RESUMO
BACKGROUND: Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. OBJECTIVES: The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010. SELECTION CRITERIA: We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998. DATA COLLECTION AND ANALYSIS: We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality. MAIN RESULTS: We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). AUTHORS' CONCLUSIONS: Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Fatores Etários , Carcinoma de Células Escamosas/mortalidade , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: This study was performed retrospectively to determine if Medicare claims data could be used to evaluate the cost effectiveness, from a payer perspective, of different radiation treatment schedules evaluated in a national clinical trial. METHODS: Medicare costs from all providers and all places of service were obtained from the Centers for Medicare & Medicaid Services for patients treated in the period 1992-1996 on Radiation Therapy Oncology Group 90-03, and combined with data on outcomes from the trial. RESULTS: Of the 1,113 patients entered, Medicare cost data and clinical outcomes were available for 187 patients. Significant differences in tolerance of treatment and outcome were noted between patients with Medicare data included in the study and patients without Medicare data, and non-Medicare patients excluded from it. Ninety-five percent confidence ellipses on the incremental cost-effectiveness scatterplots crossed both axes, indicating non-significant differences in cost effectiveness between radiation treatment schedules. CONCLUSIONS: Claims data permit estimation of cost effectiveness, but Medicare data provide inadequate representation of results applicable to patients from the general population.
Assuntos
Ensaios Clínicos Fase III como Assunto/economia , Revisão da Utilização de Seguros , Análise Custo-Benefício , Custos e Análise de Custo/métodos , Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Revisão da Utilização de Seguros/organização & administração , Medicare/economia , Neoplasias de Células Escamosas/radioterapia , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival. METHODS: Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction. FINDINGS: 15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 years; p<0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007). INTERPRETATION: Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control. METHODS: Between September 9, 1995, and April 28, 2000, 459 patients were enrolled. After undergoing total resection of all visible and palpable disease, 231 patients were randomly assigned to receive radiotherapy alone (60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks) and 228 patients to receive the identical treatment plus concurrent cisplatin (100 mg per square meter of body-surface area intravenously on days 1, 22, and 43). RESULTS: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. CONCLUSIONS: Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Cisplatino/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Risco , Análise de SobrevidaRESUMO
PURPOSE: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. METHODS AND MATERIALS: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%), and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). RESULTS: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. CONCLUSION: Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.
Assuntos
Carcinoma/secundário , Carcinoma/cirurgia , Recidiva Local de Neoplasia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Análise de SobrevidaRESUMO
PURPOSE: To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66-72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy. Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL (12.5 g/dL for women). Patients randomized to Epo received 40,000 U once weekly, starting 7-10 days before start of radiotherapy. RESULTS: A total of 148 patients were enrolled; 141 were evaluable. Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm, compared with an average 0.24 g/dL decrease in the control arm (p = 0.0001). Median follow-up was 2.5 years (3.1 years for surviving patients). There was no statistically significant difference in the primary endpoint of local-regional failure (LRF) rate between the treatment arms. The 3-year LRF rate was 36% for control and 44% for Epo (p = 0.56). There were also no significant differences in local-regional progression-free survival (LRPFS), patterns of failure, overall survival, or toxicity. The 3-year LRPFS rate was 52% for control and 47% for Epo. The overall survival rate was 57% and 56%, respectively. CONCLUSIONS: The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes. The study was not specifically designed to detect a potential negative association between Epo and tumor progression/survival.
Assuntos
Anemia/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Eritropoetina/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Hematínicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Terapia Combinada/métodos , Intervalo Livre de Doença , Esquema de Medicação , Eritropoetina/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Hematínicos/administração & dosagem , Hemoglobina A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Resultado do TratamentoRESUMO
PURPOSE: To compare clinical outcomes of patients with carcinomas of the paranasal sinuses and nasal cavity according to decade of radiation treatment. METHODS AND MATERIALS: Between 1960 and 2005, 127 patients with sinonasal carcinoma underwent radiotherapy with planning and delivery techniques available at the time of treatment. Fifty-nine patients were treated by conventional radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23 patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were treated with radiotherapy after gross total tumor resection. Nineteen patients (15%) received chemotherapy. The most common histology was squamous cell carcinoma (83 patients). RESULTS: The 5-year estimates of overall survival, local control, and disease-free survival for the entire patient population were 52%, 62%, and 54%, respectively. There were no significant differences in any of these endpoints with respect to decade of treatment or radiotherapy technique (p > 0.05, for all). The 5-year overall survival rate for patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%, respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). CONCLUSION: Although we did not detect improvements in disease control or overall survival for patients treated over time, the incidence of complications has significantly declined, thereby resulting in an improved therapeutic ratio for patients with carcinomas of the paranasal sinuses and nasal cavity.
Assuntos
Cavidade Nasal , Neoplasias Nasais/radioterapia , Neoplasias dos Seios Paranasais/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Nasais/mortalidade , Neoplasias Nasais/cirurgia , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/cirurgia , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Radioterapia/tendências , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. METHODS AND MATERIALS: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7-267 months). RESULTS: The 5- and 10-year rate estimates of local control were 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy (p = 0.0004), T4 disease (p = 0.005), and major nerve involvement (p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. CONCLUSION: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.
Assuntos
Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/cirurgia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Recidiva Local de Neoplasia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/secundário , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.
Assuntos
Receptores ErbB/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. METHODS AND MATERIALS: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD <60 vs. > or =60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. RESULTS: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. CONCLUSIONS: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD <60 vs. MVD > or =60. The study was perhaps limited by the small size of the NPC samples.
Assuntos
Neoplasias Nasofaríngeas/irrigação sanguínea , Neoplasias Nasofaríngeas/radioterapia , Neovascularização Patológica/patologia , Adolescente , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Prognóstico , Radiossensibilizantes/uso terapêutico , Taxa de SobrevidaRESUMO
PURPOSE: In a previous retrospective study, p105 AD, a proliferation-associated nuclear antigen density (AD), was found to be an independent prognostic factor for patients irradiated for locally advanced head-and-neck cancer. We sought to confirm this finding by analyzing patients entered on RTOG 9003, a Phase III randomized trial of altered fractionation radiotherapy. METHODS AND MATERIALS: Paraffin blocks of pretreatment biopsies of the primary tumor of patients with Stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, or supraglottic larynx, or Stage II squamous cell carcinoma of the hypopharynx or base of tongue entered on RTOG 9003 were prospectively collected at patient entry. From these paraffin blocks, areas of tumor were selected based on histologic examinations and sectioned. Nuclear suspensions were then prepared and processed for p105 antibody and DNA staining. Flow cytometric quantification of p105 labeling indices and DNA content were then performed for correlation with local-regional control and survival. RESULTS: Paraffin blocks of tumor biopsies from 457 of 1073 patients entered were available for p105 determination. There was no significant difference in pretreatment characteristics between patients who had paraffin blocks available or not available. The median (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (p105 LI-S), and p105 AD were 56 (range: 6-99), 8.255 (range: 0.913-23), and 67 (range: 5-364), respectively. Multivariate analysis of prognostic factors showed that T stage, N stage, Karnofsky performance status, and fractionation schedule were significant for local-regional control (p < 0.0001, 0.0011, <0.0001, and 0.007, respectively) and T stage, N stage, Karnofsky performance status, and tumor grade were significant for survival (p = 0.018, 0.002, <0.0001, and 0.0058, respectively). Neither p105 LI-C nor p105 LI-S nor p105 AD nor DNA ploidy was significant for local-regional control or survival. CONCLUSION: p105 labeling indices, antigen density, and DNA ploidy do not predict the outcome of patients irradiated for advanced squamous cell carcinomas of the head and neck.
Assuntos
Antígenos de Neoplasias/análise , Antígenos Nucleares/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/radioterapia , Proteínas Cromossômicas não Histona/análise , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/química , Neoplasias Hipofaríngeas/diagnóstico por imagem , Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/química , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Neoplasias Bucais/química , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Orofaríngeas/química , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/patologia , Neoplasias Faríngeas/química , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/radioterapia , Prognóstico , RadiografiaRESUMO
PURPOSE: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. CONCLUSION: Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.
Assuntos
Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
PURPOSE: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. METHODS AND MATERIALS: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. RESULTS: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239 patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. CONCLUSIONS: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Prega Vocal , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões por Radiação/patologiaRESUMO
PURPOSE: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. METHODS AND MATERIALS: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. RESULTS: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). CONCLUSIONS: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Causas de Morte , Intervalos de Confiança , Nutrição Enteral/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/radioterapia , Lesões por Radiação/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Tempo , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapia , Falha de TratamentoAssuntos
Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/etiologia , Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Humanos , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: To evaluate quality-adjusted survival (QAS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with 4 different radiation fractionation schedules. METHODS: QAS was calculated using the quality-adjusted time without toxicity or relapse (Q-TWiST) methodology. Utilities (patient preferences for certain health states) were obtained by threshold analysis. Q-TWiST therefore equaled TWiST + ([weight for toxicity] x [time spent in toxicity]) + ([weight for relapse] x [time spent in relapse]). RESULTS: A statistically significant increase in QAS existed for patients treated with hyperfractionated radiotherapy compared with standard fractionated radiotherapy (SFX) with a toxicity utility > or = 0.57 and relapse utility < or = 0.72. No statistically significant difference was observed for patients treated with the other 2 fractionation schedules compared with SFX. CONCLUSION: Q-TWiST analysis identified patient groups that would benefit from more aggressive therapy. Further investigation with patient-generated utilities is needed.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Qualidade de Vida , Carcinoma de Células Escamosas/patologia , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To assess whether microvessel density (MVD), an immunohistochemical marker for tumor vascularity, predicts for radiotherapy (RT) outcome in locally advanced HNSCC patients. METHODS: A total of 459 patients, enrolled on the RTOG 90-03 trial, had biopsy specimens submitted, and a value for MVD determined, prior to definitive RT. 450 patients were analyzable for this study. Tumor microvessels were stained for factor VIII-related antigen using a standard immunoperoxidase method. The mean number of stained microvessel profiles, from three x200 fields containing the highest MVD (hot spot), was recorded as the MVD. A prospective value of >or=60 was chosen as the threshold for high MVD, tumor vascularity. RESULTS: The median follow-up for the analyzable patients with MVD assessment was 22.0 months and 79.1 months for all living patients. There were no differences concerning the pretreatment characteristics between those RTOG 90-03 patients with a value for MVD and those without a value for MVD. Thus, the present study cohort possessed comparable characteristics with the entire RTOG 90-03 population. MVD values ranged from 5 to 80, with a median value of 30. Only 37 of 450 (8.2%) patients possessed an MVD >or=60. There were no outcome differences for patients with MVD <60 versus >or=60 on multivariate analysis for time to local-regional failure (P = 0.89), time to distant metastasis (P = 0.80), disease-free survival (P = 0.46), and overall survival (P = 0.39). CONCLUSIONS: In this large, correlative study, a MVD >or=60, ie, high tumor vascularity, did not predict for outcome in locally advanced head and neck squamous cell carcinoma patients treated with radiotherapy.
Assuntos
Carcinoma de Células Escamosas/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neovascularização Patológica/metabolismo , Fator de von Willebrand/metabolismo , Carcinoma de Células Escamosas/radioterapia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Técnicas Imunoenzimáticas , Masculino , Microcirculação , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
PURPOSE: To review a single-institution experience with the management of salivary gland cancers treated by radiation alone. METHODS AND MATERIALS: Between 1960 and 2004, 45 patients with newly diagnosed salivary gland carcinomas were treated with definitive radiation to a median dose of 66 Gy (range, 57-74 Gy). Distribution of T-stage was: 24% T1, 18% T2, 31% T3, and 27% T4. Histology was: 14 mucoepidermoid (31%), 10 adenocarcinoma (22%), 8 adenoid cystic (18%), 4 undifferentiated (9%), 4 acinic (9%), 2 malignant mixed (4%), 2 squamous (4%), and 1 salivary duct carcinoma (2%). No patient had clinical or pathologic evidence of lymph node disease. Median follow-up was 101 months (range, 3-285 months). RESULTS: The 5-year and 10-year rate estimates of local control were 70% and 57%, respectively. A Cox proportional hazard model identified T3-4 disease (p = 0.004) and radiation dose lower than 66 Gy (p = 0.001) as independent predictors of local recurrence. The 10-year overall survival and distant metastasis-free rates were 46% and 67%, respectively. CONCLUSION: Radiation therapy alone is a reasonable alternative to surgery in the definitive management of salivary gland cancers and results in long-term survival in a significant proportion of patients. Radiation dose in excess of 66 Gy is recommended.
Assuntos
Carcinoma/radioterapia , Neoplasias das Glândulas Salivares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The aim was to evaluate the relationship between nutrition support (NS) on host toxicity and cancer outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive radiotherapy (XRT). METHODS: We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 90-03, a prospective randomized trial evaluating four definitive XRT fractionation schedules in patients with locally advanced HNSCC, which prospectively collected data on NS delivered before treatment (BNS), during treatment (TNS), and after definitive XRT. NS data and pretreatment characteristics of the 1073 evaluable patients were analyzed against therapy toxicity and outcome. RESULTS: Patients receiving BNS experienced significantly less weight loss by the end of treatment and less grade 3 to 4 mucositis than patients not receiving BNS. However, patients receiving BNS had a poorer 5-year actuarial locoregional control rate than patients receiving TNS or no NS (29%, 55%, and 57%, respectively, p < .0001) and a poorer 5-year overall survival rate (16%, 36%, and 49%, respectively, p < .0001). Patients receiving BNS were significantly more likely to have a higher T classification, N status, and overall American Joint Committee on Cancer (AJCC) stage and initial presentation with greater pretreatment weight loss, and a poorer Karnofsky Performance Status (KPS) than patients not receiving BNS. After adjusting for the impact of these prognostic factors through a recursive partition analysis, a multivariate analysis with a stratified Cox model found that BNS was still a highly significant independent prognostic factor for increased locoregional failure (hazards ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79; p < .0001) and death (HR, 1.41; 95% CI, 1.19-1.67; p < .0001). CONCLUSION: In this study, the largest prospective evaluation of nutrition data in treated patients with cancer, BNS was associated with inferior treatment outcome in the patients with HNSCC undergoing XRT. These results should be considered hypothesis generating and encourage prospective clinical research and identification of the mechanisms underlying this finding.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Apoio Nutricional/métodos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Fracionamento da Dose de Radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estomatite/prevenção & controle , Redução de PesoRESUMO
BACKGROUND: It has been hypothesized that people in lower socioeconomic groups have worse outcomes because they present with advanced-stage cancers or receive inadequate treatment. The authors investigated this hypothesis by using education level as a proxy for socioeconomic status in patients treated on Radiation Therapy Oncology Group (RTOG) Protocol 90-03. METHODS: RTOG 90-03 was a Phase III randomized trial investigating four different radiation fractionation schedules in the treatment of locally advanced head and neck carcinomas. Overall survival and locoregional control rates were analyzed by education level as measured by patient response on the demographic form at study entry. RESULTS: A significant difference was observed in the distribution of patients by education level between the standard fractionated radiation treatment arm and the hyperfractionated radiation treatment arm. More patients in the standard fractionated treatment arm had a higher education level (P = 0.018). Patients attending college had highly and significantly better overall survival and locoregional control than the other groups combined (P = 0.0056 and P = 0.025, respectively: from Cox proportional hazards models stratified by assigned treatment with educational level, T classification, N classification, Karnofsky performance status, primary site, and race). Multivariate analysis revealed that education level was significant for predicting both overall survival and locoregional control when comparing attended college/technical school compared with all other education levels. CONCLUSIONS: Patients attending college or technical school had improved overall survival and locoregional control. These differences cannot be explained by differences in tumor stage or treatment. Poorer overall health or lack of support systems contributing to these results needs to be investigated further.