RESUMO
PURPOSE: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
Assuntos
Radioterapia de Intensidade Modulada/métodos , Neoplasias da Coluna Vertebral/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Terapia de Salvação , Medula Espinal/diagnóstico por imagem , Medula Espinal/efeitos da radiação , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida , Fatores de TempoRESUMO
PURPOSE: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer. EXPERIMENTAL DESIGN: Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B(12) and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation. RESULTS: For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m(2) plus docetaxel 35 mg/m(2) administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non-small-cell lung cancer. CONCLUSIONS: Pralatrexate (120 mg/m(2)) plus docetaxel (35 mg/m(2)) plus vitamin supplementation is well tolerated with signs of efficacy against non-small-cell lung cancer that merit phase 2 testing.
Assuntos
Aminopterina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antagonistas do Ácido Fólico/efeitos adversos , Neoplasias/tratamento farmacológico , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Adulto , Idoso , Aminopterina/administração & dosagem , Aminopterina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Suplementos Nutricionais , Docetaxel , Feminino , Antagonistas do Ácido Fólico/administração & dosagem , Homocisteína/sangue , Humanos , Masculino , Ácido Metilmalônico/sangue , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Vitaminas/administração & dosagemRESUMO
PURPOSE: To present a retrospective review of treatment outcomes for recurrent head and neck (HN) cancer patients treated with re-irradiation (re-RT) at a single medical center. METHODS AND MATERIALS: From July 1996-September 2005, 105 patients with recurrent HN cancer underwent re-RT at our institution. Sites included were: the neck (n = 21), nasopharynx (n = 21), paranasal sinus (n = 18), oropharynx (n = 16), oral cavity (n = 9), larynx (n = 10), parotid (n = 6), and hypopharynx (n = 4). The median prior RT dose was 62 Gy. Seventy-five patients received chemotherapy with their re-RT (platinum-based in the majority of cases). The median re-RT dose was 59.4 Gy. In 74 (70%), re-RT utilized intensity-modulated radiation therapy (IMRT). RESULTS: With a median follow-up of 35 months, 18 patients were alive with no evidence of disease. The 2-year loco-regional progression-free survival (LRPFS) and overall survival rates were 42% and 37%, respectively. Patients who underwent IMRT, compared to those who did not, had a better 2-year LRPF (52% vs. 20%, p < 0.001). On multivariate analysis, non-nasopharynx and non-IMRT were associated with an increased risk of loco-regional (LR) failure. Patients with LR progression-free disease had better 2-year overall survival vs. those with LR failure (56% vs. 21%, p < 0.001). Acute and late Grade 3-4 toxicities were reported in 23% and 15% of patients. Severe Grade 3-4 late complications were observed in 12 patients, with a median time to development of 6 months after re-RT. CONCLUSIONS: Based on our data, achieving LR control is crucial for improved overall survival in this patient population. The use of IMRT predicted better LR tumor control. Future aggressive efforts in maximizing tumor control in the recurrent setting, including dose escalation with IMRT and improved chemotherapy, are warranted.
Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Radioterapia/mortalidade , Medição de Risco/métodos , Terapia de Salvação/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Prevalência , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: In patients with non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. EXPERIMENTAL DESIGN: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival). RESULTS: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). CONCLUSIONS: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Cloridrato de Erlotinib , Éxons , Feminino , Gefitinibe , Genótipo , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To describe the prostate-specific antigen (PSA) pattern profiles observed after external beam radiotherapy with and without short-term neoadjuvant androgen deprivation therapy (ST-ADT) and to report the association of established posttreatment PSA patterns with long-term disease-free survival outcomes. METHODS AND MATERIALS: A total of 1,665 patients were treated with conformal external beam radiotherapy for clinically localized prostate cancer. Of 570 patients who had the requisite>10 consecutive PSA measurements for statistical analysis, 194 patients received a median of 3 months of ADT before radiotherapy and 376 were treated with radiotherapy alone. The median follow up was 103 months. RESULTS: In the group treated with ST-ADT, three distinct postradiotherapy PSA patterns were identified: a stable trend (44%), an increasing trend followed by stabilization of the PSA (25%), and an increasing trend (31%). Among the subgroup that demonstrated a rising and subsequent stabilizing patterns, PSA levels had gradually risen to a median value of 0.9 ng/mL after therapy, stabilized, and remained durably suppressed. The only identified trends among patients treated with external beam radiotherapy without ST-ADT were declining PSA levels followed by stable PSA trends or declining patterns followed by rising levels. Patients whose PSA levels stabilized after an initial rise or those with slowly rising PSA profiles had a lower incidence of distant metastasis compared to those with accelerated rises after therapy. CONCLUSIONS: For those treated with external beam radiotherapy in conjunction with ST-ADT, a significant percentage who develop a rising PSA after treatment are expected to manifest subsequent stabilization at plateaued levels of approximately 1.0 ng/mL, which can remain durably suppressed. The likelihood of distant metastasis in these patients is low despite the PSA stabilization at levels 1.0 ng/mL or higher and comparable to outcomes observed for those with lower nonrising PSA values.
Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Conformacional , Fatores de TempoRESUMO
PURPOSES: COPD is a well-known independent risk factor that is associated with primary lung cancer. There is, however, a striking paucity of women in studies demonstrating this association. The purpose of this study was to compare the prevalence of COPD as determined by pulmonary function tests (PFTs) between women and men at around the time of lung cancer diagnosis. METHODS: We retrospectively reviewed patients with newly diagnosed primary lung cancer who had undergone PFTs prior to their treatment. The diagnosis of airflow obstruction was made according to American Thoracic Society guidelines. Comparisons of the prevalence of COPD between men and women were performed using univariate and multivariate logistic regression analysis. RESULTS: Of the 294 patients in the study, 151 patients (51.4%) were men and 143 patient (48.6%) were women. Of the men, 110 patients (72.8%) had COPD compared with 75 patients (52.5%) among the women. This represented a significantly lower prevalence of COPD in women than in men (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.25 to 0.67; p = 0.0003). When adjusted for age and smoking status, a sustained lower prevalence of COPD was noted in women compared to men (OR, 0.44; 95% CI, 0.26 to 0.74; p = 0.002). In a subset of 256 smokers, there remained a lower prevalence of COPD in women compared to men (OR, 0.45; 95% CI, 0.27 to 0.77; p = 0.003). Adjusted analysis to control for age and number of pack-years of smoking in this subset again showed a sustained reduction in the OR for women presenting with COPD (OR, 0.48; 95% CI, 0.28 to 0.83; p = 0.009). CONCLUSIONS: When COPD was examined as an end point among patients who had newly diagnosed lung cancer, a significantly higher proportion of women had normal PFT results. Gender-based differences on PFT results should be considered during the screening of lung cancer, because the stratification of high-risk patients based on the presence of COPD may miss a significant proportion of women with lung cancer.
Assuntos
Carcinoma/patologia , Neoplasias Pulmonares/patologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Carcinoma/complicações , Intervalos de Confiança , Feminino , Volume Expiratório Forçado , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Prevalência , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Recent evidence suggests that microvascular endothelial apoptosis represents the primary lesion in radiation damage to the gastrointestinal (GI) tract. Rescue of endothelium by depletion of acid sphingomyelinase or i.v. treatment with basic fibroblast growth factor (FGF) prevented the lethal GI syndrome in C(57)Bl/6 mice. Here we show that basic FGF increased crypt survival after irradiation by 2-3 fold, with a dose modification factor at D(10) of 1.15 (P < 0.01). Basic FGF inhibited initial crypt damage, assessed by crypt shrinkage at 18-24 h, but did not significantly affect the regeneration of surviving crypts at 3.5 days after irradiation. These data suggest that microvascular function regulates expression of radiation-induced crypt stem cell clonogen damage in the evolution of radiation injury to the GI mucosa.
Assuntos
Jejuno/irrigação sanguínea , Jejuno/efeitos da radiação , Animais , Endotélio Vascular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/efeitos da radiação , Jejuno/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: To identify predictors of biochemical outcome following radiotherapy in patients with a rising prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer. PATIENTS AND METHODS: One hundred fifteen patients with a rising PSA after radical prostatectomy received salvage three-dimensional conformal radiotherapy (3D-CRT) alone or with neoadjuvant androgen deprivation. Tumor-related and treatment-related factors were evaluated to identify predictors of subsequent PSA failure. RESULTS: The median follow-up time after 3D-CRT was 42 months. The 4-year actuarial PSA relapse-free survival, distant metastasis-free survival, and overall survival rates were 46%, 83%, and 95%, respectively. Multivariate analysis, which was limited to 70 patients receiving radiation without androgen deprivation therapy, showed that negative/close margins (P =.03), absence of extracapsular extension (P <.01), and presence of seminal vesicle invasion (P <.01) were independent predictors of PSA relapse after radiotherapy. Neoadjuvant androgen deprivation did not improve the 4-year PSA relapse-free survival in patients with positive margins, extracapsular extension, and no seminal vesicle invasion (P =.24). However, neoadjuvant androgen deprivation did improve PSA relapse-free survival when one or more of these variables were absent (P =.03). CONCLUSIONS: Salvage 3D-CRT can provide biochemical control in selected patients with a rising PSA after radical prostatectomy. Among patients with positive margins and no poor prognostic features, 77% achieved PSA control after salvage 3D-CRT. Salvage neoadjuvant androgen deprivation therapy may improve short-term biochemical control, but it requires further study.
Assuntos
Recidiva Local de Neoplasia , Antígeno Prostático Específico/análise , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia Conformacional , Adulto , Idoso , Antagonistas de Androgênios/uso terapêutico , Intervalo Livre de Doença , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias da Próstata/patologia , Terapia de SalvaçãoRESUMO
PURPOSE: Little is known about the cost of phase I trials in cancer patients compared with that of standard treatments, yet the former is often assumed to be greater than the latter. Our objective was to utilize a new approach, using patients as their own controls, to compare in a pilot study the costs of care for patients on phase I trials with those incurred for standard treatment. PATIENTS AND METHODS: We retrospectively assessed the direct medical costs (DMCs) of 59 patients participating in one of two phase I trials (TRIAL) in solid tumors conducted at Memorial Hospital (MH): (1). perillyl alcohol, and (2). flavopiridol with paclitaxel. Paired-control DMCs were those accrued by the same patient while receiving standard chemotherapy regimens just before (PRE; n = 41) or after (POST; n = 29) the trial at MH, averaged per day. RESULTS: For the 41 PRE patients, the median and mean DMCs per day for the clinical trial versus standard treatment were (US dollars) US dollars 123 v US dollars 133 and US dollars 219 v US dollars 267, respectively. For the 29 POST patients, the median and mean DMCs for the clinical trial versus standard treatment were US dollars 157 v US dollars 152 and US dollars 226 v US dollars 226, respectively. Using a linear mixed model, there was no significant difference between TRIAL and standard treatment DMCs (P =.54). CONCLUSION: Using patients as their own controls represents a new, efficient method for evaluating the cost of phase I trials, and it warrants further study. The results of our pilot study do not suggest that phase I trials always cost payers more than standard treatment.
Assuntos
Institutos de Câncer/economia , Ensaios Clínicos Fase I como Assunto/economia , Custos de Cuidados de Saúde , Custos Hospitalares , Neoplasias/economia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Neoplasias/terapia , Seleção de Pacientes , Projetos Piloto , Estudos Retrospectivos , Estados UnidosRESUMO
PURPOSE: To identify the role of p53 pathway alteration(s) as predictors of treatment outcome in patients with advanced, resectable, squamous cell carcinoma (SCC) of the larynx and pharynx treated with larynx preservation (LP) intent. PATIENTS AND METHODS: Seventy-one patients treated on two consecutive LP protocols were studied based on availability of representative tissues. We analyzed the expression pattern of p53, its upstream regulator mdm2, and downstream transcriptional target p21/WAF1 by immunohistochemistry. Positive phenotype was defined as >or= 20% of tumor cells showing nuclear immunoreactivity. Results were correlated with treatment outcomes. RESULTS: Positive phenotype was observed in 35 (49%) of 71 cases for p53, in 52 (74%) of 70 for mdm2, and in 37 (54%) of 68 for p21. There was no correlation between p53 phenotype and p21 nuclear accumulation. The mdm2-negative phenotype was most predictive of major response at the primary tumor site (P =.088). p53-positive phenotype was associated with worse local control with LP (LCLP; 49% v 23%, P =.053) and inferior overall survival (OS; 51% v 29%, P =.017) at 5 years. On Cox regression analysis, p53-positive phenotype predicted inferior OS (P =.033) and showed a trend for worse LCLP (P =.102). When analyzed in a multivariate model as continuous variables, p53 showed a stronger correlation with inferior OS (P <.01), and mdm2 was associated with worse OS (P <.01). CONCLUSION: Among the three markers studied, our data support p53 phenotype as the most informative predictor of unfavorable outcomes in the LP setting, and suggest a role for mdm2 phenotype that requires further exploration. Our analysis does not support a p53-dependent mechanism for p21 expression. Prospective and larger studies are necessary before integration of these molecular markers as part of molecular staging and predictors for organ preservation or other outcomes.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/cirurgia , Laringectomia/métodos , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Faríngeas/metabolismo , Neoplasias Faríngeas/cirurgia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Transcrição Gênica , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non-small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P <.001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: The majority of patients with epithelial ovarian cancer (EOC) who achieve a complete remission with front-line chemotherapy develop recurrent disease. Carboplatin and paclitaxel are used for patients with platinum-sensitive recurrent disease, although there is little information regarding the response and survival in unselected patients treated with this strategy. We sought to determine the outcomes for patients with EOC treated with carboplatin and paclitaxel at the time of first recurrence. In addition, we sought to define a new paradigm for disease transition in patients with EOC. PATIENTS AND METHODS: Eighty-nine patients were identified who had a complete response to front-line platinum-based chemotherapy for EOC, relapsed 6 months after completion of front-line chemotherapy, and were treated with carboplatin and paclitaxel as second-line therapy. RESULTS: Eighty-four cases were available for analysis of survival end points, and 66 were assessable for response. The median follow-up was 27 months. The overall response rate was 70%. The median progression-free interval for the cohort was 13 months (95% confidence interval [CI], 10.7 to 13.8 months). The 3-year survival rate was 72% (95% CI, 59.4 to 86.1%). Toxicity was limited, and no deaths from treatment were observed. Using this data, it is possible to construct a disease states model of EOC, which provides risk estimates for transitions between clinically distinct categories. CONCLUSION: Re-treatment with carboplatin and paclitaxel is effective as initial therapy in recurrent EOC. This should form the basis of a randomized trial to determine the best agents for initial treatment of relapse from EOC in potentially platinum-sensitive patients.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Neoplasias Ovarianas/mortalidade , Platina/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To determine long-term survival and predictors of recurrence in a retrospective cohort of patients with epithelial ovarian cancer treated with intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS: Records were reviewed of 433 patients who received IP therapy for ovarian cancer between 1984 and 1998; follow-up data were available for 411 patients. IP therapy was provided as consolidation therapy (n = 89), or for treatment of persistent (n = 310) or recurrent (n = 12) disease after surgery and initial systemic therapy; therapy usually consisted of platinum-based combination therapy. Statistical analysis included tests for associations between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox proportional hazard model. RESULTS: The mean age of patients was 52 years (range, 25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The median survival from initiation of IP therapy by residual disease was none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1 cm, 1.2 years. In a multivariate analysis, the only significant predictors of long-term survival were grade and size of residual disease at initiation of IP therapy. CONCLUSION: Prolonged survival was observed in selected patients receiving IP platinum-based therapy. It is not possible to determine the contribution of IP therapy to survival in this study. A relationship between size of disease at the initiation of IP therapy and long-term survival was demonstrated.
Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Platina/administração & dosagem , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib. PATIENTS AND METHODS: We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib. RESULTS: Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P=.004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P<.001), never smoker status versus former/current (36% v 8%; P<.001), and Karnofsky performance status > or =80% versus < or =70% (22% v 8%; P=.03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P=.004) and being a never smoker (P=.006) were independent predictors of response. CONCLUSION: Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Broncogênico/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/farmacologia , Fumar , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido da Lavagem Broncoalveolar/citologia , Carcinoma Broncogênico/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Fator de Crescimento Epidérmico/antagonistas & inibidores , Feminino , Gefitinibe , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Tirosina Quinases/antagonistas & inibidores , Estudos RetrospectivosRESUMO
PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.
Assuntos
Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Neoplasias do Endométrio/radioterapia , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Intervalos de Confiança , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Radioterapia Adjuvante , RiscoRESUMO
PURPOSE: To examine the relationship between tumor regression grade (TRG) and outcomes in patients with rectal cancer treated with preoperative therapy. METHODS AND MATERIALS: Specimens from 144 patients with cT3,4 rectal cancer who had received preoperative radiation +/- chemotherapy and had a minimum follow-up of 3 years were retrospectively reviewed. TRG, which involves examining the residual neoplastic cells and scoring the degree of both cytological changes, including nuclear pyknosis or necrosis and/or eosinophilia, as well as stromal changes, including fibrosis (either dense or edematous) with or without inflammatory infiltrate and giant-cell granulomatosis around ghost cells and keratin, was quantified in five grades according to the Mandard score (Cancer 1994;73:2680-2686). The greater the response, the lower the TRG score. The median follow-up was 72 months (range, 40-143 months). RESULTS: Of the 144 patients, 19% were TRG1, 12% were TRG2, 21% were TRG3, 46% were TRG4, and 1% were TRG5. To simplify the analysis, TRG was combined into two groups: TRG1-2 and TRG3-5. By univariate analysis, none of the pretreatment factors examined, including age, circumference, length, distance from the anorectal ring, pretreatment T and N stage, and INDpre (defined as the pretreatment reference index size based on digital rectal examination), had an impact on 5-year outcomes, including local control, metastases-free survival, disease-free survival, and overall survival. Postoperative parameters, including pathologic T stage (pT), pathologic N stage (pN), and TRG, did significantly influence 5-year outcomes. These included local failure: pT0-2: 5% vs. pT3-4: 19%, p = 0.007; pN0: 7% vs. pN1-3: 26%, p = 0.002; TRG1-2: 2% vs. TRG3-5: 17%, p = 0.013; metastasis-free survival: pT0-2: 86% vs. pT3-4: 62%, p = 0.005; pN-: 86% vs. pN*: 42%, p < 0.001; TRG1-2: 91% vs. TRG3-5: 66%, p = 0.004; disease-free survival: pT0-2: 83% vs. pT3-4: 54%, p = 0.001; pN0: 80% vs. pN1-3: 39%, p < 0.001; TRG1-2: 91% vs. TRG3-5: 58%, p < 0.001; and overall survival: pT0-2: 85% vs. pT3-4: 65%, p = 0.007; pN0: 86% vs. pN1-3: 45%, p < 0.001; TRG1-2: 89% vs. TRG3-5: 68%, p = 0.004. By multivariate analysis combining all pre- and posttreatment parameters, only pN (p < 0.001) and TRG (p = 0.005) significantly predicted disease-free survival. Furthermore, TRG predicted the incidence of pathologic nodal involvement (p < 0.0001). CONCLUSIONS: By univariate analysis, TRG is a predictor for local failure, metastases-free survival, and overall survival. By multivariate analysis, it predicts improved disease-free survival. Given the ability of TRG to predict those patients with N* disease, it may be helpful, in combination with other clinicopathologic factors, in selecting patients for a more conservative procedure, such as local excision rather than radical surgery, after preoperative therapy.
Assuntos
Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Indução de Remissão , Estudos RetrospectivosRESUMO
OBJECTIVE: The value of sonographic evaluation of the endometrial thickness as a screening or a prognostic tool for endometrial cancer remains controversial. The objective of this study was to prospectively evaluate the endometrial thickness in women with known endometrial cancer to assess the predictive value of this modality and its preoperative use in this disease. DESIGN: In a prospective, nonrandomized trial, 29 patients with pathologically confirmed endometrial cancer had preoperative transvaginal ultrasound and endometrial thickness evaluated. Body mass index (BMI) and endometrial thickness were recorded and correlated with surgical and pathologic information. RESULTS: The median age at diagnosis of endometrial cancer was 61.6 years (range, 48-87 years). Tumor grade was as follows: grade 1, 23; grade 2, 3; and grade 3, 3. All patients had an endometrial stripe of 5.0 mm or more. The median preoperative sonographic endometrial stripe was 12.0 mm (range, 5.0-32.0 mm). After surgery, 25 patients (86%) were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I disease (IA, 8; IB, 14; IC, 3), 2 (7%) with stage II disease, and 2 (7%) with stage III disease. Median BMI was 33 (range, 20-56). The patients' BMIs were found to be directly associated with endometrial thickness (rank correlation = 0.39; P = 0.03). Stage was only marginally associated with endometrial thickness (correlation 0.23; P = 0.07). Sonographic endometrial thickness was not associated with depth of myometrial invasion. No correlation was found between endometrial thickness and patient age or tumor grade. CONCLUSIONS: Although patients with endometrial cancer and a high BMI are likely to have a thickened endometrial stripe, endometrial thickness does not correlate with tumor grade or stage. The use of preoperative transvaginal ultrasound in diagnosed endometrial cancer appears limited.
Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Endométrio/diagnóstico por imagem , Cuidados Pré-Operatórios , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Pós-Menopausa , Estudos Prospectivos , UltrassonografiaRESUMO
PURPOSE: The aims of this study were to determine the dose and schedule of i.p. cisplatin with i.p. gemcitabine in patients with persistent disease at second-look assessment, the toxicity of this regimen, and the time to treatment failure and overall survival. EXPERIMENTAL DESIGN: We performed a Phase I/II evaluation of i.p. cisplatin at 75 mg/m(2) on day 1 with planned gemcitabine at 500, 750, 1000, or 1250 mg/m(2) i.p. on days 1, 8, and 15 on a 28-day schedule for four courses. Eligible patients completed surgical cytoreduction followed by adjuvant platinum-based chemotherapy. They had second-look assessment showing microscopic or macroscopic (< or =1 cm) disease, followed by i.p. port placement. RESULTS: The Phase I dose-limiting toxicity was grade 3 thrombocytopenia at day 15 on dose level 1 (n = 5). The protocol was amended, and the Phase II portion accrued to 30 patients, who were given i.p. cisplatin (75 mg/m(2)) on day 1 and gemcitabine at 500 mg/m(2) on days 1 and 8 on a 21-day schedule for four courses. Nine patients were removed from the study: one each for hypersensitivity, cellulitis, and i.p. port malfunction; two for progression of disease; and four for renal toxicity. Other toxicities included grade 3 nausea (7%) and transient grade 3 neuropathy (3%). Grade 1 or 2 neuropathy was frequently seen (80%). Five patients (17%) returned to the operating room at a median of 6 months (range, 1-20 months) after i.p. therapy for evaluation of abdominal pain; two patients had recurrence, and all had areas of fibrous tissue with encasement of the bowel. In two patients, the fibrous tissue was causing partial bowel obstruction. No other patients had symptoms prompting surgical exploration. Pharmacokinetic (PK) studies showed a median area under the curve (AUC) i.p. of 3041 h. micro M (range, 676-5702 h. micro M) and AUC in plasma of 4.0 h. micro M (range, 0.92-8.2 h. micro M) reached between 120 and 240 min; the pharmacological advantage was 759-fold (range, 217-1415-fold) for i.p. versus plasma drug levels. The mean residence time of gemcitabine with i.p. administration was 4.7 h. The median time to progression of the intent to treat population was 15.93 months (95% confidence interval, 9.13-25.9 months), with a median overall survival of 43.5 months [95% confidence interval, (34.66- infinity)]. No statistical differences were seen with respect to overall survival if patients were grouped in terms of optimal debulking or not (median not reached versus 34.8 months, respectively; P = 0.16) or whether visible disease was present or not at the start of i.p. therapy (34.8 versus 47.7 months; P = 0.47). With regard to time to treatment failure, a statistical difference favored patients with optimal versus nonoptimal primary debulking (25.2 versus 10.2 months, respectively; P = 0.03). CONCLUSIONS: The median time to treatment failure and overall survival of 15.9 months and 43.5 months, respectively, are consistent with our historical data in patients receiving i.p. platinum-based regimens for consolidation. The fibrotic changes seen in explored patients suggest local toxicity of this combination. The absolute benefit of i.p. consolidation requires randomized trials to assess efficacy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Sob a Curva , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/farmacocinética , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamente , GencitabinaRESUMO
PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had stage IIIB or IV NSCLC and either no previous chemotherapy or progression after initial response or stable disease to one previous chemotherapy regimen. Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However, to decrease the frequency of stomatitis, the last 10 patients were treated at a dose of 135 mg/m(2). We planned to correlate PDX effects with folate and homocysteine levels and the expression of genes associated with folate transport and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom were evaluable for response. Four patients had confirmed, major objective responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4, 9, 12, and 15 months. Twelve patients (31%) had stable disease. The median survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and 36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had grade 3. No clinically significant myelosuppression occurred. No correlation between homocysteine or serum folate levels and severity of stomatitis was observed. Area under the curve (calculated using a limited sampling model) correlated with mucositis grade. A trend was noted between folate transporter expression and treatment effect. CONCLUSIONS: The broad applicability of this new antifolate with limited toxicity and proven efficacy in NSCLC encourage further development of this compound. Several trials are now underway combining PDX with other chemotherapeutic agents and testing its efficacy in other cancers.
Assuntos
Aminopterina/análogos & derivados , Aminopterina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Antagonistas do Ácido Fólico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana Transportadoras , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proteínas de Transporte/genética , Feminino , Homocisteína/sangue , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , RNA Mensageiro/análiseRESUMO
PURPOSE: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh, who receive external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that a large segment of the femur will receive full prescription dose with conventional radiation techniques. We report the dosimetric feasibility of intensity- modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. METHODS AND MATERIALS: Treatment planning was performed using both three-dimensional conformal radiotherapy (3D-CRT) and IMRT techniques for 10 patients with soft tissue sarcoma of the thigh with tumor approaching the femur. None of the patients had bony involvement. For all patients, the gross total volume (GTV) and the femur were contoured. The clinical target volume (CTV) was defined as the GTV with a 1.5-cm margin axially, except at the bone interface where the bone interface was used as CTV if the 1.5-cm axial margin extended beyond the bone interface. In the superior-inferior direction, the CTV margin placed around the GTV varied from 5 to 10 cm. The planning target volume (PTV) was defined as the CTV with 5-mm margin all around. The 3D conformal technique consisted primarily of two to three beams with wedges or partial transmission blocks as compensators. For the IMRT technique, five coplanar beams were used, chosen so as to spare much of the surrounding soft tissue and to clear the other extremity or groin areas. IMRT plans were designed to adequately treat the planning target volume and spare the femur as much as possible. RESULTS: Dose distributions and dose-volume histograms were analyzed. PTV coverage was comparable with both IMRT and 3D-CRT plans. Dose distributions were more conformal with IMRT, however, especially for patients with large variations of contours. The volume of the femur receiving at least full prescription (63 Gy) V100 decreased on average by approximately 57%, from 44.7 +/- 16.8% with 3D-CRT to 18.6 +/- 9.2% with IMRT (p < 0.01). For 3 patients with a GTV surrounding <50% of the circumference of the femur, the reduction in the V100 to the femur ranged from 61% to 79%. The hot spots in the femur, as measured by D05 (the dose encompassing 5% of volume), reduced on average from 67.2 +/- 1.8 Gy with 3D-CRT to 65.0 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the femur was on average 38.5 +/- 11.5 Gy with IMRT, compared with 40.9 +/- 12.7 Gy with 3D-CRT. The volume of the surrounding soft tissues, defined as the ipsilateral limb excluding the PTV and the femur, receiving at least prescription dose (63 Gy) was reduced on average by about 78%, from 997 +/- 660 cc with 3D-CRT to 201 +/- 144 cc with IMRT (p < 0.01). The D05 to the surrounding soft tissues was on average 58.7 +/- 4.7 Gy with IMRT, compared to 67.8 +/- 1.3 Gy with 3D-CRT (p < 0.01), a reduction of approximately 13%. The mean dose to the surrounding soft tissues was comparable in both plans. The volume of the skin (from surface to 5 mm depth) receiving prescription dose (63 Gy) declined by roughly 45%, from 115 +/- 40 cc with 3D-CRT to 61 +/- 20 cc with IMRT (p < 0.01), with IMRT providing full skin dose coverage to scars. The hot spots in the skin decreased from 68.0 +/- 1.7 Gy with 3D-CRT to 65.2 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the skin lessened from 51.5 +/- 4.7 Gy with 3D- CRT to 44.0 +/- 4.2 Gy with IMRT (p < 0.01), a reduction of 14%. CONCLUSIONS: Intensity-modulated radiation therapy techniques can reduce the dose to the femur without compromising target coverage by achieving concave dose distributions around the interface of the PTV and the femur. At the same time, IMRT can reduce the hot spots significantly in the surrounding soft tissues and skin. Whether such dosimetric improvements can translate into reduction of complications and/or improving local control needs to be investigated.