tbuckley/cabot-search huggingface dataset:
Impact of a formal human papilloma virus (HPV) education program in a childhood cancer survivor center.
Authors: Karen Cristly Burns, Debra A. Kent, Judy Correll, Cheri Cole-Jenkins, Rajaram Nagarajan
Journal: Journal of Clinical Oncology (2017)

10568 Background: The HPV vaccine has proven efficacy in preventing secondary cancers. It was approved for females age 11-26 in 2006 and for males age 11-21 in 2011. Despite this, vaccination rates in the US have been poor. The Cancer Survivorship Center (CSC) at Cincinnati Children’s Hospital Medical Center (CCHMC) instituted an education program in July, 2016 to improve education and vaccination rates in a childhood cancer survivor population. The following is a summary of program effectiveness. Methods: Providers in the CSC identified females age 11-26, and males age 11-21, presenting for annual visit from 7/1/16 thru 12/31/16. Patients received HPV education materials published by the CDC at registration. Materials were also displayed in exam and waiting rooms. During the visit, providers reviewed and documented vaccination history and discussed the importance of the HPV vaccine in preventing cancer. Patients interested in starting the vaccine series received the first vaccine in clinic and a follow-up schedule for further vaccination. Education and immunization status was documented in the electronic medical record using smart phrase trackable format. All patients were asked to sign a release to obtain vaccine records from the primary physician. A comparison group consisted of HPV eligible patients seen in the CSC during the six months prior to program initiation. Groups were compared for education completed and vaccination rate. Results: A total of 156 eligible patients were seen in the comparison group. None received HPV-directed education during their visit. Only 37 (23.7%) had any HPV vaccine, with 5 given during the clinic visit (13.5%). By comparison, 176 eligible patients were seen after initiation of the education program. All patients received materials at registration and 89% had documented education completed by a health care provider. Ninety one (55%) had any HPV vaccine, with 30 given during the clinic visit (33%). Conclusions: Through the implementation of a standardized education program in the CSC, we saw more than a 200% increase in rate of HPV vaccination. This demonstrates the importance of knowledgeable providers and the value of a dedicated HPV education program.
FOLFCIS regimen for treatment of cancer of the anal canal.
Authors: Sebasti´n Mondaca, Walid K Chatila, Jaclyn Frances Hechtman, David Bates, Andrea Cercek, Neil Howard Segal, Zsofia Kinga Stadler, Anna M. Varghese, Michael F. Berger, Marinela Capanu, Jinru Shia, Nikolaus Schultz, Leonard B. Saltz, Rona Yaeger
Journal: Journal of Clinical Oncology (2018)

3567 Background: The combination of cisplatin and 5-fluorouracil (5-FU) is a standard chemotherapy regimen for advanced anal squamous cell cancer (AC) and is associated with significant toxicity. We examined the efficacy of a modified schedule, FOLFCIS, and performed an integrated clinical and genomic analysis of advanced AC. Methods: We reviewed all patients with metastatic or recurrent locally advanced AC treated with first line FOLFCIS chemotherapy at Memorial Sloan Kettering Cancer Center (MSK) between January 2007 and July 2017. FOLFCIS, which is essentially FOLFOX with cisplatin substituted for oxaliplatin, consisted of cisplatin 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5-FU 400 mg/m2 day 1, 5-FU 1000 mg/m2/d days 1 and 2 in a 14-day cycle. Forty-one advanced AC patients underwent targeted next generation tumor sequencing of > 300 genes (MSK-IMPACT), including 23 of the patients treated with FOLFCIS. Results: Fifty-three AC patients (48 metastatic; 5 unresectable, locally advanced) received first line FOLFCIS during this period; all were platinum naive. Median age was 59 years, and 32% had metastatic disease at diagnosis. Thirteen patients (25%) received multimodal treatment for metastatic disease. Administered dose intensity of both cisplatin and 5-FU was > 70%. Response rate was 48% (95% CI, 32.6 - 63). With a median follow up of 41.6 months, progression free survival (PFS) and overall survival (OS) were 7.1 months (95% CI, 4.4 - 8.6) and 22.1 months (95% CI, 16.9 - 28.1), respectively. Among all advanced AC, most frequent genomic alterations consisted of chromosome 3q amplification (17%) and mutations in PIK3CA (24%) and KMT2D (24%). Genomic alterations affecting the phosphatidylinositol 3-kinase pathway in PIK3CA, PTEN, or AKT2 were detected in 54% of cases. TP53 mutation, YAP1 amplification, and TERT promoter mutations appeared enriched in HPV-negative AC. No genomic alteration correlated with response to platinum-containing treatment. Conclusions: FOLFCIS is effective and safe as first line chemotherapy in advanced AC patients and represents an alternative treatment option for patients with AC.
Efficacy and safety results of ramucirumab in combination with osimertinib in advanced T790M-positive <i>EGFR</i>-mutant NSCLC.
Authors: David Planchard, Helena Alexandra Yu, James Chih-Hsin Yang, Ki Hyeong Lee, Pilar Garrido Lopez, Keunchil Park, Joo-Hang Kim, Dae Ho Lee, Shuang He, Bo H. Chao, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2018)

9053 Background: Progression of EGFR-mutant non-small cell lung cancer (NSCLC) occurs in most patients (pts) despite initial benefit with a first-line EGFR tyrosine kinase inhibitor (TKI). A first- or second generation EGFR TKI + a VEGF- or EGFR-directed monoclonal antibody (mAb) has shown promising results in pts with EGFR-mutant NSCLC. Methods: This ongoing, single-arm, Phase 1study (NCT02789345) enrolled pts with T790M-positive EGFR-mutant (Ex19del or L858R) NSCLC with prior progression on first-line EGFR TKI therapy. The primary phase 1b objective was assessment of safety/tolerability of ramucirumab (Ram), a VEGFR2 mAb, + osimertinib (Osi), a novel third-generation EGFR TKI. Key secondary efficacy endpoints were investigator assessed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS). Results: Pts (N = 25) were 45-80 years (median 64) with ECOG-PS 0 (n = 3) or 1 (n = 22) and tobacco history of current (n = 5), former (n = 8), or never (n = 12). Pts received Ram 10mg/kg IV (Day 1 Q2W) + Osi 80mg QD. At interim analysis, median therapy duration was 13 cycles (IQR: 6-16) for Ram and 13 cycles (IQR: 7-15) for Osi. Median follow-up was 7.2 months (90% CI: 6.51, 7.92). All pts had ≥1 treatment-related adverse event (TRAE), most commonly hypertension (44%), diarrhea (32%), stomatitis (24%). Grade (G) 3 TRAEs were hypertension (8%), platelet count decreased (8%), anemia (4%), congestive heart failure (CHF) (4%), neutrophil count decreased (4%). No G4 TRAEs were reported. Ram was discontinued for G3 CHF in a 76-year-old pt, who subsequently experienced a G5 TRAE of subdural hemorrhage ~7 weeks after the last dose of Ram. Fifteen pts remain on study drug. ORR was 76% (19/25), with CR 4% (1/25), PR 72% (18/25), SD 16% (4/25), PD 4% (1/25), and non-evaluable 4% (1/25). DCR was 92%. Median DOR was not reached (90% CI: NR, NR). DOR rate at 6 months was 81.6% (90% CI: 59.0, 92.4). Median PFS was not reached (90% CI: 5.49, NR). PFS rate at 6 months was 64.0% (90% CI: 43.7, 78.6) with 64% of pts censored. Conclusions: Ram + Osi demonstrated encouraging antitumor activity. The safety profile was consistent with monotherapy for each drug, with no additive toxicities. Clinical trial information: NCT02789345.
Did the addition of chemotherapy to conventional radiotherapy improve outcomes in treatment of oropharynx cancer in Ontario, Canada? A marker-treatment interaction study.
Authors: Stephen Hall, Fei-Fei Liu, Brian O'Sullivan, Patti Groome
Journal: Journal of Clinical Oncology (2016)

e17533 Background: In 2001 the management of Head and Neck cancer abruptly changed with the addition of concurrent chemotherapy to radiotherapy based on randomized trials and meta-analyses. The role of Human Papilloma Virus (HPV) and its prognostic impact were subsequently identified in 2004. However there is no evidence on the efficacy of concurrent chemoradiotherapy (CRT) specifically for HPV positive or negative patients over conventional radiotherapy (RT). The objective of this study was to compare treatment effectiveness by HPV status based on a group of patients treated before and after CRT was adopted across the cancer centers of Ontario Canada Methods: A treatment-effectiveness and marker-treatment interaction study of OPC patients treated for cure in 1998, 1999, 2003 and 2004 from all treatment centers in Ontario Canada who had available tissue for HPV testing. The patients were identified using the Ontario Cancer Registry and all charts were reviewed for demographic, patient, treatment and outcome factors. 865 patients were treated for cure and tissue was available on 610. Samples were tested for p16 and if negative were tested again using in-situhybridization for HPV p16/18 viral DNA. We compared the survival of patients by HPV status and by treatment (RT vs CRT) using the Kaplan Meier method and Cox Multiple Hazards regression models. Results: There were 392 HPV +ve patients and 199 of the 610 were treated with CRT. The HPV positive patients had 40% better overall survival (OS) and CRT improved OS by 15% over RT alone. However, there was no difference in OS comparing CRT to RT alone for the HPV positive patients (log rank p = 0.57) or for the HPV negative group (p = 0.15). When the multiple variable analysis was performed including HPV status and the interaction term with treatment, the HR for treatment (RT vs CRT) for HPV +ve was 1.003 and for HPV-ve was 1.036, and the p value for the interaction term was 0.91 indicating an outcome driven by HPV status not treatment type. Conclusions: In this study of real-world patients what appeared to be improvement in OS with the addition of concurrent chemotherapy to conventional radiotherapy was confounded by HPV status.
Profiling metastatic lesions from a pembro-refractory patient to reveal distinct genomic instabilities and non-uniform response to drug combinations, ex vivo.
Authors: Chukwuemeka Ikpeazu, Munisha Smalley, Baraneedharan Ulaganathan, Allen Thayakumar, Shanthappa Basavaraja, Hans Gertje, Mark Lawson, Aaron Goldman
Journal: Journal of Clinical Oncology (2018)

e18021 Background: Tumor heterogeneity drives response or resistance to therapy. This is particularly true in cases of metastatic disease, in which distant tumors are governed by their unique microenvironments. Due in large part to these biological complexities, predicting how treatment response varies among multiple metastatic sites may impact overall outcome. Methods: Here, we profiled the genomic and transcriptomic landscape of three metastatic lesions from a HNSCC refractory to second-line Pembrolizumab. In addition, we employed CANscript, a patient-derived ex-vivo model that couples phenotypic response to therapy with a proprietary algorithm, which predicts clinical response (M-Score). Using this platform we tested two combination therapies; Carbo+Gem, and Adria+Cyclophos. Moreover, we characterized the tumor microenvironment using multiplexed immunohistochemistry. Results: We determined that the three metastatic sites profiled displayed distinct transcription and whole exome signatures wherein mutational burden was skewed in highly proliferative tissue. Based on CANscript predicted responses (M-Score) for the two combinations tested, all three sites responded in a non-uniform manner. While two metastatic sites ‘responded’ to treatment, one remained refractory under all treatments. Interestingly, each site also displayed distinct patterns of proliferating immune subsets following treatment with each combination therapy. Conclusions: Together, these findings demonstrate that, due to the underlying genetic and tumor microenvironment heterogeneity, metastatic sites might each confer distinct clinical responses to conventional cytotoxic drug regimens, even in immunotherapy-resistant disease. Moreover, we highlight the utility of ex vivo profiling as a tool to predict therapeutic response - not only at the individual patient level, but also at the level of multiple metastatic sites from a single patient. These findings underscore the importance of the entire microenvironment under pressure of anticancer drugs. Such information can revise our understanding of personalized cancer care.
Response to immune checkpoint inhibitors in recurrent/metastatic esophageal squamous cell carcinoma may be affected by tumor site and lesion size.
Authors: Jhe-Cyuan Guo, Chia-Chi Lin, Ta-Chen Huang, Min-Shu Hsieh, Li-Chun Lu, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2018)

e16099 Background: Heterogeneous tumor response has been reported in cancer patients receiving immune checkpoint inhibitors (ICIs). This study investigated whether or not tumor site and tumor size significantly affect the response to ICIs in patients with recurrent/metastatic esophageal squamous cell carcinoma (R/M ESCC). Methods: R/M ESCC patients, with measurable disease according to RECIST 1.1 and receiving anti-PD-1/PD-L1-based therapies at National Taiwan University Hospital, were enrolled. To evaluate the tumor response at different organ sites, we used an organ-specific response criteria that was modified from RECIST 1.1 by allowing a maximum of 5 measurable lesions per organ system. To evaluate the tumor response per individual tumor basis, we studied all measurable tumors and evaluate their individual tumor response following the definition of response of RECIST 1.1. The significance of tumor sites and target tumor sizes on the response were examined by logistic regression. Results: Thirty-eight R/M ESCC (M:F = 37: 1; median age of 58.0 years) were enrolled. The overall tumor response rate (RR) per RECIST 1.1 was 13.2%. Measurable tumors in lymph node (LN), lung, and liver were seen in 23, 16, and 10 patients, respectively. The organ-specific RRs were 30.4%, 31.3%, and 10.0% for LN, lung, and liver tumors, respectively (p= 0.040). Fifty-three, 34, and 32 measurable target lesions from LN, lung, and liver, respectively, were subject to individual tumor response evaluation. The mean sizes were 2.42, 1.79, and 4.22 cm for LN, lung, and liver target lesions, respectively (p< 0.001). In univariate logistic regression, tumor site (LN vs liver) was statistically significantly associated with response (p= 0.007) and lesion size (increased every 1 cm) trended to associate with response (p= 0.094). Conclusions: Our data suggest that response to ICIs is significantly different among R/M ESCC tumors at different organ sites. The underlying mechanism warrants further investigation. (Supported by the grants of MOST 105-2314-B-002 -186 -MY3, MOST 106-2314-B-002 -135 -, and 106-N3695)
Validation of a genomic risk classifier to predict prostate cancer-specific mortality (PCSM) in high-risk patients.
Authors: Jeffrey Karnes, Ashley Ross, Edward M. Schaeffer, Eric A. Klein, Nicholas Erho, Kasra Yousefi, Mandeep Takhar, Elai Davicioni, Bruce J. Trock
Journal: Journal of Clinical Oncology (2016)

5056 Background: The time course to PCSM is highly variable for men with high risk after prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions. We validated ability of the 22 gene Decipher genomic classifier (GC) to improve upon clinical variables to predict PCSM in men with high risk after RP. Methods: Men with adverse pathologic features (APF: pT3N0/N1, positive margins, or RP Gleason > 7) who underwent RP in 1988-2010 at Johns Hopkins, Cleveland Clinic, and Mayo Clinic (excluded men used to develop GC). Primary outcome: PCSM within 10 years of RP (PCSM10). We also analyzed men at very high PCSM risk: men with biochemical recurrence in < 2 years (BCR2), and men who developed metastasis after RP (MET). Logistic regression was used with GC dichotomized as < 0.6 (low-intermediate) vs. > 0.6 (high), adjusted for PSA, RP Gleason, and RP stage, or for CAPRA-S. AUC measured incremental improvement when adding GC to model of RP pathology. Results: 511 men (110 with PCSM10; 22%) had median follow-up 13.0 years. Risk of PCSM10 increased nearly 4-fold for high GC score (p < .0001), and increased AUC over RP pathology model from 0.767 to 0.804 (Table). GC score stratified PCSM10 risk from 11-46%. In men with BCR2 or MET, high GC increased PCSM10 risk 2-3 fold (p = .0007 or .005), with AUC of 0.743 and 0.671. GC similarly improved AUC when added to CAPRA-S. Conclusions: In the largest and longest followed sample to date, Decipher GC demonstrated clinically important prediction of PCSM at 10 years, independent of RP pathology features, in men at high risk due to APF, BCR2 or MET after RP. Model Odds ratio (95% CI) All Men n = 511 (110 PCSM10) Men with BCR2 n = 180 (84 PCSM10) Men with MET n = 226 (110 PCSM10) Decipher GC > 0.6 vs. < 0.6 3.9 (2.3, 6.4) 3.3 (1.6, 6.5) 2.3 (1.3, 4.0) PSA (ng/ml) 1.0 (0.98, 1.02) 1.00 (0.98, 1.02) 1.00 (0.98, 1.02) Stage Organ confined Ref Ref Ref EPE 1.3 (0.6, 2.6) 1.5 (0.6, 3.9) 1.1 (0.5, 2.6) SVI 2.0 (1.0, 4.2) 2.2 (0.9, 5.5) 1.1 (0.5, 2.4) LNI 2.7 (1.2, 6.0) 2.5 (0.9, 6.7) 1.4 (0.6, 3.4) RP Gleason score < 3+4 Ref Ref Ref 4+3 1.9 (0.9, 3.9) 1.3 (0.5, 3.3) 0.9 (0.4, 2.0) 8-10 5.0 (2.9, 8.6) 3.1 (1.5, 6.4) 2.3 (1.3, 4.4) AUC baseline model 0.767 0.693 0.633 AUC baseline+GC 0.804 0.743 0.671
Abstract 19440: Reintervention Rates Following Balloon Aortic Valvuloplasty versus Surgical Valve Repair in Isolated Congenital Aortic Valve Stenosis - A Meta-analysis
Authors: May T Saung, Courtney McCracken, Ritu Sachdeva, Christopher J Petit
Journal: Circulation (2015)

Introduction: The optimal treatment for congenital aortic stenosis (AS) is debated despite decades of experience with both balloon aortic valvuloplasty (BAV) and surgical aortic valve repair (SAV). While BAV has been the mainstay of therapy for AS, recent single-center reports suggest optimal results following SAV. Hypothesis: We propose that reintervention rates following SAV and BAV are equivalent. Methods: We queried Medline, EMBASE and Web of Science for eligible studies using the keywords: “congenital aortic stenosis”, “balloon valvotomy”, “aortic valve stenosis surgery” and “treatment outcome or reintervention”. Studies were excluded when cohort size was &lt;20 pts, when follow-up was &lt; 2.5 yrs from primary intervention, and when primary indication was not AS (e.g. SAV in the setting of aortic valve regurgitation (AR)). Outcomes analyzed included death, reintervention and moderate or severe AR. Analysis was performed using Comprehensive Meta Analysis v3 using random effects models. Results: A total of 20 studies were included in our meta-analysis: SAV alone (n=3), BAV alone (n=12), and both (n=5). The mean age at BAV was 3.1 years (range, 4 days - 7 years) with a mean follow-up duration of 6.8 years, while mean age at SAV was 2.8 years (range, 14.2 days - 7.1 years) with a mean follow-up duration of 9.1 years. Mortality rates following BAV and SAV were 12.3% (95% CI: 7.7 - 19.1) and 10.2% (95% CI: 7.0 - 14.5), respectively (p=0.27). Reintervention following initial procedure for treatment of AS was higher following BAV (35.7% [95% CI: 29 - 43.1]) compared to SAV (25.2% [95% CI: 19.9 - 31.3])(p=0.012). Long-term and mid-term follow-up in these studies showed moderate to severe AR was present in 24.1% and 28.1% of BAV and SAV patients, respectively. Conclusions: Notwithstanding publication bias, both survival rates and development of late AR following BAV and SAV are similar. However, reintervention rates are significantly higher following BAV compared to SAV.
Rate of <i>MYC-N</i> gene amplification among children of Middle Eastern descent with neuroblastoma.
Authors: Teresa Santiago, Nidale Tarek, Fouad Boulos, Caleb Hayes, Sima Jeha, Susana Raimondi, Carlos Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2018)

e22507 Background: MYC-N gene amplification recognized in about 19% of patients with Neuroblastoma (NB) is considered the single most important adverse risk factor. The prevalence of specific germline variations more frequently seen in different ethnic groups has been linked to the genetic susceptibility of sporadic NB and may define tendency to high-risk and low-risk disease. Patients of African-American or Native American descendent are noted to have a higher prevalence of high-risk disease and MYC-N amplification when compared with White-Americans, Asians, and Hispanics. However, the frequency of MYC-N amplification or high-risk disease among children of Middle Eastern Descent (MED) with NB is unknown. Methods: A retrospective review of our pathology consultations (July 2014 to July 2017) was performed. Thirty-four MED children diagnosed with NB were identified, which represent all the patients with suspected NB admitted in our Middle Eastern partner institution during the same period. The available clinicopathologic data were reviewed, including age at diagnosis, tumor location, histology, mitotic karyorrhectic index (MKI), International Neuroblastoma Pathology Classification (INPC) prognostic group, and clinical stage. Forty-four North-American descent (NAD) patients diagnosed with NB during the same period were selected as reference group. MYC-N amplification status was assessed by fluorescence in situ hybridization (FISH) in all 78 samples at our institution. Results: The only statistically significant difference between the MED and NAD patients with NB is the frequency of MYC-N amplification. Among the MED patients with NB 44.11% [15 out of 34] showed MYC-N amplification in contrast with 20.45% of NAD patients [9 out of 44] (Fisher exact test, p = 0.02). No statistical differences are noted regarding age at diagnosis, tumor location, histopathology, MKI, INPC prognostic group, or clinical stage. Conclusions: Our findings indicate that the rate of MYC-N amplification among MED patients with NB is significantly higher when compared with NAD patients. A rate of 44.11% of MYC-N amplification in our cohort of MED patients may indicate a potential genetic susceptibility to high-risk NB in this ethnic group.