tbuckley/cabot-search huggingface dataset:
Sequential monitoring of CAMLs in circulation as predictive of progression in lung cancer patients undergoing definitive radiotherapy.
Authors: Daniel Adams, Jianzhong He, Yawei Qiao, Ting Xu, Hui Gao, James M. Reuben, Ritsuko Komaki, Zhongxing X. Liao, Ignacio Ivan Wistuba, Cha-Mei Tang, Steven H. Lin
Journal: Journal of Clinical Oncology (2018)

e21062 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell common in the peripheral blood of patients with solid tumors. Further, CAMLs ≥50µm have been shown as significantly prognostic in all stages of disease, including lung cancer. However, their predictive value in monitoring progression in specific diseased cohorts has not been evaluated. Methods: A 2 year single blind prospective study was undertaken to test the relationship of ≥50µm CAMLs to progression free survival (PFS) based on imaging in lung patients before and after induction of radiation therapy. To achieve a 2-tailed 90% power (α = 0.05) we recruited a test set of 52 patients with pathologically confirmed lung cancer Stage I (n = 7), Stage II (n = 7), Stage III (n = 29) & Stage IV (n = 9), and standard PET/CT scans. Baseline (BL) blood samples were taken prior to start of therapy. 2nd blood samples (T1) were taken during radiotherapy, or after for Stage I patients (~30 days). 3rd blood samples (T2) were taken at the end of radiotherapy (~60 days). Blood was filtered by CellSieve filtration and CAMLs quantified. Analysis by CAML size of < 49 µm or ≥50 µm was used to evaluate PFS hazard ratios (HRs) by censored univariate & multivariate analysis. Results: CAMLs were found in 97% of samples averaging 2.9 CAMLs/7.5mL sample at BL, with CAMLs ≥50 µm having reduced PFS (HR = 2.9, 95%CI1.3-6.2, p = 0.015). At T1, 7 patients had increased CAML size with PFS (HR = 5.0, 95%CI2.3-10.9, p < 0.001). At T2, 7 more patients had increased CAML size further reducing PFS (HR = 7.1, 95%CI3.4-14.8, p < 0.001). In total, ≥50 µm CAMLs at BL was 65% accurate at predicting eventual progression within 24 months while ≥50 µm CAMLs at T2 was 89% accurate at predicting progression. Conclusions: Our data suggests that in lung cancer, ≥50 µm CAMLs at baseline, or appearing during radiation therapy, appears to predict progressive disease. Given the results of this test set, recruitment of a validation study was completed in 2016 with results pending. If validated, additional studies are warranted to determine if CAMLs serve as a clinically relevant blood based marker for affecting survival in lung cancer patients.
PD.2.04 Effect of Nodal Skip Metastasis on Outcomes after Robotic-Assisted Pulmonary Lobectomy for Primary Lung Cancer
Authors: R. Gerard, D. Nguyen, F. Velez-Cubian, M. Amaral, C. Moodie, J. Garrett, J. Fontaine, E. Toloza
Journal: Journal of Thoracic Oncology (2018)
Prognostic influence of waiting time in management of pancreatic ductal adenocarcinoma.
Authors: Rei Suzuki, Tadayuki Takagi, Takuto Hikichi, Hiromasa Ohira
Journal: Journal of Clinical Oncology (2017)

e15726 Background: Since pancreatic ductal adenocarcinoma (PDAC) showed aggressive progression, we hypothesized that waiting time in management might have prognostic influence on patients’ prognosis. Methods: Data on PDAC patients who underwent either chemotherapy or surgical resection in our hospital (2006 – 2016) were collected. Waiting time was classified into two groups as detection-to-diagnosis waiting time (WT1) and diagnosis-to-treatment waiting time (WT2). Median disease free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method and utilized as cut-off points to divide patients into 2 groups (short- and long-survival group). Clinical characteristics including age, sex, tumor size, location of tumor, stage of disease, the levels of serum tumor markers, waiting times, use of adjuvant chemotherapy and resectability were compared between the two survival groups. Results: In total, 149 patients were included. Seventy-two patients who underwent chemotherapy (median OS: 9.7 months) were divided into long survival group (n = 42) and short survival group (n = 30). We did not find significant differences in both WT1 (20.0 days vs. 19.0 days, P = 0.98) and WT2 (17.0 days vs. 18.5 days, P = 0.93), while proportion of patients with locally advanced disease ( P = 0.02) and combination chemotherapy ( P = 0.003) was significantly associated with long survival. Among 79 patients underwent surgical resection, median DFS after pancreatic resection was 16.4 months and OS was 35.0 months. The patients were divided into short DFS (n = 47) versus long DFS (n = 30) and short OS (n = 57) versus long OS (n = 20). We did not find significant differences in both WT1 (short vs. long DFS: 21.0 days vs. 21.0 day, P = 0.65, short vs. long OS: 21.0 days vs. 23.0 days, P = 0.45) and WT2 (short vs. long DFS: 46.0 days vs. 44.5 days, P = 0.45, short vs. long OS: 46.0 vs. 41.0 days, P = 0.36). Both advanced T- and N-stage was significantly associated with poor DFS ( P = 0.049, P = 0.03, respectively) while only advanced T-stage was significantly associated with poor OS ( P = 0.02). Conclusions: Our findings suggested that both detection-to-diagnosis waiting time and diagnosis-to-treatment waiting time might not influence on prognosis of patients with PDAC.
A two-part, open-label, randomized, phase 2/3 study of dinutuximab and irinotecan versus irinotecan for second-line treatment of subjects with relapsed or refractory small cell lung cancer.
Authors: Martin J. Edelman, Oscar Juan, Alejandro Navarro, Gil Golden, Erick Borg, Amanda Vaughn Saunders
Journal: Journal of Clinical Oncology (2018)

TPS8588 Background: Small cell lung cancer (SCLC) is characterized by rapid growth and early dissemination to distant sites. Although highly responsive to initial chemotherapy and radiotherapy, most patients relapse within one year of starting treatment (Tx). The outcome for patients with SCLC who relapse or are refractory (RR) to first-line Tx is poor. Topotecan (T) is the only FDA-approved agent for second-line (SL) Tx of platinum-sensitive patients with SCLC. Irinotecan (I) is listed by the National Comprehensive Cancer Network as an alternative agent for second and subsequent lines of therapy. Dinutuximab (D) is a chimeric monoclonal antibody that binds cell surface glycolipid disialoganglioside GD2 and induces tumor cell lysis through antibody-dependent cell-mediated and complement-dependent cytotoxicity. GD2 is expressed in a variety of neuroectoderm-derived tumors, including SCLCs. The potential for combination D and I to improve upon outcomes currently seen with single-agent SL Tx (I or T) in RR SCLC warrants exploration. Methods: A two-part, multicenter, open-label, randomized study of D and I versus I alone in subjects with RR SCLC is underway (NCT03098030). Inclusion criteria include documented progressive disease during or RR disease after first-line platinum-based Tx and an Eastern Cooperative Oncology Group performance status of 0 or 1. Subjects who are candidates for re-Tx with original platinum-based regimen as SL Tx will be excluded. Part 1 of the study involved intrasubject (n = 12) dose escalation to evaluate the safety and tolerability of D in combination with I. Part 1 results are to be presented (Edelman et al., European Lung Cancer Congress, 11-14 April 2018). Part 2 of the study is currently enrolling and is designed to determine whether combination D and I prolongs overall survival compared with I alone. Subjects will be randomized 2:2:1 to: I, D and I, or T. Randomization will be stratified by duration of response to prior platinum Tx (relapse-free period < 3 or ≥3 months). It is anticipated first data monitoring committee review will occur in April 2018. Clinical trial information: NCT03098030.
Checkpoint inhibitor induced glomerulonephritis.
Authors: Ala Abudayyeh, Maen Abdelrahim, Umut Selamet, Biruh Workeneh, Shana Machado, Amit Lahoti, William F Glass, Amanda Tchakarov, Nizar M. Tannir, Noha Abdel-Wahab, Adi Diab
Journal: Journal of Clinical Oncology (2018)

e15083 Background: Immune checkpoint (ICP) inhibitors, anti-CTLA-4 (Ipilimumab) and anti-PD-1 (Nivolumab and Pembrolizumab) have revolutionized treatment options for many types of cancers. Adverse events associated with ICP inhibitors are mainly due to uninhibited immune system inducing autoimmune diseases. Literature on nephrotoxicity of these novel agents is limited. Acute tubulointerstitial nephritis (ATIN) is the most commonly described kidney injury secondary to ICP inhibitors. In this abstract we are highlighting glomerulonephritis (GN) induced by ICP inhibitors. Methods: We retrospectively reviewed all kidney biopsies performed at MDA (2008-2017). We identified 10 cases with ICP induced nephrotoxicity. Results: We present 10 cases of biopsy proven nephrotoxicity during treatment with ICP inhibitors. Malignancies associated with the cases were as following: Renal cell carcinoma (n = 2), smoldering myeloma (n = 2), melanoma (n = 2), chondroma (n = 1), bladder cancer (n = 1), Lymphoma (n = 1) and lung cancer (n = 1). 5 out of 10 cases showed features of ATIN at kidney biopsy specimens in addition to GN. Several types of GNs were also observed: membranous GN, IgA nephropathy, pauci immune GN. One patient had AA type amyloidosis. ICP inhibitors discontinued in all cases, and treated with steroid. Steroid treatment resulted in either partial or full renal recovery in 4 out of 5 cases. In addition to steroids 3 GN cases were treated with rituximab with partial remission Conclusions: Early recognition of nephrotoxicity and utilization of kidney biopsy to delineate ATIN vs GN is essential in cases with hematuria and proteinuria after CPI treatment. Since steroids in conjunction with Rituximab maybe necessary
Abstract B013: Combined molecular targeting Src and mTOR pathways to impair prostate cancer cell survival
Authors: Yao Dai, Dietmar W. Siemann
Journal: Cancer Research (2018)

Abstract Overexpression of oncoproteins Src and mTOR has been shown to be highly associated with prostate cancer progression and poor clinical outcomes; therefore, small-molecule Src or mTOR inhibitors are being extensively evaluated in clinical trials for advanced prostate cancer. However, clinical data suggest that single treatment with any of these inhibitors only yields limited effects in patients. One possibility is that redundant signaling pathways in tumor cells exist that allow tumor cell uninterrupted upon blockade of purely one pathway. We hypothesize that Src and mTOR are two compensatory pathways that may cooperate to promote prostate cancer survival. Here we studied treatment effects of combining inhibitors targeting Src (saracatinib) and mTOR (rapamycin) on functional behaviors associated with tumor growth in prostate cancer cells with high level expression of both kinases. Combination of both inhibitors was found to inhibit cell proliferation and clonogenic survival more strongly than either single agent, as assessed by MTT and colony formation assay, respectively. Western blot analysis demonstrated that co-targeting Src and mTOR kinases leads to not only inhibition on phosphorylation of these oncoproteins but also greater blockade of multiple downstream pathways such as focal adhesion kinase (FAK), Akt, ERK, S6K, and 4E-BP1. These data indicate that combined application of small-molecule inhibitors targeting two different key pathways may cause significant impairment of phenotypes associated with prostate cancer growth and survival, suggesting that this combinative intervention modality may serve as a potential anticancer strategy that could be further tested in advanced prostate cancer models in vivo. Citation Format: Yao Dai, Dietmar W. Siemann. Combined molecular targeting Src and mTOR pathways to impair prostate cancer cell survival [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B013.
Cytogenetics and survival trends in Hispanic Latino patients with acute lymphoblastic leukemia at Los Angeles County Hospital and Norris Cancer Center.
Authors: Golnaz Vahdani, Ah-Reum Jeong, Zunera Ghaznavi, Wendy Hsiao, Mojtaba Akhtari
Journal: Journal of Clinical Oncology (2016)

e18519 Background: Recent advances in acute lymphoblastic leukemia (ALL) therapy by adapting the pediatric protocol has increased the survival rates for adult patients with ALL. However, it is not clear if there is a difference between ethnic groups as far as outcomes are concerned. We evaluated the cytogenetics and survival trends in ALL in adults treated at Los Angeles County (LAC) Hospital, and Norris Cancer Center (NCC), where the majority of patients are Hispanic Latinos. Methods: We reviewed the baseline characteristics and outcomes of adult patients age greater than 18 newly diagnosed with ALL between 2002-2015 at LAC Hospital and NCC. Demographics, cytogenetics, complete blood count at time of diagnosis, treatment, and 2-year survival rates were analyzed. Results: Total of 261 patients were treated for ALL at LAC Hospital and NCC between years 2002 and 2015. Three different protocols were used at these hospitals: standard BFM (BFM), USC ALL regimen (USC), and hyper-CVAD. 179 patients were included in the analysis for this study in which 63.1% were Hispanics. Median age at time of diagnosis was 37.8 for Hispanics and 40.8 for non-Hispanics (p = 0.26). There was male dominance in both Hispanics (64%) and non Hispanics (69%) (p = 0.49). There were 86% of B-ALL cases and 10% T-ALL cases. Chromosomal abnormalities were observed in 45% of the patients. Common abnormalities included Philadelphia chromosome (25.0%), MLL (4.8%), hypodiploidy (6.6%), and hyperdiploidy (11.3%). Complete remission was achieved in 88% of patients, with 89% and 85% in Hispanics and non-Hispanics respectively (p = 0.46). Overall 2-year survival was 37%, with 25% and 53% in the USC and BFM subgroups respectively. Conclusions: This study provides a better understanding of cytogenetic abnormalities and prognostic factors for adult Hispanic ALL patients. Development of optimal cytogenetic- and population-focused treatment protocols can improve overall outcomes.
Insurance status and patterns of late diagnosis and cancer treatment: A population-based study.
Authors: Grace L. Lu-Yao, Jianming He, Veda N. Giri, Ann Klassen
Journal: Journal of Clinical Oncology (2017)

e16553 Background: This population-based study assesses the relationship between insurance status and patterns of prostate cancer diagnosis and treatment among men under age 65. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 114,871 prostate cancer patients who were diagnosed before 65 between January 2007 and December 2013. Insurance type was classified as uninsured (3.1%), Medicaid (5.1%) and other including private insurance and coverage from the military or Veterans Affairs (91.8%). We used logistic regression model to quantify the relative risk of being diagnosed with metastasis or regional disease, and the relative likelihood of receiving radical prostatectomy or radiotherapy among those with localized cancer adjusted by, age, race, marital status, region, and diagnosis period. Results: Medicaid or uninsured patients are more likely to have late diagnosis (diagnosed with positive lymph node or metastasis) than patients with non-Medicaid insurance (Table 1). Among men diagnosed with localized prostate cancer, Medicaid and uninsured patients are less likely to receive prostatectomy. Medicaid patients are more likely to have radiotherapy than un-insured (see table). Conclusions: Compared with patients with non-Medicaid insurance, Medicaid and uninsured patients are more likely have late diagnosis and less likely to have radical prostatectomy for localized cancer, after accounting for differences in age, race, marital status, region, and diagnosis period. [Table: see text]
Long-term survival following trimodality therapy vs. medical management of malignant pleural mesothelioma.
Authors: Frédéric Larose, Yves Lacasse, Simon Martel, Loïc Lang-Lazdunski
Journal: Journal of Clinical Oncology (2018)

8560 Background: Medical management based on palliative chemotherapy is currently the standard of care in malignant pleural mesothelioma (MPM). Median survival of 12-16 months has been reported with modern chemotherapy regimens. Multimodality therapy incorporating radical surgery, systemic chemotherapy and radiotherapy has recently evolved. The MARS feasibility study suggested that extrapleural pneumonectomy might be detrimental, but recent publications suggested that pleurectomy/decortication (P/D) may lead to better outcomes with overall median survival of 30-35 months in selected patients. Retrospective studies comparing trimodality therapy vs. medical management conducted in centers where surgery is offered are obviously limited by selection bias. Our objective was to compare overall survival in patients offered trimodality therapy at a single institution to the one of patients treated at another institution where the management of MPM is exclusively medical. Methods: Retrospective analysis of two databases: 106 consecutive patients (cohort 1) treated by a single team in London (UK) from 2009 to 2016 and 98 consecutive patients (cohort 2) exclusively treated medically at the Quebec Heart and Lung Institute (Canada) during the same period were included. Results: In cohort 1, all patients had P/D with hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy and systemic chemotherapy. In cohort 2, 51% received palliative care only; 31% were treated with chemotherapy. Median survival was 32 months vs 10 months in cohort 1 and 2, respectively (hazard ratio with age, gender, pathology and TNM staging as covariates: 3.81; 95% CI: 2.66 – 5.45; p < 0.0001). Conclusions: Aggressive therapy of MPM using cancer-directed surgery, systemic chemotherapy and prophylactic radiotherapy may provide a significant survival benefit in selected patients. Trimodality therapy (n = 106) Medical therapy (n = 98) P Age (mean ± SD) 64 ± 2 70 ± 5 < 0.0001 Gender (n, % male) 83 (78%) 73 (74%) 0.16 Pathology (n, %) < 0.0001 Epithelioid 73 (69%) 57 (58%) Sarcomatoid 2 (2%) 15 (15%) Biphasic 31 (29%) 21 (21%) Unknown 0 5 (5%) Staging (n, %) 0.0005 1 -2 22 (21%) 43 (44%) 3 – 4 84 (79%) 55 (56%)
Using patient-reported outcomes measures to tailor care for complex cancer survivors: A feasibility study of HN-STAR.
Authors: Talya Salz, Andrew L. Salner, Nirupa Jaya Raghunathan, Mary S. McCabe, Ellen Dornelas, David Finitsis, Stacie Corcoran, Elizabeth Fortier, Ryan Weber, Amy Tin, Andrew J. Vickers, Kevin C. Oeffinger, Shrujal S. Baxi
Journal: Journal of Clinical Oncology (2018)

e22210 Background: Head and neck cancer (HNC) survivors commonly experience multiple ongoing health issues. We developed a web-based platform (HN-STAR) that uses patient-reported outcome measures (PROMs) to tailor survivorship visits and individualize survivorship care plans (SCPs). We aimed to evaluate the acceptability of HN-STAR for survivors and primary care providers (PCPs). Methods: HNC survivors at two cancer hospitals used HN-STAR. Prior to a clinic visit, survivors completed PROMs. During the visit, providers viewed patient concerns onscreen alongside recommended management options, in order to guide discussion and decision making. Each selected management plan populated an SCP that was given to the survivor and the PCP. Survivors were surveyed regarding acceptability of completing PROMs, the visit, and the SCP. PCPs were surveyed regarding acceptability of the SCP and their confidence managing HNC toxicities. Results: Survivors (N = 43) agreed that completing PROMs was easy (98%), improved clinic discussions (98%), and improved the quality of care (93%). Most reported that completing PROMs made them feel more in control of their care (86%). Almost all agreed that the SCP was easy to follow (98%), the SCP accurately summarized the clinic visit (98%), they would refer to the SCP later (98%), and they trust the SCP (100%). PCPs (N = 30) reported a wide range of comfort managing HNC toxicities (3-70% very uncomfortable). Among 22 PCPs who reviewed the SCP, > 90% agreed that the SCP was trustworthy, was satisfactory, will help them communicate with the survivor and oncologist, and will improve the quality of care. Conclusions: HNC survivors are comfortable reporting concerns electronically and perceive a beneficial impact on their clinic visit. PCPs need help caring for HNC survivors, and tailored SCPs may improve their comfort. A trial is necessary to test the effectiveness of HN-STAR in improving clinical outcomes.
Meta-analysis of prognostic parameters in primary (PAS) and secondary (SAS) breast angiosarcoma.
Authors: Ahmed Elkhanany, Nischala Ammannagari, Kristopher Attwood, Jessica S. Young, John Michael Kane, Kilian Elizabeth Salerno, Kazuaki Takabe, Mateusz Opyrchal
Journal: Journal of Clinical Oncology (2018)

e23525 Background: PAS and SAS are very rare tumors that share similar clinical presentations despite biological difference. Literature provides scarce and often conflicting description of variables affecting prognosis, and debates remain on best treatment options. We present meta-analysis on prognostic variables in these rare entities. Methods: Following PRISMA guidelines, SCOPUS queried for articles titled “Breast” and “Angiosarcoma”. We included articles that 1) identify or provide data for identification of PAS or SAS cohort and 2) reported treatment and follow up. Meta-Analysis was performed using random effects approach. Hazard ratios (HR) and 95% confidence intervals reported. Results: 470 articles identified, 153 before 2000, 211 case reports, 73 no follow up and 7 duplicates. 27 were screened and 21 included in final analysis. 7 articles and Roswell Park data included HRs. PAS cohort included 14 studies and 447 Pts, while SAS cohort had 14 studies with 655 Pts. Median age was 40 vs 69 years and tumor size 6.6 vs 4.7 cm. Most had high grade tumors (39 vs 40%) and received surgery (98 vs 93%). In PAS, adjuvant Chemotherapy and RT were 30% and 18%. For SAS, median time from RT to SAS was 84 months. Median months of follow up were 45 vs 42, DFS 19 vs 27 and OS 32 vs 59. In PAS pooled regression, Age > 60, distant recurrence and high grade predicted worse OS (HR 1.54[1.06-2.22], 2.64[1.69-4.12], 3.57[1.93-6.6]). When compared to lumpectomy, mastectomy predicted worse OS (HR 2.54[1.35-4.79]) that persisted after adjustment for size (HR 2.47(1.29-4.74]). Neither chemotherapy nor radiation incurred significant OS or DFS benefit, in both crude and adjusted pooled models. As per SAS, high grade was sole OS predictor (HR 1.93[1.12-3.32]). Age and tumor size modelled continuously impacted DFS (HR 1.02[1-1.04], 1.09[1.06-1.12]) but not OS. Like PAS, no OS benefit seen with use of chemotherapy or RT. Surgery type did not impact outcome. Conclusions: SAS occurs in later age and has better prognosis than PAS. Grade was found to inversely affect outcomes in both PAS and SAS. Adjuvant chemotherapy and RT did not show added benefit in either PAS or SAS. Our analysis showed conservative excision correlated with better outcomes compared to mastectomy.