tbuckley/cabot-search huggingface dataset:
Outcomes of recurrence after complete response to definitive chemoradiotherapy for stage II/III (non–T4) esophageal squamous cell carcinoma.
Authors: Hiroki Kuwabara, Ken Kato, Yusuke Sasaki, Naoki Takahashi, Hirokazu Shoji, Natsuko T. Okita, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Tetsuya Hamaguchi, Yasuhide Yamada, Narikazu Boku, Yoshinori Ito, Jun Itami
Journal: Journal of Clinical Oncology (2015)

179 Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. We examined patterns of recurrence and clinical outcomes in patients with recurrence after complete response (CR) to dCRT. Methods: We retrospectively investigated 238 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2010. From among these patients we selected 95 who had developed disease recurrence after CR. Overall survival was defined as survival time from recurrence to death and was calculated by using the Kaplan-Meier method. Univariate and multivariate analyses were performed with the Cox regression model to determine prognostic factors for survival. Results: The characteristics of the 95 patients were as follows: male: female = 84:11; median age = 64 years (range 46 to 80); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 20/31/44; and performance status at recurrence (0/1) = (51/44). Primary CRT consisted of 5-FU+cisplatin (n = 87), 5-FU+nedaplatin (n = 3), S-1+cisplatin (n = 3), 5-FU+cisplatin+ nimotuzumab (n = 1), or docetaxel (n = 1). The pattern of recurrence was locoregional failure (n = 53) or any distant failure (n = 42). Median time from the start of dCRT to recurrence was 13.0 months, and median survival time from recurrence to death was 19.6 months. Median survival time according to the pattern of failure was 34.7 months (locoregional failure) or 17.0 months (any distant failure). Application of the Cox regression model, including the additional prognostic variables of age, ECOG performance status, number of organs in which metastases were present, and LDH, revealed that any distant failure (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2 to 4.1; P = 0.01) and recurrence before 13.0 months (HR 2.1; 95% CI 1.2 to 3.6; P = 0.01) were predictors of poor overall survival. Conclusions: Early recurrence and any distant failure were associated with poor prognosis after CR to dCRT for locally advanced esophageal cancer.
Therapy with alpha interferon for advanced and metastatic giant cell tumor of bone
Authors: J. L. Gonzalez Vela, C. E. Cuervo Lozano, V. M. Sepulveda Oyervides, J. F. Gonzalez Guerrero, E. Llerena Hernandez
Journal: Journal of Clinical Oncology (2005)

9078 Background: Previous reports by Yasko et al presented at AAOS 2002 on twelve patients conclude that interferon-a can induce important responses including complete responses in pt. with locally advanced and metastatic giant cell tumor of bone. The objective of this report is to confirm these encouraging findings. Methods: Four patients were treated with alpha interferon for locally advanced (3) and metastatic (1) giant cell tumor of bone. 5 million units subcutaneously twice a week for four weeks and one week rest,for six cycles.The four patients are female with ages 21 to39 yrs. with a follow up between one and three years. Sites of disease are sacrum(1),spine(1),radius(1),and humerus and scapula(1).The pt.with the radius primary had billateral lung metastases at the moment of diagnosis.Adequate surgery was not feasable in the pts. with these tumors due to the extent of surrounding tissue invasion.or the presence of multiple metastases.Three pt. had been previously treated with radiotherapy and two had also received doxorrubicin and cisplatin.The pt with the tumor in the sacrum had also received multiple embolizations with gel foam. Results: The four patints are currently alive,two of them had a complete response,these are documented by ct scanning (sacrum and spine sustained for 36 and 12 months) the patient with the pulmonary metastases had a complete dissapearance of the lesions in the lung but persistence in the radius which was then treated with amputation and she is currently free of disease 24 mos.,the remaining pt with humeral and shoulder soft tissue involvement has important radiological and physical improvement and is asymptomatic with a better range of motion of the affected shoulder. Conclusions: Alpha interferon can induce durable response in the treatment of locally advanced and metastatic giant cell tumor of bone,and a phase II multiinstitutional trial may be warranted,to determine the best dosing and duration of treatment No significant financial relationships to disclose.
Serum IGF-1 levels in men with advanced prostate cancer treated with the ERα agonist, GTx-758.
Authors: Evan Y. Yu, Marc Gittelman, Thomas E. Keane, Ronald Tutrone, Laurence Belkoff, Robert Given, Joel Bass, Franklin Chu, Mike Gambla, Franklin Gaylis, James Bailen, Robert H. Getzenberg, Christopher Coss, Michael L. Hancock, James T. Dalton, Mitchell S. Steiner
Journal: Journal of Clinical Oncology (2013)

171 Background: The insulin pathway and, in particular, insulin-like growth factor-1 (IGF-1), has been implicated in the development of prostate cancer, and serum IGF-1 levels have been associated with advanced disease. GTx-758, an ERα agonist that is being evaluated for the treatment of advanced prostate cancer, reduces serum total testosterone (T) and free T and increases SHBG. Herein, we compare the effects of GTx-758 and leuprolide on serum IGF-1 levels in men with advanced prostate cancer treated with ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Serum samples were collected from all of the men in the study and serum IGF-1 levels (ng/ml) were analyzed by a reference laboratory. All p values describe the comparison of GTx-758 treatment groups to the leuprolide treated men. Results: Through day 90, in men receiving the 1000 mg and 2000 mg doses of GTx-758 , serum IGF-1 levels were decreased by more than 70 ng/ml (greater than 50%), while levels stayed constant or increased slightly in men on leuprolide (p&lt;0.001). As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion, and not all of the men in the study reached the 90 day treatment date (92 men reached that date). Conclusions: In men with advanced prostate cancer, the ERα agonist, GTx-758, can decrease the active form of testosterone, serum free T, to significantly lower levels than leuprolide. Patients receiving GTx-758 experienced a significant decrease in serum IGF-1. Since changes in insulin metabolism are involved in regulating prostate cancer as well as bone and systemic metabolism, the observed decreases in IGF-1 could be significant. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently ongoing to determine if similar effects can be observed with a lower rate of VTEs. Clinical trial information: NCT01326312.
Strategy for cStage4 colorectal cancer: Chemotherapy or resection of primary tumor?
Authors: Shigeyoshi Iwamoto, Madoka Hamada, Masaharu Oishi, Tatsuma Sakaguchi, Taku Michiura, Kentaro Inoue, A-Hon Kwon
Journal: Journal of Clinical Oncology (2015)

779 Background: It is controversial that the primary tumor must be removed prior chemotherapy in cStage4 colorectal cancer, because some cases prognostic factor were metastatic sites. We report cases of cStage4 colorectal cancer which were underwent intrensive chemotherapy prior the primary tumor resection. Methods: 190 cases of metastatic colorectal cancer were treated by L-OHP based chemotherapy plus bevacizumab/cetuximab/panitumumab in September 2007 to June 2012. 56 cases were treated by intensive chemotherapy prior primary tumor resection, and 44 cases were underwent surgical resection of primary tumor after evaluation of chemotherapy response. Results: 38/10/8 cases were treated by bevacizumab/cetuximab/panitumumab with L-OHP combined therapy as intensive treatment. 30 patient with obstructed primary lesion were underwent stoma surgery (53.6%). Evaluable lesions except primary lesion were liver (50.0%), lung (12.5%), LNs (33.9%). Response rate of chemotherapy were 67.9% (PR/NC/PD: 38/14/4), and 44 cases were performed resection of primary lesion in PR and SD cases. Pathological G2 and G3 response in resected primary lesion were 18.4% (G1a/G1b/G2/G3:17/18/8/2). A GI perforation and bowel obstruction in chemotherapy and 3 cases of anastomotic leakage and 6 cases of SSI in perioperable period were observed respectively. Conclusions: It is seemed to contribute improvement of QOL and local control that start with systemic chemotherapy prior primary lesion resection, therefore some cStage4 cases were difficult to R0 resection also primary lesion and systemic chemotherapy could be reduced symptom with metastatic sites. Only 18.4% of the resected primary tumor were G2/3 pathological response by systemic chemotherapy, on the other hand preoperative chemo-radiation in rectal cancer accomplished 67.3% of G2/3 pathological response (in house data). The end-point of therapy in stage 4 colorectal cancer patient are QOL and prolong survival, and should be selected treatments depending on the patient condition.
Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial
Authors: Angela Huttner, Christoph Hatz, Germie van den Dobbelsteen, Darren Abbanat, Alena Hornacek, Rahel Frölich, Anita M Dreyer, Patricia Martin, Todd Davies, Kellen Fae, Ingrid van den Nieuwenhof, Stefan Thoelen, Serge de Vallière, Anette Kuhn, Enos Bernasconi, Volker Viereck, Tilemachos Kavvadias, Kerstin Kling, Gloria Ryu, Tanja Hülder, Sabine Gröger, David Scheiner, Cristina Alaimo, Stephan Harbarth, Jan Poolman, Veronica Gambillara Fonck
Journal: The Lancet Infectious Diseases (2017)
A genomic classifier independently prognostic of prostate cancer death in a high-risk surgical cohort.
Authors: Matthew R. Cooperberg, Anamaria Crisan, Anirban Pradip Mitra, Mercedeh Ghadessi, Christine Buerki, Elai Davicioni
Journal: Journal of Clinical Oncology (2013)

60 Background: Biomarkers may improve ascertainment of progression risk after radical prostatectomy (RP). We compared two validated post-RP classifiers: the Decipher genomic classifier (GC) and CAPRA-S (based on standard clinicopathologic parameters), to predict prostate cancer-specific mortality (CSM) in a contemporary cohort of RP patients. Methods: From a cohort of 1,010 RP patients treated from 2000-06, a case-cohort design was used to analyze a subset of 219 men with one or more high risk features and available paraffin-embedded tissue. Median follow-up was 6 years. The GC, derived from expression levels of 22 biomarkers and dichotomized to denote low- and high-risk, and CAPRA-S, calculated from preoperative PSA and pathologic grade and staging variables, scores were determined. The scores were evaluated individually and in combination using concordance index, decision curve, (DC), re-classification, and Cox analyses for prediction of CSM. Results: 212 men had full data available to calculate the CAPRA-S; 27 experienced CSM. The c-index for GC (0.78) and CAPRA-S (0.76) were similar, although GC showed improved calibration and higher net-benefit on DC analysis. In 103 patients with high-risk CAPRA-S scores (≥6), GC scores were likewise high-risk for 49, among whom 19 had CSM events. The other 54 men were reclassified as low-risk by GC; among these only 1 CSM event was observed. In multivariable Cox analysis both GC and CAPRA-S were independently prognostic of CSM, with hazard ratios of 1.62 (p&lt;0.001) and 1.22 (p=0.01), respectively for unit score increases. A combined model defined based on the Cox model as (0.20*CAPRA-S + 5.68*GC) was more accurate than either score alone (p&lt;0.001 by likelihood ratio test). DC analysis indicated greater net benefit for the combined model than for either score alone. Conclusions: In men treated with RP at high risk of recurrence based on clinical and pathologic variables, both GC and CAPRA-S were significant predictors of CSM. Notably, GC was able to 'down-risk' &gt;50% of men stratified to high risk based on CAPRA-S alone. Thus the GC provides independent prognostic information, and a model integrating GC and CAPRA-S may further improve the prediction of lethal prostate cancer.
Prospective evaluation of a 12-gene assay on patient treatment decisions and physician confidence in mismatch repair-proficient (MMR-P) stage IIa colon cancer patients.
Authors: Steven R. Alberts, Lindsay A. Renfro, Margarita Lopatin, Haluk Tezcan, Jeff Sloan, Calvin Y. Chao, Mark Lee
Journal: Journal of Clinical Oncology (2014)

396 Background: The 12-gene Oncotype DXColon Cancer Assay is clinically validated as a predictor of recurrence risk in stage II colon cancer patients following surgery. We previously reported that the 12-gene assay led to 45% change in physician treatment (Tx) recommendations in a prospective study in MMR-P stage IIA colon cancer patients. Here, from the same prospective study, we report the influence of the 12-gene assay on patient Tx decisions, physician confidence, concordance in Tx choice between physicians and patients, and patient decisional conflict. Methods: Consecutive patients with resected stage IIA colon cancer who were candidates for adjuvant chemotherapy were enrolled by 105 physicians from 17 sites. Patient's tumor specimens were assessed by the 12-gene assay (RT-PCR) and MMR (IHC). Prior to and after receiving these results, patients completed surveys including (1) their Tx decisions (observation (Obs) vs. 5FU-monotherapy (5FU) vs. 5FU + oxaliplatin (Oxal)) and (2) indicators of decisional conflict. Results: 190 of 221 patients enrolled were evaluable including 139 who were MMR-P. Pre-assay: 46% of patients chose Obs, 3% 5FU, 7% Oxal, 2% other and 41% were undecided. Post-assay: 75% chose Obs, 12% 5FU, 11% Oxal, 3% other (undecided was not a possible response). Post-assay 129 (96%) of 135 definitive Tx decisions (Obs, 5FU, or Oxal) were concordant between patients and physicians compared to 49 (66%) of 74 definitive decisions pre-assay. In the majority of cases, patients (85%) and physicians (69%) reported that the assay influenced their Tx decisions. Assay results increased physician confidence in Tx recommendations in 126 (84%) and provided additional clinically relevant information to physicians in 129 (86%) of cases. Patient decisional conflict was significantly lower after assay results (p&lt;0.001). Conclusions: In this prospective study, quantitative recurrence risk information provided by the 12-gene assay influenced Tx decisions for a majority of patients and physicians, increased physician confidence, improved concordance in Tx choice between patients and physicians and decreased patient decisional conflict.
B cells expressing the transcription factor T-bet drive lupus-like autoimmunity
Authors: Kira Rubtsova, Anatoly V. Rubtsov, Joshua M. Thurman, Johanna M. Mennona, John W. Kappler, Philippa Marrack
Journal: Journal of Clinical Investigation (2017)

B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell-specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet-expressing B cells may be a potential target for therapy for autoimmune diseases.
Dasatinib in patients with hormone-refractory progressive prostate cancer: A phase II study
Authors: E. Y. Yu, G. Wilding, E. Posadas, M. Gross, S. Culine, C. Massard, G. R. Hudes, S. Cheng, P. Paliwal, C. N. Sternberg
Journal: Journal of Clinical Oncology (2008)

5156 Background: Dasatinib is an oral tyrosine kinase inhibitor (TKI), targeting BCR-ABL and Src-family kinases, EphA2, c-KIT, and PDGFR-β. Anti-proliferative and anti-osteoclastic activity observed in dasatinib pre-clinical models support the potential of dasatinib as a targeted therapy for prostate cancer. This phase II study investigated the activity of dasatinib in patients (pts) with metastatic hormone refractory prostate cancer (HRPC). Methods: Male pts with progressive metastatic prostate carcinoma, rising PSA while castrate (testosterone < 50 ng/dL), and no prior chemotherapy were eligible. The starting dose of dasatinib was 100 mg BID. Continuation of bisphosphonates was permitted if disease progression occurred while on therapy. For this two-stage Gehan design, the primary endpoint was response rate. Owing to the possible multiple mechanisms of action, this was a composite of PSA and bone scan responses and disease control by RECIST. Urinary N-telopeptide (UNTx) was determined every 4 weeks as a measure of bone metabolism. Results: 46 pts were enrolled. After the first 25 pts, the starting dose was changed to 70 mg BID for improved tolerability. The disease control rate for 15 RECIST- evaluable pts was 67% (10 had stable disease). Of 27 pts with bone scans at 12 weeks, 16 were stable and 1 was improved. Two of 5 pts with ≥ 2 bone scans at 24 weeks had stable disease. An improved PSA doubling time was seen in 29 of 36 pts (80.1%). One of 36 pts with ≥ 2 PSA measurements had a PSA response, which was a decrease from 19.3 to 3.3 ng/mL. Of the 37 pts with evaluable UNTx levels, including those who continued on bisphosphonate therapy, 21 (57%) had a ≥ 35% decrease from baseline. There were 6 grade 1–2 and 1 grade 3 pleural effusions at 70 mg BID, and 10 grade 1–2 effusions at 100 mg BID. Grade 3 leukopenia occurred in 2% of pts. Conclusions: The preliminary clinical activity, as demonstrated by measures of tumor and PSA response, and UNTx, warrants further study in pts with metastatic HRPC. 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 Bristol-Myers Squibb
Mortality risk after preoperative versus postoperative chemotherapy and radiotherapy in lymph node–positive rectal cancer.
Authors: T. E. Seery, A. Ziogas, B. S. Lin, C. G. Pan, M. J. Stamos, J. A. Zell
Journal: Journal of Clinical Oncology (2011)

3550 Background: Recently it has been shown that lymph node positive disease after preoperative (pre-op) radiotherapy (ypN+) was associated with increased mortality risk compared to lymph node positive disease in patients receiving postoperative (post-op) radiotherapy (pN+) in a population-based analysis of SEER data. Modern treatment incorporates chemotherapy with radiotherapy (chemo+XRT). Here we evaluated the mortality risk of ypN+ vs. pN+ disease in lymph node positive rectal cancer patients treated with chemo+XRT. Methods: 2,038 patients with stage III (lymph node positive) rectal cancer in the California Cancer Registry diagnosed 1994-2005 with follow-up until 2007 were analyzed. Only patients who received radical surgical resection and either pre-op or post-op chemo+XRT were included. Patients were stratified into pre-op and post-op groups. Survival estimates were generated using the Kaplan Meier method. Multivariate Cancer-Specific Survival (CSS) and Overall Survival (OS) analyses were performed using Cox proportional-hazard ratios with adjustment for age, gender, race/ethnicity, tumor grade, T stage, N stage, socioeconomic status, and time period (1994-7, 1998-2001, 2002-5). Results: 32.1% of patients received pre-op while 67.9% received post-op chemo+XRT. Median age was younger in the pre-op group, 59.0 (range 20-87) vs. 63.0 (range 15-92) years. OS was improved for pN+ patients receiving post-op chemo+XRT (median OS=87 months, 95% CI 79-102) compared to ypN+ patients receiving pre-op chemo+XRT (median OS= 62 months, 95% CI 50-69; P=0.0002). Compared to pN+ patients, ypN+ patients had increased mortality risk after adjustment for relevant clinical factors (CSS HR 1.76; 95% CI 1.42-2.17; OS HR 1.69; 95% CI 1.42-2.01). Conclusions: Among stage III rectal cancer patients, ypN+ in patients receiving pre-op chemo+XRT was associated with increased mortality risk compared to pN+ in patients treated with post-op chemo+XRT. Our finding confirmed the prior report that rectal cancer patients with pathologic lymph nodes after pre-op treatment may represent a high-risk group that could be targeted for intensive adjuvant or post-adjuvant therapies in future clinical trials.
Antimicrobials from human skin commensal bacteria protect against <i>Staphylococcus aureus</i> and are deficient in atopic dermatitis
Authors: Teruaki Nakatsuji, Tiffany H. Chen, Saisindhu Narala, Kimberly A. Chun, Aimee M. Two, Tong Yun, Faiza Shafiq, Paul F. Kotol, Amina Bouslimani, Alexey V. Melnik, Haythem Latif, Ji-Nu Kim, Alexandre Lockhart, Keli Artis, Gloria David, Patricia Taylor, Joanne Streib, Pieter C. Dorrestein, Alex Grier, Steven R. Gill, Karsten Zengler, Tissa R. Hata, Donald Y. M. Leung, Richard L. Gallo
Journal: Science Translational Medicine (2017)

Commensal skin bacteria produce previously unknown antimicrobial peptides that can inhibit Staphylococcus aureus colonization of atopic dermatitis subjects.
Azacitidine Improves the CD4+ T-Cell Repertoire in Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia with Multilineage Displasia
Authors: Claudio Fozza, Giovanna Corda, Francesca Barraqueddu, Salvatore Contini, Patrizia Virdis, Fausto Dore, Emanuele Angelucci, Maurizio Longinotti
Journal: Blood (2014)
Racial disparities in survival after young-onset colorectal cancer.
Authors: Elena Martinez Stoffel, Julie Ruterbusch, Laura S. Rozek, Michele L. Cote
Journal: Journal of Clinical Oncology (2015)

524 Background: Despite overall reductions in morbidity and mortality from colorectal cancer (CRC), racial disparities persist. In addition, incidence among individuals age &lt;50 is rising. Our aim was to compare survival of young onset CRC cases diagnosed in black and white individuals. Methods: Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we identified individuals with CRC between the ages of 20 to 49, diagnosed in 2000-2008. Kaplan-Meier and Cox proportional hazards models were used to compare stage-specific 5 year survival between black and white individuals with young onset CRC. Results: A total of 26,236 incident young onset CRC cases (22,121 white, 4,115 black) were identified during the 9 year study period. Overall survival at 5 years following CRC diagnosis was 54.8% among blacks and 67.4% among whites (p&lt;0.001), with blacks having a significantly higher hazard of death after adjusting for age, sex, stage, tumor site, and treatment history (HR 1.34, 95% CI 1.26-1.43). Stratifying by stage at CRC diagnosis, blacks had worse survival at every disease stage compared with whites, with the greatest racial disparities observed among stage II cancers of colon (HR 1.68 95% CI 1.38-2.04) and stage II and III cancers of the rectum (HR 1.78, 95% CI 1.51-2.09, and HR 1.86, 95% CI 1.54-2.24, respectively). Conclusions: Survival after diagnosis of CRC at young age is significantly worse among blacks compared to whites, even among individuals with early stage disease. These findings suggest that differences in tumor biology may play a role in racial disparities in CRC outcomes, which may have implications for adjuvant treatment.