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1.
Ann Oncol ; 24 Suppl 8: viii54-viii60, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24131971

RESUMO

The diagnostic and local treatment modalities of hereditary breast cancer (HBC) are evolving based on emerging evidence from new imaging, radiotherapy and surgical studies. The optimal selection of diagnostic and therapeutic strategies for the individual HBC patient remains an area of active research in this relatively new patient population. In this context, some rational pathways of intervention are currently available to both reduce cancer risk in mutation carriers without a cancer diagnosis, as well as to reduce the risk of recurrence or new cancers among the carriers already diagnosed with a malignancy. It is encouraging to notice to what degree certain interventions have successfully reduced both the risk of malignancy and the anxiety associated with this genetic diagnosis. This updated report aims at summarizing the most recent findings, while it identifies the areas of uncertainty that remain, and continue to present difficult challenges, particularly among younger HBC patients.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/congênito , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Humanos , Mutação
2.
Clin Transl Oncol ; 15(6): 450-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23143949

RESUMO

PURPOSE: The aim of this study was to demonstrate feasibility and analyze dosimetric differences in prone and supine position breast cancer radiotherapy in women with large or pendulous breast. METHODS: Ten post-lumpectomy breast cancer patients underwent supine and prone computed tomography-based treatment plan. On each data set, the whole breast, the ipsilateral lung and the heart were outlined. Multisegment tangential-fields plans were generated for each position. Target coverage, homogeneity, overdosage outside breast and organ at risk sparing were analyzed and compared for supine and prone position. RESULTS: Coverage and dose homogeneity of the PTV measured by D 90 and V(95)% were similar for both plans although breast maximum dose was higher in the supine plan (p = 0.017). Prone position reduced the percentage of ipsilateral lung receiving 20 Gy (V(20Gy)) from 26.5 to 2.9 % (p = 0.007), medium lung dose, as well as the percentage of the heart receiving 35 Gy heart (V(35Gy)) from 3.4 to 1.2 % (p = 0.038). Overdosage of areas outside breast PTV was also consistently reduced with prone position (p = 0.012). In addition, average number of segments and monitor units needed was reduced in prone position. CONCLUSIONS: Prone position in large breast women appears to favor normal tissue sparing in breast radiotherapy as compared to supine position, without diminishing the target coverage.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Órgãos em Risco , Projetos Piloto , Prognóstico , Decúbito Ventral , Dosagem Radioterapêutica , Decúbito Dorsal , Tomografia Computadorizada por Raios X
3.
Ann Oncol ; 22 Suppl 1: i31-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21285148

RESUMO

Risk-reduction interventions for BRCA-related breast cancer are relevant not only for clinical decisions in breast cancer patients but also for healthy subjects who are potential candidates to undergo similar interventions. The literature on the impact of different surgical options and adjuvant systemic approaches aimed towards risk reduction for ipsilateral and contralateral breast cancer recurrences is briefly reviewed. Breast-conserving surgery is associated with a higher probability of local recurrence, but is counterbalanced by effectiveness of chemotherapy in reducing this risk. Consistent support for the hypothesis that antiestrogens are effective in reducing contralateral breast cancer risks is available from the literature. On the other hand, data on chemoprevention approaches for healthy subjects are too preliminary to draw any conclusions. Studies including conventional and newer hormonal drugs are needed to demonstrate the benefit of chemoprevention approaches. These may also deepen our knowledge on possible differences in the likelihood of clinical benefit to be expected among BRCA1- and BRCA2-altered tumours.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle
4.
Magn Reson Med ; 65(5): 1437-47, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21287591

RESUMO

Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t)), perfusion fraction (f(p)), and pseudodiffusivity (D(p)). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (±standard deviation) values (2.44 ± 0.30 vs. 1.34 ± 0.39 µm(2)/msec, P < 0.01) and D(t) (2.36 ± 0.38 vs. 1.15 ± 0.35 µm(2)/msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with D(t) (1.14 ± 0.32 µm(2)/msec vs. 1.18 ± 0.52 µm(2)/msec, P = 0.88) and D(p) (14.9 ± 11.4 µm(2)/msec vs. 16.1 ± 5.7 µm(2)/msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors.


Assuntos
Neoplasias da Mama/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Pessoa de Meia-Idade , Movimento , Neovascularização Patológica/patologia , Software
5.
Clin Cancer Res ; 7(10): 3025-30, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11595690

RESUMO

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. EXPERIMENTAL DESIGN: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Paclitaxel/uso terapêutico , Proteínas , Adulto , Idoso , Apoptose/efeitos dos fármacos , Neoplasias da Mama/cirurgia , Complexo CD3/análise , Antígenos CD8/análise , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas de Ligação a Poli(A) , Proteínas de Ligação a RNA/análise , Antígeno-1 Intracelular de Células T , Resultado do Tratamento
6.
J Clin Oncol ; 19(5): 1539-69, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11230499

RESUMO

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Radioterapia Adjuvante , Axila/patologia , Neoplasias da Mama/patologia , Análise Custo-Benefício , Feminino , Humanos , Metástase Linfática , Invasividade Neoplásica , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/economia , Análise de Sobrevida
7.
Urology ; 56(3): 453-8, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10962314

RESUMO

OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to 54 Gy achieves results comparable to higher doses. We studied the effect of moderate doses of postoperative radiation therapy on urinary continence and sexual potency in prostate cancer patients who had undergone nerve-sparing prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate cancer patients were selected to undergo nerve-sparing prostatectomy. A total of 94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy to the prostatic bed, based on microscopic positive margins, seminal vesicle involvement, and/or Gleason score. Subjective patient reports regarding the potency and urinary continence status were recorded during a semistructured telephone interview at 3 or more years after treatment. The findings in irradiated and nonirradiated patients were compared and correlated to those obtained from the same patients preoperatively and 1 year postoperatively. RESULTS: At 3 or more years of follow-up no significant difference among irradiated and nonirradiated patients was detected. Most patients described optimal urinary continence and approximately one third had maintained potency after bilateral nerve-sparing prostatectomy. None of the patients who had undergone unilateral nerve-sparing surgery remained potent. Using a multivariable analysis, the significant predictors for maintaining potency were the status at 1 year postoperatively and bilateral versus unilateral nerve-sparing procedure. CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy) did not affect the long-term pattern of maintenance of either function.


Assuntos
Ereção Peniana/efeitos da radiação , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Micção/efeitos da radiação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Disfunção Erétil/epidemiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prostatectomia/métodos , Neoplasias da Próstata/fisiopatologia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Incontinência Urinária/epidemiologia
8.
Med Phys ; 27(5): 1005-10, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10841403

RESUMO

PURPOSE: To investigate the technical and physical feasibility of using a radiosurgery-like technique to irradiate a small target within the breast with a single fraction. MATERIAL AND METHODS: During diagnostic biopsy, a tantalum surgical clip is placed in the lesion identified at mammography. Transverse CT scans over the entire breast are obtained, as the patient lies prone on a special table that allows the breast to hang down. The clip is used as a reference point to define the isocenter of the radiation treatment. RESULTS: The clip is visible on port films taken with a 4 MV beam, allowing the isocenter to be set to its planned location. No movement of the hanging breast is visually detected. The possible beam directions are enclosed by a 220 degrees horizontal x 180 degrees vertical angular interval. Dosimetry of two "radiosurgical" examples, (A) seven fixed horizontal beams and (B) six 45 degrees arcs and a 90 degrees sagittal arc using a 4 MV x-ray beam with a 32 mm diameter collimator, are discussed. Both field arrangements produce adequate tumor coverage: the minimum target dose is 83% of the dose maximum in the fixed beam arrangement and 86% in the multiarc setup. In arrangement A the lung and other tissues external to the breast receive dose only from scattered radiation. In arrangement B the maximum lung dose is less than 5% of the dose to isocenter. CONCLUSION: From a dosimetric point of view both described techniques are feasible, and the radiosurgery-like treatment is executable.


Assuntos
Neoplasias da Mama/cirurgia , Radiocirurgia/métodos , Terapia Assistida por Computador/métodos , Fenômenos Biofísicos , Biofísica , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Mamografia , Interpretação de Imagem Radiográfica Assistida por Computador , Radiocirurgia/instrumentação , Radiocirurgia/estatística & dados numéricos , Terapia Assistida por Computador/instrumentação , Terapia Assistida por Computador/estatística & dados numéricos , Tomografia Computadorizada por Raios X
9.
Ann Surg Oncol ; 7(2): 145-9, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10761794

RESUMO

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/cirurgia , Mastectomia Radical Modificada , Paclitaxel/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Dosagem Radioterapêutica , Radioterapia Adjuvante , Resultado do Tratamento
11.
Radiology ; 214(3): 688-92, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10715031

RESUMO

PURPOSE: To perform a single-arm study to determine the effectiveness of and potential toxic reactions to local hyperthermia and systemic carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) for the treatment of advanced or recurrent squamous cell carcinomas of the head and neck. MATERIALS AND METHODS: Eight patients with squamous cell carcinoma of the head and neck and stage IV disease (N2 or N3 neck adenopathy) or recurrent local-regional disease and who were previously and definitively treated were included in the study. Thermochemotherapy was administered every 4 weeks. Recorded end points were tumor response, duration of response, incidence of distant metastases, survival, cause of death, and toxic reactions. RESULTS: One patient had a complete response to therapy, and two had a partial response. Five patients had no response or developed progressive disease during therapy. Six patients died after 4-13 months of progressive disease. Two long-term survivors received radiation therapy; one also underwent surgical resection for residual neck disease. Each thermochemotherapeutic session was well tolerated, with minimal discomfort. Toxic reactions included hypotension, vomiting, hyponatremia, anemia, thrombocytopenia, and infection at the site of administration. There were no life-threatening toxic reactions. CONCLUSION: The combined use of hyperthermia and carboplatin shows potential in the management of unresectable head and neck tumors and is safe and well tolerated. Further studies on thermochemotherapy are warranted to assess its potential.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/terapia , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Neoplasias Otorrinolaringológicas/terapia , Idoso , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/mortalidade , Neoplasias Otorrinolaringológicas/patologia , Cuidados Paliativos , Radioterapia Adjuvante , Taxa de Sobrevida , Resultado do Tratamento
12.
Clin Cancer Res ; 6(12): 4610-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11156210

RESUMO

The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Biópsia por Agulha , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Mitose , Paclitaxel/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Fatores de Tempo , Resultado do Tratamento
13.
Clin Cancer Res ; 6(12): 4653-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11156216

RESUMO

Previous retrospective studies suggest that the phase of the menstrual cycle at surgery (proliferative versus secretory) for breast cancer may significantly affect patient survival. Fluctuations during the menstrual cycle of the expression of genes involved in metastases in breast cancer tissue have also been reported. We hypothesized that the menstrual phase may also affect similar changes in gene expression of other cancers. We focused our attention on cancer of the uterine cervix because the hysterectomy specimen obtained at original surgery for the cancer can be used retrospectively to determine cycle phase. We analyzed tumor specimens from 36 premenopausal cervical cancer patients who had undergone hysterectomy as their primary treatment. We used reverse transcription-PCR to quantify gene expression during the different phases of the menstrual cycle as determined from the endometrial specimen. We explored a panel of genes that may affect metastatic propensity, namely, metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), cyclooxygenase 1 and 2 (COX-1 and COX-2), and vascular endothelial growth factor (VEGF). A significantly higher level of TIMP-2 and COX-2 gene expression (P = 0.007 and 0.030, respectively) was detected during the proliferative phase compared to the secretory phase of the cycle. The expression of the other genes was not significantly affected by the stage of the menstrual cycle. The finding that TIMP-2 and COX-2 expression in cervical cancer may be affected by the stage of the menstrual cycle supports the hypothesis that ovarian hormones may affect the expression of genes involved in metastasis. These findings need to be replicated, and their implications for tumor angiogenesis, invasion, and metastatic propensity need to be explored both in human studies and in experimental models.


Assuntos
Ciclo Menstrual , Metástase Neoplásica , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Colo do Útero/metabolismo , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Endométrio/metabolismo , Fatores de Crescimento Endotelial/biossíntese , Feminino , Humanos , Histerectomia , Isoenzimas/biossíntese , Linfocinas/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Proteínas de Membrana , Pré-Menopausa , Prostaglandina-Endoperóxido Sintases/biossíntese , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Neoplasias do Colo do Útero/cirurgia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
14.
Am J Clin Oncol ; 22(4): 323-31, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10440184

RESUMO

Patients with localized adenocarcinoma of the prostate gland (CaP) are frequently (approximately 50%) found at radical prostatectomy to have extracapsular disease or positive surgical margins. The management of these patients is a subject of controversy because some question the impact of this manifestation of CaP on patient survival or disease-free survival. Between 1976 and 1991, 241 patients with pathologic stage C (T3N0) were treated in this medical center. Of these 241 patients, 201 (83%) received a planned postoperative pelvic irradiation consisting of 48 Gy given to the prostatic fossa, whereas 40 (17%) patients were treated with radical prostatectomy alone. The two study urologists selected these patients not to receive postoperative irradiation based on intraoperative findings and important prognostic factors. Comparison of treatment outcomes in these two treatment groups is a subject of this report. The 201 patients treated with surgery-radiotherapy (S+RT) combination had a higher pathologic stage, greater incidence of seminal vesicle involvement, p = 0.002, and higher mean and median preoperative prostate-specific antigen level, p < 0.0001, than the 40 surgery (S) alone patients. There was no significant difference in the incidence of higher Gleason's score by the treatment group, p = 0.14. In univariate analysis, there was no significant difference in survival, disease-free survival, and time to failure between the two treatment groups. In multivariate analysis after controlling for pathologic stage and Gleason's score, the 201 adjuvant radiotherapy patients were predicted to have recurrence at 68% (95% confidence interval 39%-118%) the rate of the 40 surgery-alone patients. Local recurrence with or without metastatic disease was found in 10% of surgery-alone patients as compared to 5% in those also receiving postoperative irradiation. Treatment tolerance was very good with minor radiotherapy complications only. There was no significant difference in the incidence of incontinence between the two treatment arms. In summary: (a) The use of moderate-dose postoperative radiotherapy was of low toxicity and it did not increase the incidence of incontinence. (b) Local recurrence was 5% in S+RT and 10% in S-alone patients. (c) In multivariate analysis, S+RT patients had 68% rate of recurrence of S-alone patients. (d) Adjuvant RT probably reduces the risk of recurrence in patients with poor prognostic factors. (e) These data need to be interpreted with caution because of the nonrandomized nature of the study.


Assuntos
Adenocarcinoma/terapia , Prostatectomia , Neoplasias da Próstata/terapia , Adenocarcinoma/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Análise de Sobrevida , Resultado do Tratamento
15.
Urology ; 53(6): 1184-93, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10367850

RESUMO

OBJECTIVES: This report is an update on the outcomes in the management of pathologic Stage C (T3N0) prostate cancer (CaP) with postoperative irradiation. METHODS: Between 1976 and 1994, 311 patients with pathologic Stage C CaP were treated with radical prostatectomy. Pathologic stage was as follows: C1, 60 patients (19%), C2, 146 patients (47%), and C3, 105 patients (34%). Gleason score was 2 to 4 in 10 patients (3.2%), 5 to 6 in 121 (39%), 7 in 101 (32%), and 8 to 10 in 76 (24%); median prostate-specific antigen (PSA) level was 11.9 ng/mL. Postoperative irradiation consisted of a median dose of 48 Gy. Follow-up was up to 18 years (median 5). RESULTS: The 10-year actuarial survival was 81% and 10-year disease-free survival was 51%. Pathologic stage and Gleason score were independently predictive of recurrence, each with P >0.001 after controlling for the other. Patients with pathologic Stage C3 and Gleason score 7 to 10 were in the worst prognostic category and had 5.4 times the risk of recurrence compared with patients with pathologic Stage C1-C2, Gleason score 2 to 6. Preoperative PSA was a good (P = 0.02) predictor of disease-free survival. Clinical recurrence was seen in 28 patients (9%), including 10 (3.2%) with local recurrence. PSA recurrence (PSA greater than 0.05 ng/mL) developed in 68 patients (22%). CONCLUSIONS: With the known limitations of a nonrandomized clinical trial, on the basis of the experience of this study we recommend the use of moderate dose, limited-field postoperative radiotherapy in patients with pathologic Stage C disease with Gleason score greater than 4.


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Análise Atuarial , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia Adjuvante , Taxa de Sobrevida
16.
Hematol Oncol Clin North Am ; 13(2): 373-89, vi, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10363136

RESUMO

Radiation therapy plays an important role in the management of both invasive and noninvasive breast cancer. During the last 20 years, the availability of radiation therapy has made it possible to test the feasibility and safety of breast preservation after the diagnosis of early-stage breast cancer. This article summarizes some of the ongoing controversies concerning the use of radiation therapy in the multidisciplinary management of breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos
17.
Semin Radiat Oncol ; 9(2 Suppl 1): 34-42, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10210538

RESUMO

Few studies have evaluated the role of concurrent chemoradiation therapy in the management of locally advanced breast cancer. The availability of radiosensitizing chemotherapeutic agents that are effective in breast cancer and the encouraging results achieved by concurrent chemoradiation in other malignancies have prompted us to investigate this approach. Paclitaxel is a promising agent for use with concurrent radiotherapy because of its single-agent efficacy profile and its radiosensitizing effects. A clinical protocol of preoperative paclitaxel and radiation in locally advanced breast cancer is ongoing at our institution to test feasibility, measure pathologic response at mastectomy, and explore association of pathologic response with molecular tumor markers. Initially, the study was designed to test weekly paclitaxel at a dose of 60 mg/m2 during radiation therapy, delivered 5 days a week at 200 cGy fractions to a total dose of 50 Gy over 5 weeks. Due to severe skin toxicity in the first two patients, the protocol was amended to change the scheduling of paclitaxel to 30 mg/m2 twice weekly and to reduce the radiation to 180 cGy fractions to a total dose of 45 Gy, delivered 5 days a week over 5 weeks. Presently, 13 patients have been accrued; preliminary data indicate good tolerance to twice-weekly paclitaxel, and four of eight evaluable patients have achieved pathologic response (one patient who received the weekly regimen and three who received the twice-weekly regimen). In addition, sequential fine-needle aspirations of palpable breast cancers were obtained in patients enrolled in a parallel study of preoperative single-agent paclitaxel (200 mg/m2 every 2 weeks, for a total of four cycles before breast surgery). Preliminary results suggest that a steep increase in the mitotic index occurs during the first day after paclitaxel administration and plateaus between the second and the third day, then decreases to pretreatment values. The peak apoptotic index occurs at approximately 72 hours after paclitaxel administration and decreases at approximately 98 hours. These initial findings suggest that twice-weekly dosing of paclitaxel may optimize recruitment of cells into the G2/M phase of the cell cycle, the most radiosensitive phase.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Paclitaxel/uso terapêutico , Radiossensibilizantes/uso terapêutico , Terapia Combinada , Feminino , Humanos , Dosagem Radioterapêutica
18.
Lab Invest ; 79(3): 271-80, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10092063

RESUMO

P-glycoprotein (Pgp)-associated multidrug resistance (MDR) is related to intrinsic and acquired cross resistance to anthracyclines, vinca alkaloids, and other antineoplastic antibiotics. Expression of MDR1 is widely considered to play an important role in conferring resistance to adjuvant chemotherapy in women with breast tumor cells in women with disseminated disease, although data supporting this view is, at best, conflicting. The expression of MDR1 gene and its gene product, P-glycoprotein, was investigated in primary and advanced breast cancers (both previously untreated and previously treated on specific treatment protocols) to assess the role of P-glycoprotein in determining responsiveness to adjuvant chemotherapy. Expression was assessed by immunohistochemistry, reverse transcription-PCR (RT-PCR), Northern Blot and Western Blot. MDR1 mRNA was detected in 40% of the breast cancers tested by RT-PCR with 40 cycles of PCR amplification. When reducing the PCR amplification cycles to 28, the MDR1 gene expression signal disappeared from breast cancers of the highest expressers; however, known MDR1 positive control normal tissues, such as adrenal, kidney, and liver continued to show an expression product. Western and Northern blots failed to demonstrate the MDR1 gene product, P-glycoprotein, in these breast cancers. In contrast, physiologic levels of P-glycoprotein was clearly detected in normal adrenal, kidney, and liver by these techniques. Immunohistochemistry confirmed that breast carcinoma cells lacked P-glycoprotein expression; however, interstitial mononuclear cells, morphologically consistent with lymphocytes or macrophages did show immunostaining in some of these breast tumors. MDR1 gene expression identified by RT-PCR was not correlated either with response to paclitaxel therapy (29 patients able to be evaluated, p = 0.34, Fisher Exact Test) or overall survival (32 breast cancer patients with clinical follow-up information, p = 0.336, log rank). In conclusion, P-glycoprotein was not expressed in breast carcinoma cells at significant levels, although it was expressed in stomal lymphocytes or macrophages. These results suggest that P-glycoprotein does not play a significant role in multidrug resistance of breast cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias da Mama/genética , Carcinoma/genética , Expressão Gênica/fisiologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Western Blotting , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Ann Surg Oncol ; 5(2): 166-72, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9527270

RESUMO

BACKGROUND: Health care reform places primary care (PC) physicians in an increasingly significant role for breast cancer screening and diagnosis. This study assessed the adequacy of traditional PC resident training to prepare physicians for this front-line role. METHODS: Sixty-eight primary care residents, representing seven training programs, participated in a multidimensional needs assessment study of clinical breast evaluation skills. RESULTS: Performance deficiencies noted in each component were most significant in (1) common breast problem management (problem-solving mean 44.51 +/- 11.01); (2) breast examination skills (mean 49.65 +/- 14.48%); and (3) lump detection sensitivity (mean 40.20 +/- 17.10%). Overall examination reliability was good (alpha = .82). Factorial ANOVA revealed significant performance differences among training programs. Residency programs with higher performance levels reported dedicated breast curricula, and residents rated these programs as providing more adequate training. Programs with poorer performance in breast examination lacked curriculum emphasis, with residents describing training received as poor to fair. CONCLUSION: This study demonstrated performance deficits in the clinical breast evaluation skills of graduating PC residents that have not been captured by traditional evaluation methodologies. This may represent a limitation in the ability of many PC physicians to effectively screen and diagnose patients with breast cancer.


Assuntos
Neoplasias da Mama/prevenção & controle , Competência Clínica , Medicina de Família e Comunidade/educação , Internato e Residência , Adulto , Análise de Variância , Doenças Mamárias/diagnóstico , Doenças Mamárias/prevenção & controle , Neoplasias da Mama/diagnóstico , Currículo , Avaliação Educacional/métodos , Feminino , Reforma dos Serviços de Saúde , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos Anatômicos , Simulação de Paciente , Exame Físico , Resolução de Problemas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Int J Radiat Oncol Biol Phys ; 40(1): 139-47, 1998 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9422570

RESUMO

PURPOSE: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleason's score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleason's score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION: Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleason's score and those with high (> 25 ng/ml) PSA level at diagnosis.


Assuntos
Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Incontinência Urinária/etiologia
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