A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

BACKGROUND: Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. METHODS: Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. RESULTS: Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). CONCLUSION: RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival

Cirurgia conservadora, radioterapia externa e reforço de dose com braquiterapia de alta taxa de dose: uma nova perspectiva no tratamento de sarcomas de partes moles do adulto Limb-sparing surgery, external beam radiotherapy and boost with high-dose rate brachytherapy: a new perspective for the treatment of soft tissue sarcomas in adults

OBJETIVO: Avaliar a influência no controle local de pacientes adultos e portadores de sarcoma de partes moles em extremidades e submetidos a cirurgia conservadora do membro, com braquiterapia de alta taxa de dose (BATD) como reforço para a radioterapia externa (RT). MATERIAL E MÉTODOS: Foram avaliados 16 pacientes tratados, de 1993 até 1999. A RT foi utilizada com finalidade pré ou pós-operatória (30--55 Gy) e BATD com dose de 18--36 Gy (fx 3--6 Gy BID). Com base no modelo linear quadrático calculou-se a dose efetiva biológica ("biological effective dose" - BED) para o tumor e comparou-se seu valor a dados da literatura internacional, que utiliza tratamentos com RT e braquiterapia de baixa taxa de dose (BBTD). RESULTADOS: Os valores médios e medianos da BED para os sarcomas de partes moles foram de 78,5 Gy7 e 80 Gy7. A análise univariada mostrou que a BED para o tumor, quando utilizada BATD, era semelhante ao valor de 83 Gy7 quando utilizada BBTD (p = 0,008). As taxas de controle local, sobrevida livre de doença e sobrevida global atuarial em cinco anos foram de 83,2%, 75% e 93,7%, respectivamente. CONCLUSÕES: A BATD, quando utilizada como método complementar no reforço de dose da RT no tratamento conservador dos sarcomas de partes moles, apresenta taxas de controle local equiparáveis às da literatura internacional; no entanto, estudos com número maior de pacientes e período maior de seguimento são ainda necessários para determinar o verdadeiro potencial da BATD em substituir a BBTD.<br>PURPOSE: To evaluate the influence on local control in adult patients with soft tissue sarcomas of the limbs that underwent limb-sparing surgery and high-dose rate brachytherapy (HDRB) in association with teletherapy. MATERIAL AND METHODS: Sixteen patients treated from 1993 to 1999 were reviewed. Teletherapy was used pre- or postoperatively (30--55 Gy) in association with HDRB in a dose range of 18--36 Gy (fx 3--6 Gy BID). The linear quadratic model was used to calculate the biological effective dose (BED) and the values obtained were compared with data from the literature, of studies that employed teletherapy and low-dose rate brachytherapy (LDRB). RESULTS: Soft tissue sarcomas BED mean and median values were 78.5 Gy7 and 80 Gy7, respectively. Univariated analysis showed that BED for patients with soft tissue sarcoma of the limbs submitted to HDRB was similar to the value of 83 Gy7 of patients submitted to LDRB (p = 0.008). Actuarial local control, disease free and overall survival rates at 5-years were 83.2%, 75% and 93.7%, respectively. CONCLUSIONS: HDRB appears to be an effective complementary method to teletherapy in the treatment of soft tissue sarcomas. The local control rates are comparable to those reported in the literature. However, studies with longer follow-up and a larger number of patients are still necessary in order to determine the true potential of HDRB as a substitute for LDBR

Braquiterapia de alta taxa de dose associada a radioterapia externa no tratamento de angiossarcoma extenso do couro cabeludo: relato de caso Combination of high-dose rate brachytherapy and external beam radiotherapy for the treatment of advanced scalp angiosarcoma: case report

Os autores apresentam um caso de extenso angiossarcoma do couro cabeludo submetido a radioterapia exclusiva, pela associação de roentgenterapia de ortovoltagem e braquiterapia de alta taxa de dose utilizando um molde. Descrevem os aspectos clínicos, técnicos e a evolução terapêutica. Destacam as particularidades e a utilidade da braquiterapia de alta taxa de dose, nesta situação em particular, e fazem uma análise comparativa das dificuldades e limitações caso a braquiterapia de baixa taxa de dose fosse empregada. Concluem ser a braquiterapia de alta taxa de dose uma opção útil, prática e segura para as lesões neoplásicas superficiais do escalpe, podendo ser considerada uma alternativa ao tratamento com elétrons.<br>The authors report a case of a patient with an extensive angiosarcoma of the scalp that was submitted only to radiotherapy with a combination of orthovoltage roentgentherapy and high-dose rate brachytherapy, using a mould. The clinical and technical features as well as the therapeutic outcome are presented, and the usefulness and peculiarities of high-dose rate brachytherapy for this particular indication is discussed. A comparative analysis of the difficulties and limitations of employing low-dose rate brachytherapy is also presented. The authors concluded that high-dose rate brachytherapy might be an useful, practical and safe option to treat neoplastic lesions of the scalp, and an alternative treatment to electrontherapy