tbuckley/cabot-search huggingface dataset:
Decision impact analysis of comprehensive genomic profiling (CGP) in advanced breast cancer: A prospective study.
Authors: Raquel E. Reinbolt, Katlyn Tolliver, Mahmoud Abdel-Rasoul, Cynthia Dawn Timmers, Bhuvaneswari Ramaswamy, Rachel M. Layman, Robert Wesolowski, Ewa Mrozek, Susan Gillespie, James Lin Chen, Siraj Mahamed Ali, Sohail Balasubramanian, Charles L. Shapiro, Michael C. Ostrowski, Gustavo W. Leone, Erin Macrae Macrae, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2016)

11578 Background: Foundation Medicine Incorporated (FMI) uses comprehensive genomic profiling (CGP) to identify oncogenic drivers that suggest benefit from molecularly targeted therapies. We conducted a prospective study of CGP to determine the proportion of patients who will receive a cancer therapy based on the genomic profiles. Methods: This is a prospective, single center, single-arm trial in advanced breast cancer patients. Adult metastatic breast cancer patients within 10 weeks of starting their current therapy line and with an estimated survival of ≥ 3 months were included. A massively-parallel sequencing platform (FoundationOne) used the patient’s tumor (FFPE tissue) to sequence for 315 cancer-related genes plus select introns from 28 genes often rearranged in cancer to high depth ( > 500x). The number of gene alterations was quantified; genes with > 1 alteration were counted once. Results: We consented 136 patients to FMI testing; testing was completed, a CGP report generated, and eligibility requirements met for 100 patients (74%). A total of 515 gene alterations were detected, with a median of 5 (range 0-13) alterations per patient. The most commonly altered genes were TP53 [n = 49 (9.5%)], PIK3CA [n = 39 (7.6%)], and MYC [n = 19 (3.7%)]. The CGP report suggested a FDA approved drug for 77 of 100 patients. Everolimus (n = 72), temsirolimus (n = 70), ponatinib (n = 23), and pazopanib (n = 20) were the most frequently recommended FDA approved drugs. At least 1 clinical trial was proposed for 98% of patients. To date, 83 reports have been released to providers. For 34 patients (41%), a change in therapy was recommended by the treating physician based on CGP results; of these, 17 (50%) pursued the suggested treatment. No therapy change was made based on CGP results in 49 patients (59%). Conclusions: This prospective study shows CGP in advanced breast cancer patients is successful in over 70% of patients screened and resulted in a therapy or clinical trial recommendation for nearly all participants. To date, physicians recommended a therapy change based on CGP results for over 40% of patients. Studies will continue to identify barriers to patients’ access to these recommended targeted therapies. Clinical trial information: NCT01987726.
Efficacy of selective screening in identifying patients with hepatitis B before cancer therapy.
Authors: Jessica Hwang, Anna S. F. Lok, Scott B. Cantor, Michael Fisch, Andrea G. Barbo, Heather Y. Lin, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2016)

10133 Background: We aimed to identify and compare selective hepatitis B virus (HBV) screening strategies using predictors of HBV infection in a cohort of patients with cancer who were screened before chemotherapy. Methods: In this prospective observational study at a large comprehensive cancer center, patients awaiting first outpatient chemotherapy were identified and approached for HBV screening. Patients completed a survey about HBV risks using a CDC tool (18 questions) and were screened for HBV (HBsAg, anti-HBc). We developed a logistic regression model to identify clinical predictors of chronic (HBsAg+/anti-HBc+) or past (HBsAg-/anti-HBc+) HBV infection. The receiver operating characteristic (ROC) curve for the model was validated using bootstrap methods. False negative rate (FNR) and specificity were calculated to compare effectiveness of at least one affirmative answer to any question in the CDC tool versus our predictive model. Results: From 7/2013 to 12/2014, 2124 patients (mean age 58 years, SD 13) completed surveys and HBV screening. Of these, 54% were women, 11% Hispanic, 77% non-Hispanic white, 8% black, and 4% Asian. Nearly 20% had a hematologic malignancy, 1% liver cancer, and 79% had a solid tumor other than liver cancer. Almost 12% of patients were born outside the US. Seven patients (0.3%) had chronic and 128 (6%) had past HBV infection. We found 7 predictors (odds ratio [OR]; 95% CI) of either HBsAg+ or anti-HBc+. Black race (4; 3-7) or Asian race (4; 2-7), birthplace outside US (5; 3-9), lived with someone with HBV (2; 1-4), age > 60 (3; 2-5), < high school education (2; 1-3), ever injected drugs (10; 5-21), and a man currently having sex with another man (28; 6-137). The area under the ROC curve (AUC) to predict positive HBV tests was 0.79 (95% CI: 0.74-0.83) for our 7-question model and was 0.74 (95% CI: 0.69-0.78) for the 18-question CDC tool. For both our model and the CDC tool, FNR was 7%. The specificity of the 7-question model was 30% vs.19% for the CDC tool. Conclusions: A 7-question selective screening model based on HBV risk factors and demographics performed as well as the 18-question CDC risk tool and could be implemented in clinical practice to study the effectiveness of a selective HBV screening approach.
Differences in medical care costs for recurrent versus de novo stage IV cancer by age at diagnosis.
Authors: Matthew P. Banegas, Michael J. Hassett, Paul A Fishman, Mark C. Hornbrook, Nikki M Carroll, Angel M. Cronin, Maureen Cecelia O'Keeffe-Rosetti, Hajime Uno, Debra P. Ritzwoller
Journal: Journal of Clinical Oncology (2017)

6611 Background: To address the paucity of data on costs of cancer recurrence, this study estimated medical care costs of patients diagnosed with recurrent breast, colorectal or lung cancer, and compared costs to patients diagnosed with de novo stage IV disease. Methods: Data from patients enrolled in three health plans who were diagnosed with de novo stage IV or recurrent breast (n stage IV = 352; n recurrent = 765), colorectal (n stage IV = 1072 and n recurrent = 542) and lung (n stage IV = 4042 and n recurrent = 339) cancers between 2000-2012 were used to estimate total medical care costs in the 12 months preceding (pre-index), month of index, and 12 months following (post-index) diagnosis/recurrence date. Cancer patients were identified using tumor registry data. Recurrent cancers were validated by medical record abstraction and the RECUR algorithms –innovative tools to detect recurrence using claims and electronic health record data. We used generalized linear repeated measures regression models controlling for demographic and comorbidity variables to estimate costs (2012 US$), stratified by age at diagnosis (ages &lt; 65, ≥65). Results: Medical care cost differences in the pre-index period indicate higher costs for recurrent cancer patients than for stage IV breast (Age &lt; 65:+$2550; Age ≥65: +$1254), colorectal (Age &lt; 65:+$3295; Age ≥65: +$1653), and lung cancer patients (Age &lt; 65:+$3232; Age ≥65: +$2340). Conversely, in the index and post-index periods, costs for stage IV cancers were higher than recurrent cancer costs. Specifically, post-index period cost differences indicate higher costs for stage IV patients than for recurrent breast (Age &lt; 65:+$683; Age ≥65: +$1172), colorectal (Age &lt; 65:+$3104; Age ≥65: +$1557), and lung cancer patients (Age &lt; 65:+$1136; Age ≥65: +$1103). Conclusions: Our study provides medical care cost estimates of recurrent and de novo stage IV cancers. Cost differences between recurrent and stage IV cancers reveal heterogeneity in care patterns that merits further investigation. The reported study costs, measured in capitated care systems using standardized fee-for-service reimbursement coefficients, may serve as a benchmark for stage-specific phase-of-care oncology episode payment models.
Real world treatment utilization and outcomes of patients with metastatic bladder cancer by cisplatin eligibility in U.S. community oncology practice.
Authors: Kyle Flannery, Jenny Black-Shinn, Marley Boyd, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2017)

e16016 Background: Cisplatin(cis)-based therapy is standard first-line (1L) treatment for patients (pts) with metastatic bladder cancer (mBC). Many pts are cis-ineligible mostly due to reduced renal function (creatinine clearance (CrCl) &lt; 60) or ECOG PS of 2 or greater (ECOG2+). Methods: We retrospectively identified mBC pts treated from Jan 2010 – June 2014 fromelectronic health records of McKesson Specialty Health/US Oncology, with follow-up through July 2016. Cis-ineligibility was identified using a consensus-based algorithm (pts with CrCl &lt; 60 and/or ECOG2+ classified cis-ineligible). Results: 1155 pts received 1L treatment; median age 72 yrs (range 26-90+). The most common 1L regimens were cis/gemcitabine (gem) (26.8%), carboplatin (carbo)/gem (26.5%), carbo/paclitaxel (8.9%), and gem alone (8.3%). Among all pts, 55.2% were cis-ineligible. Cis-ineligible pts were older (mean 74.4 yrs vs 66.5 yrs; p &lt; 0.0001). 48.7% of eligible pts did not receive cis, and 25.4% of cis-ineligible pts received cis-based therapy. Interestingly, among 1L cis/gem pts, 34.5 % had CrCl &lt; 60 and 11.5% had ECOG2+. Median (95% CI) overall survival (OS) was affected by cis-eligibility and by 1L cis receipt as follows: eligible/received cis, 17.6 mos (15.1-23.6); eligible/no cis, 14.6 mos (11.5-16.7); ineligible/received cis, 13.4 mos (10.6-16.8); ineligible/no cis, 9.5 mos (8.2-11.4); (p &lt; 0.0001). Conclusions: To date, this is the largest reported cohort of real-world mBC pts. Both cis-eligibility classification and 1L cis receipt were associated with longer OS, and both were approximately equivalent and additive in their magnitude of effect. Most pts were cis-ineligible; nonetheless, cis was used in one fourth of all cis-ineligible pts despite their classification. Cis-ineligible pts have high unmet medical need given their inferior survival.
Results of a randomized phase III study of nimotuzumab in combination with concurrent radiotherapy and cisplatin versus radiotherapy and cisplatin alone, in locally advanced squamous cell carcinoma of the head and neck.
Authors: Vijay Maruti Patil, Vanita Noronha, Amit Joshi, Jaiprakash Agarwal, Sarbani Ghosh Laskar, Ashwini Budrukkar, Vedang Murthy, Sadhana Kannan, Atanu Bhattacharjee, Pankaj Chaturvedi, P. S. Pai, Devendra Chaukar, Anil K D'cruz, S Juvekar, Aparna Manjrekar, Vijayalakshmi Mathrudev, Kavita Prakash Nawale, Arti Bhelekar, Shripad Dinanath Banavali, Kumar Prabhash
Journal: Journal of Clinical Oncology (2018)

6000 Background: We conducted an investigator-initiated, phase 3 randomized study to evaluate the efficacy and toxicity of addition of Nimotuzumab during concurrent chemoradiation in locally advanced squamous head and neck cancer (LASHNC). Methods: Adult subjects (age ≥ 18 years), with stage III-IV, LASHNC, Karnofsky performance status of ≥ 70 and adequate organ function were randomized 1:1 into either radical radiotherapy (66-70 Gy) with weekly cisplatin (30 mg/m2) (CRT arm) or the same schedule of chemoradiation along with weekly Nimotuzumab (200 mg) (NCRT arm). The primary endpoint was progression free survival (PFS) and the other key secondary endpoints were disease free survival (DFS), duration of locoregional control (LRC) and overall survival (OS). Intent to treat analysis was performed. The planned sample size was 536 for superiority margin of 12%, assuming PFS of 60% with 80% power and alpha of 0.05. Results: 536 patients were equally allocated between both arms. The median follow up was 33.0 months (95%CI 30.7-35.2 months). The PFS was significantly longer in the patients treated in the NCRT arm (2 year PFS 58.9% versus 49.5%, HR = 0.74; 95% CI 0.56-0.95; P = 0.022). The median duration of PFS was 60.3 months (95% CI 29.4-NA) in the NCRT arm (P = 0.023) and 21 months (95% CI 15.1-NA) in the CRT arm. Addition of Nimotuzumab improved the LRC (HR = 0.75; 95% CI 0.57-0.97, P = 0.030), DFS (HR = 0.75; 95% CI 0.57-0.97, P = 0.030) and had a trend towards improvement in OS (HR = 0.85, 95% CI 0.65-1.10, p = 0.222). Grade 3-5 adverse events (CTCAE version 4.03) were similar between the 2 arms except for the higher incidence mucositis in the NCRT arm (66.7% versus 55.8%, p = 0.010). Conclusion: In conclusion, Nimotuzumab in combination with cisplatin and radiotherapy was superior to cisplatin and radiotherapy in improving the PFS, LRC and DFS. This combination provides a new therapeutic option in the armamentarium against LASHNC. Clinical trial information: CTRI/2014/09/004980.
Initial safety assessment of MAGE-A10<sup>c796</sup>TCR T-cells in two clinical trials.
Authors: Vincent K. Lam, David S. Hong, John Heymach, George R. Blumenschein, Ben C. Creelan, Penelope Ann Bradbury, Marcus O. Butler, Justin F. Gainor, Ramaswamy Govindan, Melissa Lynne Johnson, Raja Mudad, Ryan J. Sullivan, Francine Brophy, Natalie Hyland, Karen Chagin, Tom Holdich, Elliot Norry, Rafael G. Amado
Journal: Journal of Clinical Oncology (2018)

3056 Background: MAGE-A10 is expressed in 10-50% of urothelial, melanoma, head and neck (HNC), and non-small cell lung cancers (NSCLC). Affinity-enhanced autologous MAGE-A10c796T cells directed towards MAGE-A10 tumor antigen in the context of HLA*02 (SPEAR T-cells) are being tested in 2 ongoing clinical trials (NCT02592577: NSCLC/NCT02989064: urothelial, melanoma, HNC). Methods: These first-in-human T-cell dose escalation studies utilize a modified 3+3 design to evaluate safety. Patients are enrolled after progression on at least one line of therapy. In the first treatment groups, lymphodepletion with Flu 30 mg/m2/day and Cy 600 mg/m2/day (NCT02989064) or Cy 600 mg/m2/day (NCT02592577) is administered on days -7 to -5. The initial dose is 0.1×109 transduced cells; additional dose levels are 1×109 and 5×109. Dose-limiting toxicities (DLT) are determined regardless of attribution to cell infusion and adjudicated by a Safety Review Committee. Cohort expansion will occur at the maximum tolerated dose. Results: 8 patients were treated with 0.1×109 MAGE-A10c796TCR T-cells (29Dec17). Adverse events (AEs) in ≥3 patients included anemia, thrombocytopenia, lymphopenia, leukopenia, neutropenia, vomiting, constipation, dyspnea and tachycardia. Grade (G) 3 AEs in ≥2 patients included thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia, pancytopenia, and hyponatremia; these were not reported as related to T-cell infusion. 1 event of cytokine release syndrome (CRS) and 1 increase in serum amylase were reported as related to T-cell infusion. SAEs included G5 disease progression, G4 CRS, G4 neutropenia, G4 thrombocytopenia, G4 sepsis, G4 abdominal pain, G4 supraglottic airway obstruction, G3 shortness of breath and G2 respiratory failure. There was 1 DLT of G4 CRS in a patient with NSCLC that resolved with tocilizumab and steroids. While no anti-tumor effects were observed at this dose, transduced cells were detectable in peripheral blood. Conclusions: MAGE-A10c796TCR T-cells at the 0.1×109 transduced cell dose show no evidence of on target or off target toxicity. 1 DLT of CRS was observed. The available data support continued investigation of MAGE-A10c796TCR T-cells at higher doses. Clinical trial information: NCT02592577; NCT02989064.
Variant detection analysis on FFPE solid tumors using Illumina’s Praxis™ Oncology Panel 15*.
Authors: Karen Gutekunst, Mariela A. Cuadras, Meredith P. Millis, Dexter Lee, Jie Jenny Chen, Lei Raymond Chen, Brandy Klotzle, Matthew Harris
Journal: Journal of Clinical Oncology (2016)

e23151 Background: Cancer is a genetic disease driven by heritable or somatic mutations. Diagnosis and classification is moving away from histopathological grading and staging towards molecular categorization of the tumor. Detection of genetic alterations in cancer facilitates selecting targeted therapies, increasing the demand for identifying actionable mutations in clinical specimens. Next-generation sequencing has emerged as a powerful technique to detect genetic variations in oncology samples. Methods: We used Illumina’s investigational Praxis Oncology Panel 15 (OGP) and the MiSeqDx system to analyze molecular alterations in formalin-fixed, paraffin-embedded (FFPE) specimens. We analyzed 140 FFPE samples from different tissues using 20 ng of DNA per sample. Results: The assay results showed an overall 87% success rate; 122/140 samples generated sequencing data. Of 18 unsuccessful samples, one (0.7%) had less than 20 ng of DNA and was excluded from library preparation; 14 (10.1%) failed library QC and were not sequenced; and 3 (2.2%) failed sequencing QC. Variant analysis showed that the assay can measure variant frequencies (VF) for single nucleotide variants as low as 3%. The results show the presence of KRAS-actionable variants p.A146P and p.Q61H, as well as variants p.G12S, p.G12D, p.G13D, p.G12V, p.G12C, p.G12R approved as biomarkers in companion diagnostics in colorectal cancer in adrenal, pancreas, and ovarian tissues. We identified BRAF variant p.V600E in colon and thyroid samples; and NRAS and TP53 variants were reported in several tissues. To evaluate precision, we studied a subset of samples to confirm that variant detection by the OGP was concordant across operators, instruments, and days. Overall percent agreement was 99.97% (3066/3067). Positive percent agreement was 99.16% (118/119) with one misclassified variant that had an allele frequency of 0.022 that missed the VF filter cutoff of 0.026. Negative percent agreement was 100.00% (2948/2948). Conclusions: Illumina’s Praxis Oncology Panel 15 is capable of accurately and reproducibly detecting cancer-related variants at low VF in FFPE samples from solid tumors. *CAUTION – Investigational device. Limited by Federal law to investigational use.
Impact of timing of administration of bone supportive therapy on pain palliation from radium-223.
Authors: Kelly Khai Li Yap, William Wong, Lingyun Ji, Susan G. Groshen, David I. Quinn, Jacek K. Pinski, Alan Haruo Bryce, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2017)

5023 Background: Skeletal-related events (SREs) drive morbidity in patients with metastatic castration-resistant prostate cancer (mCRPC). In the ALSYMPCA study, Radium-223 (Ra223) was found to palliate pain in addition to prolonging survival and reducing SREs. Earlier onset of pain relief was noted when zoledronic acid (ZA) was administered within 24-48 hours of samarium; we evaluated whether the timing of bone supportive therapy (BST) affected pain palliation fromRa223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Data extracted: Ra223 administration dates, pain scores, pain medications, ZA or denosumab administration dates, alkaline phosphatase (ALP) levels, prostate specific antigen (PSA) levels, and concurrent prostate cancer therapy. Patients were evaluable for pain response if they had at least 2 pain scores documented before and after Ra223 with pain medication use data. Pain response was defined as &gt; 2 point decrease in pain on a 10 point scale; flare was defined as &gt; 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 20 had baseline pain score &gt; 0 and 34 were evaluable. Median #doses Ra223 was 5 (range 2-6). 18 patients received concurrent abiraterone (abi) or enzalutamide (enza), 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST. 6/10 (60%) patients with pain response had ALP decline but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline (6 increased, 2 stable). 6/12 (50%) and 2/22 (9%) patients on abi/enza had pain response and flare respectively, and 4/8 (50%) and 6/19 (32%) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 may be associated with increased likelihood of pain palliation and may prevent pain flare. PSA/ALP changes do not predict pain response. Concurrent use of abi/enza does not increase the likelihood of pain response and may decrease the likelihood of flare.
Weight changes at diagnosis in solid tumours.
Authors: Niamh O'Donoghue, Shiva Shrotriya, Aynur Aktas, Barbara Hullihen, Serkan Ayvaz, Declan Walsh
Journal: Journal of Clinical Oncology (2017)

e21655 Background: Unintentional weight loss is common in cancer and associated with increased morbidity and mortality. Most research to date has examined weight loss in advanced disease. The clinical significance of any weight change (WC) (loss/gain) before/at cancer diagnosis remains unclear. This study aimed to determine the prevalence and clinical significance of WC at diagnosis in out-patients with solid tumours presenting to a tertiary academic medical centre. Methods: A retrospective study of the electronic medical record (EMR) was conducted (n=6477). Those with a pre-diagnosis weight, T 0 , (recorded within 6 months of cancer diagnosis) and 2 subsequent weights (diagnosis, T 1; final visit, T 2 ) were identified (n=4258). Logistic regression and survival analysis identified WC predictors and overall survival respectively. The significance threshold was p &lt; 0.05. Results: Mean age was 61 ±12.5 years. 54% (n=2315) were male. Common tumour sites were breast (17%; n=725), prostate (16%; n=664), lung (14%; n=599) and upper GI (11%; n=470). Known metastatic disease present at T 1 =15% (n=652). 68% (n=2908) were overweight or obese (WHO BMI Classification) at T 1 . 98% (n=4159) had WC from T 0 -T 1 (loss: 58%; n=2454; gain: 40%; n=1705). Primary tumour sites significantly associated with weight loss (WL) included colon, head &amp; neck, kidney, lung and upper GI. 8% (n=320) were cachectic (&gt;5% WL in previous 6 months) and 50% (n=2134) were pre-cachectic (≤ 5% WL) at T 1 ; 3% had “Abnormal Weight Loss” (ICD 9 Code). Survival was worst with WL &gt;5% and weight gain (WG) ≥ 10% from T 0 -T 1 (p&lt;0.05). However, those with 2.5-5% WL from T 0 -T 1 were also at risk (p&lt;0.05); 0.1-2.4% WG was protective. Primary tumour site (lung, upper GI) and normal/underweight BMI at T 1 predicted poor prognosis. Conclusions: Weight changes were highly prevalent, but WL typically was undiagnosed. Most were overweight or obese at diagnosis. Nevertheless 58% (n=2454) of those reviewed at T 1 met current criteria for cachexia or pre-cachexia. Those with WL &gt; 5% or WG ≥ 10% had worst survival. The majority had evidence of significant, yet frequently undiagnosed, WC abnormalities at diagnosis.