tbuckley/cabot-search huggingface dataset:
Association between VTE and MGMT status in patients with high grade glioma.
Authors: Angela Aziz-Donnelly, Briana Richardson, Srikant Rangaraju, Alfredo Daniel Voloschin
Journal: Journal of Clinical Oncology (2018)

e14055 Background: Patients with high grade gliomas (HGG), WHO grades III and IV, are at increased risk of venous thromboembolism (VTE) compared to patients with other malignancies. This suggests a clear thrombogenic effect of these tumors. We hypothesized that patients with HGG and unmethylated methyl guanine methyltransferase (MGMT) are more likely to develop VTE compared to their methylated counterparts. To our knowledge, an association between MGMT status and VTE has not been studied. Methods: A retrospective chart review was conducted of all patients with high grade gliomas seen in the neuro-oncology clinic at Emory University between January 1, 2014 and September 30, 2016. Patients were stratified based on methylation status and baseline performance status. The incidence rate of VTE, defined as deep vein thrombosis and/or pulmonary embolism confirmed by radio-diagnostic tests, was compared between both groups in unadjusted and adjusted models using Poisson regression. Results: 159 patient charts were reviewed, and 153 included in the final analyses. The average age of diagnosis was 57 years, and was similar between groups. The average KPS score and smoking status were also similar between groups. In the unadjusted analysis, there was a higher incidence rate of VTE in the unmethylated compared to the methylated group (Incidence Rate Ratio = 1.99, p = 0.011, 95% CI 1.12-3.54). Other predictors of increased VTE incidence were KPS < 60 (p = 0.005) and history of ischemic stroke/CAD (p = 0.007). After adjusting for these variables, unmethylated MGMT status remained independently associated with a higher incidence rate of VTE (IRR = 2.14, p = 0.013, 95% CI 1.15-3.98). Data on IDH mutation will be available at the time of the conference. Conclusions: This study suggests a higher incidence rate of VTE in patients with unmethylated, compared to methylated, high grade gliomas. If confirmed in larger studies, protocols for early diagnosis and treatment of these complications should be designed for this high-risk group of patients.
Real-world dosing patterns among metastatic breast cancer patients initiating first line (1L) palbociclib (PAL) therapy.
Authors: Damion Nero, Bruce A. Feinberg, Hsing-Ting Yu, Lynn McRoy, Jack Mardekian, Jessica Chung, Jeffrey Trocio
Journal: Journal of Clinical Oncology (2018)

e13050 Background: PAL was approved for the treatment (tx) of HR+/HER2- metastatic breast cancer (mBC) in combination (comb) with endocrine therapy (ET): aromatase inhibitors (AI) in 2015 and fulvestrant (FUL) in 2016, for patients (pts) who progressed on prior ET. We report the real-world dosing patterns of PAL in comb with ET as 1L therapy in mBC pts. Methods: Female mBC pts initiating PAL or ET monotherapy between 1/1/2012 and 3/31/2017 were selected from a linked EMR-claims database (EMR and Rx/medical claims). The first regimen observed following the diagnosis of mBC was defined as the 1L therapy (index date). The type of therapy used by the pt was determined by aggregating all applicable therapeutic drugs into comb regimens. Eligibility required 1L PAL+ET (letrozole, anastrozole, exemestaneor, FUL). Exclusions: pts with a second primary malignancy prior to index, or treated as part of a clinical trial, or with evidence of other regimen after mBC diagnosis. Pts were grouped as PAL+AI or PAL+FUL. Descriptive statistics employed to summarize characteristics. Results: 473 pts were identified who initiated 1L PAL+ET after mBC diagnosis: 74.8% PAL+AI, 25.2% PAL+FUL. 35.5% of PAL+ET pts started therapy on an ET monotherapy and continued on to comb therapy. Median follow-up time was 14 mo (PAL+AI) and 10 mo (PAL+FUL). Mean age 60.7 yrs, 75.9% treated in community practice, 51.8% southern US. 369 pts (78%) had a known starting dose: for PAL+AI (n = 279), 86.7% initiated PAL at 125mg, 11.5 % at 100mg and 1.8% at 75mg; and for PAL+FUL (n = 90), 85.6% initiated with 125mg, 12.2% at 100mg and 2.2% at 75mg. 74.4% of PAL+AI and 65.7% of PAL+FUL pts started on a dose of 125mg and continued on that dose while 25.6% of PAL+AI and 34.3% of PAL+FUL of these pts had a dose adjustment. 79.3% of dose adjustment from 125mg (77.4% of PAL+AI, 84.4% of PAL+FUL) occurred within 90 days of initiation. Conclusions: Most pts initiate PAL comb therapy at the recommended starting dose and continue on that dose. For pts with a dose reduction the majority occur within 90 days of treatment initiation. Clinicians who prescribed initial PAL combination therapy at a lower dose may have been considering patient's clinical history. This study was funded by Pfizer.
Duration of anticoagulant therapy and VTE recurrence in patients with cancer.
Authors: Alok A. Khorana, Keith McCrae, Dejan Milentijevic, Daniel Yannicelli, Jonathan Fortier, Winnie W. Nelson, François Laliberté, Concetta Crivera, Patrick Lefebvre, Jeff Schein
Journal: Journal of Clinical Oncology (2016)

10112 Background: Anticoagulant therapy for minimum of 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer and clinical trials have not evaluated benefit of treatment >6 months. We have previously found significant differences in persistence and duration of treatment between injectable and oral anticoagulants. In this study we examined the association between the duration of anticoagulation and VTE recurrence. Methods: Healthcare claims from the Humana database were used to identify newly diagnosed cancer patients who had their first VTE (DVT or PE) diagnosis between 1/1/2013 and 05/31/2015 and initiated low-molecular-weight heparin (LMWH), warfarin or rivaroxaban therapy (insufficient data for other oral anticoagulants). Follow-up was calculated from index treatment initiation to end of eligibility or end of data. VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE or outpatient diagnosis with new radiology imaging for VTE. Incidence rates of VTE recurrence were evaluated and adjusted Cox proportional hazards models were used for comparisons. Discontinuation was defined as a gap > 60 days between end of supply and start date of next dispensing. Results: A total number of 1,158 patients were included (LMWH: n=376; warfarin, n=473; rivaroxaban: n=309). VTE recurrence rates by duration of therapy are shown in the Table. Adjusted analysis showed that compared to the shortest duration of therapy (0-3 months), patients treated for 3-6 months (HR [95%CI]: 0.67; 0.52-0.88), 6-9 months (HR [95%CI]: 0.55; 0.40-0.76), and >9 months (HR [95%CI]: 0.54; 0.36-0.79) were less likely to develop VTE recurrence (all p<0.01). Conclusions: Anticoagulant therapy for VTE in cancer patient population lasting longer than 3 months is associated with significant reduction in VTE recurrence. These findings should help inform patients’ and oncologists’ decisions regarding duration of anticoagulation therapy. Duration of anticoagulant therapy (months) 0-3 3-6 6-9 +9 Number of patients 629 244 172 113 Follow-up, months, mean 10.9 14.9 17.4 21.4 % of pts with VTE recurrence 36.7 29.5 25.6 26.5 VTE recurrence rate (per 100 patient-years) 43.6 25.4 18.9 16.4
Racial and social disparities on aggressiveness of end-of-life cancer care in a rural academic center.
Authors: Praveen Namireddy, Shravanti Macherla, James Thompson McClain, Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2017)

e18063 Background: Aggressive cancer care at the end of life (EOL) can impact quality of life and have major economic burden. The purpose of this study was to determine the aggressiveness of EOL cancer care, and its relation to race, gender and social factors in Eastern North Carolina with a high rural and minority population. Methods: This is a retrospective analysis of 401 stage 4 solid tumor patients who died between 2011 and 2014 at Vidant Medical Center. Aggressiveness of care was calculated by a composite score adopted from Earle et al. Scores range from 0 to 7 with higher scores indicating more aggressive EOL care. 1 point was given to each indicator of aggressiveness in the last 30 days of life: ED visits ≥2, hospital admissions ≥2, any ICU admission, hospitalized days ≥14, new chemotherapy, hospice care ≤ 3 days, and any chemotherapy in the last 14 days. Results: Among 401 patients, 217 (54%) were white and 178 (44%) were black. The mean composite score for aggressiveness (CSA) for whites was 1.18 and for blacks it was 1.87 (p&lt;0.001). In the last 30 days of life, a higher proportion of blacks had ≥ 2 ED visits 28% vs 13%(p&lt;.0001), ≥ 2 hospital admission 23% vs 13%(p=0.001), any ICU admission 29% vs 16%(p=0.0002), chemotherapy in the last 14 days 30% vs 20%(p=0.001), and ≥ 14 hospitalized days 35% vs 21%(p&lt;0.001) compared to whites. More whites were enrolled in hospice compared to blacks 53% vs 45% (p&lt;0.001). Correlation analysis using Fit Y by X model showed statistically significant differences between CSA (score ≤ 3 and &gt;3) and other variables such as whites vs blacks p &lt;0.001, females vs males p=0.0006, not married vs married p&lt;0.0001, and no family support vs family support p&lt;0.0001. Conclusions: Male, unmarried and black patients were associated with higher CSA. Patients who were white, married and with family support had higher likelihood of enrolling in hospice. [Table: see text]
Towards a molecular algorithm predicting glioma treatment response and resistance: A biomarker analysis and path to real time profiling in N<sup>2</sup>M<sup>2</sup>.
Authors: Tobias Kessler, Felix Sahm, Gnana Prakash Balasubramanian, Elke Pfaff, David T. W. Jones, Antje Wick, Juergen Debus, Andreas Unterberg, Anne Berberich, Christel Herold-Mende, Stefan M. Pfister, Benedikt Brors, Susan Dettmer, Irini Karapanagiotou-Schenkel, Frank Winkler, Martin Bendszus, Andreas von Deimling, Michael Platten, Wolfgang Wick
Journal: Journal of Clinical Oncology (2018)

12090 Background: Gliomas regularly evade current therapies through primary and acquired resistance and the effect of temozolomide is mainly restricted to the subgroup of methylguanin-O6-methyltransferase promoter (MGMT) hypermethylated tumors. Further resistance markers and pathways against chemotherapy, radiotherapy and targeted agents are unknown, but will be important in targeted warehouse studies like NCT Neuro Master Match (N2M2). Methods: The diagnostic pipeline involves clinical and molecular analysis of WHO grade III (n = 116) and WHO grade IV (n = 400) glioma patient samples focusing on methylation profiles as well as a prospective feasibility study of real time multilayer molecular profiling on various levels in 43 WHO grade IV patients with an unmethylated MGMT promoter. Results: Isocitrate dehydrogenase (IDH) wildtype glioblastomas mainly show three different methylation clusters (RTKI, RTKII and mesenchymal). Samples of Cluster 1 (RTKII) had higher prevalence of MGMT methylation, TERT methylation and TERT promoter mutation. MGMT methylation is only prognostic in this cluster, likely to be linked to TERT status. TERT promoter mutation is further associated with changes in the global methylation profile. DNA damage response (DDR) gene methylation patterns show association with survival in grade IIII and IV glioma, including POLE4 linked to radiation response. The prospective N2M2 pilot study demonstrates feasibility of complex molecular profiling within four weeks and identified high confidence markers for targeted therapy in 35% of the patients. Furthermore, a therapeutic algorithm is proposed to allocate patients with high grade gliomas to the best possible treatment based on molecular biomarkers. This algorithm is ready to be adjusted by continues input from targeted clinical and preclinical studies and in vivo CRISPR screens. Conclusions: Multilayer molecular biomarker analysis for high grade glioma is feasible and can be implemented in a therapeutic algorithm estimating the most promising therapy according to current knowledge. Specifically, the TERT-DDR axis may be involved in resistance to chemo- and radiotherapy in high-grade glioma.
Toward understanding toxicity over time (ToxT) in myeloma cooperative group trials: Feasibility of a novel longitudinal adverse event analysis in ECOG-ACRIN E1A06.
Authors: Susanna J. Jacobus, Paul J. Novotny, A. Keith Stewart, Rahma M. Warsame, Natalie Scott Callander, Rafael Fonseca, Madhu V. Midathada, Avina A. Singh, Timothy E. O'Brien, Donald MacFarlene, David L. Grinblatt, Asher Alban Akmal Chanan-Khan, S.Vincent Rajkumar, Amylou C. Dueck, Gita Thanarajasingam
Journal: Journal of Clinical Oncology (2018)

6580 Background: Given the many chronically administered agents now used in cancer therapy, there is pressing need to elucidate safety and tolerability of therapy over time. Conventional methods of evaluating adverse events (AEs) focus on the incidence of high grade toxicity. The Toxicity over Time (ToxT) analytic approach captures the AE time profile with graphs and tabular displays plus quantifies the impact accounting for AE onset, duration and patterns of severity. ToxT has been applied to Alliance trials (Thanarajasingam et al, Lancet Oncol 2016). The goal of this study was to demonstrate feasibility of application of the ToxT statistical package to an ECOG-ACRIN trial. E1A06 was of interest given results of similar efficacy between treatment arms but significant differences in toxicity and quality of life as well as overall suboptimal treatment adherence. Methods: Newly diagnosed, transplant ineligible multiple myeloma pts were randomized to MPT (melphalan, prednisone, thalidomide) or mPR (lower dose melphalan, P, lenalidomide). Pts received 12 cycles of induction (I) followed by T or R maintenance until progression. Grade (G) 3+ non-hematologic (NH) and G4+ hematologic (H) AE data were collected every cycle. Treatment-related AEs of high incidence during I were selected for initial evaluation. Analyses with ToxT incorporate Kaplan-Meier and repeated measures methods. Results: 306 pts were enrolled. G3+ NH toxicity rates over I were 36% mPR vs. 51% MPT. Median time to 1st occurrence for pts experiencing G3+ AEs was similar (48 days mPR vs. 54 days MPT) and associated with ECOG PS score and stage at baseline. Each arm had 14 cases of fatigue, occurring more gradually on MPT (37d vs. 55d). G4 leukopenia incidence rates were 4% mPR vs. 13% MPT, with median onset 19d vs. 31d, respectively. Infection incidence rates were higher and onset earlier on MPT (8%, 79d vs. 14%, 46d). Conclusions: The feasibility of applying ToxT to an ECOG MM dataset was demonstrated. Longitudinal AE analysis has the potential to guide patient education on AEs and timing of symptom control interventions, ultimately improving tolerability of chronically administered cancer therapies.
Long-term results of a phase I/II trial of nelfinavir with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.
Authors: Ramesh Rengan, Rosemarie Mick, Daniel Pryma, Lilie L. Lin, John Paul Christodouleas, John Peter Plastaras, Charles B. Simone, Anjali K. Gupta, Tracey L. Evans, James Stevenson, Corey J. Langer, John Kucharczuk, Joseph S. Friedberg, Sarah Lam, Dana Patsch, Stephen M. Hahn, Amit Maity
Journal: Journal of Clinical Oncology (2018)

8552 Background: The objective of this Phase I/II trial was to determine the response rate and overall survival (OS) of concurrent chemoradiotherapy (CT-RT) in combination with the radiosensitizer Nelfinavir in locally advanced non-small cell lung cancer (LA-NSCLC) compared to historical controls. Methods: Nelfinavir (Dose Level (DL) 1: 625mg PO BID, DL2:1250mg PO BID) was administered for 7 to 14 days prior to and during concurrent CT-RT to patients (pts) with biopsy confirmed unresectable IIIA and IIIB NSCLC. 23 pts (65.7%) had stage IIIA disease; 11 pts (31.4%) had stage IIIB disease; 1 pt (2.9%) had N2 recurrence after surgery. Median age was 60 years for all pts. 19 pts (54.2%) were male, 16 (45.7%) were female. Patients were treated with concurrent CT-RT to a dose of 66.6/1.8Gy and cisplatinum and VP-16. DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or non-hematologic Grade ≥ 3 toxicity except esophagitis and pneumonitis. Protocol specified criteria for compliance included receiving greater than 80% of the prescribed RT treatments and 70% of the prescribed Nelfinavir doses. Results: Thirty-five pts were enrolled and met protocol-specified criteria for compliance, 5 at DL1 and 30 at DL2. No DLTs were observed. The recommended phase II dose of Nelfinavir was 1250 mg PO BID. Median follow-up for all pts was 6.8 years and minimum follow-up for survivors was 5 years. 33 of the 35 pts had evaluable post-treatment CT with RECIST response rate of 94% and (31/33) stable disease rate of 6% (2/33). The cumulative incidence of local failure as site of first failure was 20%, with the median time to failure not reached (NR). The cumulative incidence of distant failure as site of first failure was 51%, with the median time to distant failure of 15.8 months. The median progression-free survival was 12 months. The median OS for all pts was 40 months; 5 year OS was 37 %. Conclusions: Nelfinavir administered with concurrent CT-RT is associated with acceptable toxicity and very promising local control, overall response rate, and survival in unresectable LA-NSCLC. These data suggest that Nelfinavir may enhance the efficacy of chemo-RT in this disease. Clinical trial information: NCT00589056.
Variations in inpatient stays for non-metastatic HER2- breast cancer (BC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) in a real world setting.
Authors: Jennifer Malin, Stacey DaCosta Byfield, Benjamin Chastek, Stephanie Korrer, Thomas Horstman, Lee N. Newcomer
Journal: Journal of Clinical Oncology (2017)

e18099 Background: We aim to compareprevalence and duration of inpatient stays during the most commonly used chemotherapy regimens for BC, NSCLC, and CRC in a commercially insured population. Methods: This analysis used clinical data obtained from a prior authorization program for chemotherapy linked with administrative claims data from 6/1/2015 to 5/31/2016. Clinical data included cancer type, stage at diagnosis, relevant biomarkers, and evidence of progression/relapse. Eligible patients included commercially insured members with a prior authorization request for one of the most commonly used NCCN recommended regimens for BC, NSCLC and CRC. Outcomes, including percent of patients experiencing an inpatient stay and number of inpatient days were tracked from the first claim for chemotherapy until end of treatment due to discontinuation, death or change in treatment, with remaining patients censored at 5/31/2016 or end of enrollment. Results: There were 1612 HER2- BC, 237 NSCLC, and 386 CRC patients who completed therapy during the study period. Incidence and inpatient stay days per 100 patient months for the most common regimens for each cancer are summarized in the table. Conclusions: The rates and duration of inpatient stays varied substantially across the most commonly used therapies for BC, NSCLC and CRC. These data show the importance of systematically incorporating the impact of hospitalizations alongside other clinical outcomes in treatment choice in routine clinical practice. As the database grows over time, these data will help clinicians and patients better evaluate regimen choices for various cancers. [Table: see text]
Risk of second primary malignancy in patient with stage IA non-small cell lung cancer in US.
Authors: Amit Khanal, Dipesh Uprety, Bibhusan Basnet, Amir Bista, Pujan Kandel, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2016)

e20027 Background: The risk of second primary malignancy is early stage non-small cell lung cancer is not well known. We evaluated the risk of second primary malignancies (SPM) in adult patients with Stage I A lung cancer. Methods: We selected adult patients ( ≥ 18 years) diagnosed with non-small cell Stage I A lung cancer from Surveillance, Epidemiology and End Results (SEER) 13. We used SEER stat multiple primary standardized incidence ratio (MP-SIR) session to calculate the risk of SPM diagnosed 6 months after the diagnosis of index Stage IA non-small cell lung cancer. Results: A total of 8,398 patients with a diagnosis of stage IA non-small cell lung cancer were reported in the SEER-13 registry during January 2004 to December 2010. The median follow up duration was 58 months (range: 6 - 107 months). A total of 987 (11.75%) patients developed 1,084 SPMs with an observed/expected (O/E) ratio of 2.04 (95% confidence interval = 1.92 - 2.17, p < .0001) and absolute excess risk (AER) of 185.23 per 10,000 populations persons. The median age at diagnosis of SPM was 73.08 years (range: 39.08 – 97.08 years). The median latency for first SPM was 31 months (range: 6 – 40 months). Significant excess risk was observed for malignancies of pharynx (O/E = 4.63, CI = 1.86-9.54, p < .01), pancreas (O/E = 1.88, CI = 1.29-2.64, p < .01), respiratory system (O/E = 6.04, CI = 5.53 – 6.58, p < .0001), urinary bladder (O/E = 2.22, CI = 1.72-2.82, p < .0001), kidney (O/E = 1.60, CI = 1.03-2.38, p < .05), thyroid (O/E = 3.48, CI = 2.21.-5.22, p < .0001) and acute myeloid leukemia (O/E = 2.12, CI = 1.06-3.79, p < .05).The increased risk of pharyngeal and bladder cancer was significant within 24 months, whereas the risk for the cancer of trachea and kidney were significant after 24 months of diagnosis of primary cancer. Similarly the increased risk for the cancer of kidney was significant in the younger ( < 60years) patients whereas the risk of pharyngeal, tracheal cancer and acute myeloid leukemia were significant in older patients. Conclusions: This study concludes that patients with early stage non-small cell lung cancer have increased risk of second primary malignancies than the general population. These patients may benefit from cancer-specific screening during follow up.