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1.
Hered Cancer Clin Pract ; 20(1): 19, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606835

RESUMO

BACKGROUND: Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT. METHODS: We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category. RESULTS: Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 - 1.28), female sex (OR=18.91; 95%CI 13.01 - 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 - 1.12), mental disorders (OR=1.53; 95%CI 1.15 - 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 - 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing. CONCLUSION: GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type. IMPACT: Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies.

2.
J Cancer Educ ; 37(5): 1532-1539, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33822316

RESUMO

Educational print materials for young women breast cancer survivors (YBCS) are supplemental tools used in patient teaching. However, the readability of the text coupled with how well YBCS understand or act upon the material are rarely explored. The purpose of this study was to assess the readability, understandability, and actionability of commonly distributed breast cancer survivorship print materials. We used an environmental scan approach to obtain a sample of breast cancer survivorship print materials available in outpatient oncology clinics in the central region of a largely rural Southern state. The readability analyses were completed using the Flesch-Kincaid (F-K), Fry Graph Readability Formula (Fry), and Simple Measure of Gobbledygook (SMOG). Understandability and actionability were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). The environmental scan resulted in a final sample of 14 materials. The mean readability of the majority of survivorship materials was "difficult," but the majority scored above the recommended 70% in both understandability and actionability. The importance of understandability and actionability may outweigh readability results in cancer education survivorship material. While reading grade level cannot be dismissed all together, we surmise that patient behavior may hinge more on other factors such as understandability and actionability. Personalized teaching accompanying print material may help YBCS comprehend key messages and promote acting upon specific tasks.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Letramento em Saúde , Compreensão , Feminino , Humanos , Internet , Smog , Materiais de Ensino
3.
Gynecol Oncol ; 156(1): 32-37, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739991

RESUMO

BACKGROUND: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. METHODS: In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. RESULTS: Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67-42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. CONCLUSIONS: Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão
4.
Int J Gynecol Cancer ; 29(1): 147-152, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640697

RESUMO

INTRODUCTION: Intraperitoneal (IP) chemotherapy improves survival in ovarian cancer but its use has been limited by toxicity with cisplatin-based regimens. The primary objective of this study was to define the maximum tolerated dose and dose-limiting toxicity of intravenous (IV) oxaliplatin and IP docetaxel in women with recurrent ovarian, fallopian tube or peritoneal cancer. Secondary objectives were response rate, time to progression, symptom interference with quality of life, and pharmacokinetics. METHODS: Patients received a constant dose of oxaliplatin 75 mg/m2 IV on day 1 and docetaxel escalating from 50 mg/m2 IP on day 2 every 3 weeks using a 3 + 3 design. Treatment continued until disease progression, remission, or intolerable toxicity occurred. Plasma and IP samples were taken to determine drug concentrations. Patients completed the MD Anderson Symptom Inventory weekly. RESULTS: Twelve patients were included. The median number of cycles was 4 (range 2-6) with a median time to progression of 4.5 months. Among eight patients with measurable disease, the best responses were partial response in two patients, stable disease in five, and progressive disease in one. A total of 14 grade 3-4 toxicities were noted, most commonly hematologic. Four patients, all dose level 3, had six dose-limiting toxicities: two with prolonged neutropenia, one with infection, one with hyponatremia, and two with abdominal pain. Dose level 3 was therefore considered intolerable. The mean±SD ratio of docetaxel area under the curve (AUC) in IP fluid to AUC in plasma was 229±111. Symptom interference with life activities steadily decreased from cycle 1 to 5. CONCLUSIONS: Oxaliplatin 75 mg/m2 IV on day 1 and docetaxel 75 mg/m2 IP on day 2 was the maximum tolerated dose. Most patients had partial response or stable disease, even in a heavily pre-treated population. At this dose level, patient-reported outcomes demonstrate temporary but tolerable decrements in quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Qualidade de Vida , Administração Intravenosa , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Docetaxel/administração & dosagem , Neoplasias das Tubas Uterinas/patologia , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Prognóstico , Distribuição Tecidual
5.
Gynecol Oncol ; 151(3): 481-488, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30322717

RESUMO

OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.


Assuntos
Mutação em Linhagem Germinativa/genética , Neoplasias Ovarianas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-29760829

RESUMO

BACKGROUND: African-American women, especially in the southern United States, are underrepresented in cancer genetics research. A study was designed to address this issue by investigating the germline mutation rate in African-American women in Arkansas with a personal and/or family history of breast cancer. Women were tested for these mutations using a large panel of breast cancer susceptibility genes. In this analysis, we discuss the challenges encountered in recruiting African-American women from an existing biorepository to participate in this study. METHODS: We attempted to contact 965 African-American women with a personal and/or family history of breast cancer who participated in Spit for the Cure (SFTC) between 2007 and 2013 and provided consent to be recontacted. The SFTC participants were invited by telephone and email to participate in the genetic study. Enrollment required completion of a phone interview to obtain a family and medical history and return of a signed consent form. RESULTS: Among eligible SFTC participants, 39.6% (382/965) were able to be contacted with the phone numbers and email addresses they provided. Of these, 174 (45.5%) completed a phone interview and returned a signed consent form. Others were not able to be contacted (n = 583), declined to participate (n = 57), did not keep phone interview appointments (n = 82), completed the phone interview but never returned a signed consent (n = 54), were deceased (n = 13), or were too confused to consent to participate (n = 2). CONCLUSIONS: Recruiting African-American women into our breast cancer genetics study proved challenging primarily due to difficulty establishing contact with potential participants. Given their prior participation in breast cancer research, we anticipated that this would be a highly motivated population. Indeed, when we were able to contact SFTC participants, only 14.9% declined to participate in our study. Innovative communication, retention, and recruitment strategies are needed in future studies to address the recruitment challenges we faced.

7.
J Adv Nurs ; 74(4): 976-987, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29117439

RESUMO

AIM: To develop and psychometrically test the validity of the Female Self-Advocacy in Cancer Survivorship Scale. BACKGROUND: Female cancer survivors need to self-advocate to overcome challenges associated with cancer yet no valid measure of self-advocacy exists. DESIGN: Instrument development. Mixed-mode cross-sectional survey design. PARTICIPANTS: We recruited adult females (18+ years; N = 317) with a history of invasive cancer from local and national tumour registries and advocacy organizations to complete online or paper questionnaires. METHODS: Between July 2014 - March 2015 to evaluate the construct validity based on evidence of the scale's: (1) internal structure consistent with the underlying model of self-advocacy; (2) sensitivity to differences between groups known to differ in self-advocacy skills; (3) relationships between self-advocacy and key potential predictors (openness and conscientiousness; information engagement; social support) and outcomes (symptom burden and healthcare utilization); (4) relationships between self-advocacy and related concepts (patient activation; self-advocacy within another patient population); and (5) relationships between self-advocacy and criterion measures. Analyses included an exploratory factor analysis, t tests, and bivariate correlations using validated, reliable measures for constructs. RESULTS: Evidence from all five hypotheses supported the construct validity of the Female Self-Advocacy in Cancer Survivorship Scale. The factor analysis confirmed the three underlying dimensions of self-advocacy resulting in a 20-item measure with strong internal consistency that explained almost half of response variance. CONCLUSION: The Female Self-Advocacy in Cancer Survivorship Scale is a valid, reliable measure of how well adult female cancer survivors can get their needs met in the face of adversity.


Assuntos
Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias/psicologia , Autoeficácia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estados Unidos
8.
Breast Cancer Res ; 18(1): 15, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26857456

RESUMO

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama Masculina/genética , Neoplasias da Mama/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único
9.
BJU Int ; 118(3): 399-407, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26589741

RESUMO

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Obesidade Mórbida/complicações , Idoso , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Renais/mortalidade , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Int J Gynecol Cancer ; 26(2): 313-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26588235

RESUMO

OBJECTIVES: Recent evidence suggests that hyperinsulinemia associated with obesity may be a significant risk factor for the development of endometrial cancer. Metformin is used in type II diabetes to lower circulating insulin levels. We sought to examine our obese patients with endometrial cancer and examine those who were on metformin to determine any impact on their cancer course. METHODS: A retrospective review of all women with the diagnosis of endometrial cancer and a body mass index of 30 kg/m(2) or higher during a 6-year period (2005-2011) at our institution was conducted. Records were reviewed for standard demographic data, use of metformin, cancer characteristics, treatment, and cancer follow-up. RESULTS: A total of 351 women were identified who were obese and diagnosed as having endometrial cancer. Of these, 64 were on metformin (M+) at the time of diagnosis of endometrial cancer. The women on metformin had a significantly higher mean body mass index (44.6 vs 41.6, P < 0.05). Age, grade, stage, and adjuvant therapy did not differ between the 2 groups. Recurrence occurred in 15.3% of the M- women versus 7.8% of the M+ women (not significant). However, for those patients with type I endometrial cancer, only 1 patient (1.9%) who was on metformin recurred versus 10.3% who were not on the drug (P = 0.05). With a minimum of 24 months of follow-up, 89.1% of metformin users were alive and free of disease versus 83.9% of nonusers (not significant). CONCLUSIONS: Obese women who developed endometrial cancer while on metformin did not seem to have pathologic risk factors different from those not on metformin. However, the type I cancer patients on metformin were less likely to recur than those not on the drug. This suggests that a prospective trial of metformin at the time of diagnosis of endometrial cancer in the obese population may be warranted.


Assuntos
Neoplasias do Endométrio/complicações , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Recidiva Local de Neoplasia/complicações , Obesidade/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Arkansas/epidemiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/prevenção & controle , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Obesidade/complicações , Estudos Retrospectivos
11.
Int J Gynecol Cancer ; 26(4): 626-31, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27051048

RESUMO

OBJECTIVE: Only 3% of patients with epithelial ovarian cancer (EOC) have a longer treatment-free interval (TFI) after second-line intravenous (IV) platinum chemotherapy than with frontline IV therapy. We sought to examine what impact second-line combination IV/intraperitoneal (IV/IP) platinum therapy might have on the ratio of second-line to first-line TFI in patients treated with second-line IP platinum chemotherapy for first recurrence after front-line IV therapy. METHODS: A retrospective analysis of women who received combination platinum-based IV/IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Patients were identified from the tumor registry, and office records from a large gynecologic oncology practice and patient records were reviewed. The first and second TFIs were defined as the time from the end of previous platinum-based therapy to the start of next therapy. RESULTS: Twenty-five women received IV/IP chemotherapy for their first EOC recurrence after IV chemotherapy. In 10 patients (40%), we observed a longer TFI after IV/IP chemotherapy than after primary IV chemotherapy. For these 10 patients, the median TFI for primary response was 22 months (range, 15-28), whereas median TFI after IV/IP chemotherapy for recurrent disease was 37 months (range, 12-61). CONCLUSIONS: For EOC patients with limited peritoneal recurrence, 40% of patients had a second-line IP-platinum TFI that exceeded their frontline IV-platinum TFI compared to published data. These data support the use of IV/IP chemotherapy as a treatment for recurrence.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Cisplatino/administração & dosagem , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Gynecol Oncol ; 138(3): 548-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26111788

RESUMO

OBJECTIVE: The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). METHODS: Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. RESULTS: Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. CONCLUSIONS: Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Neoplasias das Tubas Uterinas/metabolismo , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacocinética , Oxaliplatina , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Taxoides/farmacocinética
14.
Gynecol Oncol ; 134(1): 68-72, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24769036

RESUMO

OBJECTIVE: Hypersensitivity reactions can preclude platinum re-challenge for patients receiving second-line and higher carboplatin/cisplatin salvage therapy. The objective is to report our patient experience with oxaliplatin in recurrent or progressive epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), including those with prior hypersensitivity reaction. METHODS: A single institution, retrospective review from 1995 to 2012 of patients receiving oxaliplatin for treatment of recurrent or progressive EOC, PPC, or FTC was performed. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval(s), prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. Those who received ≥1 cycles were included. A response to therapy was determined after ≥2 cycles. RESULTS: Forty-four patients were identified. All had prior carboplatin and 38.6% had prior cisplatin therapy. Twenty-three had a prior platinum hypersensitivity reaction. Patients received a median of 2 prior platinum containing regimens and 5 chemotherapy lines prior to oxaliplatin exposure. One patient experienced grade 3 pain. No grade 4 toxicities occurred. No treatment delays for pancytopenia noted. Nausea and dysesthesias were controlled medically and weren't dose-limiting. No nephropathy or neuropathy progressed on oxaliplatin or were dose-limiting. Disease response was observed in 43.2%. Of the responders, 36.8% had a prior platinum hypersensitivity reaction. Median number of 5 cycles of an oxaliplatin containing regimen was given. Median follow-up was 15.5 months. CONCLUSIONS: In our experience, oxaliplatin is well tolerated and should be considered for platinum challenge after hypersensitivity even in patients with platinum resistant disease with a reasonable chance of response.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Carcinoma Epitelial do Ovário , Cisplatino/administração & dosagem , Adutos de DNA/metabolismo , Hipersensibilidade a Drogas/etiologia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Estudos Retrospectivos , Terapia de Salvação
15.
Cancers (Basel) ; 15(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36900239

RESUMO

Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.

16.
Gynecol Oncol ; 125(3): 677-82, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22406760

RESUMO

OBJECTIVE: Our objective was to determine the rate of BRCA1/2 deficiency in platinum-sensitive and platinum-resistant tumors from a cohort of unselect patients with advanced epithelial ovarian cancer (EOH). METHODS: BRCA1/2 mutation analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients with platinum-resistant disease. Germline DNA was analyzed in mutation carriers when normal tissue was available. BRCA expression was ascertained by quantitative rt-PCR. Associations between BRCA mutation status and expression levels and parameters of platinum response were analyzed. RESULTS: Fifteen of 53 (28.3%) EOC tumors had BRCA1/2 mutations. Twelve mutations were in BRCA1, while 3 involved BRCA2. Of the 12 mutation-carriers with normal tissue available for DNA analyses, 33.3% of the mutations were found to be somatic. Three mutations were novel. The majority of BRCA mutations (73%) were identified in patients with platinum-sensitive disease. In total, 38% of platinum-sensitive tumors were found to have a BRCA mutation, compared to 17% of the platinum-resistant patients. A statistical trend toward platinum-sensitive disease was seen in BRCA mutation carriers (p=0.079). Nineteen (36%) study patients had some form of BRCA deficiency, and these patients were less likely to have platinum-resistant tumors (OR=0.29; p value=0.048). CONCLUSIONS: BRCA mutations occurred more frequently in platinum-sensitive EOC than platinum-resistant disease. The high overall frequency of BRCA deficiency in EOC underscores the importance of tumor profiling as therapies targeting the DNA repair pathway are being investigated.


Assuntos
Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Adulto , Idoso , Proteína BRCA1/biossíntese , Proteína BRCA1/deficiência , Proteína BRCA1/genética , Proteína BRCA2/biossíntese , Proteína BRCA2/deficiência , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia
17.
Oncology (Williston Park) ; 26(2): 128-36, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22489345

RESUMO

The treatment strategy of poly(ADP-ribose) polymerase (PARP) inhibition capitalizes on the inherent defect in homologous recombination that occurs in BRCA-deficient tumors by inhibiting the alternative DNA repair pathway involving base excision repair. Although PARP inhibitors were initially considered a potential treatment specifically for tumors with germline BRCA mutations, evidence of frequent somatic deficiency in the BRCA pathway has caused reconsideration of that approach. PARP inhibitors have been shown to have activity in epithelial ovarian, fallopian tube, and primary peritoneal cancer in phase I and II clinical trials. Responses have been seen in both BRCA-deficient and sporadic tumors, and they do not appear to require platinum sensitivity. Although PARP inhibitors are well tolerated as monotherapy, additional study is required to determine their efficacy and toxicity in combination with chemotherapy and other targeted agents. Many hurdles remain along the pathway to drug registration, but the motivation of the community of ovarian cancer patients, researchers, and clinicians to find new treatments may speed the process.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases , Carcinoma Epitelial do Ovário , Ensaios Clínicos como Assunto , Descoberta de Drogas , Feminino , Humanos
18.
Int J Gynecol Cancer ; 22(3): 484-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22249576

RESUMO

OBJECTIVE: The objective of the study was to examine outcomes in stage IB2 cervical cancer patients undergoing primary surgery versus radiation. METHODS: Stage IB2 cervical cancer patients were identified from the Surveillance, Epidemiology and End Results Public-Use Database from 2000 to 2006. Patients were divided into those receiving radiation (radiation first) or surgery (surgery first) as initial treatment. Overall survival was calculated by Kaplan-Meier method and compared using log-rank test. RESULTS: In total, 770 patients were identified with stage IB2 cervical cancer; 369 received radiation, and 401 received surgery initially. The radiation-first group had larger mean tumor size than the surgery-first group (6.0 vs 5.5 cm, respectively; P < 0.0001). The overall survival was longer in the surgery-first group compared with the radiation-first group (72.0 vs 61.4 months, respectively; P < 0.0001). CONCLUSIONS: Patients undergoing surgery as initial treatment for stage IB2 cervical cancer appear to have improved outcomes in the current era of chemoradiation; however, given the lack of chemotherapy information, a randomized trial will be necessary to see if these results remain valid.


Assuntos
Carcinoma/radioterapia , Carcinoma/cirurgia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , População , Sistema de Registros , Análise de Sobrevida , Carga Tumoral/fisiologia , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
19.
Int J Gynecol Cancer ; 22(2): 232-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22080886

RESUMO

OBJECTIVES: Three large randomized clinical trials have shown a survival benefit for patients treated with intraperitoneal (IP) compared with intravenous chemotherapy for advanced stage epithelial ovarian cancer (EOC). However, the use of IP chemotherapy in recurrent EOC is controversial. The purpose of this study was to determine outcomes, completion rates, and frequency of complications in patients with platinum-sensitive recurrent EOC treated with IP chemotherapy. METHODS: A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC from January 2003 to April 2010 was conducted. Study patients were identified from the Tumor Registry and office records. Demographic factors, stage, histology, surgical findings, cytoreduction status, and subsequent therapies were abstracted. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods. RESULTS: Fifty-six women who received IP chemotherapy for their first EOC recurrence were identified. The mean age of patients was 56.7 years (range, 40-79 y). Fifty-five patients (98.3%) had previously completed at least 6 cycles of intravenous chemotherapy. Of all patients, 87.5% were initially diagnosed with advanced stage disease (stage IIA-IV). All patients underwent secondary cytoreduction at the time of IP port placement. Moreover, 67.9% of patients were considered optimally cytoreduced (<1 cm residual disease) at the end of the secondary debulking surgery. Forty-two patients (75%) were able to successfully complete at least 6 cycles of IP chemotherapy. Reasons for noncompletion were disease progression, allergic reaction, renal failure, pain, severe nausea and vomiting, death, and patient refusal. Six patients (10.7%) developed port complications including pain around port site, port malfunction, and port erosion into small bowel. Median PFS since the initiation of IP chemotherapy was 10.5 months (95% confidence interval, 7.5-16.4 months) and median OS was 51 months (95% confidence interval, 40.8-61.1 months). CONCLUSIONS: Intraperitoneal chemotherapy is a feasible option for patients with recurrent EOC, with high completion rates, low frequency of complications, and acceptable PFS and OS.


Assuntos
Adenocarcinoma Papilar/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma Papilar/mortalidade , Adenocarcinoma Papilar/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel , Pennsylvania , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Acta Cytol ; 56(4): 388-93, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22846717

RESUMO

OBJECTIVES: The American Cancer Society, the American College of Obstetricians and Gynecologists and the US Preventive Services Task Force recommend discontinuation of cervical cancer screening between 65 and 70 years of age in women with no abnormal test results in the preceding 10 years. This population-based study was undertaken to determine the incidence of cervical cancer in different age groups as a means to establish if current screening recommendations need reevaluation. STUDY DESIGN: Data from the SEER database were used to compute incidence rates for cervical cancer diagnosed between 2000 and 2006 by age and disease stage. RESULTS: We identified 18,003 women with cervical cancer. 12.18% were above the age of 69. The incidence in this age group was 8.7/100,000. Women younger than 30 comprised 5.7% of patients with an incidence of 5/100,000 and were most commonly diagnosed with stage IA1 disease. Women above 70 were most frequently diagnosed with stage IIIB. 79% of patients younger than 30 were diagnosed with an early disease (stage IA1-IIA) as opposed to only 41.2% of patients aged 69 or above. CONCLUSIONS: The incidence of cervical cancer does not decrease significantly in older women. Women over the age of 70 are frequently diagnosed with advanced stage disease which limits their treatment options. Failure to apply uniform screening across all at-risk age groups may account for the discrepancy.


Assuntos
Idoso/estatística & dados numéricos , Efeitos Psicossociais da Doença , Diagnóstico Precoce , Neoplasias do Colo do Útero/epidemiologia , Adulto , Distribuição por Idade , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Programa de SEER , Adulto Jovem
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