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PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.
Assuntos
Adenocarcinoma/radioterapia , Braquiterapia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Próstata/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24-48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24-48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal-physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy.
RESUMO
Hyperthermia has long been used in combination with radiation for the treatment of superficial malignancies, in part due to its radiosensitising capabilities. Patients who suffer superficial recurrences of breast cancer, be it in their chest wall following mastectomy, or in their breast after breast conservation, typically have poor clinical outcomes. They often develop distant metastatic disease, but one must not overlook the problems associated with an uncontrolled local failure. Morbidity is enormous, and can significantly impair quality of life. There is no accepted standard of care in treating superficial recurrences of breast cancer, particularly in patients that have previously been irradiated. There is a substantial literature regarding the combined use of hyperthermia and radiotherapy for these superficial recurrences. Most of it is retrospective in nature, but there are several larger phase III randomised trials that show an improved rate of clinical complete response in patients treated with both modalities. In this review article, we will highlight the important prospective data that has been published regarding the combined use of hyperthermia and radiation.
Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida , Ensaios Clínicos Controlados Aleatórios como Assunto , Parede Torácica/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , Recidiva , Resultado do TratamentoRESUMO
Hyperthermia (HT) has a proven benefit for treating superficial malignancies, particularly chest wall recurrences of breast cancer. There has been less research utilising HT in patients with locally advanced breast cancer (LABC), but available data are promising. HT has been combined with chemotherapy and/or radiotherapy in the neoadjuvant, definitive and adjuvant setting, albeit in series with small numbers of patients. There is only one phase III trial that examines hyperthermia in LABC, also with relatively small numbers of patients. The goal of this review is to highlight important research utilising HT in patients with LABC as well as to suggest future directions for its use.
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Neoplasias da Mama/terapia , Hipertermia Induzida , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , HumanosRESUMO
PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose-rate brachytherapy. MATERIALS AND METHODS: Generalized equivalent uniform dose (EUD), dose in Gy to 90% of the prostate gland (D(90)), and percentage of the prostate receiving 100% of the prescribed dose (V(100)) were calculated from the postimplant dose-volume histogram (DVH) for 140 patients undergoing low-dose-rate prostate brachytherapy (LDRPB) monotherapy from 1997 to 2003 at Duke University and the Durham VA Medical Center. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: Median followup after LDRPB was 50 months. There was a 7% biochemical recurrence rate (10/140) at last clinical followup. The median EUD was 167 Gy (range, 41-245). The median D(90) was 139 Gy (range, 45-203). The median V(100) was 88% (range, 44-100). The overall 5-year biochemical recurrence-free survival (bRFS) was 94.2%. The 5-year bRFS was 100% for EUD> or =167 Gy and 89.4% for EUD <167 Gy (p=0.008); 100% for D(90) > or =140 Gy and 90.4% for D(90) <140 Gy (p=0.020); 100% for V(100) > or =88%; and 90.3% for V(100) <88% (p=0.017). There was no statistically significant correlation between any of these factors and overall survival. CONCLUSIONS: In our series of 140 patients with low-risk prostate cancer treated with LDRPB alone, we observed a statistically significant correlation between EUD, D(90), and V(100) and bRFS. The generalized EUD, a calculated value that incorporates the entire prostate DVH, appears to be at least as well correlated with bRFS as D(90) or V(100), and may more completely represent the totality of the dose distribution.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Neoplasias da Próstata/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Radiometria , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
PURPOSE: Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation response. These trials, however, generally lacked rigorous thermal dose prescription and administration. We report the final results of a prospective randomized trial of superficial tumors (= 3 cm depth) comparing radiotherapy versus HT combined with radiotherapy, using the parameter describing the number of cumulative equivalent minutes at 43 degrees C exceeded by 90% of monitored points within the tumor (CEM 43 degrees C T(90)) as a measure of thermal dose. METHODS: This trial was designed to test whether a thermal dose of more than 10 CEM 43 degrees C T(90) results in improved complete response and duration of local control compared with a thermal dose of = 1 CEM 43 degrees C T(90). Patients received a test dose of HT = 1 CEM 43 degrees C T(90) and tumors deemed heatable were randomly assigned to additional HT versus no additional HT. HT was given using microwave spiral strip applicators operating at 433 MHz. RESULTS: One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned. The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7 (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the HT arm. No overall survival benefit was seen. CONCLUSION: Adjuvant hyperthermia with a thermal dose more than 10 CEM 43 degrees C T(90) confers a significant local control benefit in patients with superficial tumors receiving radiation therapy.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/terapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/terapia , Hipertermia Induzida , Melanoma/radioterapia , Melanoma/terapia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Grade > or =2 rectovaginal fistula and Grade > or =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. METHODS AND MATERIALS: Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity. RESULTS: At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p < 0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received >76 Gy to the rectum compared with those who received < or =76 Gy (100% vs. 7%, p = 0.009). CONCLUSIONS: Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should be < or =76 Gy.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias dos Genitais Femininos/radioterapia , Recidiva Local de Neoplasia/radioterapia , Lesões por Radiação , Reto/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Fístula Retovaginal/etiologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/radioterapia , Neoplasias Vaginais/radioterapiaRESUMO
Criminologists have largely neglected deviance among those with high IQs. This work uses Towers's (1988) concept of conventional genius to analyze how deviant behavior varies by gender among genius offenders. Like Bisi (2002), the authors expect female patterns of deviance to be lower than that for males even within this genius sample. Their work finds that male geniuses are significantly more likely to self-report ever having committed violent felonies. Among the authors' conventional genius sample of university students, gender differences in nonviolent felonies, misdemeanor offenses, and unethical behaviors are not significantly different between the female and male respondents.
Assuntos
Direito Penal/legislação & jurisprudência , Direito Penal/estatística & dados numéricos , Inteligência , Adolescente , Adulto , Feminino , Humanos , Masculino , Fatores Sexuais , Estados UnidosRESUMO
PURPOSE: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. METHODS AND MATERIALS: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. RESULTS: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). CONCLUSIONS: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.
Assuntos
Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de TempoRESUMO
PURPOSE: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. METHODS AND MATERIALS: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model. RESULTS: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy. CONCLUSIONS: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.
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Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/radioterapia , Hemoglobinas/análise , Oxigênio/sangue , Hipóxia Tumoral/efeitos da radiação , Animais , Velocidade do Fluxo Sanguíneo/efeitos da radiação , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta à Radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Cinética , Taxa de Depuração Metabólica/efeitos da radiação , Camundongos , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do TratamentoRESUMO
Corn rootworm larval feeding on corn roots can significantly reduce grain yield by interfering with photosynthetic rates, limiting the uptake of water and nutrients, and by increasing the plant's susceptibility to lodging. Of the techniques developed to measure the efficacy of corn rootworm larval control tactics, root damage ratings have generally been adopted as the standard because sampling roots is relatively efficient. Historically, the primary scales used for scoring root injury from corn rootworm larval feeding have been the 1-6 and 1-9 scales. A critical deficiency of those scales, however, is that each increase in a root-rating score does not reflect a linear increase in the actual amount of injury to the root system. This results in injury scores that are expressed qualitatively. We developed the node-injury scale to more accurately quantify corn rootworm larval injury based on the proportion of nodal roots that contain feeding injury. With the node-injury scale, the relationship between the numerical scale and the amount of root injury is linear and intuitive. In this article, we describe the node-injury scale, discuss sampling issues to consider when using the scale, and suggest the minimum node-injury score that causes economic damage under varying degrees of environmental stress.
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Besouros/fisiologia , Doenças das Plantas , Raízes de Plantas/anatomia & histologia , Zea mays/anatomia & histologia , Agricultura/métodos , Animais , Ingestão de Alimentos , Inseticidas , Larva/fisiologiaRESUMO
The purpose of this report was to study the results of external beam radiotherapy for patients with extranodal stage IA non-Hodgkin's lymphoma (NHL). A retrospective review was carried out on 27 patients seen between 1984 and 1998 with stage IA NHL of extranodal sites, and followed up for a minimum of 1 year. Sites involved included eye/orbit (seven), parotid (five), breast (four), Waldeyer ring (four), thyroid (three), other head and neck (two), stomach (one), and prostate (one). All patients had biopsy-proven disease and underwent staging workup to rule out other sites of disease. Histologic analysis revealed 16 patients with low-grade NHL, 9 with intermediate-grade, and 2 with high-grade. Ten patients received chemotherapy before radiation therapy, and eight of them had a complete response. The remaining 17 patients were treated with external beam radiation therapy alone. Radiation was directed to the involved field at 1.8 Gy to 2.0 Gy per fraction to a median dose of 40 Gy (range: 20-50.4 Gy). The median patient age was 71 years (range: 39-85 years); 55% were female, and 45% were male. A complete response was attained in all 27 patients after radiation therapy. There were five failures (all in uninvolved distant sites), and two deaths during the follow-up. Median disease free survival (DFS) and overall survival (OS) have not been reached. The 5-year DFS and OS are 85% and 94%, respectively. Older age at presentation showed a trend toward worse outcome (p = 0.07), but because of the relatively few events, other factors (radiation dose, grade of disease, sex, or the use of chemotherapy) showed no statistical differences among the patients. External beam radiation therapy is a highly effective treatment for stage IA NHL found in extranodal sites.
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Linfoma não Hodgkin/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Indução de Remissão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors.
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Neoplasias de Cabeça e Pescoço/terapia , Meningioma/terapia , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/patologia , Neoplasias Abdominais/terapia , Algoritmos , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Meníngeas , Guias de Prática Clínica como AssuntoRESUMO
PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose rate brachytherapy. METHODS AND MATERIALS: The biologically effective dose (BED), dose in Gray (Gy) to 90% of prostate (D(90)), and percent volume of the prostate receiving 100% of the prescription dose (V(100)) were calculated from the postimplant dose-volume histogram for 140 patients undergoing low-dose rate prostate brachytherapy from 1997 to 2003 at Durham Regional Hospital and the Durham VA Medical Center (Durham, NC). RESULTS: The median follow-up was 50 months. There was a 7% biochemical failure rate (10 of 140), and 91% of patients (127 of 140) were alive at last clinical follow-up. The median BED was 148 Gy (range, 46-218 Gy). The median D(90) was 139 Gy (range, 45-203 Gy). The median V(100) was 85% (range, 44-100%). The overall 5-year biochemical relapse-free survival (bRFS) rate was 90.1%. On univariate Cox proportional hazards modeling, no pretreatment characteristic (Gleason score sum, age, baseline prostate-specific antigen, or clinical stage) was predictive of bRFS. The BED, D(90), and V(100) were all highly correlated (Pearson coefficients >92%), and all were strongly correlated with bRFS. Using the Youden method, we identified the following cut points for predicting freedom from biochemical failure: D(90) >or= 110 Gy, V(100) >or= 74%, and BED >or= 115 Gy. None of the covariates significantly predicted overall survival. CONCLUSIONS: We observed significant correlation between BED, D(90), and V(100) with bRFS. The BED is at least as predictive of bRFS as D(90) or V(100). Dosimetric quantifiers that account for heterogeneity in tumor location and dose distribution, tumor repopulation, and survival probability of tumor clonogens should be investigated.
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Braquiterapia/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Paládio/uso terapêutico , Modelos de Riscos Proporcionais , Próstata/patologia , Neoplasias da Próstata/patologia , Curva ROC , Radioisótopos/uso terapêutico , Eficiência Biológica Relativa , Estudos RetrospectivosRESUMO
Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively (p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% (p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.
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Carga Corporal (Radioterapia) , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Contagem Corporal Total , Humanos , Masculino , Especificidade de Órgãos , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodosRESUMO
The study was designed to determine the maximum tolerated dose (MTD) of IP cisplatin [CDDP] combined with intravenous thiosulphate and concurrent whole abdomen hyperthermia for advanced, recurrent or progressive ovarian carcinoma. Between September 1991 and November 1998, 41 patients with advanced epithelial ovarian cancer received escalating doses of IP (IP) cisplatin (six cycles given every 3-4 weeks) and whole abdomen hyperthermia with intravenous thiosulphate as second line treatment. Whole abdomen hyperthermia was administrated using a BSD-2000 annular phased array system. Forty-one patients were enrolled in the phase I/II portions of the study. Forty-four per cent (18/41) had undergone sub-optimal cytoreductive surgery and 15% (6/41) had been optimally debulked of their disease. Ninety per cent (37/41) had platinum-resistant disease and 10% (4/41) had platinum-sensitive disease. No DLTs occurred in the phase I testing and the recommended dose for this combination schedule was 180 mg m-2 of IP cisplatin with thiosulphate and whole abdomen hyperthermia. The overall response rate was 44% (10 CR, 8 PR) and the median survival for all patients from protocol entry was 30 months (range 2-107 months). Median duration and survival of those achieving a pathologic CR was 14 months (range 2-27 months) and 35 months (range 14-71 months, 95% CI 16-54 months), respectively. Salvage platinum based IP cisplatin with hyperthermia did achieve pathologic CR in selected patients and was well tolerated. These promising results suggest a role for the use of adjuvant whole abdomen hyperthermia as a means of augmenting chemosensitization.