tbuckley/cabot-search huggingface dataset:
Prognostic value of soft tissue metastasis (STM) in stage D2 and stage D3 prostate Cancer (PC)
Authors: R. A. Madan, Q. Xia, S. Hwang, V. T. Chang, F. Zhong, S. Srinivas, M. Sullivan, J. Cogswell, I. Boholli, B. Kasimis
Journal: Journal of Clinical Oncology (2005)

4720 Purpose: The extent of bone involvement is a known predictor of survival in D2 PC. This study aims to determine the prognostic value of STM (lymphadenopathy or visceral) diagnosed by CT scan during the progression from stage D2 to D3 PC. Methods: We reviewed records of 205 pts with stage D2 PC and followed them thru stage D3 to death. All pts were castrated and followed at 3 month intervals. The following variables were extracted at time of D2: Gleason score (GS), Hemoglobin (HGB), LDH, Alkaline Phosphatase (ALK), PSA, bone scan (BSD2), CT scan (CTD2), race. At time of D3, we documented status of bone scan (BSD3), CT scan (CTD3), and chemotherapy administration. A 50% reduction in D2 PSA (PSA50) and the doubling time (PSADT) of PSA nadir after castration were determined. Cox proportional hazards models and log rank survival test were performed. Results: Median (M) age of 70 years (53–91) and M GS of 7 (6–10). At D2, the M HGB was 13.1 g/dl(5.0–17.3), LDH 193 IU/L(85–1239), ALK 136.5 U/L(43–2007) and PSA was 157 ng/ml(1.4–14,096). Positive BSD2 and CTD2 were seen in 84.2% and 55.8% of pts, respectively. PSA50 was achieved by 92.0% of pts and M PSADT was 5.6 months (mos) (.8–41.5). There was a trend towards improved survival with a negative CTD2 (p=.07). Besides known D2 survival predictors HGB (Hazard Ratio (HR) =0.82, p=0.04), GS (HR =1.4, p=0.005), LDH (HR=1.0, p=0.003), PSADT (HR=0.80, p=0.01), the addition of CTD3 information was an additional independent predictor of D2 survival (HR 2.84, p=0.009). Patterns of CTD2 and CTD3 findings were independent predictors of D2 survival (HR1.67, p=.025). Conclusion: The significance of soft tissue metastases is best appreciated by taking a longitudinal view of CT scan findings at both D2 and D3. The evolution of STM from stage D2 to stage D3 PC is an independent predictor of survival. A larger study is needed to confirm these results. No significant financial relationships to disclose.
Evaluation of machine learning versus Cox regression in identification of factors predicting recurrence following resection of non-small cell lung cancer.
Authors: J. K. Blayney, C. M. Grills, P. V. Jithesh, I. I. Wistuba, M. Jacobson, K. J. O'Byrne, K. M. Kerr, G. Scagliotti, R. J. Holt, D. A. Fennell
Journal: Journal of Clinical Oncology (2010)

1599 Background: To capture the influence of multiple clinicopathological factors on NSCLC recurrence following surgical resection, machine learning methods (MLMs) can provide clear stratification between subgroups of patients. In this study a clinical signature associated with recurrence-free survival is considered, comparing the performance of MLMs against Cox regression analysis (CRA). Methods: Recurrences < 3 or > 60 months from surgery were filtered, yielding 846 patients with full data comprising 14 clinicopathological factors. Neural Network classification was applied with correlation feature selection and discretisation, using the target values of recurrence and survival status. Ten-fold cross-validation was used, ranked by AUC values. Likewise, Decision Trees were applied, with Kaplan-Meier analysis (KMA) based on time to recurrence (TTR) or last follow-up. Initial results led to the removal of non-recurring patients with < 60 months follow-up time, leaving 477 patients. Results: CRA identified pathological stage (χ2 = 17.01, p < 0.0001) as the best single predictive factor, then pT, nodal status and pN. Two superior multiple factor groups were identified: nodal status, pT and stage (χ2 = 22.81, p = 3.5E-06) and nodal status, pT and pN (χ2 = 22.62, p = 3.7E-06). Classifying for recurrence, feature selection identified independent factors of stage and neoadjuvant therapy. Predicting survival status, Neural Networks correctly classed 79.8% of patients (AUC 0.87). Decision Trees, with equal results, also found 14 subgroups based on combined ranges of pT, stage, age, recurrence site and histology. TTR KMA revealed 3 significant clusters of nodes (with discretization) and 4 clusters (without ) (see Table for subgroup examples). Conclusions: Machine learning methods applied to the prediction of NSCLC recurrence postsurgery identify optimal combinations of clinicopathological variables, enhancing traditional CRA. AUC % Correctly predicted Factors % Recurrence HR 95% CI 0.86 * 82.4 pT ≠ stage III 44.4 0.23 0.12-0.45 pT = III 73.3 0.84 † 83.6 Age 53-57 Stage ≠ IIIA 32.1 0.11 0.05-0.27 Age <62 >67 Stage = IIIA 81.8 * With discretization. † Without discretization. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Almac Diagnostics Almac Diagnostics AstraZeneca, Lilly, Roche, sanofi-aventis
Phase II trial of continuous dosing of sunitinib in advanced, FDG-PET avid, medullary thyroid carcinoma (MTC) and well-differentiated thyroid cancer (WDTC)
Authors: L. Carr, B. Goulart, R. Martins, E. Keith, E. Kell, S. Wallace, P. Capell, D. Mankoff
Journal: Journal of Clinical Oncology (2009)

6056 Background: Due to the low efficacy of chemotherapy in progressive, WDTC and MTC, novel treatment approaches are needed. Thyroid cancers have elevated levels of vascular endothelial growth factor and higher microvessel density than normal thyroid tissue. Sunitinib inhibits several tyrosine kinase receptors involved in angiogenesis as well as the RET kinase frequently mutated in thyroid cancer. Here we report the results of a phase II trial investigating the use of continuous dosing sunitinib in patients with metastatic WDTC and MTC. Methods: Patients were eligible for enrollment if they had metastatic, iodine-refractory WDTC or MTC. To target those patients with more aggressive thyroid cancer, enrollment was limited to FDG-PET avid disease. Sunitinib was administered at 37.5 mg po qday on a continuous basis. Planned sample size is 35 patients. The primary end-point is response rate per RECIST criteria. Secondary end-points include FDG-PET response rate (defined as 20% reduction from baseline SUV) after 7 days of treatment, toxicity, overall survival, duration of response, and time to progression. Results: To date 33 patients have been enrolled (7 MTC:26 WDTC), and 29 patients have been evaluated for disease response. Median time on study is 7.5 months. Response rates to date: CR 7% (2/29), duration of response (9m+ and 14m+), PR 25% (8/29) (median 12 months), SD 48% (14/29) (median 6 months). Rate of disease control at 3 months (SD+PR+CR) 83% (24/29). 15 patients remain on study. Among those who have progressed the median time to progression is 6.5 months. FDG-PET was performed on 22 patients following 7 days of treatment, 36% (8/22) have a PET response. Of these patients 7 have disease control per RECIST criteria. Grade 3 toxicities seen in more than one patient include: anemia (2/33), fatigue (4/33), neutropenia (12/33), hand/foot syndrome (4/33), diarrhea (5/33), and leukopenia (11/33). One patient on lovenox therapy died of gastrointestinal bleeding. Conclusions: Continuous dosing of sunitinib is active (disease control rate 83%) in patients with high risk, metatstatic WDTC and MTC, as defined by FDG-PET avid disease. [Table: see text]
Faith-Based Organizations and Academic Global Surgery’s Moral Imperative
Authors: Richard E. Davis, Erik N. Hansen, Mark W. Newton
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Investigation of colony stimulating factor-1 receptor (CSF-1R) expression in peripheral monocytes of breast cancer patients for tumor associated macrophages (TAM): A pilot study
Authors: E. Garwood, A. Y. Lin, D. H. Moore, R. Gascon, M. McGrath, M. Campbell, L. J. Esserman
Journal: Journal of Clinical Oncology (2008)

22221 Background: Colony stimulating factor-1 (CSF-1) mediates macrophage (MØ) differentiation, proliferation, and survival through colony stimulating factor-1 receptor (CSF-1R, c-FMS, CD115). Tumor associated MØ (TAM) express CSF-1R, promote angiogenesis, tumor growth, metastasis, and correlate with adverse prognosis in breast cancer (BC). We asked if CSF-1R+ monocytes (MN) were detectable in the peripheral blood (PB) of patients (pts) with BC and if their presence correlated with adverse prognosis. Methods: From 8/30/05–9/28/07, 228 pts undergoing surgery for stage I-III invasive BC consented to participate in a biomarker trial. Blood samples from 44 pts were sent for analysis of MØ markers. Flow cytometry was used to analyze PB CSF-1R, recorded as the percent of CSF-1R+ MN/total MN. CSF-1R levels from 15 pts without invasive cancer (4 normal, 11 DCIS) and 27 pts treated with neoadjuvant (NA) chemotherapy (CTX) were used as comparison groups. Estimates of 10-year (yr) recurrence and mortality were calculated using Adjuvant! Online program. Linear regression was performed using STATA 9. Results: Mean age was 53 yrs (range 33 - 78 yr). Pts presented with stage I (59%), stage II (29.5%), and stage III (11%) invasive BC. Mean tumor size was 1.8 cm (range 0.2–6.5 cm), 82% of tumors were ER+ and 23% were her2/neu+. Mean percent CSF-1R+ was 24.2% of total MN (range 0–85%). Higher levels of CSF-1R+ correlated with higher estimated 10 yr recurrence and 10 yr mortality (p=0.049, and p=0.004, respectively, by Adjuvant! Online). The mean CSF-1R values were significantly lower for both pts without invasive cancer (7.9% of total monocytes (range 0–32%), p=0.003) and for pts treated with NACTX (14.6% of total MN (range 0–53%), p=0.03). Conclusions: CSF-1R+ MØ are found in tumors that have adverse prognosis and may be part of pathogenesis. We have demonstrated that CSF-1R+ MN can be detected in the PB of BC pts. We are currently validating CSF-1R levels of 100 pts with and without invasive BC, and pts pre and post NA therapy. Correlation between CSF-1R levels in the PB and tumor are underway and will be reported. Agents targeting CSF-1R are in phase I/II trials and CSF-1R+ MN could be an important biomarker for TAM targeted therapy. No significant financial relationships to disclose.
Integrated safety analysis of elesclomol (formerly STA-4783) co-administered with paclitaxel
Authors: S. S. Agarwala, J. Haddad, E. Jacobson
Journal: Journal of Clinical Oncology (2008)

14595 Background: Elesclomol is a novel small-molecule oxidative stress inducer known to synergize with taxanes and certain other chemotherapeutics. Co-administered with paclitaxel (E+P), it demonstrated encouraging activity in metastatic melanoma in a recent Phase 2 trial. Methods: Between 2003 and 2006 at >20 sites, a total of 3 Phase 1 (solid tumors) and 2 Phase 2 (melanoma, sarcoma) clinical trials of E+P were completed. Various dose regimens were explored, and 1 randomized, blinded study had a paclitaxel control. Exposure, adverse event (AE) and lab data were combined. All AE data were graded per CTCAE v.3 and re-coded to MedDRA 9.0. All treated patients (pts) were analyzed by treatment received. Results: 239 pts received E+P, with 224 receiving E at or above 213 mg/m2, the dose currently under investigation in a Phase 3 trial in metastatic melanoma. Of 269 total treated pts, 62% were male, 89% were Caucasian; mean age = 57. Mean E+P treatment duration = 85 d (range 1 to 554 d). The most frequent AEs for E+P pts were fatigue, alopecia, nausea, constipation, and diarrhea. The most frequent ≥ Grade 3 AEs are presented below; P-alone blinded control data (metastatic melanoma) are given for comparison. Lab data show a small incidence increase in ≥ Grade 3 neutropenia for the E+P group vs. P alone. The most frequent non-neoplastic AEs resulting in E+P discontinuation were hypersensitivity reactions, neuropathic events, and respiratory disorders; comparable %s of P-alone pts discontinued P for these reasons. Conclusions: Given via various dosing regimens to oncology populations, E+P demonstrated small toxicity increases over P alone and was generally well tolerated. Observed E+P toxicities were typical of taxane administration. No ≥ Grade 3 AE exceeded 10%. Slight incidence increases for ≥ Grade 3 neutropenia were observed; a small P-alone sample limits interpretation. Group (N) % Subjects experiencing at least 1 ≥ Grade 3 AE E+P (239) 213 mg/m2 E+P (224) P* (30) Any ≥ Grade 3 AE (MedDRA preferred term): 49 48 60 Neutropenia Anemia 6 3 7 3 0 3 DVT Dyspnea 3 3 3 3 3 3 Fatigue Hyperglycemia 3 3 4 3 7 3 Hypophosphatemia Leukopenia 3 3 3 3 3 0 Pain in Extremity 3 3 0 % Subjects discontinuing drug due to any Grade AE(s) 13 13 17 * 80 mg/m^2 once weekly×3 weeks, 1 week rest. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Synta Synta
Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response observed in adenocarcinoma.
Authors: D. Ilson, M. A. Shah, D. P. Kelsen, Y. Y. Janjigian, L. H. Tang, J. Campbell, L. Fuqua
Journal: Journal of Clinical Oncology (2010)

e14668 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial combining sorafenib with chemotherapy in GE cancer (J Clin Oncol 26:A4535;2008). We are studying single agent sorafenib in a phase II trial with the primary endpoint to assess progression free survival (PFS). Secondary endpoints include response and therapy tolerance. Methods: Patients (pts) with measurable metastatic E and GEJ cancer with no more than 3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Five pts have been treated, 2 male, 3 female, median KPS 80% and age 56, GEJ cancer 2, E cancer 3, all adenocarcinoma. An ongoing partial response (4+ months) was observed in a pt with biopsy proven metastatic neck lymphadenopathy (E primary, recurrence after prior chemoradiotherapy and surgery). A second pt (GEJ) had protracted stable disease in bulky celiac node disease (5+ months). Therapy has been well tolerated, with grade 3 toxicity limited to skin rash (1 pt) and hand foot skin reaction (1 pt). Conclusions: The observation of a response to sorafenib in GEJ cancer is remarkable. Further accrual continues to define PFS. Supported by a grant from Bayer and Onyx. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Bristol-Myers Squibb, Genentech
Effect of successful weight loss program on biomarkers for breast cancer in postmenopausal high-risk women.
Authors: C. J. Fabian, J. R. Klemp, B. F. Kimler, S. Aversman, T. A. Phillips, C. M. Zalles, D. Sullivan, B. Smith, J. Donnelly, H. Yeh
Journal: Journal of Clinical Oncology (2010)

1522 Background: The proportion of baseline weight or fat loss needed for breast cancer risk reduction in overweight women is not defined. We conducted a pilot study to determine the effect of a structured weight loss program on serum and tissue breast cancer risk biomarkers. Methods: Postmenopausal women with BMI > 25 kg/m2 not on HRT were eligible if they met risk criteria of 5-yr Gail > 1.7%, prior contra- lateral breast cancer, or precancerous biopsy; and had breast tissue harvested by random periareolar fine needle aspiration (RPFNA) indicating evidence of hyperplasia and Ki-67 > 1.5%. Our primary endpoint was to determine the proportion of women with ≥ 5% weight loss and effect on Ki-67. Due to low proportion of women with Ki-67, minimum eligibility criteria were changed to cytomorphology and a frozen aliquot. Our 6-month weight loss intervention included reduced energy diet, physical activity, and weekly meetings for behavioral strategies with other high risk women. Body composition (DEXA), fasting serum insulin, glucose, adiponectin, leptin, high sensitivity CRP, Il6, prolactin, SHBG, estradiol and testosterone were assessed pre and post intervention. Results: 68 women were screened by RPFNA, with 11 (16%) exhibiting Ki-67 > 1.5%. 27 women enrolled (7 with Ki-67 > 1.5%); but 1 was declared ineligible and 2 dropped out prior to starting diet. For 26 eligible subjects, median weight, BMI, and percent body fat at baseline RPFNA was 95 kg, 34.2 kg/m2, and 51%, respectively. Imputing no loss for the 2 subjects who dropped out, 20/26 had > 5% weight loss, For 24 biomarker evaluable subjects, median change in weight and % fat was –9.9 kg (10.9% relative) and -3.8% (-7.7% relative). Median baseline Ki-67 was 0.4% and off study 0.2% for all; and 2.2% and 0.4 % for those with baseline Ki-67 > 1.5%. Cytologic atypia was present in 10/24 at baseline and 4/24 at 6 months [p = 0.07, McNemar]. Serum breast biomarkers that showed significant improvement included adiponectin (p = 0.0015), and leptin, CRP, SHBG, and estradiol (all p < 0.001). Conclusions: Our 6-month weight loss goal of > 5% of baseline weight was achieved (most lost > 10%), with modulation of multiple tissue-based risk biomarkers. However, Ki-67 is not feasible as a primary endpoint. No significant financial relationships to disclose.
Correlation between Nottingham grade and Oncotype DX score in breast cancer: Implications for cost-effective incorporation of oncotype in the clinic.
Authors: Emily Baxter, Stephen K. L. Chia, Caroline A. Lohrisch, Malcolm Hayes, Lovedeep Gondara, Karen A. Gelmon, Ashley Davidson, Scott Tyldesley
Journal: Journal of Clinical Oncology (2014)

106 Background: Nottingham grading (NG) for breast cancer uses tubule formation (TF), nuclear polymorphism (NP), and mitotic count (MC). The Oncotype Dx recurrence score (RS) is a 21-gene assay that predicts recurrence. Both NG and RS can influence decisions about the use of adjuvant chemotherapy in patients with ER+, HER2-, T1-T2, N0 cancers. The objective was to determine the correlation of overall NG, TF, NP, MC with RS risk group in such patients. This may be useful in guiding the use of Oncotype in specific cases. Methods: 231 patients referred to the BC Cancer Agency between 2007-2011 with ER+, HER2-, T1-T2, N0 breast cancer and an Oncotype were identified. Histologic grading was assessed on the specimen used for Oncotype. Spearman’s correlation coefficients, and 95% confidence intervals (CI) were calculated for the RS risk group versus overall NG, TF, NP, and MC. This study adds to the literature as it is one of the largest cohorts examining this topic and focuses on a HER2- patient population. Results: There was a significant positive moderate correlation between RS and overall grade (Spearman coefficient 0.47, [95%CI: 0.36, 0.56])(Table 1), and RS and MC (Spearman 0.44, [95%CI: 0.33, 0.54]). There was a significant positive weak correlation between RS and TF (Spearman 0.25, [95%CI: 0.13, 0.37]) and RS and NP (Spearman 0.34, [95%CI: 0.22, 0.45]). None of the patients with low overall NG had a high risk RS. Conclusions: Patients with a low NG are unlikely to have a high risk RS (0 in 231 patients) and very few such patients would benefit from the expense of an Oncotype. Overall NG has a better correlation with RS than TF, MC, or NP components alone. [Table: see text]
Retrospective analysis of preoperative chemoradiation therapy for esophageal and gastroesophageal junction (GEJ) cancer: Lessons to be learned from expanding inclusion criteria in this patient population.
Authors: Marco Adelmo James Iafolla, Jennifer L. Spratlin, Sunita Ghosh, Karen E. Mulder
Journal: Journal of Clinical Oncology (2015)

214 Background: Preoperative chemoradiation therapy utilizing paclitaxel, carboplatin and radiation as per the CROSS Group increased survival rates among patients with potentially curable esophageal or GEJ cancer. A retrospective chart review was performed to determine: 1) the frequency of patients meeting the original trial inclusion/exclusion criteria 2) overall survival (OS), disease free survival (DFS), and pathological response rates (RR) of this patient population. Methods: Data was collected on 89 patients who received preoperative chemoradiation therapy (CROSS protocol) in Edmonton, Alberta between June 1, 2010 and April 11, 2014. Mean and standard deviation were calculated for continuous data and frequency (proportion) for categorical data. Time to event was presented using Kaplan-Meier estimates and log rank tests were used to compare the KM curves. Results: The median age of the entire patient population was 62 years with 77 (86.5%) of the patients being male. Twenty-three (26%) patients met inclusion criteria (MIC), whereas 66 (74%) patients failed to meet inclusion criteria (FMIC). Reasons for FMIC included: clinical stage (39.3%); weight loss &gt; 10% (39.0%); previous cancer history (22.5%); tumor length (9.0%); and age (5.6%). Pathological complete response (CR) occurred in 24% of all patients with a trend to increased CR in MIC vs FMIC (35% vs 20%; p=0.18). Significant improvement in DFS was observed in the MIC group compared to FMIC (p=0.004). Although a trend to improvement was seen for OS in the MIC group, it is not yet significant at this early analysis (p=0.12). Conclusions: A significant proportion of patients treated with neoadjuvant chemoradiation therapy for esophageal and GEJ cancer at our center did not meet the inclusion/exclusion criteria utilized in the CROSS trial. This had a detrimental impact on FMIC patients questioning its benefit and utility in a broader patient population. [Table: see text]