-up program may be further supported with e-health tools. Clinical trial information: NCT01783145.
SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to Restrict Colitis and Colon Cancer
Authors: Ankit Malik, Deepika Sharma, R.K. Subbarao Malireddi, Clifford S. Guy, Ti-Cheng Chang, Scott R. Olsen, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
Journal: Immunity (2018)
Occurrence of PDL1/2 copy number gains detected by FISH in adeno and squamous cell carcinomas of the lung and association with PDL1 overexpression in adenocarcinomas.
Authors: Hans-Ulrich Schildhaus, Pascal Richardt, Lea Wilsberg, Katja Schmitz
Journal: Journal of Clinical Oncology (2016)

3031 Background: PDL1 expression measured by immunohistochemistry (IHC) is used as predictive biomarker for immune checkpoint inhibitors and is becoming clinical routine at least in pulmonary adenocarcinomas. We aimed to evaluate the presence of PDL1/2 gene cluster copy number gains in NSCLC by FISH and correlate these data to PDL1 IHC levels in adenocarcinomas (AC). Methods: We investigated 107 AC and 78 squamous cell carcinomas (SQCLC) for PDL1/2 FISH. Furthermore, AC were analyzed by IHC with the clone 28-8 stained on a DAKO platform. Cut-off level was 1% ( ≥ 5% highly positive). FISH was carried out with the ZytoLight SPEC CD274,PDCD1LG2/CEN 9 Dual Color Probe. The FISH evaluation criteria included CD274,PDCD1LG2/CEN 9 ratio as well as average gene copy numbers, proportions of tumor cells with ≥ 4 PDL1/2 and ≥ 5 PDL1/2 signals as well as gene clusters. Results: 28/178 (16%) of NSCLC were FISH positive, 39% (11/28) thereof fulfilled the criteria for high level PDL1/2 amplification (PDL1,2/CEN9 ratio ≥ 2.0 or average gene copy number per cell ≥ 6.0 or ≥ 10% of tumor cells containing ≥ 15 gene signals), 4% (1/28) for intermediate level copy number gain ( ≥ 50% of cells containing ≥ 5 gene signals) and 57% (16/28) for low level copy number gain ( ≥ 40% of tumor cells with ≥ 4 PDL1/2 signals). Overall PDL1/2 amplifications occur at almost equal frequencies in AC and SQCLC, 18% and 13% respectively, but high level amplifications are more often seen in SQCLC (7/78 vs. 4/107 in AC). FISH results were independent of KRAS, EGFR, ALK, ROS1 or MET status. 35/107 AC (33%) were PDL1 IHC positive (28 high, 7 low positivity). The correlation between IHC and FISH was statistically significant (Chi square: p < 0.001). 15/18 of FISH positive AC were IHC positive (vs. 3/66 IHC negatives). 75% (3/4) high level amplified AC were highly IHC positive. Conclusions: PDL1/2 gene copy number gains occur in AC and SQCLC, but high level amplifications are more frequent in SQCLC. PDL1/2 gains seem to be associated with PDL1 overexpression in a subset of AC. PDL1/2 FISH could contribute to our understanding of PDL1 expression and could therefore be a valuable adjunct biomarker in upcoming trials with PD1/PDL1 inhibitors.