Alvin teman Cancer Center

St. Louis, MO, United States

Alvin teman Cancer Center

St. Louis, MO, United States
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Jimenez R.E.,The Surgical Center | Jimenez R.E.,University of Connecticut | Hawkins W.G.,University of Washington | Hawkins W.G.,Alvin teman Cancer Center
Surgery (United States) | Year: 2012

Background: Pancreatic fistula occurs in approximately 30% of patients after distal pancreatectomy. Fistula formation is multifactorial in nature, influenced by patient-specific anatomic features of the pancreas and operative techniques at the time of resection. Methods: In this article, we review past, present, and future strategies postulated to address this problem. Results: The results of the stapler versus hand-sewn closure after distal pancreatectomy trial are presented in detail. This trial established equivalency between these 2 techniques, putting to rest a 25-year-old controversy. The implications of the stapler versus hand-sewn closure after distal pancreatectomy trial are discussed in the context of the current revolution in minimally invasive surgery, which will likely bring stapler closure to the forefront. Technologic improvements in surgical staplers are also discussed, with a focus in their applicability to pancreatic transection. Specifically, the results of a newly -published trial from Washington University in St. Louis are presented, showing improved fistula rates when stapler closure of the pancreas is reinforced with an external prosthesis. Conclusion: Based on these results, we postulate that stapler transection with mesh reinforcement is the best currently available method of pancreatic remnant closure. Results of ongoing trials using energy sealing devices are eagerly awaited, and further research into this area is necessary to make further progress in this field. © 2012 Mosby, Inc. All rights reserved.

Devarakonda S.,University of Washington | Govindan R.,University of Washington | Govindan R.,Alvin teman Cancer Center
Cancer Discovery | Year: 2015

It is possible to decipher the clonal architecture of a tumor and the sequence in which cancer clones acquire genomic alterations through multiregion sequencing (M-seq). Serial evaluation of tumor specimens through M-seq can provide valuable information on the molecular basis of resistance to therapy. © 2015 American Association for Cancer Research.

Yang F.,University of Washington | Thomas M.A.,University of Washington | Dehdashti F.,University of Washington | Dehdashti F.,Mallinckrodt Institute of Radiology | And 4 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Purpose The aim of this pilot study was to explore heterogeneity in the temporal behavior of intratumoral [18F]fluorodeoxyglucose (FDG) accumulation at a regional scale in patients with cervical cancer undergoing chemoradiotherapy. Methods Included in the study were 20 patients with FIGO stages IB1 to IVA cervical cancer treated with combined chemoradiotherapy. Patients underwent FDG PET/CT before treatment, during weeks 2 and 4 of treatment, and 12 weeks after completion of therapy. Patients were classified based on response to therapy as showing a completemetabolic response (CMR), a partial metabolic response (PMR), or residual disease and the development of new disease (NEW). Based on the presence of residual primary tumor following therapy, patients were divided into two groups, CMR and PMR/NEW. Temporal profiles of intratumoral FDG heterogeneity as characterized by textural features at a regional scale were assessed and compared with those of the standardized uptake value (SUV) indices (SUVmax and SUVmean) within the context of differentiating response groups. Results Textural features at a regional scale with emphasis on characterizing contiguous regions of high uptake in tumors decreased significantly with time (P<0.001) in the CMR group, while features describing contiguous regions of low uptake along with those measuring the nonuniformity of contiguous isointense regions in tumors exhibited significant temporal changes in the PMR/NEW group (P<0.03) but showed no persistent trends with time. Both SUV indices showed significant changes during the course of the disease in both patient groups (P<0.001 for SUVmax and SUVmean in the CMR group; P=0.0109 and 0.0136, respectively, for SUVmax and SUVmean in the PMR/NEW group), and also decreased at a constant rate in the CMR group and decreased up to the 4th week of treatment and then increased in the PMR/NEW group. Conclusion The temporal changes in the heterogeneity of intratumoral FDG distribution characterized at a regional scale using image-based textural features may provide an adjunctive or alternative option for understanding tumor response to chemoradiotherapy and interpreting FDG accumulation dynamics in patients with malignant cervical tumors during the course of the disease. © 2013 Springer-Verlag Berlin Heidelberg.

Devarakonda S.,University of Washington | Morgensztern D.,University of Washington | Morgensztern D.,Alvin teman Cancer Center | Govindan R.,University of Washington | Govindan R.,Alvin teman Cancer Center
The Lancet Oncology | Year: 2015

Treatment for non-small-cell lung cancer is evolving from the use of cytotoxic chemotherapy to personalised treatment based on molecular alterations. This past decade has witnessed substantial progress in the treatment of patients with EGFR mutations and ALK rearrangements, and it is now possible to study complex genomic alterations in cancer using next-generation sequencing. Sequencing data from large-scale consortia, such as The Cancer Genome Atlas, as well as several independent groups, have helped identify novel drivers and potentially targetable alterations in lung adenocarcinomas. These data clearly suggest that lung adenocarcinoma is associated with distinct genomic alterations compared with other lung cancer subtypes, and highlight the widespread molecular heterogeneity that underlies the disease. In this Review, we discuss some of the key findings from genomic studies of lung adenocarcinoma. © 2015 Elsevier Ltd.

Ju N.R.,University of Washington | Jeffe D.B.,University of Washington | Jeffe D.B.,Alvin teman Cancer Center | Keune J.,University of Washington | And 3 more authors.
Breast Cancer Research and Treatment | Year: 2013

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study. © 2012 Springer Science+Business Media New York.

Kidd E.A.,Stanford University | Thomas M.,University of Washington | Siegel B.A.,Alvin teman Cancer Center | Siegel B.A.,University of Washington | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUVmax) and the variability of uptake (FDGhetero), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUVmax and FDGhetero during concurrent chemoradiation for cervical cancer and their association with post-treatment response. Methods and Materials: Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUVmax, FDGhetero, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. Results: For all patients, the average pretreatment SUVmax was 17.8, MTV was 55.4 cm3, and FDGhetero was -1.33. A similar decline in SUVmax was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDGhetero decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUVmax had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUVmax, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUVmax (P=.037), week 4 FDGhetero (P=.005), pretreatment MTV (P=.008), and pretreatment FDGhetero (P=.008) were all significantly associated with post-treatment PET response. Conclusions: SUVmax shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response. © 2013 Elsevier Inc.

Morgensztern D.,Yale Cancer Center | Waqar S.,University of Washington | Subramanian J.,University of Washington | Subramanian J.,Alvin teman Cancer Center | And 4 more authors.
Journal of Thoracic Oncology | Year: 2012

Background: Increased tumor size is a known risk for poor outcomes in patients with stage I and II non-small cell lung cancer (NSCLC), who are treated with surgery or radiotherapy. However, there is limited information regarding the impact of tumor size on the outcomes of patients with mediastinal lymph node involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to evaluate the prognostic significance of tumor size in patients with unresected stage III NSCLC. Methods: The SEER registry was queried for patients with unresected NSCLC stage III and no malignant pleural effusion, aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1-3cm), S2 (3.1-5cm), S3 (5.1-7cm), and S4 (7.1-20cm). Demographic variables included age, sex, race and histology. Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used to evaluate whether tumor size remained an independent risk factor in multivariable analysis. Results: A total of 12,315 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all subgroups of patients. Conclusion: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC, and should be considered in the stratification of patients treated in this setting after validation of this finding in additional studies. Copyright © 2012 by the International Association for the Study of Lung Cancer.

Morgensztern D.,Yale Cancer Center | Waqar S.,University of Washington | Subramanian J.,University of Washington | Subramanian J.,Alvin teman Cancer Center | And 3 more authors.
Journal of Thoracic Oncology | Year: 2012

Background: Despite its common occurrence, the influence of malignant pleural effusion (MPE) on the outcomes of patients with advanced non-small-cell lung cancer (NSCLC) with distant metastasis (M1b) is unknown. We evaluated the clinical characteristics associated with MPE at presentation and the prognostic impact of MPE at presentation in patients with stage M1b NSCLC. Methods: We extracted data from the Surveillance Epidemiology and End Results (SEER) registry from patients with NSCLC diagnosed between 2004 and 2005. Odds-ratio estimates were calculated using logistic regression, and the Kaplan-Meier method was used to estimate the overall survival. Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. Results: Among the 57,685 patients, MPE was present in 9170 (15.9%), including 3944 out of 31,506 (12.5%) without distant metastases and 5226 (20.0%) out of 26,179 with M1b. The probability of MPE was higher in patients with larger tumors, mediastinal lymph node involvement, and adenocarcinoma, NSCLC not otherwise specified, or large-cell histology. In patients with stage M1b, median overall survival (3 months versus 5 months), estimated 1-year survival (12.6% versus 24.8%), and 2-year survival (5.4% versus 11.3%) were significantly lower in patients with MPE compared with those without MPE (hazards ratio 1.49, 95% confidence interval 1.44-1.54, p < 0.0001). MPE was also an independent factor for worse survival in multivariate analysis (hazards ratio 1.36, 95% confidence interval1.30-1.43, p < 0.001). Conclusions: MPE is a common complication in patients with NSCLC and is associated with decreased survival in patients with distant metastases. If these data are validated, subsequent studies in patients with advanced NSCLC may consider stratification according to the MPE status. Copyright © 2012 by the International Association for the Study of Lung Cancer.

Miller D.A.,University of Washington | Richardson S.,University of Washington | Grigsby P.W.,University of Washington | Grigsby P.W.,Alvin teman Cancer Center
Gynecologic Oncology | Year: 2010

Objective: HDR brachytherapy to the vaginal cuff using rigid intracavitary cylinders has a limited capacity to adapt to patient-specific anatomy. This study describes the use and dosimetry of a new method of anatomically conformal post-operative vaginal cuff HDR brachytherapy using an intra-vaginal balloon applicator. Methods: Thirty consecutive patients with endometrial carcinoma underwent a hysterectomy and received adjuvant HDR brachytherapy in 6 weekly fractions using an intra-vaginal balloon. Optimal distension of the balloon to conform to the vaginal cuff was clinically determined to achieve complete balloon surface apposition with the vaginal mucosa and was confirmed radiographically. Radiation dose was prescribed to the vaginal mucosa and brachytherapy CT simulation was performed to optimize the irradiation dose in 3-D. Results: 180 brachytherapy procedures were performed. The mean volume of balloon distension was 47.3 cc (range 20.8-83.8 cc; ± 11.3 cc). The mean dose from brachytherapy to the 2 cc volume of the bladder and rectum was 48.6% and 71.1% of the prescribed vaginal mucosal dose, respectively. Bladder and rectal doses increased as a function of balloon volume. 100% of the prescribed dose covered an average of 95.6% of the vaginal cuff. There were no acute complications or vaginal cuff recurrences at a mean follow-up of 13 months. Conclusions: Post-operative vaginal cuff HDR brachytherapy using an intra-vaginal balloon applicator which conforms to the individual patient's vaginal cuff provides excellent radiation dose coverage of the vaginal mucosa with acceptable doses to the bladder and rectum. © 2009 Elsevier Inc. All rights reserved.

Yaghjyan L.,Washington University in St. Louis | Colditz G.A.,Washington University in St. Louis | Colditz G.A.,Alvin teman Cancer Center | Wolin K.,Washington University in St. Louis | Wolin K.,Alvin teman Cancer Center
Breast Cancer Research and Treatment | Year: 2012

Studies show a protective relationship between physical activity and breast cancer risk across the life course from menarche to postmenopausal years. Mammographic breast density is a known and strong breast cancer risk factor. Whether the association of physical activity with breast cancer risk is mediated through mammographic breast density is poorly understood. This systematic review summarizes published studies that investigated the association between physical activity and mammographic breast density and discusses the methodological issues that need to be addressed. We included in this review studies that were published before October 31, 2011 that were accessible in full-text format and were published in English. Weidentified 20 studies through the PubMed Central, BioMed Central, Embase, and Scopus and using the search terms "physical activity and breast density" and "exercise and breast density" as well as through manual searches of the bibliographies of the articles identified in electronic searches. We found no evidence of association between physical activity and breast density across the studies by grouping them first by the timing of physical activity assessment (in adolescence, current/recent, past, and lifetime) and then by women's menopausal status (premenopausal and postmenopausal). Given the strength of the relationship between physical activity and breast cancer and the null findings of this review, it is unlikely that the effect of physical activity is mediated through an effect on breast density. © Springer Science+Business Media, LLC. 2012.

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