tbuckley/cabot-search huggingface dataset:
Effect of nodal status compared to tumor response after neoadjuvant radiation on outcomes for patients with esophageal cancer.
Authors: Sushanth Reddy, Jacob A. Swords, Mary Glenn Waldrop, Carlo M. Contreras, Martin J. Heslin, Benjamin Wei, Robert J. Cerfolio, Thomas N. Wang
Journal: Journal of Clinical Oncology (2017)

147 Background: The CROSS trial established the role of neoadjuvant radiation in the treatment of esophageal adenocarcinoma (EAC). While response to radiation is an important factor in predicting long-term outcomes, the vast majority of patients succumb to systemic disease. The purpose of this study is to assess predictors of survival in patients with EAC following radiation therapy. Methods: All patients who underwent resection after radiation therapy for EAC at a single institution were retrospectively identified from January 2004 to December 2014. Patients who died within 30 days of surgery were excluded. Cox-proportional hazard analyses were performed to identify clinico-pathological factors associated with survival after surgery. Results: In the time period, 334 patients underwent esophagectomy for EAC. Univariable/multivariable analyses are shown in the table. The presence of a pathologic complete response (pCR) did not correlate to survival. The most important factors in predicting outcome were pre-operative albumin and initial lymph node stage by endoscopic ultrasound (EUS). Pre-treatment N0 patients had better survival than N1 patients (median survival 37.2 vs. 16.3 months, P &lt; 0.0001). Patients who remained N0 after radiation had much better outcomes than those that either developed N1 disease after radiation or were initially staged as N1 (stayed N0, N = 126, median survival 52.0 months; N1→N0, N = 85, median survival 22.9 months; N0→N1, N = 30, median survival 15.3 months; persistent N1, N = 44, median survival 11.4 months; P &lt; 0.0001). Conclusions: Pathologic response to radiation does not predict outcomes for patients with EAC. Patients with node positive EAC have poor outcomes even after neoadjuvant radiation therapy. These patients are at an increased risk of distant disease and should be offered additional systemic therapies prior to surgical resection. [Table: see text]
Prognostic significance of the AJCC staging in patients with squamous cell carcinoma of the oropharynx.
Authors: Carlos Rodrigo Acevedo-Gadea, Megan Ann Baumgart, Zuoheng Wang, Hari Anant Deshpande, Marianne Davies, Roy H. Decker, Clarence Sasaki, Benjamin Judson, Roy S. Herbst, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2012)

5529 Background: There have been significant changes in the epidemiology of head and neck squamous cell carcinomas (HNSCC), with an increase in the incidence of oropharyngeal (OP) cancer and opposite effect in other sites. Since the rise in OP cancer incidence is attributed to human papillomavirus (HPV), which is associated with a different biology and clinical behavior, we evaluated whether the current AJCC system retained its prognostic impact in this patient population. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with HNSCC diagnosed between 2004 and 2007. Overall survival (OS) was estimated by the Kaplan-Meier method and the Cox model was used to compare the survival curves for each AJCC stage. Patients were grouped into three anatomical locations: oral cavity (OC), larynx (L) and OP. Results: There were 26,520 patients meeting eligibility criteria, including 8622 OP, 7332 OC, and 10566 L. The AJCC staging retained its prognostic significance across all stages for patients with HNSCC of the OC and L. Patients with OP cancer, however, had similar 4-year survival for stages I through IVA, whereas stage IVB and IVC had a significantly decrease survival compared to IVA and IVB respectively (Table). Conclusions: The OS for stages III and IVA OP cancer is similar to those with stages I and II, in an effect that may be attributed to the increased frequency of HPV in this population, rendering the tumors more sensitive to chemotherapy and radiation. Therefore, the AJCC stage in OP cancer may be more useful in guiding the therapy than as a prognostic factor. [Table: see text]
Survival of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and peripheral T-cell lymphoma (PTCL): A propensity matched analysis of the Surveillance, Epidemiology and End Results (SEER) database.
Authors: Samyak Manandhar, Smith Giri, Vijaya Raj Bhatt, Ranjan Pathak, Gregory Bociek, James O. Armitage, Julie Vose
Journal: Journal of Clinical Oncology (2015)

8545 Background: SPTCL is a rare entity with no prior population-based study. Using the SEER database, we compared the characteristics and survival of SPTCL and PTCL. Methods: We used the SEER 18 database to identify adult patients with SPTCL and PTCL diagnosed between 1973 and 2011. Prior to 2008, T-cell receptor gamma/delta phenotype of SPTCL was not recognized as a separate entity, hence could not be excluded from this study. Actuarial, relative and cause specific survivals of SPTCL were computed. The actuarial survival of SPTCL was compared to a propensity matched cohort of PTCL. Kaplan Meier survival curves were plotted. Multivariate analysis was conducted using weighted Cox proportional hazard regression model. Results: Patients with SPTCL (n = 118), compared to PTCL (n = 3296), were more likely to be younger (median age of 47 vs. 62 years, p < 0.01), women (67 % vs 40%, p < 0.01) and diagnosed with stage I/II disease (46% vs. 36%, p = 0.01). The five year actuarial, relative and cause specific survival for SPTCL was 40%, 57% and 64% respectively. After propensity matching, the 5-year overall survival (OS) of SPTCL was better than that of PTCL (57% vs. 40%. p < 0.01). In a multivariate analysis, mortality was significantly lower among SPTCL vs. PTCL (hazard ratio, HR 0.54; 95% CI 0.39-0.75; p < 0.01) after adjusting for age, gender, race and stage of the disease. Among patients with SPTCL, advanced age (p < 0.01) and diagnosis before the year 2008 (p 0.02) were predictors of worse OS in a multivariate analysis. Conclusions: Our study provides characteristics and OS of a large cohort of this rare entity, which can be used for patient education and may provide background information for future research. As compared to PTCL, SPTCL patients were more likely to be younger, females and diagnosed at an early stage. Even though T-cell receptor gamma/delta phenotype, which has an unfavorable outcome, could not be excluded, the OS of SPTCL was found to be better than PTCL. Advanced age and year of diagnosis were the predictors of OS among patients with SPTCL.
Rationally designed treatment for solid tumors with MAPK pathway activation
Authors: V. Karantza-Wadsworth, M. Stein, A. Tan, J. Mehnert, E. Poplin, Y. Lin, E. White, R. S. DiPaola
Journal: Journal of Clinical Oncology (2009)

2532 Background: Preclinical studies shed light to the mechanism conferring paclitaxel resistance in solid tumors with active Ras/Raf/Mitogen-Activated Protein Kinase (MAPK) pathway, and determined a molecular mechanism by which addition of the proteasome inhibitor bortezomib abrogated this resistance, enabling tumor regression in animals in vivo. Methods: A Phase I study was contacted to determine the MTD of paclitaxel and bortezomib combinatorial treatment. Sixteen patients with refractory solid tumors were treated with weekly paclitaxel and bortezomib. Six patients had NSCLC; 4, colon cancer; 2, pancreatic; 2, melanoma; 1, breast; 1, ovarian. Patients with baseline neuropathy greater than or equal to Grade 1 were excluded. The starting dose was 40 mg/m 2 for paclitaxel and 0.7 mg/m 2 for bortezomib. A modified continual reassessment method (MCRM) was used for dose escalation with 3-patient cohorts treated at each dose level. The Target Toxicity Level (probability of DLT at the MTD) was set at 25%. Maximum dose escalation was no more than 75% of the previous SED level, if no Grade 3 hematologic toxicity or DLT were observed. Otherwise, the maximum dose escalation was no more than 50% of the previous SED level. The process continued until SED changes were no more than 10% for two consecutive cohorts. Results: The MTD for the combinatorial treatment was reached at 60 mg/m 2 paclitaxel and 1.0 mg/m 2 bortezomib. Of 15 evaluable patients, 1 patient with paclitaxel-resistant NSCLC had PR and 5 patients (2, NSCLC; 1, pancreatic; 1, colon; 1, ovarian) had stable disease. Median TTP was 2.3 months (0.8 to 6 months). Three NSCLC patients achieved TTP longer than 5 months. The combination of paclitaxel and bortezomib was relatively well tolerated. Paclitaxel PK parameters are being determined, and paraffin-embedded tumor specimens are being evaluated for MAPK pathway activation by IHC for phospho-ERK. Results will be correlated with clinical response. Conclusions: The MTD for the proposed combinatorial treatment is 60 mg/m 2 for paclitaxel and 1.0 mg/m 2 for bortezomib, and is relatively well tolerated. Combination of paclitaxel with bortezomib is effective in taxane-resistant NSCLC, and worthy of further investigation. No significant financial relationships to disclose.
Predictive factors for achieving a pathologic complete remission (pCR) rate after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer: Results of a multivariant analysis.
Authors: Edwin Boelke, Christiane Matuschek, Stephan L. Roth, Hans Bojar, Johann Wolfgang Janni, Werner Audretsch, Peter Arne Gerber, Vanessa Speer, Stephan Baldus, Carolin Nestle-Kraemling, Matthias Peiper, Wilfried Budach
Journal: Journal of Clinical Oncology (2012)

e11556 Background: In contrast to neoadjuvant chemotherapy they are no predictive factors to estimate the pathologic complete remission (pCR) rate after preoperative chemotherapy (NRT-CHX) in locally advanced breast cancer (LABC). Methods: 315 LABC patients were included in this trial. They were treated during 1991-1998. The last follow up was in November 2011. Radiotherapy was applied with 50 Gy (5x2 Gy / week) to the breast and the supra-/infraclavicular lymph nodes. 101 patients received a 10 Gy interstitial boost (breast conservation). Chemotherapy (CMF, EC or Mitoxantron was applied in 192 patients prior to radiotherapy and in 113 patients simultaneously. Ten patients had no chemotherapy. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time period up to surgery were examined in multivariate terms for pCR and overall survival. Results: The pCR rate for NRT-CHX after surgery was 29.2%. In multivariante analysis a longer time interval to surgery increased the probability of a pCR (HR 1,17 [95% CI 1,05-1,31], p&lt;0,01). In term of overall survival, the achievement of a pCR is the strongest predictor for long term survival (HR 0,28 [95% CI 0,19-0,56], p&lt;0,001). Conclusions: A long time interval to surgery (&gt; 2 months) increases the probability of a pCR after NRT-CHX. Like in neoadjuvant CHX the achievement of a pCR is an important prognostic factor for long term survival.
In vitro and clinical study of association between macrophage and epithelial-mesenchymal transition in hepatocellular carcinoma cells.
Authors: XiuTao Fu, Dai Zhi, Kang Song, Zhuojun Zhang, Zhengjun Zhou, Shaolai Zhou, Yiming Zhao, Yongsheng Xiao, Qiman Sun, Zhenbin Ding, Jia Fan
Journal: Journal of Clinical Oncology (2014)

e15149 Background: Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. Methods: Double-staining immunohistochemistry was used to observe the association between macrophages and epithelial–mesenchymal transition (EMT) markers in 40 clinical HCC samples. In addition, after HCC cells were cultured with macrophages for 24 hours, the effect upon HCC cell migration and invasion was assessed in vitro and the expression of EMT markers (Snail, E-Cadherin, and N-Cadherin) was investigated via western blot. The supernatant of these cultures was analyzed using a cytokine antibody array. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed by western blot, and downstream signaling pathways were also investigated. Results: In clinical HCC samples, EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. Double-staining immunohistochemistry indicated that CD68 expression which is the marker of macrophage was correlated with EMT marker levels in these samples. In addition, after being cultured with macrophages for 24 hours, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was up-regulated, and E-Cadherin was down-regulated. An antibody array assay demonstrated that IL-8 increased significantly in the supernatant of the macrophage co-culture system. Furthermore, we found that IL-8 (1) may induce EMT and promote HCC cell migration and invasion and (2) is associated with the JAK2/STAT3/Snail signaling pathway. Conclusions: Macrophages that have infiltrated tumors may induce the EMT of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. This finding offers a potential target for developing new HCC therapies.
Incidence of triple negative breast cancer phenotype in a predominantly Hispanic cohort
Authors: A. Khan, Y. E. Tovar, C. Rodriguez, A. L. Huerta, B. Rajabi, M. N. Hakim, Z. D. Mulla
Journal: Journal of Clinical Oncology (2009)

e22188 Background: In daily oncology practice, triple-negative invasive breast cancer is defined by negative immunohistochemistry for ER, PR and HER-2. Patients with this phenotype experience poor prognosis due to limited treatment options and intrinsic tumor biology. In a population-based case-control study, the Carolina Breast Cancer Study (Carey et al, JCO, 2004: suppl; abstr 9510), the triple-negative phenotype in African-American women represented 33.9% of the tumors. We aimed to identify the incidence of triple-negative invasive breast cancer in a group of women living in a predominantly Hispanic population on the Texas- Mexico border. Methods: We collected retrospective data for all invasive breast cases diagnosed between January 2005 and December 2008 at our affiliated county hospital. Clinical and pathological features were summarized. ER, PR and HER-2 was performed by immunohistochemistry. Results: 309 patients with invasive breast cancer were identified. 23.9% (74 patients) of all breast cancer patients were triple-negative. 70 of the 74 subjects (94.6%) were Hispanic. There was equal distribution of patients over and under the age of 50. Histologically all cases were invasive ductal carcinoma. The vast majority had grade 3 tumors (82%) with a high Ki-67 proliferative index (97%). Lymphovascular invasion was present in 38 patients (51.4%). Distant metastases at diagnosis was found in 4 patients (5.4%). Conclusions: In our population-based study the proportion of triple-negative invasive breast cancer phenotype was not as high as in the Carolina Breast Cancer Study, but does reflect that a quarter of the patients with invasive breast cancer in this growing Hispanic population may carry this phenotype. The triple-negative phenotype was strongly associated with high tumor grade and proliferative index. No significant financial relationships to disclose.
Gastric tube cancer after esophagectomy for esophageal cancer: A single-center experience with meta-analysis of 145 cases.
Authors: Geun Dong Lee, Yong-Hee Kim, Seung-Il Park, Dong Kwan Kim, Hyeong Ryul Kim
Journal: Journal of Clinical Oncology (2012)

e14573 Background: Gastric tube cancer (GTC) defined as carcinoma arising in the gastric conduit after esophagectomy, is often crucial in long-term survivors of esophageal cancer. The aim of this study was to determine the optimal approach to manage GTC. Methods: We reviewed data of 863 patients who underwent esophagectomy and reconstruction with the gastric conduit for esophageal cancer at Asan Medical Center from 1993 to 2011 and identified 28 cases of GTC. We also searched through the PubMed database and included additional 117 cases of GTC from 13 studies to conduct meta-analysis. Results: In our cases, the incidence rate of GTC was 3.2%. The median interval between esophagectomy and GTC detection was 3.1 (0.6-15.2) years. Twelve (42.9%) patients were asymptomatic and diagnosed by periodic endoscopy. The Most common histologic type of GTC was adenocarcinoma (57.1%) and fifteen (53.6%) were located on the lower third of gastric tube. Chemotherapy, total gastrectomy or palliative treatment was performed in 10, 5, 2 patients, respectively. Eleven (39.3%) patients refused the further treatment for GTC. Mean survival duration of 28 patients after the diagnosis of GTC was 29.1 months. In meta-analysis, The cumulative occurrence of 5, 8 years was 59.5%, 87.8%, respectively. Two-year survival rate of the patients who underwent endoscopic resection, surgical resection or palliative treatment was 100%, 61.6%, 5.2%, respectively. The patients who underwent endoscopic resection had a better prognosis than those who underwent surgical resection or those who received palliative treatment (p=0.047, p=0.000, respectively). Conclusions: After esophagectomy for esophageal cancer, patients had a constant risk of GTC occurrence up to 8 years approximately. The patients who diagnosed as advanced-state GTC had a poor prognosis. However, endoscopic resection as a minimally invasive treatment for early-GTC represented a feasible prognosis compared with those of operative resection or palliative treatment. Therefore, a long-term follow-up including detailed endoscopy is essential for the better outcomes in patients who underwent esophagectomy for esophageal cancer.
Does race affect the quality of treatment for intermediate-risk and high-risk prostate cancer?
Authors: Nina A. Bickell, Simon J Hall, Richard Stock, Kezhen Fei, Rajwanth Veluswamy, Rebeca Franco, William K. Oh
Journal: Journal of Clinical Oncology (2014)

e17678 Background: Black men are more likely to develop and die of prostate cancer than white men. Past studies show lower rates of definitive treatment among black men. However these studies included early-stage disease for which treatments may not be beneficial. We undertook this study to assess the quality of prostate cancer treatment among men with intermediate & high risk prostate cancer who could benefit from active therapies. Methods: A Steering Committee of experts in prostate cancer care reviewed the evidence to create quality measures of proven effective treatments of intermediate & high risk prostate cancer. All black and a random sample of white men with Gleason Scores of >7, diagnosed at an inner-city academic center between 2007 and 2012, were identified from pathology and charts abstracted for clinical, pathologic and treatment data. Results: Of 289 black & 266 white men identified, average age was 60y (SD=8.5) with no racial difference in age or insurance coverage. 14% of men had D’Amico intermediate and 86% high risk cancers with no significant racial difference (p=0.06). Black men were more likely to have comorbidities (30% vs 10%; p<0.001), higher PSA levels prior to biopsy (12.1 vs 7.0; p<0.01) & higher 9 year mortality risk than whites (26% vs 16%, p<0.001). Black men were less likely than white men to undergo radical prostatectomy (79% vs 90%, p<0.001), but more likely to get external beam radiation therapy (EBRT 13% vs 7%; p<0.01) & brachytherapy (11% vs 5%; p<0.05). Half of men undergoing RT received androgen deprivation therapy (ADT), with no racial difference in ADT use. Only 6% of men with intermediate and high risk prostate cancer did not receive definitive local treatment with no racial difference in underuse (7% vs 5%; p=0.17). Multivariable regression showed that men with intermediate risk (OR=14.6; 95% CI: 6.1-34.8) and those with higher 9 year mortality risk (OR=5.2; 95% CI: 1.4-18.5) were more likely to experience underuse of definitive treatment. Conclusions: The quality of care for intermediate & high risk prostate cancer is high. There is still a group of men with intermediate risk cancer who could benefit from treatment yet go untreated. Work is underway to understand if this underuse is patient or physician driven.
Safety profile of therapeutic pox virus-based vaccines for cancer
Authors: H. L. Kaufman, R. Dipaola, M. Von Mehren, J. Marshall, H. K. Lyerly, H. Streicher, J. Schlom, D. Panicali, T. Schuetz
Journal: Journal of Clinical Oncology (2004)

2513 Background: The eradication of smallpox is, in part, attributed to the effectiveness of vaccination with poxvirus vaccines. Recombinant poxviruses have now been developed as core components of therapeutic tumor vaccines. To date >700 patients received a variety of anti-tumor poxvirus vaccines in clinical trials. A major objective of these early trials was a safety assessment and this study summarizes the safety profile of the Poxvirus Tumor Vaccine Initiative. Methods: The OBA, local IRB and biosafety committees approved all trials. Case report forms or medical records for all patients treated on recombinant poxvirus clinical trials through the NCI or Therion Biologics Corporation between 1991 and 2003 were reviewed. Results: There were 707 patients treated in 29 clinical trials for a variety of tumors.. Vaccines consisted of vaccinia virus, fowlpox virus and ALVAC at doses between 106 – 109 pfu. Vaccines targeted CEA, PSA, MUC-1, gp100, MART-1, and tyrosinase. Second generation vaccines included B7.1 or TRICOM (B7.1, ICAM-1, and LFA-3) and some patients received GM-CSF and/or IL-2. Vaccines were administered through i.d., s.c., i.m., i.t., and i.v. routes. There were no deaths attributed to vaccination in the 707 evaluable patients and therapy was generally well tolerated. The most common adverse events reported were cutaneous reactions associated with local administration of the vaccines. In addition, mild systemic symptoms, such as fatigue, low grade fever, and malaise, were observed. There were 7 cases of serious events (SAEs) attributed to the vaccine following intravenous administration: 5 hypotension, 1 rash, and 1 fever/chills. Conclusions: Therapeutic vaccination with pox virus-based vectors has been tested in clinical trials including >700 patients over the past 10 years. The vaccines are well tolerated at a broad range of doses, routes of administration, tumor types, and regimens with only 7 SAEs after intravenous administration. These data demonstrate the safety profile of recombinant poxvirus vaccines and support the development of randomized trials evaluating clinical effectiveness for poxvirus vaccines in patients with cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Corp. Novartis Oncology; Therion Biologics Corp. Therion Biologics Corp.