tbuckley/cabot-search huggingface dataset:
Opportunities for interventions to reduce the financial toxicity of treatment for childhood cancer.
Authors: Rebecca Lobb, Rosie Cunningham
Journal: Journal of Clinical Oncology (2018)

e18797 Background: Cancer-related financial toxicity is an unaddressed side-effect of childhood cancer, with consequences for household financial health and quality of care, including increased risk for relapse, and decreased survival rates. This project identified opportunities along the cancer journey when interventions could reduce risk of cancer-related financial toxicity for families of children with cancer. Methods: Seventeen caregivers of children diagnosed with cancer attended focus groups (n = 3) to discuss how they navigated the financial side of cancer. We used the concept of “social navigation” to guide thematic analysis of transcripts. Social navigation is relevant to understanding the financial side of cancer because it acknowledges and examines how people act when unanticipated disruptions (e.g. health, financial) create instability in their lives. Results: Five major themes and twenty-three sub-themes emerged: 1. disruption experienced by family (emotional shock, hospital stay, travel for outpatient care, unpredictability of treatment); 2. caregiver’s management of disruption (time-off work, restructured routines); 3. financial consequences (reduced income, direct and indirect medical expenses, debt accumulation); 4. caregiver’s management of financial consequences (increased work hours, navigated insurance coverage, requested financial assistance, cut-back expenses, used financial reserves, “fight for everything”); 5. interventions (financial assistance, proactive support for insurance and resource navigation, credit advocacy, housing and meals for family during inpatient stays, parking support, online workshops, streamlined application process for financial assistance, expanded eligibility criteria for financial assistance, and research on treatment that can be administered at home). Conclusions: Focus groups identified opportunities for interventions to reduce cancer-related financial toxicity for families of children with cancer throughout the cancer journey. With collective actions from the ecosystem of for-profit, non-profit, and public sectors these opportunities can become programs that may benefit cancer patients, families, and society.
TCT-702 Magnesium-metallic bioabsorbable scaffold (Magmaris) long-term results. Analysis from pooled multicentre italian experience.
Authors: Stefano Galli, Sarah Troiano, Altin Palloshi, None Claudio Rapetto, Massimo Leoncini, Paolo Mario Ravagnani, None Piero Montorsi
Journal: Journal of the American College of Cardiology (2018)
Prognostic significance of perineural invasion in HPV (+) squamous cell oral and oropharyngeal carcinoma.
Authors: Justin Johnson, Yijin Wert, James Malone, Irina Veytsman
Journal: Journal of Clinical Oncology (2016)

e17526 Background: Squamous cell carcinoma of the head and neck is becoming more prevalent worldwide. Incidence is linked to increase in prevalence of HPV infection. Although, HPV has been linked to better prognosis, little is known of the rate and prognostic significant perineural invasion in HPV positive cancers Methods: A retrospective study of 116 patients was undertaken to evaluate occurrence and prognostic significance of perinerual invasion in relation to survival. The annual rate of perineural invasion was calculated as percent. The patient characteristics including gender, smoking status, cancer stage and lymphovascular invasion was compared between the patients with positive perineural invasion and negative perineural invasion in HPV+ cancers. A multiple logistic regression model was applied to detect any association between the patient characteristics and the positive perineural invasion. Results: Table 1 illustrates the results of this retrospective analysis. Twenty-three patients were positive for perineural invasion (19.83%) and ninety-three were negative or unknown (80%) per pathology reports. There was no significant difference in use of alcohol or tobacco between the two groups (56.53% vs 51.61%; 60.86% vs. 53.77% respectively). Incidence of lymphovascular invasion was higher in perineural invasion group (30.43% vs 16.13%) but was statistically not significant ( p = 0.1399). Mortality had a higher incidence in the HPV positive patients ( 21.74% vs. 9.69 %), but statistically insignificant (p = 0.1488). Conclusions: There was noticeable increase mortality in HPV+ cancers with perineural invasion but not statistically significant due to sample size. Further investigation is needed with more HPV positive patients to increase strength of analysis
TCT-278 Incidence, Characteristics and Management of Residual Peri-Device Leak after Percutaneous Left Atrial Appendage Occlusion
Authors: Mohamad Adnan Alkhouli, Zakeih Chaker, Muhammed Al Hajji, Fahad Alqahtani, Bryan Raybuck
Journal: Journal of the American College of Cardiology (2018)
SPEAR-bladder (study informing treatment pathway decision in bladder cancer): First- through third-line time to treatment failure in the US.
Authors: Gurjyot K. Doshi, Abhijeet Bhanegaonkar, Murtuza Bharmal, Hemant Phatak, Marley Boyd, Kathleen M Aguilar, Mairead Kearney
Journal: Journal of Clinical Oncology (2018)

4544 Background: Immune-oncology (IO) regimens have improved the clinical outlook for patients with locally advanced or metastatic urothelial carcinoma (mUC). This analysis aimed to assess time to treatment failure (TTF) among patients with mUC treated with systemic chemotherapy and IO regimens in the US community oncology setting. Methods: This is a retrospective study of patients with mUC receiving treatment from January 2015 to April 2017, with follow-up through June 2017 using the US Oncology Network electronic health records database. TTF was defined as the interval between treatment initiation in the first (1L), second (2L), or third line (3L) and discontinuation for any reason. TTF was compared between the chemo and IO cohorts using Kaplan-Meier and Cox proportional hazard modeling. Results: 523 patients initiated 1L treatment (median age, 72 years; 76.5% male), 241 2L (median age, 69 years; 75.9% male) and 50 3L (median age, 67 years; 74.0% male). Of patients receiving 1L platinum-based combinations (n = 497, 95%), 27.7% were treated with carboplatin/gemcitabine, followed by 26.0% with cisplatin/gemcitabine, and 7.3% with carboplatin/paclitaxel. IO regimens were received by 56.8% of patients in 2L and 68.0% in 3L. In the 2L setting, patients treated with IO regimens had a significantly longer TTF than those treated with systemic chemotherapies (P < 0.0001) (Table). Conclusions: These findings provide important insights into patterns of care and outcomes among patients with mUC in the community oncology setting. Comparisons between the chemo and IO cohorts were limited due to utilization of heterogenous chemotherapy regimens and small sample sizes. Patients in the IO cohort stayed on therapy for longer periods than chemotherapy-treated patients. Future real-world research may determine generalizability of the results seen in this study. TTF Line of Therapy Chemo, median, weeks IO, median, weeks Hazard Ratio (95% CI) P-Value 1L n = 497 n = 26 0.570 (0.346-0.939) 0.0274 11.3 15.1 2L n = 104 n = 137 0.552 (0.406-0.749) < 0.0001 9.1 12.1 3L n = 16 n = 34 0.461 (0.213-0.997) 0.0490 9.9 22.9
Gut microbiome alterations in breast cancer survivors with cancer-related fatigue.
Authors: Alexandre Chan, Maung Shwe, Samantha An Qi Koh, Congju Zhu, Yi Shan Chan, Si Hui Tan, Xiao Jun Ang, Wei Quan Lee, Wei Wei Thwe Khine, Yuan Kun Lee, Quek Choon Lau
Journal: Journal of Clinical Oncology (2018)

e22178 Background: Recent studies have shown that alterations in the gut microbiome are associated with chronic fatigue syndrome. However, the correlation between composition of the gut microbiome and cancer-related fatigue (CRF) has not been well established. In this study, we evaluated the changes in gut microbiome profiles and fatigue severity in survivors of breast cancer. Methods: Fatigue severity of early-stage breast cancer survivors was assessed using the validated multidimensional fatigue symptom inventory – short form (MFSI-SF). Stool samples were collected, with DNA purified and library prepared using the Next ® Ultra DNA Library Preparation Kit. 16s rRNA sequencing was performed using the Illumina HiSeq sequencer to reveal the gut microbiome profile of the survivors. Results: Thirty early-stage breast cancer survivors were recruited (mean age±SD: 52.7±8.7 years), with 56.7% regularly consumed diets that consist of probiotics. A 1.7-fold and 3.2-fold increase of Bacteroides and Ruminococcus species were found in survivors with severe fatigue, compared to patients without fatigue. Conversely, significantly lower abundance of Streptococcus and Prevotella species were found in survivors with severe fatigue compared to those without fatigue (4-fold and 5.3-fold less abundance, respectively). Relative abundance of Butyricimonas, Prevotella, Streptococcus, Bacillus, Lactobacillus and Megasphaera species were found to correlate with neurocognitive ability of survivors. Conclusions: Our results showed the compositions of gut microbiome are associated with the severity of fatigue experienced by survivors of breast cancer. Further studies with larger cohort may provide greater insights for future development of novel biomarkers and dietary interventions that would play a crucial role in the detection and alleviation of CRF.
Superior survival in adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated in pediatric vs. adult centers is only partially attributable to inadequate adoption of pediatric protocols: A population-based IMPACT Cohort study.
Authors: Sumit Gupta, Jason D Pole, Cindy Lau, Chenthila Nagamuthu, Rinku Sutradhar, Nancy N. Baxter, Paul C. Nathan
Journal: Journal of Clinical Oncology (2018)

6564 Background: Retrospective studies have shown that AYA with ALL have superior survival when treated in pediatric vs. adult centers (locus of care; LOC). Clinical studies showing superior survival using pediatric treatment protocols have led to their adoption by some adult centers. Whether this has narrowed LOC disparities in real world settings is unknown. Methods: The IMPACT Cohort is an Ontario population-based cohort that has captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15-21 year olds diagnosed with ALL between 1992-2011. Cancer outcomes were determined by both chart abstraction and linkage to provincial administrative health care databases. We examined predictors of outcome, including disease biology, treatment exposures, LOC, and time period (1992-98 vs.1999-2005 vs. 2006-11). Results: Of 271 patients, 152 (56%) received therapy at an adult center. 5-year event-free survival (EFS ± standard error) among AYA treated at a pediatric vs adult center was 72%±4% vs. 56%±4% (p = 0.03); 5-year overall survival (OS) was 82%±4% vs. 64%±4% (p < 0.001). No significant interaction was noted between pediatric vs. adult LOC and time period. Neither induction deaths nor dose reductions varied by LOC. In the latest time period, 39/59 (66%) AYA treated at an adult center received a pediatric protocol, as compared to 4/40 (10%) in the middle period. Late period AYA treated at adult centers with pediatric protocols experienced superior outcomes compared to those of contemporaneous AYA treated on an adult protocols, but inferior to those of AYA treated at pediatric centers (EFS 72%±5% vs. 60%±9% vs. 82%±3%; p = 0.02; OS 77%±7% vs. 65%±11% vs. 91%±4%; p = 0.004). Conclusions: Survival disparities between AYA treated in pediatric vs. ALL centers have persisted over time, partially attributable to inadequate adoption of pediatric protocols by adult centers. Although use of pediatric protocols has improved survival, residual survival disparities remain and do not seem to be due to excessive toxicity or dose reductions.
Outcomes of EGFR-mutant lung adenocarcinomas (AC) that transform to small cell lung cancer (SCLC).
Authors: Nicolas Marcoux, Scott N. Gettinger, Grainne M. O'Kane, Kathryn Cecilia Arbour, Joel W. Neal, Hatim Husain, Tracey L. Evans, Julie R. Brahmer, Alona Muzikansky, Philip Bonomi, Salvatore A. Del Prete, Anna Wurtz, Anna F. Farago, Dora Dias-Santagata, Mari Mino-Kenudson, Helena Alexandra Yu, Heather A. Wakelee, Frances A. Shepherd, Zofia Piotrowska, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2018)

8573 Background: 5-10% of EGFR-mutant ACs undergo SCLC/neuroendocrine transformation (SCLC-T) but the clinical course of such pts is poorly characterized. Methods: We identified 50 pts with EGFR-mutant SCLC-T seen at our institutions. Medical records were reviewed retrospectively after IRB approval. Demographics, disease features and outcomes were analyzed. Results: Among 50 pts (27F/23M), median (med) age was 55. At diagnosis, 44 had AC histology; 5 had de novo SCLC or mixed AC/SCLC. All but the 5 cases with baseline SCLC received ≥1 EGFR TKI prior to SCLC-T; 93% were on a TKI at the time of SCLC-T (24 erlotinib/gefitinib, 5 afatinib, 9 osimertinib, 4 other). Med time from original diagnosis to SCLC-T was 17.8 mo (95% CI 13.0-25.9). 44/50 cases had tissue genotyping at first evidence of SCLC (albeit with varied assays); all maintained their founder EGFR mutation; among 16 with prior T790M-positivity, 13 lost T790M at SCLC-T, 3 were T790M-pos at SCLC-T. Other recurrent mutations included TP53 (24/33, 73%), Rb1 (13/21, 62%) and PIK3CA (10/36, 28%). The most common therapy given upon SCLC-T was platinum-etoposide (n = 35); this regimen had a clinical response rate (cRR) of 51% and med PFS of 2.8 mo (95% CI 2.1-4.8). 20 pts received taxane-based therapy at some point after SCLC-T: cRR = 50%, med PFS = 3.1 mo (95% CI 0.9-3.2). None of 15 pts receiving immunotherapy (including 6 ipi/nivo) for SCLC-T responded. Med OS from stage IV cancer diagnosis was 36.8 mo (95% CI 25.0-41.5) and med OS from time of SCLC diagnosis was 10.9 mo (95% CI 7.3-13.8). Conclusions: EGFR-mutant AC with SCLC-T is a rare but recurrent phenomenon, often characterized by Rb1, TP53 and PIK3CA mutations. The SCLC-T subclone is typically distinct from the T790M subclone in pts with serial biopsies. The med OS of 10.9 mo after SCLC-T is similar to newly diagnosed, EGFR wild-type advanced SCLC. Responses to platinum-etoposide and taxanes were frequent but transient, while no responses were seen with immunotherapy. Interestingly, med OS from initial diagnosis was similar to that of pts that never transform to SCLC at 36.8 mo. Further investigation is needed to better elucidate optimal strategies for this group.
Efficacy of CD19-targeted chimeric antigen receptor T cells in the treatment of relapsed extramedullary B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL).
Authors: Yongxian Hu, Zhao Wu, Jian Yu, Jiasheng Wang, Guoqing Wei, Wenjun Wu, Yi Luo, Jimin Shi, Lei Xiao, He Huang
Journal: Journal of Clinical Oncology (2017)

e14549 Background: Chimeric antigen receptor T cells directed at CD19 (CART19) have shown promising results in the treatment of refractory/relapsed acute lymphoblastic leukemia and chronic lymphocytic leukemia. Evidence of efficacy on mass lesions such as extramedullary ALL and non-Hodgkin’s lymphoma is still emerging. Methods: Patient-derived T cells were transfected ex vivo with lentiviral vector encoding anti-CD19 scFv, human 4-1BB, and CD3ζ signaling domains. 2 patients with relapsed extramedullary ALL and 2 patients with relapsed DLBCL were enrolled (median age 25.5, range 17~35). Lymphodepletion regimens were fludarabine 50mg/m 2 infused over 3 days, and cyclophosphamide 750mg/m 2 infused over 3 days in DLBCL patients or over 2 days in ALL patients. CART19 were infused one time or fractionated over 3 days with dose from 1×10 6 /kg to 1×10 7 /kg. Results: The 2 ALL patients received prior allogenic HSCT; one relapsed with isolated testicular ALL, the other with mammary/axillary lymph node ALL with 15% blast cells in the bone marrow. The other two patients relapsed with DLBCL. After CART19 therapy, all patients achieved complete remission (CR) within a median of 30d (range 29~52d). With a median follow up of 53.5d (range 52~153d), the 2 DLBCL patients remained in CR; the testicular B-LBL patient relapsed with isolated testicular involvement on +153d and received a second CART19; the other B-LBL patient relapsed with isolated bilateral mammary glands involvement on +52d and remained in stable disease. Grade 2 cytokine release syndrome (CRS) were observed in the 2 DLBCL patients (50%). CRS self-resolved within 10d without treatment. Conclusions: CART19 was effective and safe against mass lesions such as relapsed extramedullary ALL and DLBCL with high CR rate. CART19 can induce rapid remission in lymphoma patients around one month.
Genome-wide identification and characterization of aberrant tRNA-derived RNA fragments in non-small cell lung cancer.
Authors: Lin Yang, Wenhan Yang, Peikun Ding, Zheng Wang, Rihong Zhai
Journal: Journal of Clinical Oncology (2018)

e20539 Background: tRNA-derived RNA fragments (tRFs) represent a new class of non-coding single-stranded RNAs with 14-35 nt in length. Recent studies suggest that tRFs play important roles in cellular processes and are involved in multiple cancers. However, rather little is known about the role of tRFs in non-small cell lung cancer (NSCLC), one of the most common cancers worldwide. Methods: We used RNA-sequencing to compare the expression profiles of tRFs in 10 pairs of pre- and post-operation plasma samples from patients with NSCLC. We validated the expression of differentially expressed (DE-) tRFs using qPCR. We further investigated the biological functions of DE-tRFs in three NSCLC cell lines (A549, NCI-1650, and NCI-226). Results: We detected 6660 unique tRFs, among them tRF-5 is the most abundant class of tRFs, followed by tRF-3 class. We identified 8 DE-tRFs that were differentially expressed (DE-) between pre- and post-operation plasma samples (fold change ≥1.5, P<0.05). We found that these DE-tRFs contained seed sequences targeting genes enriched in cancer-related pathways such as Wnt signaling and carbon metabolism. Transfection of AS-tDR-007333 and AS-tDR-010968, two up-regulated tRFs in pre-operation plasma samples, into NSCLC cell lines promoted proliferation, migration, and apoptosis. While knockdown of AS-tDR-007333 and AS-tDR-010968 suppressed cell proliferation, migration, and apoptosis. Conclusions: Our study provides a systematic catalogue of circulating tRFs and their dysregulation in NSCLC that can serve as the basis for further research on the roles of tRFs in diagnostic biomarker and therapeutic target in NSCLC.
A phase I//II study of computed tomography-guided interstitial high-dose-rate brachytherapy in combination with regional positive lymph node intensity-modulated radiotherapy for locally advanced peripheral non-small cell lung cancer.
Authors: Li Xiang, Jing-Bo Wu, Sheng Lin, Jianwen Zhang, QingLian Wen, PeiRong Ren, Bo Yang, Haowen Pang
Journal: Journal of Clinical Oncology (2018)

e20508 Background: To evaluate the results and toxicity of CT-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node IMRT for patients with locally advanced peripheral non-small cell lung cancer (NSCLC). Methods: This studies was a phase I /II trial reporting 3-year survival data as well as the incidence of toxicities.Thirty-two patients with histologically proven T1–3 N1-2 M0(IIb/IIIa/IIIb:3/9/20) NSCLC were enrolled in the prospective trial.Primary tumors were treated via HDR brachytherapy. The dose to 90% of the gross lung tumor volume, D90%, received at single 30 Gy. The dose to 95% of the planning target volume of malignant lymph nodes , D95%, received at least 70Gy. The patients received concurrent or sequential chemotherapy.We assessed treatment efficacy, radiation toxicity and life quality, especially on the lung function . The stratified analysis was used to estimate the relationship between the size and location of the primary lesion and the radiation toxicity. Results: The median follow-up was 46 months (range, 19–67 months). There are 25 patients who were followed up more than 3 years. After the brachtherapy, 5 patients developed mild pneumothorax. Grade 3 or 4 acute hematologic toxicity was observed in 7 patients, which mainly include leukopenia. During follow-up, there is no case of 1-degreee radiation pneumonia or above, according to late toxicity criteria of RTOG. The overall response rates for the primary mass and positive lymph nodes were 100% and 94.5%, respectively. The 3-year overall survival (OS) rate were 50%, respectively, with a median OS of 27.8 months.The 3-years local control(LC) rate for the primary tumor is 80.8%,with a median LC of 32.1months. Conclusions: HDR brachytherapy in combination with regional positive lymph node radiotherapy results in good tolerability and outcome in patients with peripheral locally advanced NSCLC.A single dose of 30Gy delivered to primary tumor has showed excellent local control, with no significantly increase the incidence of radiation injury. Clinical trial information: NO.: ChiCTR-ONC-12002715.
TCT-40 Diagnostic accuracy of intracoronary optical coherence tomography-based quantitative flow ratio for assessment of coronary stenosis
Authors: Wei Yu, Jiayue Huang, Dean Jia, Shaoliang Chen, Christopher Raffel, Daixin Ding, Feng Tian, Jing Kan, Su Zhang, Fuhua Yan, YunDai Chen, Hiram Bezerra, William Wijns, Shengxian Tu
Journal: Journal of the American College of Cardiology (2018)
CYP2D6 phenotype and tramadol-related adverse events in breast cancer patients.
Authors: Nikola Besic, Vita Dolzan, Katja Goricar, Jakob Jeriha, Branka Strazisar
Journal: Journal of Clinical Oncology (2018)

e22186 Background: Tramadol is commonly used for pain treatment in breast cancer patients after axillary lymph node dissection, but some patients experience insufficient pain relief or adverse events. CYP2D6 is the main metabolizing enzyme of tramadol, leading to the formation of the metabolite with the highest analgesic activity. Genetic variability in highly polymorphic CYP2D6 gene could therefore contribute to differences in response to tramadol. The aim of this study was to evaluate the association of predicted CYP2D6 phenotype with tramadol-related adverse events. Methods: The study included 112 breast cancer patients receiving tramadol for pain relief after breast cancer surgery including axillary lymph node dissection as part of an ongoing clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for CYP2D6 rs35742686 (*3 allele), rs3892097 (*4 allele), rs5030655 (*6 allele), rs1065852 (*10 allele), and rs28371725 (*41 allele) single nucleotide polymorphisms, as well as gene deletion and duplication. Patients were categorized as poor (PM), intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers and the association with tramadol-related adverse events within four weeks after surgery was evaluated using Fisher’s exact test. Results: Minor allele frequencies were 2.2% for CYP2D6*3, 19.6% for CYP2D6*4, 1.3% CYP2D6*6, 21.0% for CYP2D6*10, and 9.8% for CYP2D6*41. Gene deletion and duplication were detected in 3.6% and 4.5% of patients, respectively. Regarding predicted CYP2D6 phenotype, 7.1% of patients were poor, 37.5% intermediate, 52.7% extensive and 2.7% ultrarapid metabolizers. In 13 patients tramadol was discontinued due to adverse events in less than four weeks. Among other patients, 36.7% experienced nausea, 9.1% vomiting, 48.5% constipation and 35.4% dizziness. CYP2D6 phenotype was significantly associated only with constipation (P = 0.005); none of the CYP2D6 PMs experienced constipation or vomiting. Conclusions: CYP2D6 phenotype may be associated with tramadol-related adverse events in breast cancer patients and genotyping could help achieve more personalized treatment. Clinical trial information: 2015-000992-28.