tbuckley/cabot-search huggingface dataset:
Role of the expression of PD-L1 and CD47 on circulating tumor cells (CTCs) in the prediction of outcome in metastatic breast cancer (mBC) patients.
Authors: Sofia Agelaki, Maria A. Papadaki, Panormitis G Tsoulfas, Despoina Aggouraki, Alexia A Monastirioti, Katerina A Merodoulaki, Konstantina Thomopoulou, Chara Papadaki, Dimitrios Mavroudis
Journal: Journal of Clinical Oncology (2019)

e14045 Background: CTCs expressing innate (CD47) and adaptive (PD-L1) immune checkpoints may have enhanced potential to escape immunosurveillance. In the current study, we evaluated the incidence and clinical relevance of CTCs expressing CD47 and/or PD-L1 in patients with mBC. Methods: Blood was obtained from 98 mBC patients before the initiation of first-line therapy. Triple immunofluorescence staining for cytokeratins (CK), CD47 and PD-L1 was performed on peripheral blood mononuclear cells (PBMC) cytospins and 1*10 6 PBMCs per patient were analyzed using the Ariol microscopy system. CD47 and PD-L1 expression levels on CK+ CTCs were normalized using MDA.MB.231 breast cancer cells as controls. Results: CK+ CTCs were detected in 22 out of 98 patients (22.4%) (total CTC No: 43; range: 1-12). High CD47 and PD-L1 expression was identified in 41.9% and 11.6% of CTCs, respectively, whereas in 9.1% of CTCs, high expression was observed for both markers. CTCs with high expression of at least one marker ( CD47 high and/or PD-L1 high ) were identified in 11.2% of patients, albeit with a differential distribution among patients with triple-negative, hormone receptor-positive and HER2-positive primary tumors (27.3%, 12.5% and 0%, respectively, p = 0.040; Chi-square test). CD47 high and/or PD-L1 high CTCs were associated with disease progression (27.8% vs 5.6%, p = 0.005; Chi-square test) and shorter PFS [median: 5.8 (4.1-7.5) vs 13.3 (11.4-15.2) months, p = 0.010; Kaplan-Meier], whereas the detection of PD-L1 high CTCs only was correlated with reduced OS [median: 23.8 (5.8-41.8) vs 35.7 (29.9-41.4) months, p = 0.043]. Multivariate Cox-regression analysis revealed that CD47 high and /or PD-L1 high CTCs predicted for increased risk of relapse [HR: 2.7 (95% CI: 1.3-5.7); p = 0.009], whereas PD-L1 high CTCs were associated with high risk of death [HR: 4.8 (95% CI: 1.4-16.6); p = 0.011]. Conclusions: The immune checkpoints CD47 and PD-L1 are co-expressed in a subset of CTCs in mBC patients. The detection of high CD47 and/or PD-L1 expression on CTCs is associated with triple-negative tumors, disease progression and poor patient outcome and could serve for the refinement of prognosis in mBC. Patients bearing this CTC population may benefit from anti-CD47 and anti-PD-L1 immunotherapy strategies.
Burden of cytokine release syndrome (CRS) and neurologic events (NE) in patients (Pts) with relapsed/refractory non-Hodgkin lymphoma (NHL) receiving lisocabtagene maraleucel (Liso-cel; JCAR017) in TRANSCEND NHL 001.
Authors: Jeremy S. Abramson, Tanya Siddiqi, Jacob Garcia, Christine Dehner, Andy Nguyen, Sophie Snyder, Matthew Gitlin, Karen C. Chung
Journal: Journal of Clinical Oncology (2019)

6637 Background: We assessed incidence, healthcare resource utilization (HCRU), and costs of CRS and NE in pts in TRANSCEND receiving liso-cel, an investigational, anti-CD19 CAR T cell product administered as a defined composition of CD4+/CD8+ CAR T cells. Methods: HCRU within the dates of onset and resolution of CRS and NE was identified from case report forms and trial management guidelines. Costs associated with grade (G) of CRS or NE were applied using public databases and literature on national average costs from a provider perspective. Results: Of 102 pts, 21 (21%) had CRS only (no G≥3), 6 (6%) had NE only (no G≥4), 6 (6%) had nonconcurrent CRS and NE, and 11 (11%) had concurrent CRS and NE (including 1 G4 CRS). Most pts had G≤2 events (31/44, 70%). Of pts with both CRS and NE, 16/17 (94%) had CRS first. Of pts with nonconcurrent events, NE developed a median of 2 days after CRS resolved. Of 10/11 pts with concurrent events and CRS before NE, NE developed a median of 3.5 days after CRS onset. 11/38 pts with CRS (29%) received tocilizumab and 21/44 with CRS and/or NE (48%) received dexamethasone. Overall median costs for G≤2 vs G≥3 CRS and/or NE were $16,479 vs $70,549. Management costs for CRS and/or NE were largely driven by hospitalizations (Table), and ranged $177–24,947 for G≤2 CRS or NE only, $30,749 for G≤2 concurrent CRS and NE, and $43,974–264,149 for G≥3 CRS and/or NE. Conclusions: In TRANSCEND, incidences of G≥3 CRS and NE were low. G≥3 events resulted in a 328% increase in overall median costs vs G≤2 events. Clinical trial information: NCT02631044. [Table: see text]
Clinical and FDG-PET markers of immune checkpoint inhibitor (ICI) response in patients with metastatic Merkel cell carcinoma (mMCC).
Authors: Alison Weppler, Prachi Bhave, Paolo De Ieso, Jeanette Raleigh, Athena Hatzimihalis, Anthony J. Gill, Shiva Balachander, Jason Callahan, Andrew Pattison, Margaret Chua, George Au-Yeung, Grant A. McArthur, Rodney J. Hicks, Richard Tothill, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2019)

9540 Background: mMCC is a rare, highly aggressive neuroendocrine cancer with a poor prognosis. ICIs have favourable efficacy and safety in clinical trials. We outline single centre experience utilising ICIs in mMCC. Methods: Medical records of patients (pts) with mMCC treated with ICIs from Aug 2015 to Dec 2018 at Peter MacCallum Cancer Centre in Australia were retrospectively analysed. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples were performed. Baseline tumor volumes and responses were assessed with FDG-PET scans using the Hicks criteria. Results: 23 pts with mMCC were treated with ICIs. Pt characteristics are summarised in Table. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 7 pts. Objective responses (OR) were observed in 14 pts (61%); 10 (44%) complete metabolic responses (CMR) and 4 (17%) partial metabolic responses (PMR). Median time to response was 9 weeks (range 4 to 11) and 12-month progression-free survival (PFS) rate was 32%. Increased OR were seen in pts aged less than 75 (OR 8/10, 80% vs 46%), no prior history of chemotherapy (OR 10/14, 71% vs 44%), pts with an immune-related adverse event (irAE) (OR 6/6, 100% vs 47%) and in MCPyV negative pts (OR 9/11, 82% vs 50%). Pts with a CMR had lower mean-tumor volume on baseline FDG-PET scan (CMR: 35.7mL, no CMR: 187.8mL, p value 0.05). 10 pts received radiation (RT) during ICI: 4 pts started RT concurrently (OR 75%, CMR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. 6 pts (26%) had a Grade 1-2 irAE. Conclusions: ICIs showed efficacy and safety consistent with trial data. Younger age, negative MCPyV status, no prior chemotherapy, lower baseline FDG-PET tumor volume and irAEs are potentially associated with better responses. [Table: see text]
SAT0545 A COMPARATIVE STUDY OF NAILFOLD CAPILLAROSCOPIC CHANGES IN IDIOPATHIC INTERSTITIAL PNEUMONIA WITH IDIOPATHIC INTERSTITIAL PNEUMONIA AUTOIMMUNE FEATURES
Authors: Kunal Kishore, Vivek Vasdev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Lung involvement especially interstitial lung disease (ILD), can be the first manifestation of an underlying connective tissue disorder (CTD). About 25% of ILD occurs in the context of an "undifferentiated" CTDs, characterized by signs and symptoms that are not specific for any of the described CTD entities, now known as IPAF. Nailfold capillaroscopy (NFC) is an important tool, which helps us in early recognition of microvascular changes in patients with ILD <h3>Objectives</h3> To study the various patterns on Nailfold Capillaroscopy in patients of Interstitial Pneumonia with autoimmune features (IPAF) and compare them with those having Idiopathic Interstitial Pneumonia (IIP). <h3>Methods</h3> The study population consisted of 50 patients each of IIP and IPAF who fulfilled ERS/JRS/ALAT 2011 revised diagnostic criteria for IIP and ERS/ATS classification criteria for Interstitial pneumonia with autoimmune features respectively. The study also included 50 age and sex matched controls, having normal respiratory examination clinically, normal CXR and normal PFTs. All patients underwent NFC at room temperature and the following parameters were recorded: capillary density, presence of megacapillaries, tortousity, avascular areas, disarrangement and neo-angiogenesis. <h3>Results</h3> Our study consisted of 23 (46%) female patients and 27 (54%) male patients for IPAF group and 19 (38%) female patients and 31 (62%) male patients for IIP group. The mean capillary density was significantly reduced in IPAF group and also had presence of abnormal capillary morphologic patterns (microhemorrhages, neoangiogenesis and megacapillaries). <h3>Conclusion</h3> This single centre study found that Nailfold Capillaroscopy (NFC) is an important adjunct to differentiate between patients of IPAF and IIP demonstrating a higher frequencies of abnormalities (microhemorrhages, megacapillaries and reduced capillary density) among patients with IPAF. <h3>References</h3> [1] Harari S, Caminati A. Update on diffuse parenchymal lung disease. Eur Respir Rev2010;19:97-108. [2] Morgenthau AS, Padilla ML. Spectrum of Fibrosing Diffuse Parenchymal Lung Disease. Mount Sinai J Medicine 2009;76:2-23. [3] Singh S, et al. Interstitial Lung disease in India. Results of a prospective Registry. Am J Respir Crit Care Med2017; 195-196. [4] Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet2012; 380: 689–698. [5] Tzelepis GE, Toya SP, Moutsopoulos HM. Occult connective tissue diseases mimicking idiopathic interstitial pneumonias. Eur Respir J2008; 31: 11–20. <h3>Disclosure of Interests</h3> None declared
Evaluation of the multi-kinase inhibitor regorafenib in the Pediatric Preclinical Testing Consortium osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma in vivo models.
Authors: Douglas James Harrison, Jonathan Benjamin Gill, Michael Roth, Wendong Zhang, Beverly Teicher, Stephen W Erickson, Gregory Gatto, Raushan Kurmasheva, Peter Houghton, Malcolm A. Smith, E. Anders Kolb, Richard Greg Gorlick
Journal: Journal of Clinical Oncology (2019)

10038 Background: Regorafenib is a multi-kinase inhibitor, developed by adding a fluorine atom to the phenyl ring of sorafenib. Regorafenib inhibits multiple kinases including BRAF, FGFR1, KIT, PDGFRB, RAF, RET, and VEGFR1-3, many at a higher potency than sorafenib. Prior studies within the Pediatric Preclinical Testing Consortium (PPTC) demonstrated sorafenib exhibited intermediate activity for tumor growth inhibition in more than 50% of the sarcoma models tested at a dose of 60mg/kg by oral gavage daily (5 days/wk for 6 consecutive weeks). The in vivo effects of regorafenib were studied in the PPTC osteosarcoma (OS), rhabdomyosarcoma (Rh) and Ewing (EW) sarcoma xenograft models. Methods: The in vivo anticancer effects of regorafenib were assessed in a panel of 6 osteosarcoma models (OS2, OS9, OS31, OS33, OS36, OS60), two rhabdomyosarcoma models (Rh30, Rh41), and one Ewing sarcoma model (EW5). Regorafenib was administered by oral gavage at a dose of 30 mg/kg/day given daily for 21 consecutive days. Time to event and tumor volume responses were defined and analyzed utilizing standard PPTC statistical methods. Results: Regorafenib induced significant improvements in event-free survival (EFS) compared to control in 100% (9/9) of sarcoma models tested. Most models showed pronounced slowing of tumor growth compared to control during the 21 days of regorafenib treatment, with tumor growth generally approximating control rates soon after completion of regorafenib treatment. Three out of 8 sarcoma models demonstrated EFS T/C values &gt; 2 (1/6 OS, 2/2 Rh, 0/1 EW). Minimum relative tumor volumes ranged from 0.74 to 1.60, with no models meeting criteria for objective response. Conclusions: Regorafenib induced modest inhibition of tumor growth in the PPTC sarcoma models evaluated. The overall pattern of response to the multi-kinase inhibitor regorafenib against the PPTC sarcoma models appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models that is limited to the period of agent administration being the primary treatment effect.
An FDA analysis of the association between adverse events and outcome in patients with urothelial cancer receiving a programmed death protein 1 or programmed death ligand 1 (anti-PD-1/L1) antibody.
Authors: Chana Weinstock, Virginia Ellen Maher, Laura L. Fernandes, Shenghui Tang, Sundeep Agrawal, Michael Holman Brave, Yang-Min Ning, Harpreet Singh, Daniel L. Suzman, James Xu, Kirsten B. Goldberg, Rajeshwari Sridhara, Amna Ibrahim, Marc Robert Theoret, Julia A. Beaver, Richard Pazdur
Journal: Journal of Clinical Oncology (2019)

4549 Background: To assess the relationship between tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti-PD-1/L1 antibodies. Methods: We examined seven trials that led to drug approval and which included 1747 patients with metastatic or locally advanced urothelial cancer treated with an anti-PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy and two enrolled patients who were cisplatin-ineligible. The datasets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the Investigator. Immune-mediated adverse events were defined as AESIs treated with topical or systemic corticosteroids. Results: In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti-PD-1/L1 antibody while a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared to those with no related AESI [hazard ratio (HR) 0.42; 95% CI: 0.37, 0.49]. Fifty-seven percent of responding patients with a related AESI reported a related AESI prior to documentation of response. Conclusions: Patients who responded to treatment with an anti-PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not appear to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.
Prospective trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.
Authors: Mohamed S. Zaghloul, John Paul Christodouleas, Tarek Zaghloul, Andrew Smith, Ahmed Abdalla, Hussein Mustafa Khaled, Hany William, Wei-Ting Hwang, Brian Christopher Baumann
Journal: Journal of Clinical Oncology (2020)

515 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemo or decline it. Adjuvant radiotherapy (RT) is an alternative (or complementary) adjuvant therapy, but is rarely performed, with most of these patients being observed. In a prospective trial, we compared RT vs adjuvant chemo &amp; hypothesized that RT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial at the National Cancer Institute (Cairo) compared adjuvant RT (standard of care in Egypt) vs. chemo+RT after RC for LABC. A 3rd arm, adjuvant chemo, was added later (gemcitabine/cisplatin x 4). Herein, we report results of RT vs adjuvant chemo. Patients ≤70 y/o with ≥1 of the following (pT3b/T4a, grade 3 or pN+) with negative margins after RC were eligible. RT was delivered with 3-D conformal RT to the pelvis (45 Gy in 1.5 Gy BID). Routine follow-up &amp; pelvic CT q 6 months were performed. Post hoc non-inferiority exploratory analysis was performed. Results: 123 were enrolled (78 RT/45 chemo). 51% had urothelial carcinoma; 49% had squamous cell carcinoma. The arms were well-balanced except for gender (p=0.06). Two-year outcomes &amp; overall adjusted hazard ratios (HR) for RT vs chemo were 54% vs 47% for DFS [HR 0.65(95%CI 0.35-1.19, p=0.16]; 92% vs 69% for local-regional recurrence-free survival [HR 0.28(95%CI 0.10-0.82), p=0.02]; 75% vs 79% for distant metastasis-free survival [HR 2.39(95%CI 0.94-6.09), p=0.07]; 61% vs 60% for overall survival [HR 0.94(95%CI 0.52-1.69), p=0.83]. In the urothelial cohort, there were no differences in DFS or OS. Late grade ≥3 GI toxicity was observed in 6 RT patients (8%) &amp; 1 chemo patient (2%). Based on our data, there is a &gt;90% probability that the true difference in 2-year DFS is &lt;10%, the prespecified non-inferiority margin. Conclusions: This prospective study demonstrates that adjuvant RT has superior local control vs adjuvant chemo with no statistically significant differences in DFS or OS. Results suggest that RT can be an option for patients with LABC after RC where an alternative to chemo is desired by the patient or physician. Clinical trial information: NCT01734798.
Prospective study of pain outcomes associated with contralateral prophylactic mastectomy in women with nonhereditary breast cancer.
Authors: Demetria Joy Smith-Graziani, Patricia A. Parker, Susan K. Peterson, Isabelle Bedrosian, Yu Shen, Dalliah MaShon Black, Sarah Marie DeSnyder, Kelly Hunt, Wenli Dong, Abenaa M. Brewster
Journal: Journal of Clinical Oncology (2019)

6587 Background: Women with nonhereditary breast cancer are increasingly undergoing contralateral prophylactic mastectomy (CPM). We examined pain severity and the impact of pain on the lives of women who underwent CPM compared to those who did not. We also examined the associations between age, race/ethnicity, reconstruction and pain outcomes. Methods: Between 2012 and 2015, we recruited women with newly diagnosed nonhereditary breast cancer who were planned for surgery. We assessed pain with the Brief Pain Inventory at initial surgical consultation and at 1, 6, 12, and 18 months after surgery. The repeated measures model was used to assess the association between pain severity or interference and CPM status over different time points adjusting for other covariates. Results: Of 288 women enrolled (mean age 56 years, 58% non-Hispanic White, 17% non-Hispanic Black), 50 underwent CPM, 163 had unilateral mastectomy, and 75 had breast conserving surgery. Mean pain severity was higher at 1 month (2.78 vs 1.9, p = .01) and 6 months (2.79 vs 1.96, p = .03) after surgery in women with CPM versus those without. In the multivariable repeated measures model adjusted for time, age, race/ethnicity and reconstruction status, there was a significant interaction between time and CPM for pain severity (p &lt; .01) but not interference (p = .13). This suggests that CPM patients had higher pain severity in the first 6 months after surgery, but their pain scores decreased by 12 months becoming similar to women without CPM. Black women had higher pain severity (mean difference 1.35, standard error [SE] 0.35; p &lt; .01) and interference (mean difference 0.91, SE 0.32; p &lt; .01) compared to White women with or without CPM. There was no association between age or reconstruction status and pain severity or interference. Conclusions: Pain severity in patients undergoing CPM is highest during the first 6 months after surgery. Women considering CPM should be counseled about this potential outcome. Race/ethnic disparities exist in pain management, pain perceptions and communication of pain. Black women undergoing breast surgery report worse pain outcomes than White women regardless of CPM status.
A survey of healthcare professionals and oncology patients at the McGill University Health Centre reveals enthusiasm towards establishing a post-mortem rapid tissue donation program.
Authors: Matthew Dankner, Julien Senecal, Noah Neubarth, Nicholas Bertos, Morag Park, Badia Issa-Chergui, Jamil Asselah, Peter Siegel, Nathaniel Bouganim
Journal: Journal of Clinical Oncology (2019)

e23005 Background: In the early developmental phase of a post-mortem Rapid Tissue Donation (RTD) program for metastatic cancer patients, we surveyed health care professionals (HCPs) and oncology patients at the McGill University Health Centre (MUHC) to assess their knowledge and attitudes pertaining to RTD from metastatic cancer patients for research purposes. Methods: A 23-item survey was developed and distributed to HCPs at tumour board meetings, and a related 26-item survey was developed and distributed to oncology patients at the MUHC Cedars Cancer Centre. Results: 73 HCPs, including 37 attending physicians, and 102 oncology patients participated in the study. Despite the fact that 88% of HCPs rated their knowledge of RTD as none or limited, 42% indicated that they would feel comfortable discussing RTD with their cancer patients. 67% of HCPs indicated that their current knowledge of RTD would impact their decision to discuss such a program with patients, implying the importance of educating HCPs to facilitate enrolment of patients into an RTD program. 78% of patients indicated that they would not be uncomfortable if their doctor discussed RTD with them, and 61% indicated that they would like for their doctor to discuss RTD with them. HCPs and patients felt that the best time for patients to be approached about consenting to an RTD program is in the transition to palliative care when there are no treatment options remaining. Conclusions: HCPs and patients at the MUHC are generally enthusiastic about adopting an RTD program for metastatic cancer patients. Education of HCPs and patients will be an important determinant of the program’s success.
Overall survival with or without brain metastases from diagnosis of metastatic renal cell carcinoma.
Authors: I. Alex Bowman, Alana Christie, Tri Cao Le, Alisha Bent, James Brugarolas
Journal: Journal of Clinical Oncology (2019)

e16112 Background: Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have historically been associated with a poor prognosis. We have previously reported improved outcomes for RCC patients diagnosed with brain metastases prior to or during 1 st line systemic therapy among patients treated with modern systemic and local therapies. Here we report outcomes in all mRCC patients regardless of the timing of BM diagnosis. Methods: A retrospective database of mRCC patients treated at our institution between 2006 and 2015 was compiled and patients with BM identified. Overall survival (OS) was analyzed by the Kaplan-Meier method from the diagnosis of metastatic RCC, according to BM status and by IMDC risk group. Results: 271 patients with mRCC were identified, including 79 (29.2 %) diagnosed with BM. Clear-cell histology was more common among BM (94.2 v 81.0%, p = 0.01), otherwise patient characteristics were similar. BM were diagnosed prior to systemic therapy (44.3%), or after one or more lines of therapy (one 26.6%, two 13.9%, three 5.1%, four 6.3%, five 3.8%). Among BM patients, 54 (68.4%) received local therapy with stereotactic radiosurgery (SRS) and/or surgical resection, 14 (17.7%) received WBRT alone, and 11 (13.9%) had no CNS-directed treatment. Local therapy consisted of SRS in 43 (54.4%) and surgical resection in 18 (22.8%), with some patients receiving both. Medial OS from metastatic diagnosis for those with BM was not significantly different from those without BM (26.4 v 28.7 mo, p = 0.305). This remained true when analyzed according to IMDC risk factors (see table). Conclusions: OS from the diagnosis of metastatic RCC did not significantly differ with or without BM in a cohort treated with modern systemic and CNS-directed therapies regardless of the timing of BM diagnosis or presence of IMDC risk factors. [Table: see text]