B Ashleigh Guadagnolo

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (63)279.61 Total impact

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    ABSTRACT: Background: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes. Methods: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome. Results: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R. Discussion: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.
    No preview · Article · Feb 2016 · Annals of Surgical Oncology
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    ABSTRACT: Trimodality therapy (chemoradiation and surgery) is standard of care for Stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between density of radiation oncologist and travel distance to receipt of RT.
    No preview · Article · Dec 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Objectives: Determine association of MRI features of extra-abdominal desmoid tumors (DTs) with prognosis. Methods: MRIs for 90 patients with DT were retrospectively reviewed for imaging features associated with biological behavior. The primary endpoint was progression (for lesions managed with chemotherapy, radiation therapy and observation) or recurrence (following surgery). Time to event was studied using univariate and multivariable Cox proportional hazards regression models when accounting for demographic, clinicopathological, and imaging variables. Kaplan-Meier plots were used to estimate event-free rate (EFR). Results: Univariate analysis revealed a significant relationship between EFR and treatment, location, and compartment of origin (subcutaneous, superficial fascial, intramuscular, and deep fascial/intermuscular). None of the imaging features commonly associated with biological behavior of DTs (e.g., shape, enhancement, T2 signal, etc.) or surgical margins (in surgical cases) was associated with EFR. Multivariate analysis showed that treatment modality and compartment of origin were independent predictors of EFR. Superficial and deep fascial lesions had a significantly worse EFR as a group (HR: 3.9; 95% CI: 1.83-8.32; p=0.0004) compared to the subcutaneous and intramuscular lesions as a group. Five-year EFR for the fascial lesions was 18% (95% CI: 6-36%), compared to 57% (95% CI: 25%-79%) for the subcutaneous and intramuscular group. Conclusion: Intra-muscular or subcutaneous DTs may be associated with improved prognosis. If validated on multi-reader and prospective studies, these results can provide for rapid risk stratification at the time of initial MRI. Advances in knowledge: This work has shown that imaging features commonly associated with biological activity of desmoid tumors (e.g., shape, T2 signal, and enhancement) do not appear to be associated with prognosis in patients undergoing a variety of treatment modalities. The compartment of origin of the lesion, which can be determined on pre-operative MRI, was shown to be associated with prognosis, and can allow for risk stratification in patients with DTs.
    No preview · Article · Nov 2015 · The British journal of radiology
  • A.J. Bishop · G.K. Zagars · B.S. Moon · P.P. Lin · V.O. Lewis · B.A. Guadagnolo

    No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or ≥ 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non-privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment. © 2015 by American Society of Clinical Oncology.
    Preview · Article · Aug 2015 · Journal of Clinical Oncology
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    ABSTRACT: To report survival outcomes and local control in patients with solitary fibrous tumors (SFT) treated using surgery and radiation therapy (RT). We reviewed the medical records of 31 consecutive patients definitively treated for SFT with surgery and RT between 1982 and 2012. The median age was 51 years (range, 23 to 88 y) and tumors were evenly distributed between the head and neck (n=9, 29%), trunk (n=10, 32%), and lower extremities (n=9, 29%). The majority of tumors were large (>5 cm) (n=23, 72%). Specimens had a median of 2 mitoses/10 HPF (range, 0 to 8). Nearly half the cases were treated with postoperative RT (n=14, 45%; median dose, 58 Gy) and the other 17 patients (55%) received preoperative RT (median dose, 50 Gy). Median follow-up time was 59 months (range, 18 to 349 mo). The 5-year rates of local control, overall survival, and distant metastatic-free survival were 100%, 95%, and 92%, respectively. There were no local or nodal relapses and the 10-year complication rate was 6% (n=2). Treatment of soft tissue SFT using combined surgery and RT results in excellent local control.
    No preview · Article · Aug 2015 · American journal of clinical oncology
  • Zhengfu Fan · Shreyaskumar Patel · Valerae O Lewis · B Ashleigh Guadagnolo · Patrick P Lin
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    ABSTRACT: Extraosseous osteosarcoma is rare, and the most appropriate therapy is unclear because there are few studies regarding its treatment. The effectiveness of radiation and chemotherapy remains uncertain owing to conflicting results in previous reports. To review our experience with contemporary multimodality treatment, we asked: (1) What is the disease-specific survival and local relapse-free survival? (2) Does American Joint Commission on Cancer (AJCC) stage, tumor size, or location relate to disease outcome? (3) Does radiation therapy improve local control or survival? (4) Do doxorubicin and ifosfamide improve local control or survival? Between 1990 and 2012, we treated 40 patients for localized, high-grade extraosseous osteosarcoma. In this retrospective study, we could determine the status of 36 patients (90%) either to death or for a minimum of 24 months of followup; four (10%) were lost to followup before 24 months. There were 11 patients with AJCC Stage IIA and 25 with Stage III disease. All patients underwent wide surgical excision. Of the patients with Stage IIA disease, four received radiation and none received chemotherapy. Of the patients with Stage III disease, six received radiation, seven were treated with chemotherapy, and six received radiation and chemotherapy. During the study period, high-dose doxorubicin and ifosfamide was the preferred chemotherapy regimen for patients younger than 60 years with normal cardiac and renal function. Local relapse-free survival and disease-specific survival were determined by Kaplan-Meier analysis using a prospectively maintained institutional database supplemented by information from the institutional tumor registry. The Cox proportional hazard model was used to determine the effect of various factors on local recurrence and patient survival. At 5 years, local relapse-free survival was 47% (95% CI, 27%-64%), and disease-specific survival was 53% (95% CI, 35%-68%). In multivariate analysis, AJCC stage, which depends on tumor size, was the strongest predictor of local relapse-free survival (hazard ratio [HR] = 0.17, p = 0.02), while tumor depth was the best predictor of disease-specific survival (HR = 5.6, p = 0.02). Radiation improved local relapse-free survival (HR = 0.30, p = 0.03) but not disease-specific survival in multivariate analysis. A regimen of doxorubicin and ifosfamide was associated with better local relapse-free survival for patients with Stage III disease (HR = 0.16, p = 0.04) but not disease-specific survival (HR = 0.32, p = 0.08). With the limited number of patients in our study, it appears that extraosseous osteosarcoma behaves differently than osteosarcoma of bone. Multimodality treatment that includes doxorubicin and ifosfamide-based chemotherapy, radiation, and surgery may be a valid therapeutic strategy for Stage III disease, but larger, prospective studies will be needed to verify our preliminary observations. Level III, therapeutic study.
    No preview · Article · Jul 2015 · Clinical Orthopaedics and Related Research
  • B Ashleigh Guadagnolo · Kai-Ping Liao · Sharon H Giordano · Linda S Elting · Ya-Chen T Shih
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    ABSTRACT: To investigate end-of-life care for Medicaid, Medicare, and dually eligible beneficiaries dying of cancer in Texas. We analyzed the Texas Cancer Registry (TCR)-Medicaid and TCR-Medicare linked databases' claims data for 69,572 patients dying of cancer in Texas from 2000 to 2008. We conducted regression models in adjusted analyses of cancer-directed and acute care and total costs of care (in 2014 dollars) in the last 30 days of life. Medicaid patients were more likely to receive chemotherapy and radiation therapy. Medicaid patients were more likely to have >1 emergency room (ER) [odds ratio (OR)=5.27; 95% confidence interval (CI), 4.76-5.84], and were less likely to enroll in hospice (OR=0.59; 95% CI, 0.55-0.63) than Medicare patients. Dual eligibles were more likely to have >1 ER visit than Medicare-only beneficiaries (OR=1.19; 95% CI, 1.07-1.33). Black and Hispanic patients were more likely to experience >1 ER visit and >1 hospitalization than whites. Costs were higher for nonwhite Medicare, Medicaid, and dually eligible patients compared with white Medicare enrollees. Variation in acute care utilization and costs by race and payer suggest efforts are needed to address palliative care coordination at the end of life for Medicaid and dually eligible beneficiaries and minority patients dying of cancer.
    No preview · Article · Jul 2015 · Medical care
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    ABSTRACT: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Treatment guidelines for preoperative RT for RPS are presented. An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · May 2015 · Cancer Research
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    ABSTRACT: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001). Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: In the United States, an estimated 48 million individuals live without health insurance. The purpose of the current study was to explore the Variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. A total of 688,794 patients aged 18 to 64 years who were diagnosed with one of the top 25 incident cancers (representing 95% of all cancer diagnoses) between 2007 and 2010 in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patient characteristics included age, race, sex, marital status, and rural or urban residence. County-level demographics included percent poverty level. Insurance status was defined as having non-Medicaid insurance, Medicaid coverage, or no insurance. On multivariate logistic regression analyses, younger age, male sex, nonwhite race, being unmarried, residence in counties with higher levels of poverty, and rural residence were associated with being uninsured versus having non-Medicaid insurance (all P <.001). The highest rates of non-Medicaid insurance were noted among patients with prostate cancer (92.3%), melanoma of the skin (92.5%), and thyroid cancer (89.5%), whereas the lowest rates of non-Medicaid insurance were observed among patients with cervical cancer (64.2%), liver cancer (67.9%), and stomach cancer (70.9%) (P <.001). Among uninsured individuals, the most prevalent cancers were lung cancer (14.9%), colorectal cancer (12.1%), and breast cancer (10.2%) (P <.001). Lung cancer caused the majority of cancer mortality in all insurance groups. Rates of insurance coverage vary greatly by demographics and by cancer type. The expansion of health insurance coverage would be expected to disproportionally benefit certain demographic populations and cancer types. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    No preview · Article · Apr 2015 · Cancer
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    ABSTRACT: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · International journal of radiation oncology, biology, physics
  • B Ashleigh Guadagnolo · Jinhai Huo · Thomas A Buchholz · Daniel G Petereit
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    ABSTRACT: We sought to compare hospice utilization for American Indian and White Medicare beneficiaries dying of cancer. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases to analyze claims for 181,316 White and 690 American Indian patients dying of breast, cervix, colorectal, kidney, lung, pancreas, prostate cancer, or stomach cancer from 2003 to 2009. A lower proportion of American Indians enrolled in hospice compared to White patients (54% vs 65%, respectively; P < .0001). While the proportion of White patients who used hospice services in the last 6 months of life increased from 61% in 2003 to 68% in 2009 (P < .0001), the proportion of American Indian patients using hospice care remained unchanged (P = .57) and remained below that of their White counterparts throughout the years of study. Continued efforts should be made to improve access to culturally relevant hospice care for American Indian patients with terminal cancer.
    No preview · Article · Nov 2014 · Ethnicity & disease
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    ABSTRACT: Objectives: We established the level of awareness of risk factors and early symptoms of head and neck cancer among American Indians in South Dakota and determined whether head and neck cancer screening detected clinical findings in this population. Methods: We used the European About Face survey. We added questions about human papillomavirus, a risk factor for head and neck cancer, and demographics. Surveys were administered at 2 public events in 2011. Participants could partake in a head and neck cancer screening at the time of survey administration. Results: Of the 205 American Indians who completed the survey, 114 participated in the screening. Mean head and neck cancer knowledge scores were 26 out of 44. Level of education was the only factor that predicted higher head and neck cancer knowledge (b = 0.90; P = .01). Nine (8%) people had positive head and neck cancer screening examination results. All abnormal clinical findings were in current or past smokers (P = .06). Conclusions: There are gaps in American Indian knowledge of head and neck cancer risk factors and symptoms. Community-based head and neck cancer screening in this population is feasible and may be a way to identify early abnormal clinical findings in smokers.
    Full-text · Article · Oct 2014 · American Journal of Public Health

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
  • L.K. Ballas · J. Huo · B. Guadagnolo

    No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Purpose: The purpose of this study was to determine the association of insurance status with disease stage at presentation, treatment, and survival among the top 10 most deadly cancers using the SEER database. Patients and methods: A total of 473,722 patients age 18 to 64 years who were diagnosed with one of the 10 most deadly cancers in the SEER database from 2007 to 2010 were analyzed. A Cox proportional hazards model was used for multivariable analyses to assess the effect of patient and tumor characteristics on cause-specific death. Results: Overall, patients with non-Medicaid insurance were less likely to present with distant disease (16.9%) than those with Medicaid coverage (29.1%) or without insurance coverage (34.7%; P < .001). Patients with non-Medicaid insurance were more likely to receive cancer-directed surgery and/or radiation therapy (79.6%) compared with those with Medicaid coverage (67.9%) or without insurance coverage (62.1%; P < .001). In a Cox regression that adjusted for age, race, sex, marital status, residence, percent of county below federal poverty level, site, stage, and receipt of cancer-directed surgery and/or radiation therapy, patients were more likely to die as a result of their disease if they had Medicaid coverage (hazard ratio [HR], 1.44; 95% CI, 1.41 to 1.47; P < .001) or no insurance (HR, 1.47; 95% CI, 1.42 to 1.51; P < .001) compared with non-Medicaid insurance. Conclusion: Among patients with the 10 most deadly cancers, those with Medicaid coverage or without insurance were more likely to present with advanced disease, were less likely to receive cancer-directed surgery and/or radiation therapy, and experienced worse survival.
    No preview · Article · Aug 2014 · Journal of Clinical Oncology
  • B Ashleigh Guadagnolo · Victor Prieto · Randal Weber · Merrick I Ross · Gunar K Zagars
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    ABSTRACT: In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma. The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years (median age, 66 years). The location of the primary tumor was in the head and neck region in 62% of patients. Only 5 patients (4%) had lymph node involvement at the time of presentation. The median follow-up was 6.6 years (range, 11 months-24 years). Overall survival rates at 5 years and 10 years were 69% and 53%, respectively. Disease-specific survival rates were 84% and 80%, respectively, at 5 years and 10 years. The actuarial rate of local recurrence was 17% at 5 years and beyond. Of the patients who underwent surgery without receiving postoperative RT, 14 (24%) experienced local recurrence. Of the 71 patients treated with surgery and postoperative RT, 5 (7%) experienced local recurrence. In a Cox multivariate regression model, improved local control was significantly associated with the receipt of postoperative RT (P = .009). Surgery followed by postoperative RT appears to provide superior local control compared with surgery alone for patients with desmoplastic melanoma. Cancer 2013. © 2013 American Cancer Society.
    No preview · Article · May 2014 · Cancer