tbuckley/cabot-search huggingface dataset:
Pre-treatment and treatment related risk factors for severe late toxicity after chemo-RT for head and neck cancer: An RTOG analysis
Authors: M. Machtay, J. Moughan, A. Trotti, A. S. Garden, R. S. Weber, J. S. Cooper, R. S. Swann, K. K. Ang
Journal: Journal of Clinical Oncology (2006)

5500 Background: Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) improves tumor control, but its toxicity is formidable. This study evaluates factors that might predict for severe late toxicity following CCRT. Methods: Patients treated with CCRT were analyzed from three RTOG trials of locally advanced SCCHN: 91–11 arm #2 (XRT + high dose cisplatin for larynx cancer); 97–03 (phase II study of various doublets of chemotherapy with XRT); and 99–14 (phase II study of accelerated XRT + high dose cisplatin). Severe late toxicity was defined in this secondary analysis as late (&gt;180 days from the start of XRT) Grade 3–4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system); requirement for a feeding tube ≥2 years after registration; or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed to determine factors predictive of severe late toxicity, with a multivariate logistic regression model that included pre-treatment and treatment potential factors. Results: The total sample size of patients treated with CCRT from these three studies was 479; 226 were evaluable (119 patients had severe pre-treatment laryngopharynx dysfunction and 134 had persistent/recurrent cancer). There were 98 cases (patients with severe late toxicity) and 128 controls. In the multivariate model, significant predictors of severe late toxicity were older age (odds ratio 1.05 per year, p = 0.002); advanced T-stage (odds ratio 2.21; p = 0.014); larynx/hypopharynx tumor site (odds ratio 3.20; p = 0.011); and neck dissection (ND) after XRT (odds ratio 2.22; p = 0.029). Radiotherapy dose intensity and chemotherapy dose intensity were not predictive. Among 47 patients who underwent post-XRT ND, the crude rate of severe late toxicity was 55%, compared with 40% for the subgroup of 179 patients who did not undergo post-XRT ND (p = 0.05). Conclusions: Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/hypopharynx primary site were independent risk factors. Neck dissection after CCRT may be associated with an increased risk of these complications. This work was supported in part by the Commonwealth of Pennsylvania (Tobacco Settlement Grant). No significant financial relationships to disclose.
A phase II, open-label, randomized clinical trial of panitumumab plus gemcitabine and oxaliplatin (GEMOX) versus GEMOX alone as first-line treatment in advanced biliary tract cancer: The Vecti-BIL study.
Authors: Francesco Leone, Donatella Marino, Roberto Filippi, Stefano Cereda, Carmen Belli, Rosella Spadi, Guglielmo Nasti, Massimo Montano, Alessio Amatu, Giuseppe Aprile, Celeste Cagnazzo, Gianpiero Fasola, Salvatore Siena, Libero Ciuffreda, Michele Reni, Massimo Aglietta
Journal: Journal of Clinical Oncology (2015)

281 Background: Biliary tract cancer (BTC) is a rare and lethal disease with very few therapeutic options. Preclinical data suggest that Epithelial Growth Factor Receptor (EGFR) pathway activation could be involved in BTC pathogenesis, envisaging a potential role of anti-EGFR monoclonal antibodies. Methods: Patients (pts) with metastatic or unresectable BTC, harboring wild-type KRAS status, with ECOG performance status 0-2, without prior systemic therapy, were randomized to GEMOX (gemcitabine, 1000 mg/m² and oxaliplatin, 100 mg/m²) therapy with (arm A) or without (arm B) panitumumab (6 mg/kg), q2w for up to 12 cycles. Maintenance therapy with panitumumab alone was allowed in arm A in case of clinical benefit after 12 cycles. The primary endpoint was the progression-free survival (PFS). The target hazard ratio was 0.60 requiring 88 pts for 74 PFS events (80% 1-β power, α = 0.10, log-rank test 1-sided). Secondary endpoints were objective response rate (RR) (RECIST vers.1.1), overall survival (OS), and safety. Results: From 06/2010 to 09/2013, 89 pts were enrolled (median age 64 years; metastatic 78%; gallbladder 32%, extra-hepatic 21%, intra-hepatic 47%). After a median follow-up of 8.6 months (mo), with six pts (two progression-free) in arm A, and eight pts (none progression-free) in arm B still in follow-up, median PFS was 7.7 mo in arm A (95% CI 4.7–10.6) and 5.5 mo (95% CI 3.2–7.8) in arm B (p=0.10). RR was 25.0% in arm A and 18.2% in arm B. No differences in survival were seen, being median OS 9.5 mo (95% CI 5.7-13.3) in arm A and 9.9 mo in arm B (95% CI 5.1-14.6), p= 0.49. The most common all grade toxicities were skin toxicity (71%), nausea (67%), and fatigue (53%) in arm A; nausea (64%), neurotoxicity (57%), and fatigue (52%) in arm B. The most common grade 3 or 4 toxicities were: hepatic toxicity (20%), diarrhea (13%), and nausea (13%) in arm A; cholestasis (14%), dyspnea (9%), and diarrhea (9%) in arm B. Conclusions: Although the results are not fully mature, the combination of GEMOX and panitumumab showed a trend towards better PFS and RR in KRAS wild-type BTC pts as compared to GEMOX alone. No impact on OS seems evident. Clinical trial information: NCT01389414.
Abstract 17154: Impact of Myocardial Bridging on Coronary Endothelial Dysfunction and Atherosclerotic Plaque Formation
Authors: Shigemitsu Tanaka, Ryotaro Yamada, Jennifer A Tremmel, Ingela Schnittger, Paul G Yock, Peter J Fitzgerald, Yasuhiro Honda
Journal: Circulation (2013)

Background: Recent studies have demonstrated that myocardial bridging (MB) can cause adverse outcomes, presumably resulted from hemodynamic disturbance that leads to endothelial dysfunction at the ...
Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample
Authors: M B Stein, J R Walker, G Anderson, A L Hazen, C A Ross, G Eldridge, D R Forde
Journal: American Journal of Psychiatry (1996)

The authors investigated whether histories of childhood physical or sexual abuse were reported more frequently in a clinical sample of patients with anxiety disorders than in a matched community comparison sample.A standardized interview with an extensive series of trauma probes was administered to 125 patients with DSM-IV anxiety disorders (panic disorder, social phobia, or obsessive-compulsive disorder) and to 125 age- and gender-matched subjects drawn from a random community sample.Childhood physical abuse was higher among both men (15.5%) and women (33.3%) with anxiety disorders than among comparison subjects (8.1%). Childhood sexual abuse was higher among women with anxiety disorders (45.1%) than among comparison women (15.4%) and was higher among women with panic disorder (60.0%) than among women with other anxiety disorders (30.8%).These findings confirm the association between anxiety disorders and reported childhood physical and sexual abuse and extend earlier findings by pointing to a particular association between sexual abuse and panic disorder in women.
Cost-effectiveness of letrozole (LET) versus anastrozole (ANA) in postmenopausal women (PMW) with hormone receptor-positive (HR+) early-stage breast cancer (EBC) based on indirect comparison of BIG 1-98 and ATAC.
Authors: T. E. Delea, M. A. Lipsitz, S. C. Zelt, A. Guo
Journal: Journal of Clinical Oncology (2010)

e11013 Background: BIG 1-98 and ATAC demonstrated that, in PMW with HR+ EBC, 5 y of initial adjuvant endocrine therapy (ET) with the aromatase inhibitors (AIs) LET or ANA is superior to tamoxifen (TAM). Whereas no difference in overall survival (OS) with ANA vs. TAM was observed in ATAC, exploratory analyses of final OS from BIG 1-98 suggest that LET improves OS vs. TAM. However, because ANA will become available generically 1 year before LET, there may be savings in medication costs by using ANA. Methods: A Markov model was used to estimate cost per quality-adjusted life year (QALY) gained of initial adjuvant ET with LET vs. ANA from the U.S. health care system perspective. Probabilities of recurrence for patients receiving TAM were based on data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis. The relative risk (RR) of recurrence with AI vs TAM was assumed to be the same for LET and ANA (HR = 0.76) based on results of BIG 1-98 and ATAC. The RRs of non-breast-cancer death (NBCD) for LET vs. TAM (0.90), ANA vs. TAM (1.08), and TAM vs. no ET (1.05) were obtained from BIG 1-98, ATAC, and ECTCG respectively. Effects of AIs were assumed to carry-over for 5 y. Costs of AIs were assumed to decline by 75% with generic availability (at therapy initiation for ANA; one year subsequently for LET). Other probabilities, costs, and utilities were obtained from published studies. Results: Total lifetime costs are $3696 greater with LET vs ANA. LET increases QALYs by 0.18 vs. ANA. Cost-effectiveness of LET vs ANA is $20,891 per QALY gained. Cost-effectiveness was sensitive to the RRs of NBCD with LET vs TAM and ANA vs. TAM. There was a 69% probability that LET is preferred given a threshold of $50,000 per QALY. Conclusions: Based on an indirect comparison of BIG 1-98 and ATAC, LET may be cost-effective compared with ANA as initial adjuvant ET in PMW with EBC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Use of “intracrine androgen signaling signature'' to predict benefit from abiraterone acetate (AA) in patients with castrate-resistant prostate cancer (CRPC).
Authors: E. Efstathiou, S. Tu, A. Aparicio, A. Hoang, S. Wen, P. Troncoso, L. A. Smith, N. Chieffo, A. Molina, C. Logothetis
Journal: Journal of Clinical Oncology (2010)

4547 Background: To detemine effects of AA plus prednisone in CRPC in bone and their association to patient (pt) and tumor characteristics. Methods: Study pts had progressive CRPC with <50 ng/dl serum testosterone (S-T), bone metastases and agreed to serial bone marrow biopsy. Pts received oral AA 1,000 mg QD and prednisone 5 mg BID. Results: Between 10/07 and 4/09, 56 pts with median age 70 yrs (range 48-87), PS-ECOG 2 (range 0-2) and baseline PSA concentration 95.3 ng/dl (range 3-2,725), enrolled. Thirty-six (64%) had DES and/or ketoconazole, 47 (84%) prior chemotherapy [≥2 regimens: 34 (61%)]. Forty six (82%) had ≥10 bone lesions, 20 (36%) lesions in lymphnodes and 11 (20%) in the liver or other sites. Maximum PSA decline of ≥50% and ≥90% was observed in 25 (45.5 %) and 9/55 (16 %) evaluable pts respectively, with median treatment 33.3 weeks (95 %CI 28-59.3) (range 4-117+). Median survival is 18.6 months (95% CI 17.7-27+ ms). There are two profiles of clinical progression, immediate [12/55 (22%) pts] and delayed following benefit. Four Grade 3 adverse events included elevated liver function tests (2), hypertension, and hypokalemia. No pt required eplerenone for mineralocorticoid excess. No correlation between baseline S-T (median 23.7 ng/dl range <10-41) and bone marrow aspirate testosterone (BM-T) levels (median 15.4 ng/dl, range <10-81) was noted (Spearman's r 0.28, p= 0.2). Decline below detectable levels (<10 ng/dl) in S-T and BM-T occurred consistently in treated pts. Depleted baseline BM-T (<10 ng/dl) correlated with early progression (p=0.05). An
Pilot study of carboplatin/radiotherapy plus ‘dose-dense’ pemetrexed for locally advanced non-small cell lung carcinoma
Authors: M. Machtay, M. Werner-Wasik, A. DeNittis, R. A. Axelrod, P. Gilman, J. Lavarino, T. Meyer, J. Treat, W. J. Curran
Journal: Journal of Clinical Oncology (2008)

7571 Background: This is a prospective Pilot/Phase I dose-seeking clinical trial of dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) and carboplatin for locally advanced non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy (conventional fractionation) with carboplatin (AUC = 6) during Weeks 1 and 5 of XRT, and pemetrexed during Weeks 1, 3, 5, and 7 of XRT. Vitamin prophylaxis (B12/folate) was started prior to treatment. The starting dose level of pemetrexed was 300 mg/m2, with plans to dose escalate after 3–6 patients had at least 30 days of evaluability post-treatment without dose-limiting toxicity (DLT). DLT was defined as any Grade 4 toxicity, selected Grade 3 toxicities (chemo-XRT pneumonopathy, esophagitis lasting > 14 days), and/or inability to complete at least 54 Gy of XRT). Consolidation carboplatin (AUC=6) and pemetrexed (500 mg/m2) q3 weeks × 2 cycles was also planned. Results: Fourteen patients were enrolled; 10 are evaluable for feasibility/toxicity; 9 are evaluable for response. All 10 patients received both doses of concurrent carboplatin; 9/10 received a full dose of XRT. Five of 10 patients received four doses of pemetrexed; the median cumulative concurrent pemetrexed dose delivered was 1,150 mg/m2. The main toxicity of concurrent chemo-XRT was neutropenia, with a median ANC nadir of 1.4; three patients had Grade ≥ 3 neutropenia. One patient had multiple Grade 4 toxicities (infection, multi-organ failure) and a 2nd patient had prolonged Grade 3 esophagitis - these were considered DLTs and the study was amended to require reduced XRT field size (involved field). No patient had Grade ≥3 chemo-XRT pneumonopathy. All patients recovered from their acute toxicities; there were no treatment-related deaths and no unusual/unexpected toxicities. In-field local tumor responses were observed in 7 of 9 evaluable patients. Conclusions: Although generally well tolerated, feasible and active, XRT/pemetrexed/carboplatin as given in the original design of Dose Level I exceeded pre-defined DLT boundaries. Study accrual continues, using involved field XRT, and updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Serum albumin as an independent prognostic indicator in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy
Authors: S. W. Shin, W. J. Sung, J. W. Lee, J. S. Jung, S. J. Kim, J. H. Seo, Y. H. Kim, J. S. Kim, I. K. Choi
Journal: Journal of Clinical Oncology (2005)

5549 Background: Low serum albumin concentrations have been associated with poorer than expected outcomes in a variety of malignant diseases. However, its value as a independent prognostic indicator in patients with advanced head and neck cancer who treated with concurrent chemoradiation therapy remains unclear. Methods: We investigated the effect of baseline serum levels on 61 consecutively treated patients who were diagnosed with advanced head and neck cancer and treated with concurrent chemoradiotherapy, from May 1, 1999 to September 31, 2003, at our institution. We investigated the effect of low levels of serum albumin (less than 4.0 g/dl) using univariate survival statistics and the multivariate Cox proportional hazards model. Results: Demographically, the median age of the patients was 62 years (range to 87 years). Twenty eight were nasopharyngeal cancer and thirty three patients were hypopharyngeal squamous cell carcinoma. Majority of the patients (n=42) were stage 4 with extensive regional lymph node metastasis. The patients were treated with 2–3 cycle of 5-fluorouracil and cisplatin combination chemotherapy concurrently with conventional fraction of radiation up to 72 Gy. The Cox proportional hazards model found that higher level of levels of pre-treatment serum albumin (equal or greater than 4.0 g/dl) reduced mortality by 27% (p = .0248). The only other variable to achieve statistical significance in the Cox model was advanced lymph node metastasis (p <.0001). Conclusions: We found that a baseline serum albumin level was a powerful prognostic variable in patients with head and neck cancer patients treated with concurrent chemoradiotherapy No significant financial relationships to disclose.
Optical-Based Analysis of Soft Tissue Structures
Authors: Will Goth, John Lesicko, Michael S. Sacks, James W. Tunnell
Journal: Annual Review of Biomedical Engineering (2016)

Fibrous structures are an integral and dynamic feature of soft biological tissues that are directly related to the tissues’ condition and function. A greater understanding of mechanical tissue behavior can be gained through quantitative analyses of structure alone, as well as its integration into computational models of soft tissue function. Histology and other nonoptical techniques have traditionally dominated the field of tissue imaging, but they are limited by their invasiveness, inability to provide resolution on the micrometer scale, and dynamic information. Recent advances in optical modalities can provide higher resolution, less invasive imaging capabilities, and more quantitative measurements. Here we describe contemporary optical imaging techniques with respect to their suitability in the imaging of tissue structure, with a focus on characterization and implementation into subsequent modeling efforts. We outline the applications and limitations of each modality and discuss the overall shortcomings and future directions for optical imaging of soft tissue structure.
RNAi-based adjuvant therapy in a NSCLC mouse model prevents the development of distant metastasis
Authors: C. Müller-Tidow, E. Bulk, A. Hascher, B. Sargin, J. Vormoor, M. Hotfilder, W. E. Berdel, H. Serve
Journal: Journal of Clinical Oncology (2007)

18089 Background: Surgery cures about 50% of the patients with early stage NSCLC. Although adjuvant chemotherapy improves outcome, a considerably fraction of patients still dies due to development of distant metastasis. Microarray analyses revealed that S100P expression is a strong adverse prognostic factor in early stage NSCLC. Methods: In a mouse NOD/SCID metastasis model based on subcutaneous xenotransplants of NSCLC cell lines we analyzed the effects of S100P expression on metastasis development after curative resection of the primary tumor. Tumors were resected 3–4 weeks after inoculation into the left flank after tumors reached a specified size. Adjuvant RNAi (shRNA based) therapy against S100P was i.v.-administered on the 5 days surrounding tumor resection. Results: S100P overexpression in HTB56 lung cancer cells led to more rapid tumor growth as xenografts. After tumor resection, metastasis developed in 14% (2/12) of the control mice but in 67% (8/12) of the S100P expressing tumors p&lt;0.05. shRNA plasmids were developed and confirmed to be active in downregulating S100P. When these plasmids were i.v.-injected before resection, a significant decrease in S100P protein expression occurred. Control plasmid did not have any effect. The size of S100P-shRNA treated tumors decreased after 2 i.v.-applications. Metastasis developed in 69% (11/16) of the mice treated with the control plasmid. In S100P-shRNA treated mice only 28% (5/18) developed metastasis (p&lt;0.05). After i.v.-injection of NSCLC cells with endogenous S100P expression, all mice (100% - 10/10) developed metastasis when adjuvant treatment was administered with control shRNA. However, when the mice were treated with S100P-shRNA in the first week after i.v.-injection of the tumor cells 33% of the mice (3/9) did not develop lung metastasis. Conclusion: Expression of S100P is a negative adverse prognostic marker in early stage NSCLC. S100P enhances metastasis formation in a mouse metastasis model. Adjuvant therapy with shRNA against S100P is feasible and effective in at least two murine NSCLC metastasis models. These findings suggest that S100P is a potentially important target to inhibit NSCLC metastasis and RNAi based therapy approaches might offer novel ways for targeted therapy in adjuvant situations. No significant financial relationships to disclose.
A randomized clinical study of surgery versus radiotherapy in the treatment of resectable esophageal cancer
Authors: J. Yu, R. Ren, X. Sun, Y. Yin, Z. Fu
Journal: Journal of Clinical Oncology (2006)

4013 Background: To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy (LCAHFR) for patients with resectable thoracic segment esophageal cancer. Methods: From June 1998 to September 2002, 269 patients with resectable thoracic esophageal cancer were randomized into two groups. 135 were with surgery and 134 with late-course accelerated hyperfractionated (LCAF) radiotherapy. Chemotherapy only for clinical recurrence and salvage therapy. Results: The 1-, 3- and 5- year overall survival rate were 88.6%, 56.2% and 34.7% in the surgery group and 93.3%, 61.5% and 36.9% in the radiotherapy group. There was no statistical difference between the two groups (P =0.58). Median survival was 28.5 months and 30.5 months respectively. The 1-, 3-and 5-year progression-free survival rate was 73.3%, 39.7% and 20.6% in the surgery group and 75.9%, 43.7% and 23.1% in the radiotherapy group (P =0.65) . There was no difference between the two groups in survival rates including different location and length (P &gt; 0.05). The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group (16.6% and 13.3% respectively ) was lower than in the surgery group ( 25.3% and 20.3 % respectively ), there was no significance between them. The incidence of local failure in the radiotherapy and surgery group was 57.3% and 27.8% respectively (P = 0.001) The incidence of death by local reasons was higher than in the surgery group (P = 0.02 ). The incidence of death by distant metastasis was lower than in the surgery group (P = 0.02 ). Conclusion: The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable. No significant financial relationships to disclose.