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Publications (10)56.11 Total impact

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    ABSTRACT: Melanoma that metastasizes to distant sites is associated with a grave prognosis. The objectives of the study were (1) to identify predictive factors for the development of brain metastases from the time of diagnosis of stage III/IV disease, (2) to identify predictive factors for the development of central nervous system (CNS) metastases from the time of diagnosis of primary melanoma, and (3) to assess whether the incidence of brain metastasis is more frequent in patients who had no tumor response to systemic therapy for stage III/IV disease compared with those who had partial or complete response. We collected and retrospectively analyzed information of 740 patients with advanced metastatic melanoma treated at MD Anderson Cancer Center over 15 years. Three hundred and twenty-nine patients had CNS metastases. The characteristics of these patients in terms of median age, sex, primary site, Breslow thickness, stage at first visit, baseline serum parameters, and response to systemic therapy were compared with those of patients who did not develop CNS metastasis. Cox proportional hazards models were used to analyze the cause-specific hazard function for CNS metastasis and deaths without CNS metastasis. We identified that M-stage [stage M1b vs. stage III or M1a, hazard ratio (HR)=2.64; stage M1c vs. stage III or M1a, HR=2.13, P<0.0001] and lactic acid dehydrogenase (LDH) (elevated vs. normal LDH, HR=1.51, P<0.001) at diagnosis of unresectable stage III/IV disease can independently predict the risk of developing CNS metastasis from the time of diagnosis of stage III/IV disease. Older age (HR=1.01, P=0.076), chemoresistance (stable disease+progressive disease vs. complete response+partial response HR=2.91, P<0.0001), low level of albumin (vs. normal HR=2.87, P<0.0001), elevated LDH (vs. normal HR=1.55, P=0.0004), and M-stage (M1c disease vs. stage III or M1a HR=1.89, P<0.0001) can independently predict shorter time to death without CNS metastasis from the diagnosis of stage III/IV disease. The location (head and neck vs. limbs HR=1.56, P=0.028; trunk and abdomen vs. limbs HR=1.45, P=0.029; unknown site vs. limbs HR=8.43, P=0.036) and pathology [Clark level (CL)=3 and/or BR2 to 4 mm vs. CL≤2 and/or BR<2 mm HR=1.60, P=0.037; CL>3 and/or BR> 4 mm vs. CL≤2 and/or BR<2 mm HR=2.03, P=0.001) of the primary melanoma can independently predict CNS metastasis-free interval from the time of diagnosis of primaries. Age (HR=1.012, P=0.034) and pathology of the primary melanoma (CL>3 and/or BR>4 mm vs. CL≤2 and/or BR<2 mm HR=1.54, P=0.024) can independently predict time to death without CNS metastasis from primaries. We identified the predictive factors associated with the development of CNS metastasis in patients with unresectable metastatic melanoma.
    American journal of clinical oncology 12/2010; 34(6):603-10. · 2.21 Impact Factor
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    ABSTRACT: Hematopoietic stem-cell transplantation (HSCT) is associated with high rates of gonadal failure, which is distressing for younger patients desiring to start a family. The perceived importance and optimal timing of discussing fertility- and menopause-related information with women undergoing aggressive treatment such as HSCT is not well defined. Questionnaires were sent to 532 patients who underwent HSCT between January 1987 and September 2004 at the ages of 16 to 50 years. The questionnaire assessed demographic data, the need for fertility- and menopause-related information at various times during treatment, and standardized measures of anxiety, quality of life, and menopausal symptoms. The return rate was 40.2%, with 196 patients participating. Of these, 38% reported that they had discussed fertility-related issues with health-care providers since their diagnosis; 54% had discussed menopause-related issues. At the time of diagnosis, participants considered receiving information on fertility and menopause as being of equal importance. However, after HSCT, information about menopause was considered more important than information on fertility (P < or = .0001). Being <40 years, being childless, desiring to bear children in the future, and having a high score on the State-Trait Anxiety Inventory (STAI) correlated with higher ratings of importance for both fertility- and menopause-related information. Our results suggested that healthcare providers should provide information on fertility and menopause repeatedly throughout the treatment period, and that menopause-related information should be reemphasized after HSCT. Such counseling is crucial for patients who are young and childless.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 15(11):1465-74. · 3.15 Impact Factor
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    ABSTRACT: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival.
    Journal of the American Dietetic Association 08/2008; 108(8):1323-9. · 3.80 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time.
    Blood 12/2007; 110(9):3456-62. · 9.78 Impact Factor
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    ABSTRACT: Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience. The authors reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at The University of Texas M. D. Anderson Cancer Center. The mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7 patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan-Meier estimates of 5-year and 10-year overall survival (OS) rates were 51% and 24%, respectively. Bladder-sparing therapy with intravesical bacillus Calmette-Guerin therapy was attempted in 27 of 44 patients with nonmuscle-invasive disease; 67% (18 patients) developed disease progression (>or=cT2), including 22% who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (<or=cT4a), 23 received neoadjuvant chemotherapy and 32 were treated with initial cystectomy, with no significant difference noted in stage distribution between the 2 groups. For the 23 patients treated with neoadjuvant chemotherapy, the median OS was 43.2 months with 32% of patients still alive at 5 years. For the 32 patients treated with initial cystectomy, the median survival had not been reached at the time of last follow-up, with 71% still alive at 5 years. Micropapillary bladder cancer is associated with a poor prognosis. Intravesical therapy appears to be ineffective in this disease and patients with surgically resectable disease should be offered early radical cystectomy.
    Cancer 08/2007; 110(1):62-7. · 5.20 Impact Factor
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    ABSTRACT: Transplant-associated microangiopathy (TAM) is a life-threatening complication after allogeneic HSCT, particularly with the use of calcineurin inhibitors as post-transplantation immunosuppressive therapy. We report our experience with TAM after HSCT with tacrolimus-based GVHD prophylaxis in a single-center study. Sixty-six of 1219 transplant recipients developed TAM with a cumulative incidence of 5.9%. Risk factors for TAM were female gender, lymphoid malignancy, receipt of a matched unrelated donor, and grade II-IV aGVHD. Most patients had infection and/or active GVHD at the diagnosis of TAM (82%). In the absence of renal dysfunction or encephalopathy, tacrolimus was generally continued, maintaining blood levels within the lower therapeutic range. Sixty-three patients were treated with plasma exchange. The cumulative incidence of response of TAM was 60%. Only 1 patient had a response of TAM without resolution of concomitant infections or GVHD. Six-month survivals were 0% and 50% for TAM nonresponders and responders, respectively. In conclusion, TAM is a common, life-threatening complication of allogeneic hematopoietic transplantation using tacrolimus prophylaxis. Control of TAM generally requires response of associated infections and GVHD. TMA response may occur despite continuation of tacrolimus treatment.
    Biology of Blood and Marrow Transplantation 05/2007; 13(4):469-77. · 3.94 Impact Factor
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    ABSTRACT: Micropapillary bladder carcinoma is a rare variant of UC. Due to paucity of data regarding treatment outcomes, patients with nonmuscle invasive micropapillary UC often receive intravesical therapy in an attempt at bladder preservation. We reviewed the records of all patients evaluated at our institution who had micropapillary UC of the bladder. Of these, 44 had nonmuscle invasive disease at presentation and form the basis of this report. Mean patient age was 64.3 years (range 45 to 81) with a male-to-female ratio of 13:1. Stage distribution at presentation was 5 Ta (11%), 4 CIS (9%) and 35 T1 (80%). Median CSS was 81 months. Kaplan-Meier estimates of 5 and 10-year CSS rates were 64% and 26%, respectively. Intravesical BCG therapy was attempted in 27 patients (61%). Of these 27 patients, 67% (18 of 27) had progression (cT2 or greater), including 22% in whom metastatic disease developed. Only 19% of patients (5 of 27, all T1) remain disease-free with an intact bladder at a median followup of 30 months. A total of 30 patients (68%) underwent cystectomy. Among patients who underwent cystectomy after progression (18), median CSS was 61.7 months with no patient surviving 10 years, whereas among those undergoing cystectomy as initial therapy (12), median survival was not reached and the 10-year CSS rate was 72%. Intravesical BCG therapy appears to be ineffective against micropapillary UC. Our results suggest that the optimal treatment strategy for nonmuscle invasive micropapillary UC is radical cystectomy performed before progression.
    The Journal of Urology 03/2006; 175(3 Pt 1):881-5. · 3.70 Impact Factor
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    ABSTRACT: Nodal disease in the setting of metastatic renal cell carcinoma is associated with poor prognosis. However, to our knowledge the biology of nodal metastases in the absence of metastatic disease is unknown. We reviewed our experience with treating this subset of patients with aggressive surgical resection. A total of 2,643 patients underwent nephrectomy at our institution between 1993 and 2003, including 40 with positive lymph nodes but no systemic metastases. All 40 patients underwent nephrectomy with extended retroperitoneal lymphadenectomy and they are the subjects of this study. Pathological characteristics and clinical outcomes were assessed. Median patient age was 58 years and 62% of the patients were male. Median tumor size was 11 cm. Local stage was T1 in 3% of cases, T2 in 17%, T3a in 30%, T3b in 47% and T4 in 3%. Perinephric fat invasion was present in 77% of patients and positive margins were identified in 17%. Nodal status was N1 in 30% of patients and N2 in 70%, including 10 with masses of matted nodes. Histology was conventional in 63% of cases and papillary in 17%. The remaining 20% of patients had sarcomatoid dedifferentiation. Excluding the 10 patients with matted nodes the median number of nodes harvested per patient was 7 with a median of 2 that were positive. Extranodal extension was present in 70% of cases, while in 70% disease recurred at a median of 4.9 months. Median actuarial disease specific survival was 20.3 months. At a median followup of 17.7 months 30% of patients had no evidence of disease, 8% had disease and 62% had died. On multivariate analysis more than 1 positive node was predictive of decreased recurrence-free survival (HR 2.83, 95% CI 1.06 to 7.61, p = 0.039) and overall survival (HR 9.33, 95% CI 1.85 to 47.09, p = 0.007). Nodal metastasis with renal cell carcinoma is an independent predictor of prognosis in patients with M0 disease. Even in the absence of distant metastatic disease patients with positive nodes should be targeted for aggressive surgical resection, followed by clinical trials of adjuvant therapy to improve the outcome.
    The Journal of Urology 03/2006; 175(3 Pt 1):864-9. · 3.70 Impact Factor
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    ABSTRACT: The production of chimeric mice is a complex process, requiring the careful coordination of tissue culture cell growth, production of a large number (30-75) of competent blastocysts and the availability of appropriately timed pseudo pregnant female mice. Failure at any of these steps can impinge upon the rapid production of chimeras. One potential improvement for the efficient generation of chimeric mice would be the utilization of cryopreserved embryos suitable for injection. C57Bl/6 morulae were frozen using a standard 2-step protocol with ethylene glycol as the cryopreservation agent. We determined that cryopreserved morulae could thaw, culture to blastocyst stage in KSOM media and survive injection at rates equivalent to control embryos. Cryopreserved morulae were also equivalent to controls at all later stages in the process of production of chimeric mice, including birth rate, percentage chimerism of resulting animals and ability to produce germline progeny. Hence, cryopreservation of morulae for blastocyst injection is a suitable option to enhance the efficiency of chimeric mouse generation.
    Transgenic Research 11/2005; 14(5):685-90. · 2.61 Impact Factor
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    ABSTRACT: Fludarabine and cyclophosphamide (FC), which are active in treatment of chronic lymphocytic leukemia (CLL), are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines. A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >/= 50%. We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL. Flow cytometry was used to measure residual disease. Results and safety were compared with a previous regimen using FC. The median age was 58 years; 75 patients (33%) had Rai stage III to IV disease. The CR rate was 70% (95% CI, 63% to 76%), the nodular partial remission rate was 10%, and the partial remission rate was 15%, for an overall response rate of 95% (95% CI, 92% to 98%). Two thirds of patients evaluated with flow cytometry had less than 1% CD5- and CD19-coexpressing cells in bone marrow after therapy. Grade 3 to 4 neutropenia occurred during 52% of courses; major and minor infections were seen in 2.6% and 10% of courses, respectively. One third of the 224 patients had >/= one episode of infection, and 10% had a fever of unknown origin. FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69% of patients were projected to be failure free at 4 years (95% CI, 57% to 81%).
    Journal of Clinical Oncology 07/2005; 23(18):4079-88. · 18.04 Impact Factor