tbuckley/cabot-search huggingface dataset:
Whole exome sequencing (WES) of circulating tumor DNA (ctDNA) in patients with neuroendocrine prostate cancer (NEPC) informs tumor heterogeneity.
Authors: Himisha Beltran, Alessandro Romanel, Nicola Casiraghi, Michael Sigouros, Matteo Benelli, Jenny Xiang, Francesca Demichelis
Journal: Journal of Clinical Oncology (2017)

5011 Background: We recently identified mechanisms underlying the clonal evolution of castration-resistant prostate adenocarcinoma (CRPC-Adeno) to a neuroendocrine resistance phenotype (Beltran et al, Nat Med 2016). We aimed to develop a non-invasive approach to identify patients that are developing NEPC. Methods: We performed whole exome sequencing of matched ctDNA, germline DNA, and metastatic biopsies from patients with CRPC-Adeno and NEPC. After applying ad hoc partial duplication filtering, we used FACETS and extended CLONET to calculate the fraction of tumor DNA and clonality of genomic lesions. Results: 64 CRPC patients were prospectively enrolled. The spectrum of alterations captured by WES of ctDNA was consistent with those commonly observed in CRPC validating the feasibility of the approach. The similarity of copy number alterations between tumor tissue and ctDNA was higher in NEPC compared to CRPC-Adeno (p = 0.0001) suggesting less heterogeneity in NEPC. There was enrichment of RB1 and TP53 loss in NEPC ctDNA and ARgains in CRPC-Adeno. The overall fraction of mutations shared by ctDNA and tumoral tissue was ~80%. We compared three different tumor biopsy time-points of patient PM161—CRPC-Adeno (lymph node), CRPC-Adeno (bone), NEPC (liver). Unexpectedly the baseline ctDNA profile (at time of CRPC-Adeno) displayed genomic features most similar to the NEPC liver biopsy. These data suggest that NEPC alterations are detectable in the circulation potentially prior to the development of NEPC clinical features. We compared the ctDNA of another patient PM0 with 6 sites of NEPC metastases obtained 6 days later at autopsy; the relative contribution of tumor alterations in ctDNA was highest for the liver metastasis (similarity 0.59) versus other sites suggesting differential contribution of metastatic sites in the circulation, with implications for the interpretation of single site clinical biopsies. Conclusions: This is the first study to show that WES of ctDNA is feasible in CRPC and can help elucidate intra-patient heterogeneity and identify the spectrum and frequency of NEPC genomic changes. ctDNA may improve the detection of patients transforming towards NEPC.
Molecular analysis of cell-free DNA to identify distinct molecular mutational burden and its effect on first-line chemotherapy in patients with NSCLC from a phase III trial.
Authors: Caicun Zhou, Xuefei Li, Tao Jiang, Shengxiang Ren, ChunXia Su, Chao Zhao, Wenbo Han, Jianfei Wang, Henghui Zhang, Bo Du
Journal: Journal of Clinical Oncology (2017)

e20660 Background: To investigate the predictive significance of molecular mutational burden via genetic analysis of circulating cell-free DNA (cfDNA) in NSCLC patients treated with first-line platinum-based chemotherapy. Methods: Eligible patients were enrolled in a phase III trial (NCT01560195). Blood samples were collected at baseline, every two cycles of chemotherapy and at disease progression. Both cfDNA fragment and genomic DNA were isolated and subjected to enrichment for a 1.15M size panel covering exon regions from 1,086 genes. The captured sequencing data was further processed to identify somatic mutations, including single nucleotide variants (SNV) and short insertions/deletions (indels). Results: Forty-eight patients were enrolled. 17 genes alterations were frequently found from 15 patients (training set). Patients with partial response (PR, n = 3) had significantly lower total mutational burden of these genes than that with stable disease (SD, n = 9) and progression disease (PD, n = 3) (P &lt; 0.05). Based on these results, we further developed a predictive model including 6 genes ( PIK3CA, KIF5B, CD74, XRCC1, MTHFR and KRAS) in the validation set (n = 33). The results showed that the mutational burden of 6-genes panel had the promising predictive yield in patients with PR (n = 7) vs. SD+PD (n = 25) (AUC = 0.962, P = 0.000), PR vs. SD (n = 18) (AUC = 0.960, P = 0.000) and SD vs. PD (n = 8) (AUC = 0.964, P = 0.003). Notably, there was no significant difference in the baseline cfDNA concentration among patients with PR, SD and PD (P &gt; 0.05). Patients with PR experienced a reduction of molecular mutational burden of cfDNA while patients with SD or PD experienced no change or increased molecular mutational burden of cfDNA after two or four cycles of chemotherapy. However, it did not reach the statistically significant difference. Conclusions: The current study demonstrated that molecular characteristics of cfDNA was significantly associated with the effect of first-line platinum-based chemotherapy in patients with NSCLC. The mutational burden of six-genes panel had the promising predictive value in NSCLC patients treated with first-line chemotherapy.
PET/CT assessment of tumor perfusion (TP) in metastatic renal cell cancer (RCC) patients (pts) on sunitinib (S) using 62Cu-ETS.
Authors: Theodore F. Logan, James W. Fletcher, Mark A. Green, Jacob Aaron Eitel, Sandra K. Althouse, Susan M. Perkins, Gary Hutchins
Journal: Journal of Clinical Oncology (2018)

e16567 Background: Assessment of TP using 62Cu-ETS PET/CT has been demonstrated in pts with RCC (Fletcher et al, J Nuc Med 2015; 56:56-62, Logan et al, ASCO 2014; abstr 11110) compared to 15O-water PET/CT. Methods: 14 pts to be treated with (S) were entered upon this IRB approved trial with 62Cu-ETS PET/CT assessed TP at baseline and 3-4 weeks after starting S. TP was reported as standard uptake value (SUV) based on either mean (SUV MEAN) or maximal values (SUV MAX) of all measured lesions within each patient.TP values both baseline (N = 14) and percent change on S from baseline (N = 12) were grouped above or below the median TP values and compared by Log rank p-values for progression and survival. Results: Accrual was from 2/2012 to 8/2013, 12/2 M/F and average age 60.7 years. At final data lock (8/10/2017) 4 pts were alive, the number of S cycles/pt varied from 4-38 and there were 3/9/2 favorable, intermediate and poor prognosis pts by MSKCC and Heng prognostic groups. The best observed response by RECIST was 4 PR, 8 SD, 1 PD and 1 untreated. The PFS was not significantly different for higher or lower TP measured by SUV MEAN or MAX for baseline or on treatment. However OS was nearly significant by baseline TP measured by SUV MAX (11 vs 52 months, lower vs higher, P = 0.09) suggesting higher baseline TP was associated with longer OS. OS was significantly different when the percent change in TP with S was measured by SUV MEAN (non-estimable (NE) vs 18 months P = 0.01) or SUV MAX (NE vs 36 months P = 0.09) suggesting less change in TP was associated with longer OS. Conclusions: These data are hypothesis generating and preliminary but do suggest that TP measurements made before and within the first cycle of S by PET/CT using 62Cu-ETS as tracer may be predictive of outcome in RCC pts treated with S. Clinical trial information: NCT01502228.
Tracking health seeking behavior during an Ebola outbreak via mobile phones and SMS
Authors: Shuo Feng, Karen A. Grépin, Rumi Chunara
Journal: npj Digital Medicine (2018)

The recent Ebola outbreak in West Africa was an exemplar for the need to rapidly measure population-level health-seeking behaviors, in order to understand healthcare utilization during emergency situations. Taking advantage of the high prevalence of mobile phones, we deployed a national SMS-poll and collected data about individual-level health and health-seeking behavior throughout the outbreak from 6694 individuals from March to June 2015 in Liberia. Using propensity score matching to generate balanced subsamples, we compared outcomes in our survey to those from a recent household survey (the 2013 Liberian Demographic Health Survey). We found that the matched subgroups had similar patterns of delivery location in aggregate, and utilizing data on the date of birth, we were able to show that facility-based deliveries were significantly decreased during, compared to after the outbreak (p < 0.05) consistent with findings from retrospective studies using healthcare-based data. Directly assessing behaviors from individuals via SMS also enabled the measurement of public and private sector facility utilization separately, which has been a challenge in other studies in countries including Liberia which rely mainly on government sources of data. In doing so, our data suggest that public facility-based deliveries returned to baseline values after the outbreak. Thus, we demonstrate that with the appropriate methodological approach to account for different population denominators, data sourced via mobile tools such as SMS polling could serve as an important low-cost complement to existing data collection strategies especially in situations where higher-frequency data than can be feasibly obtained through surveys is useful.
Patient reported outcomes in acute inpatient rehabilitation in a comprehensive cancer center.
Authors: Amy Ng, Diane D Liu, Swati Bansal, Janet L. Williams, Jack Brian Fu, Ying Guo, Rajesh R. Yadav, Ki Shin, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

e21579 Patient Reported Outcomes in Acute Inpatient Rehabilitation in a Comprehensive Cancer CenterBackground: Cancer survivors often face severe debility and loss of functional independence after treatment. The objective of this study is to determine the overall perception of usefulness of the acute inpatient rehabilitation unit in a comprehensive cancer center. Methods: Prospective study assessing 200 cancer patients admitted to acute inpatient rehabilitation from September 2014 to July 2015. Demographics, rehabilitation characteristics, Functional Independence Measure (FIM) scores were analyzed. Patients also completed a 22 Likert-type scale anonymous survey at the end of their rehabilitation stay. Patients: Patients admitted to the acute inpatient rehabilitation unit from September 2014 to July 2015. Results: Of 327 patients admitted, 239 patients (73%) were approached and 200 patients (84%) were enrolled with completed surveys. Patients agreed that rehabilitation helped with physical function (193, 97%), regained physical independence (181, 91%) and prepared to deal with self-care tasks (183, 94%). Patients agreed that rehabilitation improved hope (187, 94%), mood (176, 84%), anxiety (180, 90%), and spiritually (182, 94%). Significant FIM score improvement from admission to discharge were observed in all functional domains and FIM efficiency (change in FIM score / Length of Stay) was also significant across all domains. Overall respondents believed their rehabilitation stay was extremely good (128, 64%) or very good (60, 30%). Overwhelmingly, 198 patients (99%) reported they would recommend this rehabilitation program. Conclusions: This prospective anonymous survey found that patients strongly perceived their rehabilitation stay as highly beneficial in multiple aspects. The objective FIM measurements also found an improvement in their functional abilities as a result of intensive rehabilitation provided by an acute inpatient rehabilitation setting. More research is necessary to determine the benefits of inpatient rehabilitation for the growing population of cancer survivors.
Identification of actionable genomic alterations utilizing cfDNA.
Authors: Nora Sylvia Sanchez, Ann Marie Bailey, Chetna Wathoo, Kavitha Balaji, Mehmet E. Demirhan, Dong Yang, Michael Kahle, Ahmed Omar Kaseb, Milind M. Javle, Cathy Eng, Vivek Subbiah, Filip Janku, Victoria M. Raymond, Richard B. Lanman, Kenna Rael Shaw, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2018)

12110 Background: Cell-free DNA (cfDNA) next-generation sequencing has become a more accessible, non-invasive approach for genomic testing. We report alteration identification frequency and clinical actionability in patients with advanced/metastatic cancer. Methods: Enrollment criteria for prospectively consented patients: Active metastatic/local inoperable advanced cancer, considering trial enrollment within next 2 lines of therapy, and either exhausted tissue block, archival tissue > 1 year, available tissue block but progressed on compelling intervening therapy. Patients had cfDNA testing on a CLIA-certified panel (Guardant360) for point mutations, indels, amplifications, fusions. Alterations were assessed and ranked for functional impact, therapeutic implications and patient’s overall actionability profile was determined. Results: 295 patients with ≥ 6 months follow-up were evaluated. Major diseases represented (≥ 10 patients): hepatocellular (59), pancreatic (51), bile duct/cholangio(37), appendiceal(24), breast(20), sarcoma(18), lung(15), and colorectal(12). Majority of patients were male(167), Caucasian(222), median age 54.5 years. ECOG performance status (PS) upon enrollment: 0(72), (185), 2(26), 3(2). 77.9% of patients (230/295) had ≥1 alteration detected; 56%(128/230) had an alteration in gene associated with FDA approved drug for specific biomarker/tumor type. Evaluation of variant functional significance in context of patient’s disease identified 30.5 % (39/128) of patients as high potential for clinical action. Of these, 18%(7/39) were matched to targeted therapy: clinical trial enrollment(4), off label drug use(1), standard of care (SOC)(2). Amongst unmatched patients, 37.5% (12/32) did not return to institution/lost to follow up, 31.4%(11) had poor PS after return of results, while the rest enrolled on another trial(2), continued existing therapy(2) or other(6). Conclusions: cfDNA testing represents a readily accessible method for genomic testing and allows for detection of genomic alterations in most patients with advanced disease. Utility may be higher in patients with interest in genomically selected therapy, adequate PS, and enhanced by earlier testing in treatment course.
Immune status parameters in lung cancer patients with various levels of circulating tumor cells.
Authors: Elena Yurievna Zlatnik, Inna Arnoldovna Novikova, Andrey Vladimirovich Bakhtin, Olesya N. Selyutina, Galina I. Zakora, Yuriy N. Lazutin, Sergey P. Pyltsin, Tamara G. Ayrapetova, Igor A. Leyman, Anna V. Chubaryan, Pavel A. Anistratov, A. S. Shogenov, M. A. Gappoeva, M. Kh. Afaunov
Journal: Journal of Clinical Oncology (2017)

e20018 Background: The purpose of the study was to evaluate parameters of cellular immunity in lung cancer patients with various levels of circulating tumor cells (CTCs) and different tumor histogenesis. Methods: Blood samples of 28 patients (24 men, 4 women, mean age 62±1.3 years) were studied. 18 (64.3%) patients had neuroendocrine tumors (small cell lung cancer, SCLC), and 10 (35.7%) patients had adenocarcinoma (AC). 11 (39.3%) patients were diagnosed with stage III disease and 17 (60.7%) – stage IV. CTCs were detected in the blood before treatment using the CellSearch System (Janssen Diagnostics, LLC) with iron microparticles coated with antibodies to EpCAM, CD45 and cytokeratins 8, 18 and 19; subsets of lymphocytes, including minor ones, were studied on FACSCantoII flow cytometer (BD). Results: CTCs were found in 25 patients (89.3%); their number ranged 1-6888. 15 (83.3%) patients with SCLC had 0-6888 CTCs, with an average of 655.7, median 38.5. All 10 patients with AC had 1-486 CTCs, with an average of 57.2, median 5.0. The number of CTCs in CTC-positive patients with SCLC was, despite high individual variability, significantly higher than in patients with AC (786.9±474 vs. 57.2±47.9, respectively; p &lt; 0.05). Such differences were accompanied by higher levels of Th-lymphocytes with activation/apoptosis markers (CD3+CD4+CD95+): 84.2±2.7 vs. 72.2±3.7%, and cytotoxic CD16bright/56dim NKcells: 91.4±1.8 vs. 83.4±3.7%. Patients with CTC+ AC had higher levels of IFNγ-producing NK-cells, compared to SCLC patients (15.3±3.8 vs. 7.2±1.6%), as well as levels of Th with the early activation marker (CD4+CD38+) (27.8±3.5 vs. 17.4±2.3%). Presence of CTCs in SCLC patients was associated with lower levels of activated lymphocytes of various subsets: T-cells (CD4+CD38+, CD8+CD38+, CD3+CD8+HLA-DR+) and NК-cells (Granzyme B+ and CD335+). Conclusions: Levels of CTCs were significantly higher in patients with SCLC than in those with AC; immune status parameters had a number of differences in CTC+ tumors with various histogenesis. The presence of CTCs in SCLC was accompanied by reduced blood levels of activated T- and NK-cells. The reported study was partially supported by RFBR, research project No. 16-34-00244mol_a
A retrospective review of patient-reported understanding of survivorship care plans.
Authors: Natalie Garces, Myra M Robinson, James Thomas Symanowski, Beth York, Chasse Margot Bailey-Dorton, Wendy G. Brick
Journal: Journal of Clinical Oncology (2016)

e21559 Background: Treatment summaries and survivorship care plans (TS/SCP) have been recommended by national survivorship advocacy organizations for more than 10 years and are a requirement for accreditation for many cancer organizations. Studies measuring effectiveness of TS/SCPs have yielded conflicting results and additional research is needed. This is a retrospective review of data emerging from a quality initiative, evaluating patient-reported understanding of key survivorship topics prior to delivery of the TS/SCP and assessing whether explanation of TS/SCP resulted in improved patient-reported understanding. Methods: Between 6/2015 and 1/2016, cancer patients at our institution who completed active treatment within the previous 6 months were invited to a one-time transition visit with an advanced care provider (ACP) or physician from their treatment team. A survey was administered immediately before and after the visit. Paired responses were analyzed using Generalized McNemar’s tests. Results: A total of 85 subjects (median age 57 years), majority of which were female (95.3%), had breast cancer (90.6%), and had the TS/SCP administered by an ACP (88.2%), completed at least one question both pre- and post-TS/SCP. Because the data were collected as a quality initiative, calculated p-values are descriptive measures only, but the results (Table 1) indicate a positive impact of delivery of TS/SCP on subject-reported understanding. Conclusions: These preliminary positive results for the impact of the TS/SCP on patient-reported understanding suggest that a designed research study formally evaluating impact of delivery of TS/SCP on patient-reported understanding would be valuable. Comparison of subject-reported understanding before and after delivery of TS/SCP. Question Completely Understand Somewhat Understand Don’t Understand p-value* Pre (%) Post (%) Pre (%) Post (%) Pre (%) Post (%) Q1 57.1 92.9 38.1 7.1 4.8 0.0 <0.0001 Q2 40.2 90.2 50.0 9.8 9.8 0.0 <0.0001 Q3 23.8 90.5 40.5 8.3 35.7 1.2 <0.0001 Q4 23.8 97.6 53.6 1.2 22.6 1.2 <0.0001 Q5 30.5 97.6 45.1 2.4 24.4 0.0 <0.0001 Q6 45.8 96.4 47.0 2.4 7.2 1.2 <0.0001 Q7 43.5 96.5 37.7 2.4 18.8 1.2 <0.0001 Q8 43.2 96.3 40.7 3.7 16.1 0.0 <0.0001 *Generalized McNemar’s test.
Clinicohistopathological features and treatment outcomes in testicular lymphomas: A single center experience.
Authors: Ali Murat Sedef, Nazım Emrah Kocer, Ali Ayberk Besen, Huseyin Mertsoylu, Ahmet Sezer, Ahmet Taner Sümbül, Fatih KOse, Ozgur Ozyilkan
Journal: Journal of Clinical Oncology (2018)

e16533 Background: Testicular lymphoma is the most common malignant testicular tumor in men over 60 years.DLBCL is the most common subtype.Analyzing the experience at a center is an important process since testicular lymphoma are rather rare tumors. With this study, we aim to evaluate testicular lymphoma patients who were followed up in our hospital Methods: 10 testicular lymphoma patients followed by Baskent University Department of Medical Oncology between 2007 and 2017 were included. Results: Median age was 54 years old (range 36-73). All patients had testis lymphoma The Right and left side tumor localizations were founded in 60 % (n = 6), 40 % (n = 4), respectively. Diffuse Large B-cell Lymphoma (DLBCL) was % 80 (n = 8) of all patients. 2 patients (20 %) were diagnosed with lymphoblastic lymphoma. 1 patient was stage 1 and There were 3 patients with stage 2, 3 patients with stage 3, and 3 patients with stage 4. Three patients (30 %) received combination of chemotherapy, radiotherapy and intrathecal methotrexate and other patients received chemotherapy and radiotherapy. Complete response was obtained in 8 patients and they had no recurrence. 1 patient died from postoperative respiratory insufficiency and 1 patient died from blastic transformation of disease. Conclusions: In addition to systemic chemotherapy, the treatment of primary testicular lymphoma should incorporate irradiation of the involved-field and contralateral testis plus central nervous system (CNS) prophylaxis with either intrathecal chemotherapy or high dose systemic methotrexate. Given the high rates of relapse at sites protected from the effects of systemic chemotherapy, prophylactic therapy directed at the testes and CNS should be given. Data regarding the treatment of primary testicular lymphoma come from small retrospective studies and nonrandomized trials. For this reason, each case series in the literature is valuable. Most of our patients have had complete response. 2 patients were death. In our study histopathological type frequency and response rates were consistent with the literature
Idiotype network induced by anti-GD2 immunotherapy is associated with long-term survival in patients with neuroblastoma.
Authors: Maya Suzuki, Irene Y. Cheung, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2016)

10570 Background: Human anti-mouse antibody (HAMA) response after mouse anti-GD2 antibody therapy was demonstrated to correlate with overall survival (OS) in patients with neuroblastoma [Cheung et al. JCO 33:755, 2015]. Association of OS with idiotype network (anti-GD2 antibody(Ab3’) or anti-anti-idiotypic antibody (Ab3) was proposed [Cheung et al. Clin Cancer Res 6:2653, 2000]. We test this hypothesis in a large cohort of patients with long term follow up. Methods: 395 children with high risk stage 4 ( > 18 months or MYCN amplification) neuroblastoma received anti-GD2 antibody 3F8 therapy between 1991 and 2010. By 18 months most patients have completed all 3F8 cycles. Upon receiving high dose chemotherapy, their B cell function would have returned to normal range [Small et al. Blood 76:1847, 1990]. Anti-GD2 antibody titers (Ab3’) in sera before 3F8 treatment and at 18 months (± 30 days) after starting 3F8 were analyzed. OS and progression free survival (PFS) from date of sampling were estimated using Kaplan-Meier method. The impact of Ab3’ on survival was examined using log-rank test. Results: Among these patients, the ability to mount HAMA response at any time before relapse was associated with improved survival from first 3F8 treatment. Available serum samples from all patients alive at 18 months from the beginning of 3F8 were studied, including those treated with 3F8 in first remission (n = 72), second remission (n = 16), and those with primary refractory disease (n = 41). Fifty-three patients (41%) had positive Ab3’ response associated with significantly better OS (5-year survival: 83% vs 66%, P < 0.05) with median follow up of 64 months (3-236 months). Similar trend was found in PFS but statistically insignificant (5-year PFS: 68% vs 57%, P = 0.31). Univariate analysis showed that pretreatment variables (gender, age at diagnosis, MYCN amplification, and autologous stem cell transplant) were not predictive of OS. Conclusions: Long term followup demonstrated that idiotype network after 3F8 treatment was associated with improved OS in patients with high risk stage 4 neuroblastoma.