RESUMO
BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.
Assuntos
Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Terapia de SalvaçãoRESUMO
BACKGROUND: Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. PATIENTS AND METHODS: We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). CONCLUSION: Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Doença da Artéria Coronariana/tratamento farmacológico , Hipertensão/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Receptores Adrenérgicos beta/efeitos dos fármacos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia , Seleção de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de RiscoRESUMO
BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Hormônio-Dependentes/terapia , Neoplasias da Próstata/terapia , Idoso , Comorbidade , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/patologia , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The purpose of this study was to review the clinical course of patients diagnosed with vulvar melanoma. Charts of patients diagnosed between 1970 and 1997 were reviewed for demographics, lesion characteristics, disease duration and extent, and treatments. Actuarial survival curves were computed by the Kaplan Meier method and compared by Cox proportional hazards regressions. Fifty-one patients (median age 54) with vulvar melanoma presented with a vulvar mass (39%), pain (30%), bleeding (24%), and itching (20%). Anatomical distribution was mucosa of the vulva (65%), vulvar epidermal site (21%), or unspecified vulva (14%), with 20% having multifocal disease at diagnosis. Histologic types were superficial spreading or nodular (50% each). Median lesion characteristics were diameter 2 cm, Breslow index 4.4 mm, and Clark level IV. Distribution of patients per American Joint Committee on Cancer (AJCC) stage was 29%, 50%, 16%, and 7% for stages I, II, III and IV, respectively. Inguinal node metastases were unilateral in 16% and bilateral in 7%. Despite complete surgical resection, 32 patients (63%) recurred. Median survival for all patients was 41 months (range, 5-324), with 91% 5-year survival for patients with stage I and 31% for stage >or= IIA (P = 0.0002). As with cutaneous melanoma, the AJCC classification, Breslow's thickness, and Clark's levels are the major predictors of overall survival (P = 0.0001 each) and disease-free survival (P Assuntos
Melanoma/mortalidade
, Melanoma/patologia
, Recidiva Local de Neoplasia
, Neoplasias Vulvares/mortalidade
, Neoplasias Vulvares/patologia
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Feminino
, Humanos
, Prontuários Médicos
, Melanoma/cirurgia
, Pessoa de Meia-Idade
, Estadiamento de Neoplasias
, Prognóstico
, Modelos de Riscos Proporcionais
, Estudos Retrospectivos
, Análise de Sobrevida
, Texas/epidemiologia
, Neoplasias Vulvares/cirurgia
RESUMO
Chemotherapy given sequentially or concurrently with external beam radiation therapy has emerged as a standard for the treatment of locally advanced lung cancer. Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. However, no information is available on the combined effects of p53 gene transfer, chemotherapy, and radiation therapy on lung cancer growth in vitro and in vivo. Therefore, we developed two-dimensional and three-dimensional isobologram modeling and statistical methods to evaluate the synergistic, additive, or antagonistic efficacy among these therapeutic agents in human non-small cell lung cancer cell lines A549, H460, H322, and H1299, at the ID50 and ID80 levels. The combination of these three therapeutic agents exhibited synergistic inhibitory effects on tumor cell growth in all four cell lines at both the ID50 and the ID80 levels in vitro. In mouse models with H1299 and A549 xenografts, combined treatment synergistically inhibited tumor growth in the absence of any apparent increase in toxicity, when compared with other treatment and control groups. Together, our findings suggest that a combination of gene therapy, chemotherapy, and radiation therapy may be an effective strategy for human cancer treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Divisão Celular/efeitos dos fármacos , Neoplasias Pulmonares/terapia , Paclitaxel/farmacologia , Taxoides , Proteína Supressora de Tumor p53/fisiologia , Adenoviridae/genética , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Divisão Celular/genética , Divisão Celular/efeitos da radiação , Terapia Combinada , Docetaxel , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Radioterapia , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Transforming growth factor beta (TGF-beta) is an important family of cytokines that may promote tumor growth in vivo through several mechanisms including interference with antitumor T-cell immune responses, alteration of factors in the stroma and matrix, and the promotion of angiogenesis. TGF-beta isotypes have been detected in malignant and normal ovarian tissues. We have determined by quantitative immunohistochemistry the density of TGF-beta1, TGF-beta2, and human leukocyte antigen (HLA) Class I and Class II antigens on malignant cells in paired primary and metastatic specimens from 10 patients with ovarian carcinoma. Cryostat sections of specimens from the carcinomas and from normal ovaries of three women of similar age without ovarian cancer were stained respectively with specific antibodies to TGF-beta1, TGF-beta2, and HLA Class I and II antigens, and with isotype-matched control antibodies. Antigen density was quantitated blindly as mean absorbance on a SAMBA 4000 image analyzer. TGF-beta1 and TGF-beta2 were overexpressed in both primary and metastatic tumor specimens in comparison with normal ovarian tissue. No statistical correlation was found between the expression of TGF-beta1 or TGF-beta2 and HLA class I or HLA class II, which suggests that TGF-beta isotypes could have effects on the immune system other than down-modulation of these HLA molecules. Furthermore, the lack of association between levels of TGF-beta expression and the reduced expression of HLA molecules could suggest that tumor cells expressing both HLA and TGF-beta may be suitable targets for adaptive immunotherapy. Additional studies are necessary to determine whether TGF-beta expressed by ovarian cancer cells merits evaluation as a therapeutic target.
Assuntos
Neoplasias Ovarianas/química , Fator de Crescimento Transformador beta/análise , Idoso , Feminino , Antígenos de Histocompatibilidade Classe I/biossíntese , Antígenos de Histocompatibilidade Classe II/biossíntese , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Especificidade de Órgãos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Fotomicrografia , Isoformas de Proteínas , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: We have previously argued against the calculation of cancer-specific death rates as philosophically undefined and biased. Deaths attributed to cancer during a particular year occur in patients diagnosed during an unknown distribution of past times, so cancer-specific death rates cannot be used to assess changes in the impact of cancer on survival of the population at specific periods of diagnosis. PURPOSE: Our goal was to develop and analyze three measures of the impact of cancer on population survival that do not use the attributed cause of death: 1) the age-adjusted proportion of the population diagnosed with cancer in a particular year and projected to be dead of any cause by a particular age; 2) the same measure corrected for population mortality; and 3) the expected years of life lost to a 20-year-old individual because of the possibility of a diagnosis of cancer. METHODS: Data on all adults diagnosed with any cancer during the period from January 1973 through December 1990 were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The measures were calculated separately for various combined sex and race groups. Three 2-year diagnosis periods spaced 5 years apart were considered: 1975-1976, 1980-1981, and 1985-1986. A statistical model was used to extrapolate survival beyond observation; the same model was used for patients diagnosed in the three time periods to minimize the effect of possible model misspecification on changes. RESULTS: Cancer incidence increased for three of the four sex-race groups; age-adjusted changes from 1975 through 1976 to 1985 through 1986 were +11.5% for white men, +6.9% for white women, +15.1% for black men, and -9.2% for black women. Human immunodeficiency virus (HIV)-related cancers were responsible for an increased cancer incidence at early ages in white men in the latest time period studied. There was a decrease in the incidence of gynecologic cancers at early ages; the decrease was greater among black women (-55.1%) than among white women (-39.3%). Age- and incidence-adjusted 5-year survival increased by 17.9% for white men, 2.3% for white women, and 7.4% for black men and decreased by 14.1% for black women. When the data from 1985 through 1986 were compared with those from 1975 through 1976, the expected number of years lost to a 20-year-old individual because of cancer changed as follows for the various sex-race groups: +1.4% for white men (-4.0% if HIV-related cancers were not included in the calculation), +2.1% for white women, +12.2% for black men, and +8.8% for black women. CONCLUSIONS: For white men and women, there has been an increase in both the incidence of and survival following the diagnosis of cancer; the two effects nearly cancel in our measures. The experience of black men and women has worsened because of increasing incidence or decreased survival.
Assuntos
Neoplasias/mortalidade , Taxa de Sobrevida , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Viés , Causas de Morte , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etnologia , Distribuição por Sexo , Estados Unidos/epidemiologiaRESUMO
PURPOSE: This study was conducted to test for the relationship between tumor and normal tissue radiosensitivity, by comparing local tumor control to the severity of acute and late normal tissue reactions in head and neck cancer patients treated by definitive radiotherapy. METHODS AND MATERIALS: Two hundred eighty-six patients with head and neck cancer who were treated at the University of Texas M. D. Anderson Cancer Center between 1983 and 1993 were selected for the study. Of these, 124 (43%) were treated by a concomitant boost regimen and 162 (57%) by hyperfractionation. All patients had at least 1 year of follow-up. The tumor stage distribution according to the 1992 American Joint Committee on Cancer (AJCC) staging system was as follows: T1, 3%; T2, 53%; T3, 40%; T4, 4%. The average doses delivered were 71.2 Gy and 76.2 Gy for the concomitant boost and hyperfractionation regimens, respectively, with no significant variation between patients. Acute and late reactions were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) grading system (0 to 4). The median follow-up period was 38 months (range: 12-107 months). The time to local tumor recurrence was analyzed in relation to the severity of acute and late reactions expressed as the maximum recorded grades, and to the time intensity of acute mucositis, expressed as the area under the curve of mucositis grade vs. time. Univariate and multivariate analyses also included T stage, N stage, and site of origin as other prognostic variables, and were carried out using a proportional hazards model. RESULTS: Fifty-four patients (19%) suffered local failure. T stage was found to significantly influence local control (p = 0.009). There was a nonsignificant trend for higher failure rates in patients with maximum Grade 1 or 2 vs. those with Grade 3 or 4 acute mucositis (28 and 18%, respectively; p = 0.17). No correlation was found between the severity of late reactions and local tumor control after radiotherapy. Analysis by time intensity of mucositis revealed a wide variation between individuals with a nonsignificant trend for higher local failure rates in patients with low mucositis time intensity scores. CONCLUSIONS: These clinical results suggest a possible relationship between normal tissue and tumor radiosensitivity. However, additional studies with a larger numbers of patients, and using refined normal tissue endpoints that incorporate a time function are needed to fully elucidate this question.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/patologia , Estomatite/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos da radiação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Índice de Gravidade de Doença , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Metastatic colorectal cancer is generally incurable. The most active regimen available, 5-fluorouracil (5-FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl-lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl-lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer. METHODS: The methyl-lomustine/5-FU/Leucovorin (MFL) regimen consisted of methyl-lomustine (110 mg/m2), administered on Day 1 of each 8-week cycle with six weekly boluses of 5-FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5-FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8-week cycle. RESULTS: Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl-lomustine/5-FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3-4 neutropenia: MFL = 56 patients, FL = 27 patients, P < 0.001; Grade 3-4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P < 0.001; Grade 3-4 anemia: MFL = 15 patients, FL = 6 patients, P < 0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P < 0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P < 0.001). CONCLUSION: Because the addition of methyl-lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5-FU remain the treatment choice for treating patients with metastatic colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Semustina/administração & dosagemRESUMO
The bremsstrahlung spectrum from an 8-MeV linear accelerator has been measured using a NaI(T1) spectrometer system. The spectrum shows a low-energy cutoff at 0.4 MeV and the maximum photon energy to be approximately 6% greater than the nominal energy. The maximum emission of energy fluence was 1.6 and 1.8 MeV for measured and calculated values, respectively. The fast neutron dose in the photon beam was approximately 0.09% of the x-ray dose. The weighted mean energy was 2.3 MeV, measured value, and 2.4 MeV, calculated value.