tbuckley/cabot-search huggingface dataset:
Cachexia Index utilization in patients with non-small cell lung cancer.
Authors: Douglas William Rybar, Ronald Ng, Mary J. Fidler, Samantha Kerns, Selina Sayidine, Sanjib Basu, Jeffrey Allen Borgia, Arkadiusz Z. Dudek, Philip Bonomi, Palmi Shah, Martha Menchaca
Journal: Journal of Clinical Oncology (2016)

e20642 Background: The impact of cancer cachexia in non-small-cell lung cancer (NSCLC) is significant, however the most meaningful measure of cachexia is unknown. Recently Jafri et al proposed the Cachexia Index (CXI) as a marker to assess the degree of cachexia using computed tomography derived values at the third lumbar vertebra (L3), a level not routinely captured in standard chest CT scans. The aim of this study was to correlate CXI scores derived from T12/L1 level, with overall survival (OS) in stage IV NSCLC patients receiving first line platinum doublet chemotherapy. Methods: Patients from University of Illinois Hospital (UIH) and Rush University Medical Center (RUMC) were analyzed in a retrospective study. Subjects received first-line platinum-doublet chemotherapy, had pretreatment and longitudinal CT scans. Skeletal Muscle Index (SMI) was collected from CT images at the T12/L1 level using standard software (SliceOmatic V5.0 - Magog, Canada), which enables specific tissue demarcation using Hounsfield unit thresholds. CXI was calculated as: (SMI x Alb)/NLR (Alb is serum albumin, and NLR is the neutrophil to lymphocyte ratio). Patients were dichotomized into two cachexia groups: Stage I cachexia CXI ≥ 35 and Stage II cachexia CXI < 35 based on primary literature. Mann-Whitney was used to compare results across institutions. Multivariate Cox PH analysis was used to assess impact of variables on survival. Results: There was no statistical difference in CXI score between the UIH and RUMC cohorts (n = 40 UIH; 63 RUMC) (p = 0.6625). There was also no significant difference in age, sex, histology and ethnicity between the Jafri CXI stage I and II groups. In multivariate Cox PH analysis, after adjustment by age, Jafri CXI < 35 was significantly associated with worse OS (HR = 1.64, p = 0.041). The association with CXI < 35 remained marginally significant (p = 0.072) when adjusted by age, cohort, ethnicity, histology, and gender. Conclusions: Using more accessible areas for SMI reading at the T12/L1 level, the Jafri CXI adjusted for age remained an objective measure to classify NSCLC patient cachexia symptoms. This may be used to identify patients who are at high risk for early progression of cancer who may benefit from trials targeting cancer cachexia.
Low dose rate brachytherapy vs standard external beam radiotherapy vs stereotactic body radiotherapy for low risk prostate cancer: A cost-utility analysis.
Authors: Joelle Antoine Helou, Sofia Torres, Hima Bindu Musunuru, Patrick Cheung, Danny Vesprini, Hans T. Chung, Laura D'Alimonte, Ananth Ravi, Murray Krahn, Gerard Morton, Andrew Loblaw
Journal: Journal of Clinical Oncology (2016)

6628 Background: Radiation is a standard option in the management of prostate cancer (PC). Multiple options are available with similar outcomes, yet substantially different costs. SBRT is non-invasive and convenient but has never been compared to LDR. Herein we conduct a cost-utility analysis comparing SBRT, LDR and standard EBRT. Methods: A decision-analytic Markov model was developed from the Ontario payer perspective to simulate the history of a 66 year old man with low risk PC. The model followed patients yearly over their lifetimes. Three radiation options were considered: SBRT 35 Gy, LDR 145 Gy and EBRT 76 Gy. Health states included ‘Recurrence free’, ‘biochemical recurrence (BR)’, ‘metastatic’ and ‘death’. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario’s health system and departmental costs. Outcomes included quality adjusted life-years (QALYs), costs and incremental cost-effectiveness ratios. All outcomes were discounted at 5%. A willingness-to-pay threshold of 50,000$/QALY was used. Results: LDR and SBRT were less expensive and more effective than EBRT. These findings were robust to changes in input variables. SBRT was the dominant strategy with 0.008 LYs and 0.029 QALYs gained and a reduction in cost of $2,615 when compared to LDR. However, these results were sensitive to the BR probability. LDR becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR is 0.76*[baseline BR_LDR]. When assuming the same BR for both strategies, LDR becomes more effective with 0.009 QALYs gained at a cost of 272,848 $/QALY. Conclusions: In Ontario and comparable jurisdictions, SBRT might represent an economically attractive radiation strategy; however longer-term follow-up and higher quality evidence are needed. Effectiveness Cost Life-Years Incremental Costs QALYs Life-Years CAD QALYs SBRT 11.174 9.926 72,378 - - - Dominant LDR 11.166 9.897 74,993 0.008 0.029 2,615 Weakly Dominated EBRT 10.936 9.404 77,644 0.23 0.493 2,651 Dominated
Factors influencing first-line therapy of acute myeloid leukemia (AML) patients (pts) in the Connect MDS/AML Disease Registry.
Authors: Christopher R. Cogle, Daniel Aaron Pollyea, Mehrdad Abedi, Michael A. Thompson, Gail J. Roboz, Chrystal Ursula Louis, E. Dawn Flick, Melissa Nifenecker, Pavel Kiselev, Arlene S. Swern, Harry Paul Erba
Journal: Journal of Clinical Oncology (2018)

7037 Background: Historically, only about 40% of AML pts ≥ 65 y of age receive first-line therapy (1LTx) due to high adverse event and low 5-y survival rates. With the introduction of new agents to treat AML, we sought to identify current factors influencing 1LTx across clinical practice settings. Methods: The Connect® MDS/AML Registry (NCT01688011) is an ongoing US, prospective observational cohort study of pts with newly diagnosed AML (≥ 55 y) or MDS. Baseline demographics, median census income per capita (determined by ZIP code), disease characteristics, and genomic and treatment data were collected on AML pts enrolled from Dec 2013 to Oct 2017. Pts were categorized as receiving 1LTx (low- or high-intensity) or best supportive care (BSC) based on care provided ≤ 45 d after AML diagnosis (dx). Pts participating in clinical trials (n = 11) were excluded to focus on standard treatment practice. Uni- and multivariable logistic regression identified factors associated with 1LTx. Results: Data on 378 AML pts from 100 institutions (19 academic, 81 community/government) were analyzed. Median age was 70 y (range 55–92), 64% were male, and 83% were white. Most had private/Medicare insurance coverage (86%); average median income was USD 25,984. 77% of the cohort received 1LTx; 23% received BSC. 11% died ≤ 45 d after dx, of whom 90% had received 1LTx (P < 0.05). 77% had FISH or cytogenetic testing and 71% had molecular genetic testing, with 46% harboring ≥ 1 gene mutation. While age and comorbidities were predictors of 1LTx (P < 0.1) in univariable analyses, they were not independent predictors in multivariable analyses. In multivariable modeling, independent predictors of 1LTx were insurance coverage (P < 0.01), income (P < 0.01), and diagnostic genomic testing (P < 0.05). Probability of receiving 1LTx was lower in the Midwest (P < 0.01). Conclusions: In this preliminary analysis, 1LTx in AML pts was more strongly associated with diagnostic genomic testing and social determinants of health, such as income, insurance coverage, and geographic location. This highlights access and cost as potential barriers to AML pts receiving beneficial treatment. Clinical trial information: NCT01688011.
Effectiveness of the Moreau strain of Bacillus Calmette-Guerin (BCG) for nonmuscle invasive bladder cancer.
Authors: Daher Cezar Chade, Andre Machado, Ricardo Waksman, Guilherme Garcia, Paulo Esteves, Sanarelly Adonias, Luis Botelho, Mauricio Cordeiro, Claudio Murta, Leopoldo Ribeiro-Filho, Alvaro Sarkis, Diogo Assed Bastos, Carlos Dzik, Miguel Srougi, William Carlos Nahas
Journal: Journal of Clinical Oncology (2017)

4539 Background: Intravesical instillation therapy of Bacillus Calmette-Guerin (BCG) for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection has been widely shown to be more effective than any other adjuvant treatment. However, there are several different BCG strains not appropriately evaluated in clinical setting, but in current use. BCG Moreau is by far the most utilized strain in Brazil and has been recently introduced to the European market to cover the issue of BCG shortage, but there is insufficient data regarding its oncologic efficacy. Methods: We retrospectively analyzed 336 consecutive patients, who received adjuvant intravesical instillation therapy with BCG Moreau for intermediate- and high-risk NMIBC between January 2005 and February 2015 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. Results: Median age was 62 years (interquartile range 54-76, mean 64.3 years). In addition to induction BCG therapy, 228 (67.9%) patients received maintenance BCG. However, 35 (15.4%) patients interrupted maintenance BCG due to toxicity. Overall, after at least a complete induction BCG therapy, 87 (25.9%) patients presented with disease recurrence and 33 (9.8%) patients had disease progression. When analyzing on patients who received BCG maintenance in addition to induction therapy, 31 (13.6%) patients had disease recurrence and 10 (4.4%) had disease progression. The 5-year recurrence-free survival and progression-free survival rate was 69.8% (95% CI 52.8-77.2) and 86.2% (95% CI 69.9-93.2), respectively. Conclusions: BCG Moreau has shown to be safe and effective as adjuvant intravesical treatment in intermediate and high-risk NMIBC patients. Since results are comparable to other strains, wider use of BCG Moreau may be encouraged and prospective clinical trials stimulated for higher level of evidence.
The impact of four dimensions CT simulation on planning target volume in radiotherapy for primary lung cancer.
Authors: Fawzi Jamil Abuhijla, Lubna Abdelrahman Hammoudeh, Ramiz Ahmad Abu-Hijlih, Jamal Khader
Journal: Journal of Clinical Oncology (2017)

e20091 Background: 4D CT simulation has been evolved to estimate the internal body motion and considered as a useful tool for intra-thoracic tumor definition. This study aimed to evaluate the impact of using 4D simulation on the planning target volume (PTV) for primary lung tumor. Methods: Patients who underwent CT simulation for primary lung cancer radiotherapy between 2012-2016 using 3D- (free breathing) and 4D- (respiratory gated) institutional protocol were included in this retrospective review. For each patient, gross tumor volume (GTV) was contoured in free breathing scan (3D-GTV), exhale scan (e-GTV) and inhale scan (i-GTV). The corresponding CTVs (3D-CTV, e-CTV and i-CTV) were created by adding 1 cm in all directions. 3D-internal target volume (3D-ITV) was generated by 0.5 cm cranio-caudal expansion of 3D-CTV, while 4D-ITV was created by combination of e-CTV and i-CTV. Subsequently, a 0.5 cm margin was added to generate the 3D-PTV and 4D-PTV respectively. The volumes of 3D-PTV and 4D-PTV were compared to examine the impact of 4D CT simulation on changes in the volume of PTV. Univariable and multivariable analysis were performed to test the impact of volume and location of GTV on the changes of PTV volume by more than 10 % between free breathing and respiratory gated scans. Results: A total of 10 patients were identified. The median [range] GTV, i-GTV, e-GTV volumes were 13.55 [1.44-628.66], 13.17 [1.77-627.36], 12.85 [1.34-630.25] cc respectively. The 3D-CTV, i-CTV, e-CTV volumes were 86.37 [23.76-1209], 84.97 [25.5- 1220.4], 83.40 [23.36-1224.12] cc respectively. 3D-ITV and 4D-ITV median volume was 106.06 [3.99-1422.8], 88.02 [20.51-1338.18] cc respectively. 3D-PTV was significantly larger than the 4D-PTV; median [range] volumes were 182.79 [58.65- 1861.05] vs. 158.21 [52.76-1771.02] cc, p = 0.0068). On multivariable analysis, neither the volume of GTV (p = 0.4917), nor the location of the tumor (peripheral, p = 0.4914 or lower location, p = 0.9594) had an in impact on PTV differences between free breathing and respiratory gated scans. Conclusions: The use of 4D simulation reduces the PTV for primary lung cancer, and it should be routinely implemented in clinical practice regardless the tumor volume or location.
Histology determination of lung cancers: A report on genomic profiling of lung cancer of mixing histology.
Authors: Ming Tang, Neda Kalhor, Maheshwari Ramineni, Junya Fujimoto, Jianhua Zhang, Jun Li, Chi-Wan Chow, Xizeng Mao, Xingzhi Song, Latasha Little, Curtis Gumbs, Carmen Behrens, William N. William, Annikka Weissferdt, J. Jack Lee, Stephen Swisher, John Heymach, Ignacio Ivan Wistuba, Andrew Futreal, Jianjun Zhang
Journal: Journal of Clinical Oncology (2017)

8570 Background: Histopathology, largely determined by morphology, plays a critical role in choosing appropriate treatment for lung cancer. The understanding of molecular determination of lung cancer histology is rudimentary. Our recently published data (Zhang, Science, 2014 and Liu, Nature Communications, 2016) have demonstrated that within the same patients with identical genetic background and identical exposure, tumor regions with different morphologic appearances may have very similar genomic profiles while tumors with the same morphology may have distinct genomic landscape. Methods: We collected 12 lung cancers of mixing histology with 2 to 4 histologic components within each tumor. In total, 26 tumor regions including 9 adenocarcinomas, 6 large-cell neuroendocrine carcinoma, 6 small cell carcinomas and 4 squamous cell carcinomas and one poorly differentiated lung carcinoma were microdissected and subjected to whole exome sequencing. Results: A substantial number of identical mutations were shared between different histologic components within the same tumor in all 12 patients. However, the proportion of shared mutations varies in different patients ranging from as little as 4% to as much as 99%. Mutation spectrum is also similar between different histologic components within the same tumors suggesting similar mutational process in place. Identical canonical cancer gene mutations including TP53, KRAS, PIK3CA, SOS1 and STK11 are generally shared between different histologic components within the same tumors. Canonical mutations in FBXW7 and MTHFR were detected in squamous component, but not small-cell component in one patient. Conclusions: Different histologic components of lung cancers of mixing histology are likely derived from the same progenitor cells, but the molecular timing of branch separation of subclones giving rise to different histologic components varies in different tumors. Although genomic aberrations may play a role in a subset of tumors, histologic features may not be determined at genomic level for most lung cancers. Gene expression and methylation analyses from these tumors are underway.
Comprehensive analysis of tumor NGS data to demonstrate pathways pointing to therapeutic targeting options.
Authors: Subha Krishnan, Ally Perlina, Alex Thomas, Boyko Kakaradov, Wayne Delport, Ramlah B Nehring, Eve Shinbrot, Thanemozhi G Natarajan, Corine K Lau, Alexandra E Gylfe, Rachana Sainger, Kimberly Pelak, Heather L Smith, William Biggs, Brad Perkins, Ezra E.W. Cohen, Kenneth Joel Bloom
Journal: Journal of Clinical Oncology (2017)

e23153 Background: Recent advancements in NGS technology have enabled precision medicine based on tumor-specific genomic alterations. However, the complex nature of tumor biology demands an integrative analysis of genomic variations to identify converging downstream targets potentially regulated by multiple pathways. Methods: Genomic alterations from whole-genome sequencing results were interpreted in the context of pathways. Beyond listing the implicated known pathways based on genomic alterations, we explored protein interactions cross-linking the pathways to converging downstream targets. An in-house analytical pipeline was used to prioritize candidate pathways from MetaBase™, which contains manually curated pathways and interactions based on published experimental results. Custom pathway diagram was then designed manually to depict the most actionable pathways. The manual review consists of context-checking and addressing the concordant/discordant nature of all interactions. Factor such as mutational impact, directionality, mechanism of interaction and known targeted action are taken into account. Results: Comprehensive analysis of the genomic variations in three tumors types revealed activation of multiple oncogenic signaling pathways. Key events driving the tumor in a melanoma sample were NF1/RAS/MEK/ERK, WNT/beta-catenin pathway, and MITF signaling. Three interconnected signaling pathways, WNT, PI3K/AKT, and P53 were impacted by genomic alterations in a colorectal sample, which point to activation of converging downstream targets- CDK6, VEGFA, and COX-2. Integrated discovery of genomic alterations in an esophageal adenocarcinoma sample suggested potential activation of PI3K/AKT/MTOR and p16/Cyclin D1/CDK pathways. This could synergistically activate downstream converging targets- VEGFA, Cyclin D1, CDK6, CDK4, AURKA; some of which also showed relative RNA overexpression, supporting our pathway findings. Conclusions: Comprehensively analyzing the genomic alterations in context of cell signaling pathways provides us insights on how the pathways synergistically affect downstream targetable events, which in turn can impact therapeutic decisions.
Prognostic value of PET/CT volumetric prognostic index in operable NSCLC patients.
Authors: Haiyan Liu, James Zhang, Cassie A Simon, Mark K. Ferguson, Yonglin Pu
Journal: Journal of Clinical Oncology (2016)

8548 Background: We developed a PET/CT volumetric prognostic staging system (PVP index) using risk-based models integrating hazard of death from both whole-body metabolic tumor volume (MTVWB ) and TNM stage, and showed its greater prognostic power than TNM stage in NSCLC of different stages and treatments. This study is designed to further confirm its prognostic value in operable NSCLC patients. Methods: We performed an IRB-approved retrospective review of 377 operable patients with a new NSCLC diagnosis from 2004 to 2015. Clinical TNM stage, initial PET MTVWB , and long-term survival data were collected. 27 patients refused surgery, 350 patients had surgical treatment (187 surgery alone, 82 surgery+chemotherapy, 11 surgery+radiation, 70 surgery+chemoradiation). Ten of 350 surgically treated patients who died within 1 month after surgery were excluded. 367 patients were included in the analysis, with a median age of 68.7 years, 58% women, and mean follow-up among survivors of 4.43 years. TNM stage was IA (37.3%), IB (16.9%), IIA (11.2%), IIB (4.1%), IIIA (15.0%), IIIB (5.5%) and IV (10.1%). Cox regression analyses were performed to derive Gonen and Heller's Concordance Index (GHCI) to evaluate the discriminatory power and prognostic accuracy of the PVP index and TNM stage, respectively. Bootstrapping was conducted to test the statistical difference between the GHCIs. Results: A lower PVP index was significantly associated with better overall survival (univariate Cox regression P< 0.001 and multivariate P< 0.001, respectively).Univariate analysis showed that PVP index (GHCI = 0.6238, P< 0.01) has greater discriminatory power than TNM stage (GHCI = 0.6155). Multivariate analyses showed that the model with PVP index has greater overall discriminatory power (GHCI = 0.6983, p < 0.01) than TNM stage (GHCI = 0.6839) with other identical co-variables. The adjusted hazard ratio for the PVP index was 2.03 (95% CI = 1.52 to 2.73, p < 0.001), after controlling for age, gender, performance status, treatment received and tumor histology. Conclusions: The PVP index shows equivalent performance and may contain richer information about operable NSCLC patient prognosis than the current TNM staging system, and hence deserves further investigation.
TCT-600 The Impact of Diabetes Mellitus on the Long-term Risk for Heart Failure in Patients who Underwent Coronary Revascularization
Authors: Yasuaki Takeji, Hiroki Shiomi, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Hidenori Yaku, Tomohisa Tada, Junichi Tazaki, Takao Kato, Michiya Hanyu, Tatsuhiko Komiya, Kenji Ando, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2018)
Analysis of hereditary cancer syndromes in patients from the United Arab Emirates.
Authors: Shaheenah S. Dawood, Angela Apessos, Maroun Elkhoury, Faraz Khan, Falah Khatib, Milicent Bello, Annette Hamadi
Journal: Journal of Clinical Oncology (2018)

e13509 Background: Hereditary cancer accounts for approximately 10% of all cancers. An estimated 15-20% of all cancer patients have positive family history. However, until recently mutations in highly penetrant genes were only identified in approximately 20% of high-risk families. Technological advances in DNA sequencing, commonly designated as “Next Generation Sequencing-NGS” allowed to identify new genes responsible for the missing heritability, allowing the application of this knowledge in the diagnostic setting. Methods: Between 2015 and 2017, 276 patients were tested at two institutions in Dubai, UAE for BRCA1 and BRCA2 genes and the common CHEK2 c.1100delC mutation. In 2017, testing was extended to include 33 genes for 89 patients tested. Testing for all 276 patients was conducted at a single laboratory with testing criteria based on NCCN guidelines. Results: At the time of testing, median age was 44 years (range 26–72 years) with the majority of patients diagnosed with breast cancer. Patients tested were from a diverse ethnic group the majority of whom were from the Middle East and Asia pacific region. 24/276 (8.7%) had a pathogenic variant identified in the BRCA (n = 13), BRCA2 (n = 8) or c.1100delC in CHEK2 (n = 3) gene and 30 (10.8%) patients had a VUS in one of the three genes. Of the 89 patients tested with the 33 gene panel, additional pathogenic variants were identified in 7 (7.8%) patients involving the MUTYH (n = 4), RAD51C (n = 1), RAD50 (n = 1) and PALB2 (n = 1) genes and at least one VUS was reported in 35 (39%) patients. The most commonly mutated genes across the whole cohort were BRCA1 and BRCA2, accounting for 55% of the mutations identified. Two (11%) of the mutations identified were large genomic rearrangements of several exons of the BRCA1 and RAD51C genes. Conclusions: Our results support the clinical significance of analysis of a panel of genes involved in hereditary cancer predisposition. In our series, pathogenic variants were identified in all but one case in genes for which enough data has been collected allowing for the formulation of clinical management guidelines. These patients have therefore received results which will alter their clinical management.