tbuckley/cabot-search huggingface dataset:
Understanding the impact of settings of care and the development of chemotherapy-induced nausea and vomiting within a population of commercially insured patients.
Authors: Timothy J Inocencio, Claudio Faria, Russell L. Knoth, Richard H. Chapman, Barnabie C Agatep, Michael Johnsrud, Annette Powers
Journal: Journal of Clinical Oncology (2014)

298 Background: Research evaluating the impact of different clinical practice patterns according to settings of care and oncology patient outcomes is limited. This study describes chemotherapy-induced nausea and vomiting (CINV) rates in chemotherapy (CT) naïve cancer patients starting CT in a hospital outpatient (HOP) or community outpatient (COP) setting. Methods: Using the Optum Normative Health Information Database, patients with a new claim of CT and ≥1 outpatient cancer diagnosis claim between 1/1/06 – 6/30/12 were identified. Patients with previous inpatient cancer diagnoses, multi-day CT regimens or Medicare/Medicaid patients were excluded. CINV was defined using relevant claims-based ICD-9-CM diagnosis and procedure codes or a prescription claim for antiemetics within days 2-7 of 1 st 8 CT cycles or 1 st 6 months following the index CT claim. CINV events were evaluated descriptively and using regression models Results: Patients receiving CT in HOP vs. COP were similar in age. Patients receiving CT in COP vs. HOP setting were more likely to be female (78.7% vs. 62.8%), breast cancer patients (66.8% vs. 46.7%), live in the South region (49.7% vs. 44.1%) and have higher baseline healthcare costs (mean $24,950 vs. $24,629) (all p&lt;0.05). Patients in the HOP vs. COP settings had higher Charlson Comorbidity Index scores (mean 3.9 vs. 3.3, p &lt; 0.05). More CINV events were reported for patients in COP vs. those in HOP settings (p &lt; 0.05) (Table). After adjusting for clinical and demographic factors, number of CINV events remained higher for COP vs. HOP settings. However, we were unable to control for antiemetic prophylaxis use or CT emetogenic potential, due to coding irregularities. Conclusions: Results suggest cancer patients starting CT in COP vs. HOP settings may have more CINV events. However, further analyses are needed to explore the impact of antiemetic prophylaxis use or CT emetogenic potential on CINV events between settings of care. [Table: see text]
Can Gleason 7 prostate cancer ever be low-risk? Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
Authors: Kathleen F. McGinley, Xizi Sun, Lauren E. Howard, William J. Aronson, Martha K. Terris, Christopher J. Kane, Christopher L. Amling, Matthew R. Cooperberg, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2015)

57 Background: Overtreatment of low-risk prostate cancer (PC) is a major issue. Increasing use of active surveillance (AS) will ease this burden. Limited data are available on including men with intermediate risk PC (i.e. Gleason 7) into AS protocols. We examined if a subset of men with Gleason 7 (3+4) PC could be reasonable AS candidates. Methods: We used SEARCH to identify men who had radical prostatectomy from 2001-13 with &gt;8 cores on biopsy and complete data. We compared men who fulfilled low-risk disease criteria (cT1c/T2a; biopsy Gleason ≤6; PSA ≤10 ng/mL) with the exception of biopsy Gleason 7 (3+4) vs. men who met all 3 low-risk criteria. Logistic regression models were used to test the association between biopsy Gleason 3+4 vs. ≤6 and pathological features. Biochemical recurrence (BCR) was examined using multivariable Cox hazards analysis adjusted for clinical and demographic features. To examine if there was a subset of men with low-volume Gleason 7 who would have comparable outcomes to low-risk men, we repeated all analyses limiting the percent positive cores to ≤ 33% and positive cores to ≤ 4, ≤ 3, or ≤ 2. Results: 885 men met inclusion criteria: 505 had low-risk PC and 380 had Gleason 7 low-risk PC. Overall, the Gleason 7 low-risk men had increased risk of pathological Gleason ≥4+3 (p&lt;0.001), positive margins (p=0.069), extracapsular extension (p&lt;0.001), and seminal vesicle invasion (p&lt;0.001) on univariable analysis. Men in the Gleason 7 low-risk group had significantly higher BCR risk (HR 1.65, p=0.004). Analyses were repeated using increasingly strict definitions of low-volume PC. With the exception of higher pathological Gleason score (p&lt;0.001), at ≤3 positive cores, there was no difference in adverse pathological features between groups (all p&gt;0.1). Among men with ≤3 positive cores who met the other low-risk criteria (cT1c/T2a; PSA ≤10 ng/mL), BCR risk was similar in men with Gleason 6 or Gleason 7 (3+4) (HR 1.30; p=0.347) PC. Conclusions: Among men with PSA≤10 ng/mL and stage cT1c/T2a, those with Gleason 7 (3+4) PC in ≤3 positive cores have similar rates of adverse pathology and BCR as men with Gleason ≤6 PC. This finding may expand inclusion criteria of AS protocols to reduce PC overtreatment.
Validation of a genomic classifier that predicts metastatic disease progression in men with high-risk pathologic features postprostatectomy.
Authors: Mercedeh Ghadessi, Eric J. Bergstralh, Nicholas Erho, Anamaria Crisan, Elai Davicioni, Christine Buerki, Anirban Pradip Mitra, Darby J. S. Thompson, Rachel Carlson, Zaid Haddad, Benedikt Zimmermann, Karla V. Ballman, Thomas M. Kollmeyer, Thomas Sierocinski, Ismael A. Vergara, Timothy J. Triche, Peter C. Black, R. Houston Thompson, R. Jeffrey Karnes, Robert B. Jenkins
Journal: Journal of Clinical Oncology (2013)

36 Background: Following radical prostatectomy (RP), 30-40% of patients have adverse pathology and are deemed at high risk for metastatic progression. The objective of this study was to validate the ability of Decipher, a genomic classifier (GC), to improve prediction of metastatic disease progression compared with clinical variables in order to better identify candidates for therapy intensification. Methods: A previously developed 22-feature GC model was validated in a prospectively designed case-cohort study of a clinically high-risk population (i.e., with one or more adverse pathological features) of 1,010 RP patients treated at Mayo Clinic between 2000-2006. A random sample of 20% of the cohort was subjected to microarray analysis and GC scores were generated for 219 patients. The primary endpoint, the c-index for predicting metastatic disease progression (i.e., positive bone or CT scans) was evaluated in a blinded analysis. Cox modeling and decision curve analyses were used to compare the performance of GC to individual clinical variables and prediction models. Results: GC had a c-index 0.79 (95% CI 0.71-0.86) that was significantly better than any single clinical variable. Cumulative incidence curves in the cohort showed that 72% of patients had low GC scores with only 3% and 6% incidence of metastatic disease at 5 and 10 years post RP. In contrast, for the 28% of patients with high GC scores, the cumulative incidence was 17% and 25% at 5 and 10 years post RP. Decision curve analysis showed that the GC model had higher overall net benefit compared to clinical variables over a wide range of ‘decision-to-treat’ thresholds for risk of metastasis. In multivariable modeling with clinicopathologic variables, GC remained the only significant independent predictor of metastasis (HR=1.51, for each 0.1 unit increment, p&lt;0.001). Conclusions: GC can better predict metastatic disease progression compared with clinical variables and may select among patients with adverse pathology a majority that is in fact at low risk for metastasis.
Quality and value of subspecialty reinterpretation of outside thoracic CT scans of patients referred to a tertiary cancer center.
Authors: Brett W. Carter, Jeremy J. Erasmus, Mylene Truong, Reginald F. Munden, Jo-Anne O. Shepard, Ryan Kristopher Clarke, Joseph Rodgers Steele
Journal: Journal of Clinical Oncology (2016)

265 Background: At tertiary cancer centers, physicians frequently request reinterpretation of imaging studies performed at outside institutions. The purposes of this study were to determine the quality of outside computed tomography (CT) scans of the chest and compare the accuracy of accompanying radiology reports from outside institutions and our multidisciplinary cancer center. Methods: Two thoracic radiologists graded the quality of 59 outside chest CT scans and generated independent reports for 52 of the scans. A third thoracic radiologist scored the outside reports and reinterpretations for quality. Fisher’s exact tests were used to compare the frequency with which crucial items appeared in outside reports and reinterpretations. Next, two outside thoracic radiologists identified discrepancies between outside reports and reinterpretations (first radiologist) and determined whether the outside report or reinterpretation was more accurate in each case (second radiologist). Finally, the impact of discrepancies on management was evaluated, largely based on NCCN guidelines. Results: Of the 59 outside CT scans, 35 (59%) were of poor quality. Reinterpretations were more likely than outside reports to include information about lymph nodes, adrenal and liver metastasis, tumor nodules, and tumor texture. In 19 of 52 cases (37%), discrepancies were identified between outside reports and reinterpretations. In 17 of these cases, the reinterpretation was superior; in 2 cases, the reinterpretation and outside report were of equal quality. Among these 17 cases, reinterpretation allowed staging in nine cases that could not be staged with information from the outside reports; resulted in upstaging without management change in one case and upstaging with management change in four cases among the five cases with staging information present in both sets of reports; and revealed a significant omission (2 cases) or error (1 case) that changed management in three cases. In total, reinterpretation resulted in significant changes to 16 of 52 (31%) of CT scans. Conclusions: Subspecialty reinterpretation of chest CT scans can substantially improve clinical management.
Metastatic bladder neoplasms treated with stereotactic body radiosurgery.
Authors: Ariel Joseph Lederman, Mordecha Loksen, Thomas Lowinger, Daniel Izon, Gilbert S. Lederman
Journal: Journal of Clinical Oncology (2016)

397 Background: Stereotactic Body Radiosurgery (SBR) as treatment for metastatic bladder cancer delivers high dose radiation precisely to the site of cancer. In our prospective data analysis, 20 sites of extravesical bladder cancer treated with SBR were analyzed. Methods: Twenty metastatic bladder neoplasms were treated in 15 patients. Sixteen were transitional cell carcinoma, 2 adenocarcinoma, 1 squamous cell carcinoma, and 1 rhabdomyosarcoma. Ages ranged from 39 to 82 years (mean 64) with 4 females and 11 males. Tumor volumes ranged from 10.2 to 563 cc (mean 129.8 cc). Patients were treated with 500-900 cGy (median 800) in 5-8 fractions (median 5) for a total dose of 3000-4500 cGy (median 4000). Cancers were radiographically evaluated with contrast CT and/or MRI studies and reviewed independently by radiologists. Disease control is defined as cessation of growth, shrinkage or disappearance of the tumor after treatment. Results: Follow-up ranged from 1 to 20 months (mean 8 months). The overall control rate was 90%. Both patients who did not respond to treatment were males with transitional cell carcinoma. By dose, volume, age, sex and prior treatment, there was no statistically significant difference in outcome among the 20 patients treated. Conclusions: SBR for metastatic bladder cancer offers a well-tolerated, non-invasive technique with a high rate of tumor control. Patients continue to be evaluated for longer follow up, possible benefits of local control and potential survival advantage. SBR remains an option for those whom standard approaches have not produced desired results or in patients seeking an alternative to surgical or chemotherapeutic treatment.
Assay result variability during determination of mismatch repair deficiency status using immunohistochemistry: A transatlantic comparative study.
Authors: G. Hutchins, K. Handley, F. L. Baehner, M. Lopatin, H. Yaziji, M. Lee, M. T. Seymour, D. J. Kerr, R. G. Gray, P. Quirke
Journal: Journal of Clinical Oncology (2011)

403 Background: Colorectal cancer patients with deficient mismatch repair (dMMR) have significantly fewer recurrences and may respond less well to chemotherapy. Immunohistochemical (IHC) determination of MMR status is therefore recommended to identify patients in whom adjuvant therapy is not indicated, but little is known regarding the variability of assay results. We aimed to define MMR IHC assay variability in formalin-fixed, paraffin-embedded (FFPE) material from the QUASAR-1 colorectal cancer trial contained within heterogeneity-prone tissue microarrays (TMAs) Methods: TMA sections of FFPE material from the QUASAR-1 trial were distributed to 2 independent laboratories (Leeds, UK and Vitro Molecular Laboratories [VML], FL, USA) for MMR IHC assays. Serial TMA sections were stained with MLH1/MSH2 using techniques blinded to the other laboratory. Each stained section was double-scored independently and results compared to determine inter-assay variability. Results: Matched MMR data were available for 1224 cases of MLH1 and 1223 cases of MSH2. Of these, loss of expression of MMR (dMMR) was reported in 160 cases (13.1%) by VML and 179 cases (14.6%) by Leeds. 140 (11.4%) were dMMR in both labs, 20 cases (1.6%) by VML alone and 39 (3.2%) by Leeds alone. Discordant dMMR status was observed in 56/166 (34%) dMMR cases identified with MLH1 and 10/34 (29%) cases identified with MSH2. Kappa coefficients for inter-assay agreement were 0.798 (95% CI = 0.748 - 0.848) for MMR status overall, 0.778 (95% CI = 0.722 - 0.835) for MLH1 and 0.823 (95% CI = 0.714 - 0.932) for MSH2. 85% (33/39) of discordant Leeds dMMR colon cancers were in the right colon where dMMR is more common, compared to 47% of VML discordant dMMR cases. Conclusions: Independent determination of MMR status by IHC on TMAs is associated with excellent inter-assay agreement. The reasons for MMR case discordance are under further investigation. These results further support routine MMR testing by IHC. No significant financial relationships to disclose.
Colorectal high-grade neuroendocrine carcinoma: A single institution experience.
Authors: Bruno Conte, Ben George, A. Dasari, Michael J. Overman, Jeannelyn Estrella, Zhiqin Jiang, Karime Machado, Celso Lopes Mello, Renata Ferrarotto, Paulo M. Hoff, James C. Yao, Asif Rashid, Scott Kopetz
Journal: Journal of Clinical Oncology (2014)

540 Background: Colorectal high-grade neuroendocrine carcinoma (HGNEC) is a rare and aggressive disease that lacks standard management recommendations. Methods: The records of all patients with colorectal HGNEC diagnosed at MD Anderson Cancer Center between 1991 and 2013 were retrospectively reviewed for clinicopathological features and clinical outcomes. Results: One hundred patients with histologically confirmed colorectal HGNEC were identified. Median age at diagnosis was 55 years with 51 males. Family history of cancer was present in 59% (first degree) of patients and a tobacco smoking history in 54%. Most frequent symptoms at diagnosis were: abdominal or rectal pain (52%), rectal bleeding (49%) and change in bowel habit (52%). Small cell carcinoma was the most common histology (89%), with large cell neuroendocrine carcinoma in 8% and mixed histology 2%. The expression of chromogranin, synaptophysin and neuron specific enolase was positive in 58%, 93% and 87%, respectively. In our institution, 40% of HGNECs arise in the rectum, compared to 25% of adenocarcinomas (P&lt;0.001 for comparison). Sixty four patients (64%) presented with metastatic disease at diagnosis. Median overall survival (OS) was 11.8 months, with 19.3 versus 8 months for localized and metastatic disease, respectively (p&lt;0.01). Two and five year OS was 23% and 8%, respectively. Cecal primaries had a higher rates of metastatic disease at presentation (OR=5, P=0.026), but stage-specific outcomes did not differ by tumor location. Treatment with a platinum-based chemotherapy (CT) was used in 63 (81%) patients in first line palliative CT and the objective response rate was 43%. For localized disease, neoadjuvant treatment was used in 36% of patients and adjuvant therapy in 47% and was associated with a trend toward improved survival (median OS 20.4 versus 15.4 months, P=0.08). Conclusions: Colorectal HGNEC has an aggressive biology with rectum being the most common site and cecum the site most associated with distant metastases at diagnosis. For localized disease early diagnosis and multimodality approach are important for better outcomes while systemic CT appears to be the mainstay of treatment for advanced disease.
Assessing the impact of restricted follow-up and small sample sizes on survival estimations in prostate cancer using registry data.
Authors: Dhvani Shah, Victoria Paly, Andrew Briggs, Manpreet Sidhu, Esprit Ma, Vijayveer Bonthapally
Journal: Journal of Clinical Oncology (2016)

294 Background: Economic evaluations in oncology aim to assess the value of new therapies in the long term based on clinical trial data that often have restricted follow-up times (&lt; 5 years) and small sample sizes (&lt; 500 patients). This requires the use of extrapolation assumptions on long-term survival that go beyond the observed data. In this analysis, differences in survival extrapolation methods are tested in samples of sizes and follow-up reflecting typical clinical trials against a background of known survival in prostate cancer from a US based cancer registry. Methods: Data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry on long-term survival in patients with stage IV prostate cancer were employed. The data set comprised those patients diagnosed between 1988 and 2003, with follow-up data available until 2012. Additional survival for those who received surgery (compared to those who did not), was estimated based on extrapolations using standard parametric statistical models (exponential, Weibull, log-logistic, log-normal, Gamma) fitted to the observed data. Survival analyses were run for 5 sample size scenarios (n = 27,670, 1000, 500, 200, 50) and 6 follow-up scenarios (follow-up years = 25, 20, 10, 5, 2, 1) yielding 30 combination scenarios. Performance of the methods was tested relative to the maximum follow-up, maximum sample size scenario (i.e. reference case) from the SEER registry. Results: Log-logistic and log-normal models were associated with flat tails which led to inflated survival estimations. For scenarios with smaller sizes, gamma models often did not converge. Exponential models were the most frequently reported as best model fit (in approximately 50% of scenarios). Also, gains in OS were consistent when exponential models were selected, and closely matched gain in OS from the reference case. Conclusions: Since clinical trials in oncology are often associated with small patient sample sizes and restricted follow-up, selecting an exponential model may lead to the most consistent and stable results based on the experiment constructed here. Further research should confirm these results for other types of cancer.
Generalizability of results from oncology clinical trials: Toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer
Authors: V. C. Tam, S. Rask, T. Koru-Sengul, S. Dhesy-Thind
Journal: Journal of Clinical Oncology (2008)

6633 Background: The relevance of oncology clinical trial results in clinical practice depends on whether the trial participants are similar to the entire population of patients with the malignancy and whether the patients are treated similarly in both circumstances. Irinotecan treatments are associated with high rates of severe diarrhea, and may be even more toxic in patients with poor performance status and advanced age, who are usually not included in clinical trials. Methods: A retrospective chart review was performed including all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy (irinotecan monotherapy, FOLFIRI, IFL, XELIRI) from January 2004 to September 2006 at Juravinski Cancer Centre, Hamilton, Ontario, Canada. We aimed to determine the toxicity of these irinotecan regimens in clinical practice compared to those published in corresponding large phase 2 and 3 clinical trials. The primary endpoint was incidence of grade 3/4 diarrhea. A subgroup analysis of elderly patients older than 75 years of age was also conducted. Results: A total of 206 patients met our inclusion criteria and were included in the analysis. 18 patients (9%) were older than 75 years of age, while 21 (10%) and 7 (3%) had an ECOG performance status of 2 and 3, respectively. The rates of grade 3/4 diarrhea for FOLFIRI (n = 103), IFL (n = 14), irinotecan monotherapy (n = 71) and XELIRI (n = 18) were 11%, 14%, 21% and 17%, respectively, compared to 10% (Colucci, 2005), 23% (Saltz, 2000), 31% (Saltz, 2000) and 20% (Patt, 2007) in the clinical trials. The rates of grade 3/4 neutropenia in our study were 22%, 14%, 18% and 11%, respectively. The number of patients with at least one hospital admission for adverse effects from irinotecan chemotherapy were 11%, 21%, 18% and 6%, respectively. The incidence of grade 3/4 diarrhea in patients 75 years of age and younger was 15% compared to 11% for patients older than 75 years of age. Conclusions: Overall, the toxicity rates of irinotecan chemotherapy in non-trial patients do not appear to be in excess of those quoted in published clinical trials. This may be due to a cautious patient selection process on the part of the prescribing oncologists at our institution. No significant financial relationships to disclose.
Association of a combined panel of tumor infiltrating lymphocytes, plasma cells, and macrophages with recurrence of localized clear cell (cc) renal cell carcinoma (RCC) undergoing surgery.
Authors: Pooja Ghatalia, Jennifer Gordetsky, Sejong Bae, Stacey M Watkins, Sunil Sudarshan, Gurudatta Naik, Guru Sonpavde
Journal: Journal of Clinical Oncology (2016)

502 Background: Tumor infiltrating Programmed-Death (PD)-1 and FoxP3-expressing lymphocytes and macrophages appear to be associated with higher risk of recurrence in patients (pts) with ccRCC undergoing surgery for localized disease. We aimed to combine the presence of morphologically identified lymphocytes, plasma cells and macrophages into a readily available composite immune cell panel and to evaluate its association with tumor recurrence. Methods: We identified pts with ccRCC who underwent nephrectomy at UAB for whom we had annotation for objective tumor recurrence and a minimum follow-up of 2 years. Central pathology review was conducted by a single urologic oncology certified pathologist to capture pathologic variables (stage, grade, necrosis, histologic components, cystic changes) and immune cell (lymphocyte/plasma cell/macrophage) infiltration. Logistic regression (univariate and multivariate) analyses were conducted to evaluate the association of these variables with tumor recurrence. Results: Of the 159 identified and evaluable pts, 33 (20.7%) recurred and 126 did not. On univariate analyses, sarcomatoid/rhabdoid histologic components, lymphocyte/plasma cell infiltration, necrosis, pathological T stage and histologic grade were all statistically significantly associated with a risk of recurrence (p &lt; 0.05). On multivariate analysis, in addition to pathologic stage (p = 0.0018), only the combination of higher lymphocyte/plasma cell and macrophage infiltration (p = 0.0347) was independently associated with recurrence; patients were 8.7 times more likely to recur (95% CI: 1.66, 45.28). Conclusions: A readily available and widely applicable composite panel of morphologically identified lymphocytes, plasma cells and macrophages infiltrating the tumor predicts recurrence of pts with localized ccRCC undergoing surgery, after controlling for clinical and pathologic prognostic factors. Our hypothesis-generating data require validation and further interrogation of specific markers expressed on immune cells may refine an immune panel that confers prognostic impact.