tbuckley/cabot-search huggingface dataset:
Costs associated with induction chemotherapy in adult acute myeloid leukemia (AML) managed in a tertiary care specialized unit.
Authors: Shannon Gleason, David H Howard, Yuan Liu, Daniel A. Goldstein, Martha Lucia Arellano, Anand P. Jillella, Manila Gaddh, Vamsi Kota, Elliott F. Winton, Leonard T. Heffner, Amelia A. Langston, Gregory Esper, Hanna Jean Khoury
Journal: Journal of Clinical Oncology (2016)

e18503 Background: Induction chemotherapy with cytarabine/anthracycline remains the standard for AML. Regimen-related toxicities and profound myelosuppression lead to a prolonged hospitalization. In a specialized leukemia unit, a team of dedicated providers can deliver cost-effective care using streamlined processes Methods: Analysis of costs of hospitalization for induction in an academic center leukemia unit. Results: Between 1/2006 - 7/2011, 110 consecutive adult AML patients (pts) received induction. Median age was 60 (19-79), median white blood cell count (WBC) was 18.7 x103/mcL (0.3-348), with WBC ≥ 100 x103/mcL in 17. Cytogenetic (CTG) risks were favorable in 21%, intermediate in 47%, unfavorable in 29%, and unknown in 3%; 22 had secondary AML. Length of stay (LOS) was 28 d (9-56), and 12% required ICU care for a median of 3 d (2-17). Overall, 36% required 1, and 24% ≥ 2 consultations from non-hematology specialists. Median follow-up for survivors is 78 months (60-110). 30 d survival was 94%, mortality was 0 vs. 13% for pts < vs. ≥ 60 (p = 0.013), 4 vs. 18% for WBC < vs. ≥ 100 (p = 0.03), and 23% (vs. 4%) for pts requiring ICU care. Age was the only significant predictor of early death by MVA (p = 0.018). OS was 53 vs. 38% for pts < vs. ≥ 60 (p = 0.04), 51 vs. 23% for de novo vs. secondary AML (p = 0.001), and 74, 50, and 22% for favorable, intermediate and high-risk CTG (p = 0.001). Age (p = 0.04), CTG (p = 0.005) and ICU care (p = 0.017) were predictors of OS by MVA. Median hospitalization cost was $58,065 (8,493-442,349), and was affected by LOS (p < 0.001) and the need for ≥ 2 consultants (p = 0.025). Cost for < 20 d LOS was $33,289 (8,493-42,172), $58,370 (10,666-299,991) for 20-39 d, and $80,007 (13,379-124,180) for ≥ 40 d. Costs for pts not requiring consultation from a non-hematologist were $56,395 (8,493-100,766); $56,805 (10,666-299,991) and $72,981 (13,379-$182,311) for those requiring 1 vs. ≥ 2 consultants, respectively. Conclusions: We have reported costs associated with induction for AML in a specialized unit. These costs can serve as benchmark for comparisons. The number of non-hematologists consulted and LOS, both surrogate markers of complexity, were the major drivers of these costs.
Picosecond Laser Treatment for Acquired Bilateral Nevus of Ota–like Macules
Authors: Tin Hau Sky Wong
Journal: JAMA Dermatology (2018)

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Abstract 14086: Seattle Heart Failure Model Identifies Patients Most Likely to Have Improved Survival With Cardiac Resynchronization Therapy Defibrillators - An NCDR Analysis
Authors: Kenneth C Bilchick, Alan Cheng, Yongfei Wang, Jeptha Curtis, Kumar Dharmarajan, Wayne Levy
Journal: Circulation (2016)

Introduction: In the Sudden Cardiac Death in Heart Failure Trial, lower Seattle Heart Failure Model (SHFM) risk was associated with an increased survival benefit with implantable cardioverter defibrillators (ICDs), but the impact of SHFM risk on the survival benefit with cardiac resynchronization therapy defibrillators (CRT-D) remains to be determined. Hypothesis: Increasing SHFM risk will be associated with a greater impact of CRT-D on survival in the National Cardiovascular Data Registry (NCDR) ICD Registry. Methods: The study cohort consisted of patients with CRT-D from the NCDR ICD Registry with current criteria for CRT-D implantation. The control cohort consisted of patients from the University of Washington Registry, Italian Heart Failure Registry, Swedish Heart Failure Registry, COMET, Val-HeFT, and PRAISE trials who met standard criteria for CRT-D but who did not receive CRT-D. Multivariable logistic regression with receiver operating characteristic (ROC) analysis and multivariable Cox proportiona...
Radium-223 treatment for metastatic prostate cancer: One year data in a single institution experience.
Authors: Norma Sidek, Gail Buchanan, David Dodds, J. Martin Russell, Gerry Gillen, Carolynn Lamb, Jan Wallace, Robert J Jones, Abdulla Alhasso, Azmat Sadozye, Balaji Venugopal
Journal: Journal of Clinical Oncology (2018)

e17037 Background: Radium-223 treatment for bone only metastatic disease from metastatic castrate resistant prostate cancer (mCRPC) received approval from Scottish Medicines Consortium (SMC) on 13 October 2015 and we started delivering Radium-223 treatment in May 2016. We share our early experience within clinical service context from patients who started treatment in May 2016- May 2017 (complete or intention to complete). Methods: Data on 52 patients with mCRPC including information on initial PSA at diagnosis (iPSA), clinical trial involvements prior to treatment, the types of first, second and third line treatments, if palliative radiotherapy treatment was delivered within 12 weeks prior, prior treatment with bisphosphonates, median time from the last cycle of Radium to time of death, reasons for stopping treatment, prior blood transfusions,side effects profile, Pain-score at first and last cycle. Statistical analysis was using SPSS. Results: Majority had iPSA of > 100, 6 had been involved with clinical trials prior , majority received prior Docetaxel treatment as first line and Enzalutamide as second line therapy. Radium-223 was the most common third line treatment. 8 patients needed palliative radiotherapy within 12 weeks prior to starting their first cycle, 16 patients received bisphosphonates prior and. 14 required prior blood transfusion. Mean survival from time of starting Radium-223 treatment until time of death is 102 days. 28 patients completed 6 cycles of Radium-223. Majority who failed to complete 6 cycles had progressive disease. From those who completed 6 cycles of Radium, there were 11 deaths. Side effects included were 12% diarrhoea with 5% required medications, neutropenia 1.4% and thrombocytopenia 1.4% . Median pain score 5/10 for first cycle and 2/10 for final cycle of treatment. 6 patients had worsened pain score on completion. Conclusions: There discrepancies in survival between Alsympca trial and our clinical experience data which do not compare favourably. 53.8% patients completed 6 cycles. This treatment has been successful in reducing the pain score and is well tolerated.
Potential therapeutic target for PD1/PDL1 blockade in microsatellite medullary carcinomas based on PDL1 expression by tumor cells and infiltration by numerous PD1+ T lymphocytes.
Authors: Celine Bossard, Eva Ott, Delphine Dansette, Adrien Ouary, Anne Jarry, Stephane Bezieau, Claire Toquet, Jean-François Mosnier
Journal: Journal of Clinical Oncology (2017)

e14599 Background: PD1/PDL1 blockade showed therapeutic efficacy in only microsatellite (MSI) colorectal carcinomas (CRC), however, the profile of PDL1 and PD1 expression in CRC is only partially described. Methods: We thus analyzed on FFPE whole-tissue sections of 80 CRC, the expression profile of PDL1 by tumor and/or immune cells by immunohistochemistry (clone E1L3N) depending on the MSI status and the histological subtype, and correlated to the density of PD1+ and Tbet+ (able to secrete IFNg known to induce PDL1) tumor-infiltrating lymphocytes (TIL). Results: 78% of MSI CRC (32/41) overexpressed PDL1 either by tumor or immune cells versus 46% of MSS CRC (18/39) (p 0.005). This overexpression was heterogeneous within the same tumor in most of cases. Among MSI CRC, PDL1 was preferentially overexpressed in medullary carcinomas (MC, 19/21, 90%) compared with 65% (13/20) in non medullary adenocarcinomas (p 0.06). PDL1 expression by tumor cells was only observed in MSI CRC (19/41, 46% with PDL1 expression in more than 5% of tumor cells – score 1), and preferentially in MC (57% vs 5% in no medullary adenocarcinomas, with PDL1 expression in more than 50% of tumor cells – score 3, p 0.0005). Conversely, PDL1 expression by immune cells was observed in MSI CRC (23/41, 56% with PDL1 expression by more than 5 sheets of 50 positive cells) but also in MSS CRC (18/39, 43%) (p 0.5). The density of PD1+ cells was significantly correlated to the PDL1 expression, as well as the density of Tbet+ TIL. Conclusions: PDL1 expression is 1) heterogeneous in CRC, among CRC but also within the same tumor, 2) preferentially observed in MSI CRC (78%), especially in MC (90%), where PDL1 is expressed by tumor cells, 3) correlated with the density of PD1+ or Tbet+ TIL, and 4) observed in a significant proportion of MSS CRC (46%) by immune cells only. From a clinical point of view, PDL1 expression has to be determined at best in full tissue section and besides its preferential expression in MSI CRC, its significant frequency and expression profil (only by immune cells) in MSS CRC should be taken into account in the future clinical trials testing the efficacy of anti-PD1/PDL1 antibodies.
Risk of gastrointestinal and hepatic toxicities in patients with cancer treated with regorafenib: A systematic review and meta- analysis of randomized controlled trials.
Authors: Rachana Yendala, Kyaw Zin Thein, Anita Sultan, Sriman Swarup, Lukman Tijani, Fred L. Hardwicke, Catherine Jones
Journal: Journal of Clinical Oncology (2018)

e22118 Background: Regorafenib is an oral small molecule inhibitor of multiple tyrosine kinases, including VEGFR, KIT, RET, RAF1, BRAF as well as PDGFR and FGFR, and is proven to be beneficial in different types of tumors. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through August 2017 were queried. Phase 3 RCTs that mention nausea, vomiting, diarrhea, stomatitis, elevated aspartate aminotransferase (AST),alanine aminotransferase (ALT) and hyperbilirubinemia as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Four phase 3 RCTs with a total of 1723 patients were eligible for analysis. All studies compared regorafenib versus placebo. The RR of all-grade side effects were as follows: nausea, 1.429 (95% CI: 1.043–1.957; p = 0.026); vomiting, 1.831 (95% CI: 1.0015–3.304; p = 0.044); diarrhea, 4.145 (95% CI: 3.084 – 5.571, p < 0.0001); stomatitis, 5.90 (95% CI: 3.745 – 9.296, p < 0.0001); elevated AST, 1.535 (95% CI: 1.179–1.997; p = 0.001); elevated ALT, 1.632 (95% CI: 1.117–2.384; p = 0.011) and hyperbilirubinemia, 3.616 (95% CI: 2.121–6.165; p < 0.0001). The RR of high-grade adverse effects were as follows: nausea, 1.166 (95% CI: 0.209–6.507; p = 0.861); vomiting, 2.423 (95% CI: 0.276–21.247; p = 0.424); diarrhea, 5.321 (95% CI: 1.513–18.709, p = 0.009); stomatitis, 2.764 (95% CI: 0.534–14.307, p = 0.226); elevated AST, 1.139 (95% CI: 0.676–1.918; p = 0.626); elevated ALT, 1.951 (95% CI: 0.997–3.821; p = 0.051) and hyperbilirubinemia, 1.999 (95% CI: 1.046–3.821; p = 0.036). Conclusions: Our meta-analysis demonstrated that Regorafenib contributed to significant toxicity of all-grade GI and hepatic toxicities as well as high-grade diarrhea and hyperbilirubinemia. Recognizing these toxicities may help physicians in delivering good supportive care and improving patients’ quality of life.
Identification and referral of women at risk for <i>BRCA</i> mutations.
Authors: Cecelia Bellcross, April Hermstad, Christine L. Tallo, Chelsea Leonard, Ioana Pencea, Christine L. Stanislaw, Wendy Kohlmann
Journal: Journal of Clinical Oncology (2018)

1514 Background: It is estimated that less than 10% of BRCA1/2 mutation carriers have been identified, despite well-documented evidence of reduced cancer morbidity and mortality with targeted screening and prevention. The United States Preventive Services Task Force endorsed the Breast Cancer Genetics Referral Screening Tool (B-RST) as one of several validated screening tools to assist clinicians in identifying women appropriate for cancer genetics referral. The purpose of this study was to implement B-RST in mammography clinics to determine the most effective means of follow-up for screen positive women. Methods: Women undergoing routine screening mammography at one of four Emory clinics were approached to complete the B-RST. Participants were given written information about their results and appropriate resources. Those who screened positive, indicating increased risk for a BRCA1/2 mutation, were randomized to one of three follow-up groups: self-referral (Group 1), electronic health record (EHR) messaging (Group 2), or direct contact (Group 3). We compared genetic counseling (GC) appointment scheduling and completion rates by group. Those who did not schedule an appointment were invited to participate in an online survey. Results: Of 2,422 participants, 610 (25.2%) screened positive. Demographic factors did not differ between the three groups. GC appointments were scheduled by 9.2% of Group 1 participants, 19.7% of individuals in Group 2, and 12.5% of Group 3 participants (p = 0.001). Challenges to scheduling included lack of physician response to EHR messages and unsuccessful direct contact. Among those scheduled (n = 76) 69.7% completed the appointment. with no difference in completion rate between the three groups. The most common barriers to scheduling reported by survey respondents (n = 97) were lack of physician recommendation (71%), health insurance concerns (67%) and indecision about GC (66%). However, 52% reported interest in future GC contact. Conclusions: B-RST can be used effectively in mammography settings to identify high-risk women for cancer genetics referral. While follow-up via EHR was the most effective, additional strategies are needed to facilitate completion of the GC process in routine clinical practice. Clinical trial information: NCT02786147.
Influence of facility (Fac) annual caseload (AC) on survival of patients (pts) with respectable urothelial carcinoma (UC) of the bladder.
Authors: Sarmad Sadeghi, Primo Lara, Mihir Desai, Siamak Daneshmand, David F. Penson, Seth P. Lerner, David I. Quinn, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2018)

e16513 Background: The impact of AC on outcomes of oncological surgeries are increasingly being recognized. This study explores this effect in UC. Methods: Using National Cancer Database (NCDB) 25973 pts undergoing radical cystectomy (RC) or pelvic exenteration (PEx) between 2006 and 2013 for UC were identified. Age, gender, comorbidities, clinical stage, pathologic node (pN) status, surgical margins (SM), neoadjuvant (NAdj) & adjuvant (Adj) chemotherapy (chemo) were analyzed. Facs were divided into 4 volume groups (VG) based on their AC: VG 1: < 50th, 2: 50th-74th, 3: 75th-89th and 4: > 90thpercentile. Univariable & multivariable Cox proportional hazards ratios (HR) model were used to examine the influence of these variables on overall survival (OS) from diagnosis to the time of death or last follow up. Results: 12973 (50%) of pts were treated at VG 4 Facs (> 12 AC) while 2610 (10% 0-2 AC), 4325 (17% 3-5 AC) & 6065 (23% 6-11 AC) were treated at VG 1, 2 and 3 Facs, respectively. 80% of VG 4 Facs were academic centers. 52, 61 and 54 % of VG 3, 2 and 1 Facs were comprehensive community cancer programs. 88% of pts at VG 4 Facs had negative (neg) SM whereas 86, 84 and 80% had neg SM at VG 3, 2, and 1 Facs, respectively. Pts were more likely to be given NAj chemo when indicated at VG 4 Facs vs lower VG Facs. Lower VG Facs were more likely to use Adj where NAdj chemo was indicated. Univariable model showed an improvement in OS as AC increased with a 21% (p < 0.001) mortality risk reduction (MRR) for VG 4 vs 1. In multivariable model, MRR was 11% (p < 0.001) for VG 4 vs 1 and 9% (p = 0.01) for VG 3 vs 1. Conclusions: AC is an important predictor of outcome for resectable UC. This is not accounted for by the rate of positive SM or # of nodes examined. Variable HR P VG 1 Ref 2 0.95 0.17 3 0.91 0.01 4 0.89 0.00 Chemo NAdj indicated and given with < pT3 Ref NAdj indicated and given with > = pT3 2.76 0.00 No chemo indicated or given 1.04 0.53 Adj indicated but not given 2.66 0.00 Adj indicated and given 1.88 0.00 NAdj indicated, Adj given 1.94 0.00 Radiation (RT) No RT Ref RT after RC/PEx 1.35 0.00 SM Negative Ref Positive 1.48 0.00 # of nodes examined 0 Ref 1-14 0.78 0.00 15-29 0.69 0.00 30-89 0.60 0.00 Comorbidities 0 Ref 1 1.21 0.00 2 1.48 0.00 pN 0 Ref 1 1.66 0.00 2 2.33 0.00 3 2.72 0.00
Effect of assaying the matched normal on clinical cancer sequencing results.
Authors: Elena Helman, Michael James Clark, Ravi Alla, Sean Boyle, Selene Virk, Shujun Luo, Nan Leng, Deanna Church, Richard Chen
Journal: Journal of Clinical Oncology (2016)

11561 Background: Interpretation of a cancer variant’s origin and therapeutic impact poses analytical challenges. Recent studies have indicated that analyzing a tumor with its matched normal can discriminate between somatic and germline mutations. Moreover, a NHGRI/NCI Clinical Sequencing Tumor Working Group released guidelines recommending that laboratories performing cancer sequencing tests include germline variants. However, procurement of a matched sample is often impractical in the clinic. In the absence of the normal, databases and analytical techniques are used to identify cancer variants. Whether the benefits outweigh the added burden of sequencing the matched normal for accurate detection of cancer mutations remains an open question. Methods: We collected > 100 FFPE and fresh frozen cancer samples across tumor types with matched normal blood tissue. We performed exome and cancer gene panel sequencing. The data was analyzed using bioinformatic pipelines that detect base substitutions, small insertions/deletions, copy number alterations in both tumor-only and tumor/normal modes. Variants were annotated using clinical actionability filtering and secondary findings of germline variants were analyzed. Results: We find that 67% of mutations detected in tumor-only mode are reclassified as germline when analyzed together with the matched normal. These include mutations in hereditary cancer genes, such as BRCA1, VHL and other ACMG genes that warrant germline variant classification and management. Clinically actionable mutations may be miscalled as somatic; however, we find the definition of ‘actionable’ greatly impacts the results of this analysis. Finally, newly available datasets, such as ExAC, substantially decrease the number of miscalled somatic variants in the absence of the normal. Conclusions: Mutations of putative germline origin may be important for hereditary cancer knowledge and tumor treatment. For NGS-based cancer interpretation to guide clinical decisions in a practical and cost-effective manner, highly optimized tumor-only and tumor/normal analyses must be available with proper attention to germline consent, classification and education.
Metabolic tumor volume to predict event free survival in patients with relapsed/refractory HL treated with brentuximab vedotin-based salvage therapy.
Authors: Somali C. Gavane, Kimiteru Ito, Craig H. Moskowitz, Alison J. Moskowitz, Heiko Schöder
Journal: Journal of Clinical Oncology (2016)

11566 Background:To investigate the role of PET/CT parameters in patients with relapsed/refractory Hodgkin’s lymphoma. Methods: PET/CT scans of 45 patients (pts) 25 M/ 20 F, median age 31 (range13-65 yrs) with relapsed/ refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen enrolled in non-randomized, single-centre, phase 2 trial (NCT01508312) were reviewed. All patients underwent tissue biopsies to confirm relapsed /refractory Hodgkin's lymphoma and had PET-positive disease.All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin (BV) on days 1, 8, and 15 for two 28-day cycles. Those who achieved normalization of PET (Deauville 1 or 2) proceeded to high dose therapy and autologous stem-cell transplant (HDT/ASCT). Those with persistent abnormalities on PET/CT after BV(Int-PET) received 2 cycles of augmented-ICE (ifosfamide, carboplatin, etopsoide) followed by repeat PET/CT and consideration for HDT/ASCT. All images were reviewed on a GE PET VCAR station. SUVmax and SUVpeak of the hottest lesion, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured for each patient.The percent change (ΔSUVmax, ΔSUVpeak) for the hottest lesions and ΔMTV and ΔTLG between time point 1 (B-PET) and time point 2 (Int-PET)) was calculated. PET/CT status was assessed for its ability to predict event-free survival (EFS). Results: Three pts were excluded from this preliminary analysis due to technical issues in assessment of PET parameters on PET VCAR software. In the remaining 42 pts, baseline SUV max ranged from 3.5 to 33.7 (median 12.9), SUV peak ranged from 2.8 to 28.7 (median 9.8), MTV from 9.0 to 781.5 (median 91.3), and TLG from 34.7 to 6472.14 (median 620.3). Median event free survival follow-up was 33.75 months. Among the baseline parameters, MTV, TLG and SUV peak were independent predictors of EFS (p < 0.01), but SUVmax was not. Int- PET imaging parameters, including SUVmax or MTV did not correlate with EFS. Conclusions: MTV, TLG and SUV peak on baseline PET/CT provide prognostic information in relapsed/refractory Hodgkin’s lymphoma. Further analysis and follow up on this patient cohort is ongoing. Clinical trial information: NCT01508312.