tbuckley/cabot-search huggingface dataset:
Does metabolic tumor volume predict tumor regression grade after neoadjuvant therapy for borderline resectable pancreatic cancer?
Authors: Will Jin, Eric Albert Mellon, Sarah E. Hoffe, Jessica M. Frakes, Gregory M. Springett, Pamela Joy Hodul, Barbara Centeno, Richard D. Kim, Amit Mahipal, Jose Mario Pimiento, Mokenge Peter Malafa, Kujtim Latifi
Journal: Journal of Clinical Oncology (2016)

214 Background: Metabolic tumor volume (MTV) based on FDG-PET has been shown to be prognostic for overall survival (OS) in patients with resectable, borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). Tumor regression grade (TRG) following neoadjuvant therapy has also been shown to correlate with OS. No data currently exists evaluating whether metabolic response defined by MTV can predict pathologic response in BRPC. Methods: This IRB approved retrospective review evaluated 40 non-metastatic BRPC patients. All patients underwent staging imaging including FDG PET/CT. They then received induction multi-agent chemotherapy followed by five fraction stereotactic body radiation therapy (SBRT) with a median maximum dose of 35 Gy. Repeat pre-operative FDG PET/CT was performed for re-staging. Patients then underwent pancreatectomy. For this study, the diagnostic images were transferred to a software system that analyzed the pre-treatment, re-staging, and change in (differential) MTV values. We analyzed SUVmax and each of MTV2.5, MTV3.0, MTV4.0, and MTV5.0, as defined as the tumor volume with SUV above each threshold. At our center, each surgical specimen is assigned TRG using the College of American Pathology (CAP) criteria. The TRG scores regression from 0 – 3, with 0 indicating complete response and 3 indicating no response. Univariate ordinal logistic regression was used to correlate TRG with pre-, post-, absolute differential, and percent differential MTV 2.5-5.0 and SUVmax. Results: Of the sample population, TRG was as follows: TRG 0 n = 4, TRG 1 n = 17, TRG 2 n = 14, TRG 3 n = 5. TRG correlated with rradiologist reported re-staging SUVmax (p = 0.001) and percent differential SUVmax (p = 0.044). TRG did not correlate with pre-treatment SUVmax, absolute differential SUVmax, or any MTV measurements (all p &gt; 0.05). Conclusions: We identified a correlation between SUVmax and percent change in SUVmax after neoadjuvant therapy with TRG (CAP scale). This analysis did not identify an association between any MTV threshold and TRG before or after neoadjuvant therapy. Future work seeks to identify alternate methods of neoadjuvant response assessment.
A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant accelerated and blast phase chronic myeloid leukemia (CML): Results from CA180002
Authors: C. L. Sawyers, N. P. Shah, H. M. Kantarjian, J. Cortes, R. Paquette, J. Nicoll, S. A. Bai, E. Clark, A. P. Decillis, M. Talpaz
Journal: Journal of Clinical Oncology (2005)

6520 Background: Response to imatinib in accelerated phase (AP) and blast phase (BP) CML is inferior to chronic phase (CP). Relapse is frequent and associated with Bcr-Abl point mutations which interfere with imatinib binding. BMS-354825 is an orally available, dual SRC/ABL kinase inhibitor with 300-fold greater potency than imatinib. BMS-354825 has preclinical activity against 14 of 15 imatinib resistant Bcr-Abl mutants (Shah et al, Science, 2004). Methods: CA180002 is a phase I, dose-escalation study of BMS-354825 in patients with resistance or intolerance to imatinib. The study was initially restricted to CP CML but was amended to include AP and BP CML and Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients. Intrapatient dose escalation is permitted. Patient samples are analyzed for pharmacokinetics (PK), Bcr-Abl mutations, and CRKL, HCK, and LYN phosphorylation. Results: From May through November 2004, 8 AP, 18 BP CML and 3 Ph+ ALL patients were treated with 35 mg - 90 mg BID. Imatinib-resistance mutations were identified in 16 of 28 patients with mutation data. The hematologic response rates (complete + partial) are 75% for AP, 76% (13/17) for BP and 100% for Ph+ALL (2/2) patients. Responses are durable for 2+ to 6+ months in 19 patients. The major cytogenetic response rate in BP patients is 53%. Responses occurred in 15 patients with imatinib-resistance mutations. 4 patients had primary resistanced documented after 2 months; 2 relapsed within 2–3 months after an initial response. The T315I mutation, which confers cross-resistance to both drugs in preclinical models, was identified in 4 of the 6 resistant patients. BMS-354825 has been well tolerated. Myelosuppression was observed, with grade 4 thrombocytopenia in 8 patients. Grade 3/4 fluid retention (1) and tumor lysis syndrome (2) occurred in 3 patients. Conclusions: BMS-345825 appears to be safe, effective therapy for patients with imatinib-resistant advanced disease CML and Ph+ ALL, producing durable hematologic and cytogenetic responses. The phase I study is ongoing evaluating higher dose levels to determine the maximally tolerated dose. No significant financial relationships to disclose.
An investigator sponsored phase Ia/Ib trial of selinexor in combination with irinotecan in patients with adenocarcinoma of stomach and distal esophagus.
Authors: Heloisa P. Soares, Richard D. Kim, Khaldoun Almhanna, Irene Willians-Elson, Nishi Kothari, Amit Mahipal
Journal: Journal of Clinical Oncology (2016)

TPS176 Background: The karyopherin protein Exportin 1 (XPO1) is highly expressed and associated with poor prognosis in gastroesophageal tumors. XPO1 is responsible for nuclear export of major tumor suppressor proteins and other proteins including topoisomerases leading to carcinogenesis and drug resistance. KPT-330 (selinexor) is an oral, first in class, covalent Selective Inhibitor of Nuclear Export that specifically blocks XPO1. In gastric cancer xenograft models, treatment with selinexor resulted in &gt; 75% inhibition of tumor growth. Synergistic activity has been observed with the combination of XPO1 inhibitors and topoisomerase inhibitors. Methods: This is a phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary endpoint is to evaluate the safety, tolerability and determine the maximally tolerated dose (MTD) of selinexor in combination with irinotecan. Patients with recurrent, metastatic or unresectable histologically confirmed gastric or distal esophageal adenocarcinomas are eligible for this study. Patients must have received at least one line but less than three lines of prior systemic therapies. Secondary endpoints are to explore the safety, tolerability and efficacy of this combination at the established MTD and characterize its pharmacokinetics. Correlative studies will be performed to assess if differential levels of serum and tissue biomarkers including XPO1, cytokine levels and changes in gene expression, before and after selinexor dosing, correlate with clinical outcomes. Circulating tumor cells will be collected in the expansion cohort. Up to 18 patients will be enrolled in 3 dose level cohorts (40, 50 and 65mg/m2) of selinexor in combination with irinotecan (125mg/m2). Selinexor will be given orally on days 1, 3, 8 and 10 of a 21 days cycle. Irinotecan will be given on days 1 and 8. The MTD is defined as the highest dose level at which 1 or less of 6 patients experience a DLT. An additional cohort of 15 patients will be accrued once the recommended dose for expansion is determined. As per September 2015, 3 patients have been included on cohort 1. Clinical trial information: NCT02283359 Clinical trial information: NCT02283359.
Incorporation of externally generated next-generation tumor genotyping into clinical and research workflows: Successes and lessons learned.
Authors: Matthew J. Rioth, David Staggs, Jeremy Warner
Journal: Journal of Clinical Oncology (2014)

156 Background: The future of oncology will increasingly utilize information about tumor genomics. A growing number of tumor subtypes require genomic information as standard of care to inform treatment decisions. Clinical decision support (CDS) systems are able to improve healthcare and ensure best practices, but rely on machine-readable data. Typically, 3rd party genotyping results are returned in PDF reports that are not computable for standard presentation, CDS, or research purposes. Proposed oncology CDS platforms (such as CancerLinQ) will require computable tumor genomic information. Methods: A 3rd party CLIA-certified laboratory performed targeted exome tumor sequencing for a subset of cancer patients seen at Vanderbilt University (VUMC). The variants considered “actionable” were packaged into a standardized extensible markup language (XML) message and transmitted securely to a clinical server on a daily basis; the full PDF report was also transferred electronically. These messages were automatically received and parsed to match patients and display mutation data in their electronic medical record (EMR) for clinicians. This information was also placed into the VUMC Research Derivative (see Danciu et al. J Biomed Inform 2014 for more details). Results: The XML message, including specimen metadata, was successfully created by the 3rd party lab and received by VUMC after an iterative testing process was conducted. Clinicians were notified automatically when results were ready, within their EMR workflow. Because the primary purpose of the test is clinical, variants of unknown significance were not included in the XML transfer (these were however available in the PDF report). Conclusions: To our knowledge, this is the first demonstration of the automated incorporation of tumor genotype information from a 3rd party lab into a clinical EMR. Electronic transfer of genotype data enables rapid consumption of results by clinicians within their standard workflow, passive CDS (e.g. pointers to external knowledge bases), active CDS (e.g. standard and clinical trial treatment recommendations), and secondary use: all activities that improve the quality of cancer care.
Is there evidence of diminishing disparities in treatment (tx) with adjuvant (adj) chemotherapy (Ch) among elderly (E) stage 3 colon cancer (CC) patients (pts)? An analysis of 8,374 pts from SEER-Medicare data
Authors: A. J. Davidoff, M. A. Choti, I. H. Zuckerman, N. Obeidat, T. Rapp, E. Onukwugha, P. Sullivan, J. F. Gardner, C. D. Mullins, N. N. Hanna
Journal: Journal of Clinical Oncology (2008)

6574 Background: Despite effectiveness of adj Ch for Stage 3 CC, prior research documented lower tx rates in E and African American (AA) pts. This population-based study identified sociodemographic factors that affect probability (Pr) of adj Ch, and determined whether disparities in tx decreased over time. Methods: Stage 3 CC pts aged >65, diagnosed from 1997–2002 were identified from SEER cancer registries; Medicare claims measured adj Ch use, defined as receipt of 5FU regimen w/in 6 mos of diagnosis. Logistic regression estimated effects of race, age, income, Medicaid enrollment, urban residence and year on receipt of Ch, controlling for tumor characteristics, comorbidities, and exploratory claims-based indicators of poor performance status (PS; e.g. hospital stay, O2 use, wheelchair use) prior to diagnosis. Interaction (product) terms w/ year tested whether differences by race, age, or Medicaid enrollment changed over time. Results are % point changes in Pr of Ch, relative to the reference category. Result: Adj Ch was received by 52% of 8,374 pts. Unadjusted time trends were ns; adjusted estimates indicate increasing Ch in 2000. Pr of adj Ch was lower for AA relative to white (- 10.5, p<.001), older ( e.g. -8.8, p<.001 for 70–74 yr and -60.5, p<.001 for 85+ relative to age 66–69). Income & urban residence ns, but Medicaid prior to dx was associated with lower rates of Ch (-14.1, p<.001). The Pr of receiving Ch also decreased with higher Charlson comorbidity index (-7.4, -11.9, and -18.6, p <.001 for score of 1, 2, and 3+ relative to 0), increased w/ positive node count: 3.8 (p<.05), 7.4 (p<.001) and 7.6 (p<.01) points more likely to receive Ch (for pts w/ 2–3, 4–7, and 8+ positive nodes vs 1 positive node), and poor PS. Interaction terms between year & race, age, and Medicaid enrollment were ns, thus there was no evidence of a decrease in disparities. Conclusion: 1. Only half of E Stage 3 CC patients received adj Ch. 2.Disparities in use of adj Ch were confirmed for AA, older-old, and Medicaid enrolled, but not for income or urban/rural status. 3. Despite policy emphasis, there was no evidence of a reduction in tx disparities over time. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
A practical program for measuring the quality of ambulatory oncology care in the United States: The Quality Oncology Practice Initiative.
Authors: M. N. Neuss, K. K. McNiff, P. Kadlubek, J. O. Jacobson, J. V. Simone
Journal: Journal of Clinical Oncology (2010)

9160 Background: It has become accepted that the keystone to improvement is comparative measurement of patient outcomes and the processes that influence these outcomes. Universal measurement is a goal, though this is possible only with systematic collection of information tied to accepted and explicitly defined data elements and analytic specifications. ASCO's Quality Oncology Practice Initiative allows this to occur on large groups of patients from geographically and structurally diverse practices at an acceptable cost. Methods: Retrospective medical records abstraction conducted at ambulatory hematology-oncology practices across the United States. Abstracted data are submitted twice per year into the QOPI limited data set, using a secure web-based system (JCO Sep 1 2005: 6233-6239). Results: Representative from the spring 2009 data collection period are presented below. In spring, 248 practice sites reviewed 18,131 records providing information concerning 81 measures and in fall, 313 sites reviewed 21,146 records concerning 85 measures. The results are stable though participating groups have changed. The standard error of site based means is small. Conclusions: These data indicate both that practices can achieve a high level of performance and that other practices have room for improvement on their achievement of quality care of patients. While these data are representative of only process measures, they are measures that are associated with standard excellent care. The definition of data fields will allow incorporation of these measures into Electronic Health Records and prospective collection of this information on a universal population of patients. Levels of achievement on representative measures 2009 Measure group Measure name Low performance (Site average) Mean Best site rate Standard error (site mean) No. of observations NCCN ASCO Spr09 % Fall09 % Spr09 % Fall09 % Spr09 % Fall09 % Spr09 Fall09 Spr09 % Fall09 % Adjuvant Hormone Breast Received 80 77 97 97 100 100 0.77 0.61 1,960 2,582 Adjuvant Chemo Breast Received 83 75 95 95 100 100 0.82 0.90 715 1,230 End of life Entered Hospice or referred for Palliative Care 3 18 56 59 97 95 1.96 1.75 2,873 3,612 Received Chemo Last 14 days of life (Lower Better) 50 64 18 18 0 0 1.20 1.70 2,040 1,495 General Consent for Chemotherapy Obtained 8 0 88 86 100 100 1.22 1.36 13,421 16,503 Pathology Report Available 79 80 97 98 100 100 0.32 0.18 17,600 21,334 Staging Completed within Two Office Visits 50 35 82 83 100 100 0.67 0.58 17,239 21,049 Risk of Infertility Discussed with Pt Before Chemo 0 0 21 20 100 86 2.30 1.81 1,111 1,591 No significant financial relationships to disclose.
Novel stratification of the recurrence risk following surgical extirpation of clear cell renal cell carcinoma using tissue biomarkers in the mammalian target of rapamycin pathway.
Authors: Laura-Maria Krabbe, Oussama M Darwish, Ganesh Raj, Ramy F. Youssef, Payal Kapur, Aditya Bagrodia, Michael Belsante, Yair Lotan, Vitaly Margulis
Journal: Journal of Clinical Oncology (2013)

4581 Background: Aberrant activation of the mammalian target of rapamycin (mTOR) pathway promotes invasiveness and metastatic potential in a variety of malignancies. The aim of the present study was to evaluate the association of altered expression of mTOR pathway components with recurrence outcome in non-metastatic clear cell renal cell carcinoma (ccRCC) patients. Methods: Immunohistochemistry for phos-S6, phos-mTOR, mTOR, phos-AKT, HIF-1α, RAPTOR, PTEN, PI3K, and phos-4EBP1 was performed on tissue microarrays of patients treated for non-metastatic kidney cancer between 1997-2010. Patients were defined as having a low (&lt;) or high risk (≥) of nomogram predicted recurrence (2001 MSKCC RCC post-op) using an 8% cutoff. The relationship between individual marker expression, as well as combined marker score (low, intermediate and high defined as ≤ 3, 4-5, &gt;5 altered biomarkers; respectively) with the actual and predicted relapse rates was assessed. Results: The study included 419 non- metastatic ccRCC patients (pT1-T2 79.5%, pT3-T4 20.5%, Fuhrman nuclear grade 1-2 in 69%, 3-4 in 31%). 219 and 200 patients had low (&lt;8%) and high (≥8%) nomogram-predicted 5-year risk of recurrence respectively. With a median follow-up of 2.2 years, recurrences were detected in 5 (2.3%) of the predicted low risk and 30 (15%) of the predicted high risk patients. mTOR pathway biomarker profiles were not predictive for patients at low predicted risk of recurrences. For patients at high predicted risk of recurrence, low, intermediate and high combined marker scores were found in 84 (42%), 79 (39.5%), and 37 (18.5%), respectively. The actual rates of recurrence were noted for 8.3% of low, 13.9% of intermediate and 32.4% of high combined marker score in a statistically significant distribution (p=0.027). Conclusions: The cumulative number of aberrantly expressed mTOR biomarkers correlates with a higher rate of recurrence. The combined marker score may help further stratify patients with high nomogram predicted risk of recurrence. Our data supports prospective evaluation of these biomarkers to augment current clinico-pathologic predictors of outcomes in ccRCC.
Use of 8-Gy radiotherapy fractions for the treatment of lung cancer in fragile patients.
Authors: J. Jove, A. Arellano, R. Ballester, V. Tuset, M. Caro, E. Luguera, I. Planas, A. Mañes, S. Villà, C. Moretones, A. Melero, J. Molero, J. A. Antón
Journal: Journal of Clinical Oncology (2011)

e17504 Background: The purpose of this study is to evaluate the tolerance and suitability of treatment with high dose radiotherapy (RT) fractions (fr) for fragile patients (pts) with lung cancer who are not candidates for surgery or chemotherapy (CT) in the daily clinical practice. Methods: 30 pts (29 males) were treated between April 2007 and December 2010. Median age was 73.5 (range 54-86). All of them except 2 were pts with severe limitations on pulmonary function, high surgical risk or bad physical condition; 2 pts had relapses of previous lung cancer that did not respond to CT. Curative-intent RT was administered twice weekly at doses of 56 Gy in 7 fr (24 pts), 48 Gy in 6 fr (2 pts), 40 Gy in 5 fr (3 pts) and 16 Gy in 2 fr (1 patient (pt) who could not complete RT). Median RT duration was 21 days (range 11-25). In one pt concurrent erlotinib was maintained. Stage of disease was I in 20 pts (67%), II in 4 pts (13%), III in 3 pts (10%) and IV in 3 pts (pulmonary or pleural metastases). Histology was squamous cell carcinoma in 14 pts, adenocarcinoma in 14 pts and undifferentiated carcinoma in 2 pts. Results: Local response was complete remission (CR) in 18 pts (60%), partial remission (PR) in 6 pts (20%), stable disease (SD) in 3 pts (10%), disease progression (DP) in 2 pts (7%) and non-evaluable in 1 pt (3%). With a median follow-up of 7 months (range 1-43), 14 pts are alive without DP (10 pts in CR, 1 pt in PR, 3 pts with SD), 3 pts are alive with DP, 1 pt developed metastases with local CR, 6 pts died of other causes (4 pts had CR of their tumors, 1 pt achieved a PR and 1 pt died of respiratory complications before completing RT), and 6 pts died of DP. 3-year overall survival (OS) is 51.6%, 3-year overall specific survival (OSS) is 73.7%, and 3-year disease free-progression survival (DFPS) is 53.1%. In the group of pts without advanced or metastatic disease, 3-year OS, OSS and DFPS are 80.2%, 60.5% and 50.4%, respectively. No treatment-related deaths were registered. Toxicity was limited to local radiologic pneumonitis in nearly all pts and dermatitis in some. Conclusions: Irradiation of localized lung tumors with high dose RT fractions in fragile pts who are not candidates to other types of therapy allow for good rates of both response and survival, with minimum toxicity and lower treatment period.
A phase II trial of combination oxaliplatin, capecitabine, and celecoxib with concurrent radiation for patients with newly diagnosed resectable rectal cancer.
Authors: Waheed Murad, M Houman Fekrazad, Ronald Schrader, Benny J. Liem, Yehuda Z. Patt, Fa-Chyi Lee
Journal: Journal of Clinical Oncology (2013)

487 Background: The goal of preoperative chemoradiation in rectal cancer is complete surgical resection without impairing sphincter function and to decrease local recurrence. The primary objective of the study was to determine complete pathological response rate (pCR) with capecitabine, oxaliplatin and celecoxib with concurrent radiation therapy. The secondary objectives were down staging rate, sphincter preservation rate, incidence and severity of adverse events. Methods: A total 37 out of 55 planned patients (pts) were enrolled by New Mexico cancer center consortium from 2005 to 2012. Inclusion criteria were: Resectable adenocarcinoma of the rectum within 12 cm of the anal verge, biopsy proven T3-4 N1-2 M0 based on endoscopic ultrasound, performance status of 0-2, adequate bone marrow reserve and liver functions. The neoadjuvant chemoradiation treatment was: capecitabine 850 mg/m2 bid Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 IV, celecoxib 200 mg bid with concurrent 45 gray radiation therapy in 25 fractions over 5 weeks. Results: Only 21 of 37 pathology reports were assessable for the primary objective of pCR. 7/21 pts (33%, 95% CI, 0.14-0.56) had pCR and 4 had only microscopic residual disease. Thus, 11/21 pts (52%, 95% CI, 0.30-0.74) had an excellent response following chemoradiation. The secondary outcome analysis showed 19/21 pts (90%, 95% CI, 0.69-0.98) were down staged. Sphincter preservation rate was 71% (15/21) (95% CI, 0.47-0.88). Grade 3 and 4 toxicities were observed in 23% and included nausea, vomiting, diarrhea, dehydration, hypokalemia, lymphopenia and fatigue. Conclusions: We report the highest pathological CR so far in stage III rectal cancer with these early results. This could be due to anti-inflammatory activity of celecoxib leading to better tolerance of radiation therapy and possible synergistic anti-tumor activity. Final results will be reported upon completion of the trial. Clinical trial information: NCT00250835.