tbuckley/cabot-search huggingface dataset:
Real-world patterns of systemic therapy utilization in high risk and metastatic melanoma: evidence from the SEER-Medicare linked database
Authors: D. Mitra, K. L. Davis, S. Kotapati, U. Iloeje
Journal: Journal of Clinical Oncology (2008)

6640 Background: Patterns of systemic therapy in melanoma have not been widely examined using administrative data from real- world practice settings. We analyzed retrospective claims data to document systemic treatment (tx) use in Medicare enrollees with high-risk (stage IIB/C, IIIA/B, IIIC) or metastatic (stage IV) melanoma. Methods: Data are from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database combining clinical information on incident cancer cases in the US from 1991 to 2002 with longitudinal (1991–2005) Medicare claims. Subjects aged ≥65 years with ≥1 stage IIB + melanoma diagnosis were selected. An index date was defined as the date of the first stage IIB + diagnosis. Therapy patterns were evaluated from index date until death, interruption of benefits (≥6 months), or database end (12/31/2005). Patients' (pts) 1st line regimen was defined as the first observed mono or combination systemic tx, while 2nd line therapy as initiation of an alternative regimen following a switch, augmentation, or discontinuation of the 1st line tx. Results: A 1st line regimen was identified for 789 subjects, of whom 136 also received 2nd line tx. Single-agent interferon (IFN) was the predominant 1st line regimen in stages IIIA/B (received by 58% of subjects) and IIIC (69%), but was less common in stages IIB/C (37%) and IV (31%). The next most prevalent 1st line regimens were single-agent dacarbazine (DTIC), received by 15%, 17%, 11%, and 23% of stage IIB/C, IIIA/B, IIIC, and IV subjects, respectively, and DTIC-based combinations (11%, 7%, 14%, and 18%, respectively). Single-agent chemotherapy (CT) (primarily DTIC and paclitaxel) was the predominant 2nd line regimen (by respective stage, 54%, 44%, 33%, and 37% of 2nd line subjects), followed by combination CT (42%, 25%, 55%, and 25%, respectively) and single-agent immunotherapy (4%, 17%, <1%, and 19%, respectively). Conclusions: Results suggest that practitioners have followed recommendations supporting IFN as the standard for initial systemic therapy in high risk melanoma pts treated outside of clinical trials. Findings of relatively low DTIC usage, despite its wide acceptance as a standard CT in melanoma, highlight an unmet need in pts with high risk or metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Role of sentinel lymph node biopsy (SLNB) and preoperative MRI in the management of patients with pure high-grade ductal carcinoma in situ (DCIS).
Authors: Rajitha Sunkara, Charu Taneja, Dorcas Chi, Gail Wolfe, Christine Segal, Allison Keel, Phoebe Olhava, Leslie A. Martin
Journal: Journal of Clinical Oncology (2013)

87 Background: The overall incidence of SLN metastases in pure DCIS is &lt; 1% and the results of SLNB do not usually impact treatment or survival but adds significant surgical morbidity. In addition, there is no evidence regarding the role of preoperative MRI in the management of DCIS. The purpose of our study was to identify the efficacy of SLNB and the benefit of preoperative MRI in high-grade DCIS. Methods: We performed retrospective review of 364 patients with DCIS, identified through our cancer registry database, that were seen from 2003 to 2012 at our institution. Of these, 62 patients were diagnosed with high-grade DCIS (Grade 3 or 2 with comedonecrosis) by core needle biopsy, and underwent SLNB. The remaining 302 patients had either low-grade DCIS or did not have a SLNB. Results: Median age was 56 years (range 33-80). Sixty two patients had high-grade DCIS on definitive excision and 2/62 patients were noted to have small invasive focus of disease. 15/62 (24.19%) patients underwent mastectomy and 47/62(78.1%) underwent lumpectomy. No patient had a positive SLN (0/62). 15/62 (24.2%) patients had breast MRI preoperatively and among them, in 5 (33.3%) patients, MRI findings changed the surgical decision to mastectomy. Among these 5 mastectomy patients, four of them (80%) had pathologically confirmed findings consistent with preoperative MRI suspicions. In lumpectomy patients, close margin of less than 1mm was seen in 4/9 (44.4%) patients with staging MRI and in 24/38 (63.15%) patients without MRI (p = 0.45. Fisher’s exact test). However the positive margin leading to re-excision was seen in 2/9 (22.2%) patients who underwent lumpectomy with staging MRI, and 9/38 (23.6%) patients who underwent lumpectomy without staging MRI. Conclusions: In our study, no patient with high grade DCIS had a positive sentinel node suggesting that routine sentinel node biopsy is not necessary in DCIS patients. The use of MRI changed the surgical planning in 33.3% of patients, but did not improve the surgeon's ability to achieve clear margins.
Phase II trial of cisplatin (C), etoposide (E) and radiation (RT) followed by gemcitabine (G) vs G and docetaxel (D) in stage III A/B unresectable non-small cell lung cancer (NSCLC)
Authors: B. Movsas, C. Langer, L. H. Wang, R. M. Jotte, F. Xu, C. Huang, K. E. Hood, Z. Ye, M. Monberg, C. K. Obasaju
Journal: Journal of Clinical Oncology (2006)

7120 Background: SWOG 9504 demonstrated the benefit of D consolidation after E + C with radiation therapy in pts with locally advanced NSCLC. This study was developed to assess the feasibility and efficacy of consolidation with either G alone or with D after the same chemoradiation schedule as SWOG 9504. Methods: The treatment schema included concurrent C 50 mg/m 2 Day 1, 8 + E 50 mg/m 2 Day 1–5 for two 28-day cycles + RT 180 cGy daily for 7 weeks after which pts were randomized to consolidation treatment of either G 1000 mg/m 2 Day 1, 8 (Arm A) or G 1000 mg/m 2 Day 1, 8 + D 75 mg/m 2 Day 1 (Arm B) every 21 days for 3 cycles. Forty-six pts have been accrued; data is currently available in 28. Conclusions: Preliminary data indicate that G or G + D following chemoradiation in locally advanced NSCLC is well tolerated. The doublet, as expected, results in more toxicity, particularly myelosuppression and fatigue. Response, survival and TTP data will be presented at the time of the meeting. [Table: see text] [Table: see text]
Neutrophil-to-lymphocyte ratio as a prognostic biomarker in bladder cancer: A REMARK-guided secondary analysis of SWOG 8710.
Authors: Eric Ojerholm, Andrew Smith, Wei-Ting Hwang, Brian Christopher Baumann, Kai N. Tucker, Seth P. Lerner, John Paul Christodouleas
Journal: Journal of Clinical Oncology (2016)

361 Background: Pre-operative risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Recent studies suggest baseline neutrophil-to-lymphocyte ratio (NLR) correlates with survival in BC, but these results are threatened by methodological limitations. We tested whether NLR is prognostic for overall survival (OS) in BC following principles detailed by the REMARK biomarker guidelines. Methods: SWOG 8710 was a randomized, phase III trial assessing radical cystectomy (RC) ± neoadjuvant chemotherapy (NAC). It enrolled 317 patients with T2-T4aN0 BC. Baseline NLR was calculated from prospectively-collected pre-treatment complete blood counts. We performed a secondary analysis on 230 patients with valid NLR who successfully completed RC (119 patients) or NAC + RC (111 patients). We evaluated the association of NLR with OS in univariable and multivariable Cox regression models, adjusting for pre-specified factors (age, gender, T-stage, lymphovascular invasion [LVI], and treatment received). Model assumptions of linearity and proportional hazards were checked. We estimated an 80% power to detect a hazard ratio (HR) of ≥ 1.11 for death with each unit increase in NLR at α = 0.05. We addressed missing values via multiple imputation and defined OS from date of treatment to death. Results: There were complete data for all covariates except a small portion ( &lt; 7%) of LVI values. Median baseline NLR was 2.7 (IQR 2.0-4.1), and NLR was not significantly associated with any other covariate. During a median follow-up of 18.6 years, there were 172 deaths. On multivariable analysis, older age (HR 1.05, 95% CI [1.04-1.07], P &lt; 0.001) and treatment with RC alone (HR 1.39, 95% CI [1.03-1.88], P = 0.03) were associated with worse OS. Baseline NLR was not associated with OS in either univariable (HR = 1.03, 95% CI [0.97 – 1.10], P = 0.30) or multivariable models (HR = 1.04, 95% CI [0.98 – 1.11], P = 0.24). Conclusions: In contrast to previous studies, this analysis of prospectively-collected trial data suggests baseline neutrophil-to-lymphocyte ratio is not prognostic for OS in patients with muscle-invasive bladder cancer.
Efficacy and safety of single agent (SA) or combination (CO) adjuvant chemotherapy (AC) in elderly patients with colon cancer: A Canadian Cancer Institute experience.
Authors: Christina Kim, Jennifer L. Spratlin, Sunita Ghosh, Dawn Elizabeth Armstrong, Karen E. Mulder
Journal: Journal of Clinical Oncology (2013)

e14715 Background: AC for colon cancer is recommended in the fit elderly. The pattern of AC use in elderly patients (pts), the toxicity profile, and survival benefit is unclear. We sought to: 1) determine whether patients ≥65 years old with stage III colon cancer were being offered SA or CO AC; 2) evaluate the reason for selecting SA vs. CO AC; 3) evaluate the toxicity profile of SA and CO in the elderly; and 4) determine whether a survival benefit exists for elderly pts receiving CO AC. Methods: Pts ≥65 diagnosed with stage III colon cancer at the Cross Cancer Institute from 2004-2010 were identified from the provincial cancer registry. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, AC protocols used, toxicity, dose reductions, dose delays and survival. Results: 258 pts ≥65 years old were diagnosed and treated with AC from 2004-2010. Of these, 168 were treated with SA and 90 with CO AC. The most common reasons for choosing SA AC were patient preference (64%), comorbidities (17%), and lack of drug coverage by provincial formulary (16%). 93 pts ≥age 75 were treated with SA AC, whereas only 20 pts ≥75 were treated with CO AC. Grade 3 and 4 non-hematologic toxicity was more common with CO AC (43% vs. 27%). 20% of all pts had initial dose reductions, with most common reasons being age and comorbidities. 67%, 71% and 29% received dose delays, reductions or drug discontinuation in the SA group, respectively. 72%, 58% and 34% received dose delays, reductions or drug discontinuation in the CO group respectively. 76% of pts received ≥75% of the expected cumulative dose in the SA group, and 81% in the CO group. The 5 year overall survival (OS) of pts who received &lt;75% of expected AC cycles was 63%, compared to 79% in those who received &gt;75% of expected cycles. The 5 year OS was 73% in pts who received SA AC, compared to 84% in those who received CO AC. Conclusions: In elderly pts treated with AC for stage III colon cancer, SA AC is used more frequently than CO AC, based on age, comorbidities, and patient choice. Toxicity with CO AC in elderly pts is high, but may carry a potential a survival benefit for those who receive it.
Sequential use of targeted therapies for metastatic renal cell carcinoma: A physician survey and chart review of community oncology practices in the United States.
Authors: Nicholas J. Vogelzang, James E. Signorovitch, Peggy L. Lin, Zhimei Liu, Kenneth W. Culver, Jeffrey A. Scott, Sumanta Kumar Pal, Eric Jonasch
Journal: Journal of Clinical Oncology (2013)

418 Background: Multiple targeted agents are available to treat metastatic renal cell carcinoma (mRCC) and no consensus has been reached for optimal treatment sequencing. This study describes physician-reported treatment preferences, reasons for treatment choices, and current treatment patterns for mRCC in the community setting. Methods: A physician survey and retrospective chart review was conducted during May and June 2012 among community-based oncologists or hematologists who had ≥5 mRCC patients under their care in 2011. Charts were reviewed for adult mRCC patients initiated on 2 nd -targeted therapy after January 2010 to collect information on current treatment sequence in mRCC patients and reasons for treatment choices. A parallel survey collected physician treatment preferences for 1 st -, 2 nd -, and 3 rd -targeted therapies for mRCC patients with good or poor prognosis. Results: The study included surveys from 36 physicians and charts from 433 mRCC patients. The majority of patients (77%) received a tyrosine kinase inhibitor (TKI) and the rest (23%) received a mammalian target of rapamycin inhibitor (mTOR) as the 1 st -targeted therapy. Sunitinib was the most common TKI and temsirolimus was the most common mTOR in the 1 st -line setting. Among patients receiving 1 st -line TKI, 34% received TKI (pazopanib was most used TKI) and 66% received mTOR (everolimus was most used mTOR) in the 2 nd -line. Among 1 st -line mTOR users, 94% used TKI (sunitinib was most used) and 6% mTOR (everolimus was most used) for 2 nd -line. TKI-mTOR-TKI was the most commonly observed treatment sequence. Physician-stated preferences for 1 st and 2 nd targeted therapies were largely consistent with the results from the chart review, though actual mTOR use in the 2 nd -line was greater than expected. Treatment guidelines and evidence from clinical trials were the top-ranked factors impacting treatment choices. Conclusions: In this large, retrospective chart review, TKI-mTOR-TKI was the most commonly observed treatment sequence for mRCC in the community setting.
Current state of genetic biomarkers for prostate cancer.
Authors: Meghan Anastasia Cooper, Jae K Lee, Julio Pow-Sang
Journal: Journal of Clinical Oncology (2015)

135 Background: The heterogeneity of prostate cancer presents a challenge in accurately predicting disease behavior. Several biomarker models have recently been developed to allow better risk stratification and more definitive treatment. Methods: We surveyed the literature to find relevant articles on three commercially available prostate cancer biomarkers: Prolaris, Decipher and Oncotype DX. Articles were chosen based on the following criteria: adequate sample size for reliable statistical analysis, original and validation studies utilizing datasets from independent patient cohorts, and studies reporting appropriate statistical evaluations. Results: After screening 32 articles, eight were chosen for review that met the aforementioned criteria. Hazard ratio, odds ratio, area under the curve (AUC), or precision and reproducibility were used to quantify the assay’s predictive capability (Table). Conclusions: From our independent review we concluded that these biomarker models have not yet fully justified their claimed clinical utilities. Also, it is difficult to directly compare performance of these markers and no prospective studies have been reported to validate these assays. [Table: see text]
Association of the MDM2 T309G polymorphism and gastroesophageal reflux disease (GERD) with overall survival (OS) in esophageal adenocarcinoma (EAC).
Authors: D. J. Renouf, B. Sun, R. Zhai, W. Xu, R. S. Heist, M. Kulke, L. Su, D. C. Christiani, G. Liu
Journal: Journal of Clinical Oncology (2011)

10595 Background: MDM2 is an oncogene that regulates p53. The MDM2 T309G polymorphism has been found to be prognostic in several cancers. GERD is an important risk factor for the development of EAC. This study aims to validate the prognostic significance of MDM2 T309G in patients (pts) with EAC, and to assess the impact of GERD on the genotype-outcome relationship. Methods: A cohort of 348 pts with EAC from 1999-2004 were included. DNA was extracted and genotyped for MDM2 T309G (rs2279744) using TaqMan. Clinical data including GERD history and survival were collected for all pts. Associations between genotype, GERD, and genotype-GERD strata with OS were assessed using Kaplan-Meier Method and log rank test. Adjusted hazard ratios (AHR) and genotype-GERD interactions were determined using Cox proportional hazards models, adjusting for age, stage, performance status (PS), and smoking status. Results: Median age was 64 (range 21-91). Pts were 89% male, 82% PS 0-1, Stage I or II (31%), Stage III (50%), Stage IV (19%). 69% of pts were treated with cisplatin-based therapy. 216 (62%) pts had a history of GERD. Median follow up was 32 mo and median survival was 29 mo. In the 348 pts the polymorphism followed Hardy-Weinberg equilibrium (37% T/T, 49% T/G, 14% G/G). For the entire cohort, G/G was associated with significantly shorter survival (median OS 20.9 mo for G/G vs. 30.4 mo for T/-, p<0.001; AHR 1.6, 95% C.I. 1.1-2.3). GERD status alone was not prognostic (p=0.52). When genotype was analyzed by GERD status, G/G was associated with significantly shorter survival in pts without GERD (median OS 9.2 mo for G/G vs. 29.1 mo for T/-, p<0.001; AHR 3.4, 95% C.I. 2.0-5.9). There was no association between G/G and survival in pts with GERD (median OS 27.1 mo for G/G vs. 32.6 mo for T/-, p=0.19; AHR 1.1, 95% C.I. 0.7-1.7). The genotype-GERD interaction was significant (p=0.002). Conclusions: In a large EAC cohort, the MDM2 T309G G/G genotype was associated with decreased OS. When analyzed by GERD, G/G was associated with a 3.4 fold increased risk of death in pts without GERD, but not prognostic in pts with GERD. This suggests that there may be important biological differences between GERD positive and GERD negative EAC.
Sensitive, specific, and modular KRAS, NRAS, and BRAF assays for simultaneous detection of 30 important point mutations in colorectal cancer specimens.
Authors: Kiran Madanahally Divakar, Alvin Concepcion, Jessica Shea, Smriti Gupta, Lilly Kong
Journal: Journal of Clinical Oncology (2016)

547 Background: Point mutations in KRAS, NRAS, and BRAF are implicated in the oncogenic RAS/RAF/MEK/ERK pathway and are prognostic and predictive markers in treating metastatic colorectal cancer patients. Here, we report the performance of three single tube highly multiplex and modular KRAS/NRAS/BRAF Assays capable of detecting 30 point mutations from FFPE-extracted DNA on the fully automated Modaplex System. Methods: Primers for multiplex KRAS/NRAS/BRAF Assays to detect 13, 13, and 4 point mutations for KRAS, NRAS, and BRAF genes, respectively, were designed using proprietary technology. Analytical sensitivity of each mutation was assessed using mutation specific ultramer oligos or Horizon Dx Mockblock specimens. Analytical specificity was determined on known wild-type FFPE DNAs. The assays were tested on DNA extracted from clinical FFPE specimens that were characterized by pyrosequencing. Modaplex data on these specimens were compared to pyrosequencing for concordance. Results: The modular Modaplex KRAS/NRAS/BRAF point mutation panels detect and differentiate 30 mutations in the KRAS, NRAS, and BRAF genes in three wells. Each assay requires just 5 µL of clinical sample extract (10-50ng DNA per assay) with a setup time of 15-30 minutes. The total run time including data analysis and setup is 4 hours. The kit includes an internal control to determine mutation status; and calibration controls to determine amplicon size. Analytical studies demonstrate the assays are sensitive (number of copies detected in one reaction), selective (mutant to wild-type ratio), and specific (relative to wild-type genomic DNA background). Nearly 110 clinical FFPE samples were tested, and the assays showed more than 95% concordance with pyrosequencing method (98% for BRAF, 97% for KRAS, and 100% for NRAS). Conclusions: Modaplex KRAS/NRAS/BRAF assays provide an accurate and sensitive method of mutation detection. These automated multiplexed assays to detect key mutations in three genes can be performed on a single platform facilitating clinical or translational research. *Modaplex KRAS/NRAS/BRAF Assays are for Research Use Only. Not for clinical diagnostic use.
Mammography screening among women 40-49 years old, before and after USPSTF guideline changes.
Authors: John Hsu, Jie Huang, Bruce Fireman
Journal: Journal of Clinical Oncology (2013)

113 Background: The age at which to start breast cancer screening is controversial. The US Preventive Task Force (USPSTF) recommended against routine mammography screening in women 40-49 years old in November 2009 (the 2002 report had recommended screening), and instead suggested that women consult their physicians. We examined the frequency of screening among 40-49yo, and characteristics of the screened. Methods: We examined mammography screening among 85,650 women who were continuously enrolled in a prepaid integrated delivery system and who were between 40-45yo in 2006. We excluded women with any cancer diagnosis (2005-2009). Using logistic regression, we examined the association between screening in 2010 and several traits, e.g., mammogram cost-sharing, screening behavior before 2010, comorbidity score, race/ethnicity, and neighborhood socio-economic status indictors. In 2010, 75% of women had free mammograms; for the others, the median cost-sharing amount was $10. Results: Nearly all subjects (92%) received at least one mammogram between 2006-10: 14% received one; 37% received two; 33% received three; 6% received four; and 1% received 5+ mammograms. The unadjusted percent screened during each year increased slightly from 2006-2009 (38% to 47%) before dropping in 2010 (45%). Among women screened before the guideline changes, 47% received a mammogram in 2010. After adjustment, subjects who had any cost-sharing (OR=0.96 vs. free screening, 95%CI: 0.93-0.99) or who lived in lower SES neighborhoods (OR=0.94 vs. higher SES, 95%CI: 0.90-0.97) were less likely to receive a screening mammogram in 2010. Subjects with frequent earlier screening (e.g., OR=4.44 for four mammograms vs. none, 95%CI:3.99-4.94) and who were Asian (OR=1.05 vs. White, 95%CI: 1.01-1.09) were more likely to receive a 2010 mammogram; Black and Hispanic subjects had similar odds as Whites. Conclusions: In this integrated system, mammography screening among women 40-49 years old decreased slightly after the 2009 USPSTF recommendation against routine screening. Better alignment of insurance benefits with screening guidelines could improve adherence with recommendations.