16 Cervix Carcinoma

354 Cervix Cancer

Table 14.5: Results of trials comparing low dose-rate and high dose-rate in cervix cancer brachytherapy Authors Stage

Patients (n) HDR LDR 102 120 35 39 90 93 111 114 42 28 59 121 11 88 143 106 32 28 80 61 147 82

5-yr survival (%) HDR LDR

Local control (%) HDR LDR

Gupta (48) Patel (83)

I-III

80 85 91 92 76 78 71 76 Not available

I II III I II III

78 73 64 62 43 50 83 89 75 76 37 52 60 56

Rotte (102)

Shigematsu (106) Teshima (111)

IIB-III

92 72

I II III

66-89 61-78 47-45

87-100 87-87 82-54

11.1.3 Concomitant radio-chemotherapy. In patients considered at high risk of recurrence including pelvic failures and distant metastases i.e. patients with a tumour size greater than 4 cm or with unfavourable prognostic factors after initial surgery, nine randomized controlled trials have been published in the last years assessing the role of concomitant chemoradiotherapy (46). Six of them showed a statistically significant benefit with radiochemotherapy. A systematic review of these trials and meta-analysis demonstrated a potential absolute survival benefit of 12% with concomitant radiochemotherapy, with a highly significant reduction of distant metastases as well as local recurrences for both platinum and non-platinum groups (46). In the trials however, it must be pointed out that 68% of enrolled patients had Stage I and II disease and that patients with para-aortic node involvement were excluded. It is therefore difficult to extrapolate these results to patients with locally advanced disease, Stage III and IV (46, 112). There has been some controverse as well, because the reported results in the randomized arms with radiation alone, without chemotherapy, were rather poor, as compared to the largest series published in the literature. Potential explanations were a low total dose of irradiation and an overall treatment time exceeding 52 days in most trials. It has even been stated that the potential loss of local control due to an increased overall treatment time was equal to the benefit of concomitant radiochemotherapy (45,85). In the trials, the use of concomitant chemotherapy during brachytherapy was not systematically included so that the value of this combined treatment cannot be clearly stated. Acute toxicity was not systematically reported in detail in all trials. From the meta-analysis, however, it was concluded that acute toxicity was significantly increased in all trials (haematological and gastrointestinal toxicity). Late toxicity was recorded only in few trials (three of them) without there being any long-term follow-up. Long-term toxicity was defined as beginning 42 to 90 days after completion of radiation. No evidence of differences between the treatment groups was observed (46) but longer follow-up is obviously necessary.