tbuckley/cabot-search huggingface dataset:
Comparison of real-world direct healthcare costs for metastatic colorectal cancer patients treated with cetuximab vs. bevacizumab as first-line therapy.
Authors: Stephen Johnston, Sarika Ogale, Ellen Riehle, Helen Varker, Paul Juneau, Kathleen Wilson
Journal: Journal of Clinical Oncology (2015)

e17785 Background: This study compared healthcare costs between metastatic colorectal cancer (mCRC) patients treated with cetuximab (CET) vs. bevacizumab (BEV) as first-line (1L) therapy. Methods: Using a large U.S. commercial/Medicare supplemental insurance claims database, patients with mCRC initiating 1L therapy for mCRC with CET or BEV between 7/1/2008-11/30/2013 were identified. Per-patient per-month (PPPM) healthcare costs were measured over a follow-up period beginning at initiation of 1L therapy and ending at the first of discontinuation of 1L therapy, inpatient death, insurance disenrollment, or 12/31/2013. Generalized linear models (log link/gamma error) compared PPPM total healthcare costs between CET vs. BEV-treated patients. Results: In all settings of care, mean/median unadjusted PPPM healthcare costs were numerically higher among CET-treated patients (Table). In the multivariable-adjusted analyses, PPPM total healthcare costs were 19% higher for CET than for BEV-treated patients (P<.0001). Findings were consistent in sensitivity analyses. Conclusions: This real-world observational study of mCRC patients in first-line setting, found that per-patient per-month total healthcare costs were significantly higher for CET-treated patients than for BEV-treated patients. Study Results Bevacizumab N=5,635 Cetuximab N=518 Mean (SD; median) follow-up days 203 (152; 177) 166 (151; 124) Mean (SD) age in years 58.8 (11.7) 60.0 (12.3) % Female 45% 39% Unadjusted mean (SD; median) PPPM costs Inpatient and outpatient medical $8,786 ($12,108,$5,980) $11,638 ($18,309,$7,291) Outpatient pharmacy $407 ($966; $130) $566 ($1,093; $184) Chemotherapy and administration $5,986 ($5,718; $4,880) $3,887 ($4,926; $2,050) Biologic drug and administration $7,197 ($5,985; $5,963) $11,309 ($9,029; $9,920) Total healthcare costs $22,376 ($16,639; $18,684) $27,400 ($22,866; $22,191) Adjusted PPPM Total healthcare cost results (Bevacizumab=reference) Cost ratio (95% CI) Cost ratio=1.19 (95% CI=1.13 to 1.25) P<.0001 Mean cost difference (95% CI) $3,821 ($1,908 to $7,093) CI=confidence interval; SD=standard deviation.
Analysis of outcomes of patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Naveen Pemmaraju, Deborah A. Thomas, Hagop Kantarjian, Susan Mary O'Brien, Naval Guastad Daver, Aziz Nazha, Sherry Pierce, Guillermo Garcia-Manero, Jorge E. Cortes, Stefan Faderl
Journal: Journal of Clinical Oncology (2012)

6578 Background: BPDCN, formerly known as CD4 + CD56 + hematodermic tumor or blastic NK cell lymphoma, is a rare and aggressive hematologic malignancy. Little is known about outcomes of pts with BPDCN. Methods: We conducted a retrospective review of pts meeting following criteria: pathological diagnosis of BPDCN confirmed by an experienced hematopathologist and age ≥ 18. Results: 13 pts, diagnosed October 1998-July 2011, were identified. Median (med) age: 62 years (range 20-86 years), 12 (92%) were male. Bone marrow (BM) involved in 9 (69%), skin 8 (62%), lymph nodes 5 (38%), brain 1 and uterine/ovarian 1 pt. Immunophenotype by flow cytometry: CD4+ (11/11 pts), CD56+ (10/11 pts), TCL-1+ (4/4 pts). Karyotype (8 pts): del(12) (1pt), complex (2), and diploid (5). Med CBC: WBC 5.8 x 10 9 /L (1.7-76.5), Hb 12.3 g/dL (8.3-17.0), platelet 107 x 10 9 /L (44-255). Med BM blasts: 22% (0-77). 10 pts received first-line therapy with Hyper-CVAD alternating with high-dose methotrexate(MTX) and cytarabine (HCVAD) (in 1 pt following one cycle of CHOP), CHOP (2), oral MTX (1). Med follow-up time: 9 months (mo) (2-14 mo). Med number chemotherapy regimens: 1 (1-5). Complete remission (CR) in 10 pts. Med CR1: 19 mo (4-39 mo). Med overall survival (OS) 29 mo (1-44 mo). 9 pts have died, unknown cause (3), multi-organ failure (6). 10 pts received HCVAD as part of first line therapy: med OS: 29 mo (1-44 mo), med CR1: 21 mo (4-39 mo), 9/10 (90%) pts achieved CR1; 1 pt did not achieve CR1 (died, pneumonia, day 15). 9 pts (69%) had BM involvement (7 with other organs involved besides BM). 4 (31%) pts had no BM involvement; all 4 of these pts had skin involvement only. Med OS, med CR1 of pts with BM involvement: 23 mo (1-44mo), 22 mo (4-39mo), respectively. Med OS, med CR1 of skin only pts: 29 mo (2-31 mo), 7 mo (6-19 mo), respectively, p=not significant. 4 pts received stem cell transplant (SCT) (2 allogeneic ,2 autologous). Med OS for pts receiving SCT (n=4) was 31 mo(8-31 mo) versus med OS for non-SCT group (n=9) of 29 mo (1-44), p=not significant. Conclusions: Despite intensive multi-agent chemotherapy and SCT, response rates are low and survival is short. Better understanding of the biologic basis of this disease and novel treatment approaches for treatment of BPCDN are crucial.
Agreement validation between axial imaging modalities and endoscopic ultrasonography in staging resectability of pancreatic cancer.
Authors: Nghia Pham, Sam G. Pappas, Ebenezer Enchia, Adam Gliniewicz, William Small, Neil Gupta, Christine M. Dudiak, Faaiza Mahmoud, Aakash Ahuja, Thomas Aquisto, Nihal Gooneratne, Tejvir Nanda, Timothy Ozga, Brendan Martin, Tarita Thomas
Journal: Journal of Clinical Oncology (2017)

273 Background: Vascular involvement is a key determinant of resectability and treatment sequencing in pancreatic cancer (PC). Current staging requires multidetector CT (MDCT) and endoscopic ultrasonography (EUS), but there are still occasions when vascular involvement cannot be fully assessed. Current NCCN guidelines recommend using magnetic resonance imaging (MRI) for clarifying these ambiguities. The primary aim of our study is to access the accuracy of CT, MRI, and EUS in staging resectabilty of PC. The secondary aim is to assess internal consistency in the evaluation of vascular involvement among different staging modalities. Methods: We retrospectively reviewed 40 medical records of patients who were treated at LUMC for PC from 2006 to present. We evaluated 8 MDCT scans and 8 MRI scans in addition to their EUS reports. Seven board certified radiologists analyzed the 16 imaging studies using a standardized template. Unweighted Kappa statistic and observed agreement analysis was calculated to assess inter-observer agreement on vessel involvement between the imaging studies compared to the EUS reports. We sought to examine degree of concordance for involvement of the superior mesenteric artery (SMA), superior mesenteric vein (SMV), and main portal vein (MPV) with the pancreatic tumor. Results: Low Kappa and observed agreement in respect to vascular involvement between MDCT and EUS was found for SMV (K = 0.33, 62.5%), SMA (K = -0.2, 62.5%), and MPV (K = 0.38, 75%), indicating low concordance. Low Kappa and observed agreement in respect to vascular involvement between MRI and EUS was found for SMV (K = 0.09, 37.5%), SMA (K = 0.14, 62.5%), and MPV (K = 0.47, 75%). Low Kappa and observed agreement in respect to vascular involvement between MRI and MDCT in comparison to EUS was found for SMV (K = 0.11, 50%), SMA (K = 0.20, 75%), and MPV (K = 0.14, 62.5%). Conclusions: Concordance was shown within each imaging modality when analyzed by radiologists. Due to high discordance across different staging modalities, however, MRI and CT scans complement each other in determining degree of vascular involvement. We believe both imaging modalities should be used in staging borderline resectable PC.
Postrecurrence survival for pediatric extracranial malignant germ cell tumors: A report from the Malignant Germ Cell Tumors International Collaborative (MaGIC) Group.
Authors: Furqan Shaikh, Ha Dang, Mark D. Krailo, Juliet Hale, James Nicholson, Carlos Rodriguez-Galindo, Thomas Arthur Olson, Matthew Murray, James Amatruda, Claire Thornton, Suren Arul, Deborah Billmire, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2014)

10074 Background: Post-recurrence survival (PRS) of children and adolescents with malignant germ cell tumors (MGCTs) has not previously been described, due to the limited sample size of relapsed patients in clinical trials. Methods: Data from 7 pediatric extracranial GCT trials conducted by the Children’s Oncology Group (COG, United States) or the Children’s Cancer and Leukemia Group (CCLG, United Kingdom) between 1985-2009 were merged. The COG and CCLG trials differed mainly in the type of platinum agent used for upfront treatment (cisplatin or carboplatin, respectively), and event-free survival after either treatment were not significantly different, as previously reported. Kaplan-Meier survival curves and Cox regression were used to analyze the effects of potential predictor variables on PRS. Results: Among 1,107 children in the pooled dataset, 700 MGCT patients received treatment with platinum-based chemotherapy. 72 of these patients experienced a relapse or refractory disease. For these 72 patients, the 5-year PRS was 38% (95% confidence interval (CI) 26% - 49%). The 5-year PRS was significantly higher for 29 children who had been treated upfront with carboplatin regimens (51% , CI 31% - 67%) compared to 43 children treated upfront with cisplatin regimens (28%, CI 15% - 43%; log-rank p=0.046). PRS was not significantly associated with age at diagnosis, tumor site, stage, initial AFP, or time to relapse. In a multivariable model where the known prognostic factors for upfront pediatric GCT (age, stage, and site) were added, the effect of chemotherapy regimen remained significant (hazard ratio 2.06, CI 1.03 - 4.10; p=0.041). Data on post-recurrence treatment regimens were not available. Conclusions: Though limited by the lack of data on type of salvage therapy, we observed a significantly higher PRS after upfront carboplatin regimens compared to upfront cisplatin regimens. This observation should be explicitly tested in a prospective trial. This finding also suggests that overall survival, rather than relapse-free survival, should be utilized as the primary end-point in reduction-of-therapy trials for treatments with differences in PRS.
Survival and FEV<sub>1</sub>Decline in Individuals with Severe Deficiency of α<sub>1</sub>-Antitrypsin
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Subjects ⩾ 18 yr of age with serum α1-antitrypsin ( α1-AT) levels ⩽ 11 μ M or a ZZ genotype were followed for 3.5 to 7 yr with spirometry measurements every 6 to 12 mo as part of a National Heart, Lung, and Blood Institute Registry of Patients with Severe Deficiency of Alpha-1-Antitrypsin. Among all 1,129 enrollees, 5-yr mortality was 19% (95% CI: 16 to 21%). In multivariate analyses of 1,048 subjects who had been contacted ⩾ 6 mo after enrolling, age and baseline FEV1% predicted were significant predictors of mortality. Results also showed that those subjects receiving augmentation therapy had decreased mortality (risk ratio [RR] = 0.64, 95% CI: 0.43 to 0.94, p = 0.02) as compared with those not receiving therapy. Among 927 subjects with two or more FEV1 measurements ⩾ 1 yr apart, the mean FEV1 decline was 54 ml/yr, with more rapid decline in males, those aged 30 to 44 yr, current smokers, those with FEV1 35 to 79% predicted, and those who ever had a bronchodilator response. Among all subjects, FEV1 decline was not different between augmentation-therapy groups (p = 0.40). However, among subjects with a mean FEV1 35 to 49% predicted, FEV1 decline was significantly slower for subjects receiving than for those not receiving augmentation therapy (mean difference = 27 ml/yr, 95% CI: 3 to 51 ml/yr; p = 0.03). Because this was not a randomized trial, we cannot exclude the possibility that these differences may have been due to other factors for which we could not control.
Next-generation sequencing in metastatic lung cancer patients: Translation from sequence data into clinical practice.
Authors: Jessica Ribeiro Gomes, Raphael Brandao Moreira, Renata D'Alpino D'Alpino, Marcelo Rocha S Cruz, Tercia Tarciane Soares de Sousa, Marcus Paulo Fernandes Amarante, Marcos André Costa, Fabio Schutz, Carolina Kawamura Haddad, Rafael Schmerling, Fernando C. Maluf, Antonio C. Buzaid
Journal: Journal of Clinical Oncology (2015)

e12521 Background: Several patients with lung cancer (LC) maintain good performance status even after disease progression following all standard therapies. More recently, targeted therapies have been improving prognosis of patients with advanced LC. We aim at exploring the role of a next-generation sequencing (NGS) assay in identifying therapeutic targets for refractory LC. Methods: Patients diagnosed with metastatic LC with available paraffin-embedded tissue evaluated by the method of NGS (Foundation Medicine, USA) were included. Hybridization capture of 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥ 50 ng of DNA extracted from 12 LC specimens and sequenced to high, uniform coverage. Genomic alterations (GA) were reported for each patient sample. Actionable GA were defined as those identifying anti-cancer targeted therapies available on the market or in registered clinical trials. Results: Twenty-nine patients were included (86.2% adenocarcinoma, 6.9% squamous cell carcinoma). Median age was 59 years (range 30-80); 65.5% were male and 55.2% were smokers or previously smokers. A total of 40 GA were identified: 29 patients (72.4%) harbored ≥ 1 GA, and 16 patients harbored ≥ 1 actionable GA (55.2%). The most frequent actionable GA were detected in EGFR (24.1%), AKT2 (10.3%), STK11 (10.3%), MET (6.8%), HER2 (3.4%), ROS1 (3.4%), and FGFR1 (3.4%). Non-actionable GA were mostly detected in TP53 (48.3%), MCL1 (17.2%), and CDKN2A (13.8%). The use of trastuzumab in a patient with mutated HER-2 yielded a time to progression (TTP) of 8 months. Five patients previously identified as wild-type EGFR were found to actually have EGFR mutation, with a median TTP of 11 months (1-16m) with tyrosine kinase inhibitors. Conclusions: Comprehensive NGS may identify novel mutations in LC patients with potential clinical utility and serve as genetic biomarkers for personalized therapeutics.
Recurring breast and arm cellulitis in patients with early breast cancer.
Authors: Faisal Cheema, Maliha Agloria, Glenn Morris Mills, Runhua Shi, Benjamin Li, Quyen Chu, Roger Hoon Kim, Fred Ampil, Gary Von Burton
Journal: Journal of Clinical Oncology (2013)

e20600 Background: Breast and arm cellulitis (BAC) is a recognized risk following treatment for early stage breast cancer with case reports suggesting an incidence &lt;3%. However, there is limited information relative to risk factors, management, recurring BAC and outcome. We reviewed all incidences of BAC in patients (pts) with early stage breast cancer seen at our institution and correlate with co-morbid conditions, recurrent BAC events and treatment outcomes. Methods: A review of all pts with Stage I-III breast cancer seen between 2001-2011 identified pts with at least 1 episode of BAC. Data on age, race, stage, treatments, co-morbid conditions, lymphedema, incidence and recurrence of cellulitis, and antibiotic (Abx) therapy was extracted. We defined incident BAC to occur &gt;30 days post chemotherapy/radiation completion. Chi-square test was used to assess variables associated with BAC recurrence. Results: 391,603 breast cancer pts (2.5%) were identified with BAC with median age 59 years. The median interval between completion of primary treatment and incident cellulitis was 330 days (30 – 3,650 days). 13 out of 39 pts (33%) had recurring BAC (range 1-7 events). Median duration of Abx therapy was 30 days (7 – 2,190). Lymphedema (p=0.04), chemotherapy (p=0.01), Stage &gt; I (p=0.02) and initial poor response to Abx (p=0.003) were significantly associated with recurring BAC. Positive bacterial cultures were obtained in 4 of 62 BAC events. Initial Abx failure was lowest with vancomycin (Vanc). A protracted course (30 days) of oral Abx after initial Vanc was associated with a lower risk of early recurrence. Chronic Abx therapy, for pts with 3 episodes, appeared to reduce subsequent recurrent episodes. Conclusions: Results indicate that while BAC is relatively uncommon following breast cancer therapy, pts with BAC are at significant risk for recurring events. Lymphedema, higher stage and initial poor response to Abx proofed as parameters for recurrence. Despite treatment with Abx a significant number will have recurring events. For pts presenting with these variables we recommend a protracted course of initial Abx. Pts with recurring BAC should receive chronic Abx suppressive therapy. This approach was associated with good long term control in our pts.
Impact of site of service on chemotherapy costs: Influence of geographic location and diagnosis.
Authors: Michael A. Kolodziej, Bob Cullum, Kevin Hastings, Maria Sipala, Amy Supraner, Cheryl Dubois, Harold Paz, Ira Klein
Journal: Journal of Clinical Oncology (2015)

6601 Background: Site of service strongly influences the cost of cancer treatment. The migration of community oncology practices to the hospital based practice setting has generated considerable discussion about the cost differential between these sites. Methods: We examined claims paid for chemotherapy by Aetna from August 2013 through July 2014 for all malignancies as well as breast/colon/lung cancer (BCL). Results: Over this period of time, Aetna paid chemotherapy claims for 46,000 unique members, including 17,000 members with breast, colon and lung cancer (BCL). For all members receiving chemotherapy as well as for members with BCL, 69% received chemotherapy in the office setting (O) and 31% received chemotherapy in the hospital outpatient setting (H). Despite this patient distribution, chemotherapy allowable reimbursement share was 42% for H and 58% for O, indicating a disproportionate share of chemotherapy reimbursement to H. When considering average chemotherapy allowed per member, patients treated in H for all cancers were 59% more costly per member, while patients treated for BCL were 40% more costly per member. When examining site of service by state, considering only states with more than 100 members treated in H, there was great variation in site distribution, from a high of 79% (Massachusetts) to a low of 15% (Florida). The allowed chemotherapy costs per unique member were 229% for all malignancies and 190% for BCL in the most costly H state compared to the most costly O state. Paying H the average O allowable would generate $100 million savings. Conclusions: The impact of site of service on chemotherapy costs is complex. Only 30% of patients treated with chemotherapy receive treatment in H but H received a disproportionate share of reimbursement for all malignancies as well as the most common malignancies (BCL). These differences are remarkably variable from state to state both with respect to the distribution of patients by site of service as well as the cost of care by site of service. For a large commercial payer, the site of service differential increases cost of care substantially. Given the geographic variability, a simple solution is not likely.
Oncotype DX in <i>BRCA</i>-associated vs. sporadic breast cancers: Differences based on germline mutation status and potential implications for adjuvant systemic therapy (AST).
Authors: Payal Deepak Shah, Sujata Patil, Maura N. Dickler, Kenneth Offit, Clifford A. Hudis, Mark E. Robson
Journal: Journal of Clinical Oncology (2015)

519 Background: Biological differences between BRCA-associated and sporadic breast cancer (BC) could warrant different recommendations for AST among patients (pts) with phenotypically similar cancers. Oncotype DX (Genomic Health Inc., CA) is prognostic, quantifies predicted benefit of AST, and is used to guide clinical decisions in pts with early-stage hormone receptor-positive (HR+) BC. The results of this assay have not been described in pts with deleterious germline BRCA(gB) mutations. Methods: Pts seen at MSKCC for HR+, stage I/II, node-negative BC with Oncotype DX results, were retrospectively ascertained and medical records reviewed. B1/2 mutation carriers (cases) were identified and matched 1:2 to noncarriers (controls), based on age at diagnosis and tumor size. Two sample nonparametric tests were used to compare B1 vs. B2 pts. Conditional logistic regression (SAS v 9.4) assessed differences in Oncotype DX recurrence scores (RS) and risk stratification by mutational status. Results: 50 cases (B1: n = 19, B2: n = 31) and 100 controls were included. Cases and controls were well-matched for age (p = 0.9) and tumor size (p = 0.6). Cases were more likely to have high-grade tumors (p = 0.004). Median RS was 23 for B1 and 24 for B2 carriers (p = 0.6). Stratification into low-, intermediate-, and high-risk categories was similar between B1 and B2 carriers (p = 0.3). Median RS was significantly higher for cases than for controls (RS 24 vs. 16, p < 0.0001). Risk stratification also differed based on mutational status (p = 0.0002). Cases had more high-risk (28% vs. 7%) and intermediate-risk (56% vs. 36%) disease than controls. Cases had less low-risk disease than controls (16% vs. 57%). Cases were significantly more likely to receive AST (74% vs. 46%, p = 0.002). Conclusions: Presence of a gB1/2 mutation may be a biomarker for intrinsically less favorable disease in pts with early-stage, HR+ BC. Few affected gB carriers have RS indicating clear absence of benefit from AST. Increased use of, and benefit from, AST in gB carriers may mitigate otherwise inferior outcomes, accounting for the similar prognoses for carriers and noncarriers reported in the literature.