After radiotherapy for cervical carcinoma

Cervical carcinoma can be treated with the association brachytherapy and surgery. With this technique, the incidence of rectal complication is low, about 1 %104-106. Perez107,108 has compared preoperative radiation followed by surgery with radiation alone in a randomized and in a retrospective trial: major rectal complications were more frequent with radiation alone, but not significantly: 5.7 % versus 0 %, and 3.4 to 6 % according to the tumour stage versus 1 to 4.5%.

Using radiation alone (external beam irradiation and brachytherapy) the incidence of severe rectal complications is variable. Perez109 in 1456 patients found respectively 4.1 %, 3%, and 3 % of major rectal, bladder and small intestinal complications. The most frequent grade 2 sequelae were proctitis (3%) and cystitis (0.7%) (Table 2.2.8-1).

Several studies have shown the superiority of concomitant chemo-radiotherapy versus radiotherapy alone, or concomitant chemo-radiotherapy more surgery versus radiotherapy more surgery for locally advanced or high-risk disease112-117. Whitney116 found the same incidence of late intestinal or urinary major complications at 3 years (about 16%) but chemotherapy was given in the 2 arms.

Morris113 who compared radiotherapy alone and radiotherapy more 5 Fluoro-uracil and cisplatin found no significant difference in "late" effects (occurring or persisting more than 60 days after the completion of the treatment): about 7.5% and 1% of severe rectosigmoideal and bladder complications. Tseng118 found no difference in late intestinal or urinary complications too. However these studies are recent, with a short follow-up; Grigsby119 reported higher complication rates in a series of patients treated with concomitant chemoradiotherapy (5 fluorouracil and cisplatin).

Table 2.2.8-1. Major complications at 5 years, using radiation alone

Number of patients

Colon

Small intestine

Bladder

Komaki110 1995

1686

8.7%*

5 %*

Pernot106 1 995

(bowel)

361

2.2%

2 %

(gastro-intestinal

Eifel111 1995

tract)

1784

2.3%*

3.9 %*

2.6%*

Perez109 1 999

(Stage IB)

(rectum)

1456

4.1%

3%

3%

(Stage IB to

IVA)

* Actuarial rates

Prior abdominal surgery, stage and diabetes are risk factors for rectal complications97'111'120. It's now established that old age is not one97,99,111,121. Pignon121 in a meta analysis including 1619 patients (nine EORTC trials of radical radiotherapy for pelvic cancers) found no difference in late intestinal or urinary complications according to the age (about 9%). Conversely the cumulative risk is greater for patients treated at a young age97,111 (before 40 years for Lanciano97).

The risk of proctitis increased as a function of rectal dose122-124. For Montana122, the rate is 2% for patients receiving less than 50 Gy to the rectum, and 18% for those receiving more than 80 Gy, with a significant relationship between rectal dose and severity of proctitis. For Pourquier123, when mean and maximal rectal doses do not exceed 60-70 Gy, the percentage of complications remain between 5 to 10%, and are less severe; there is a rapid rise in the number of complications above 75-80 Gy. The paracentral radiation dose is also correlated to the risk of complications and may reflect the dose to bowel and bladder; Lanciano97 in 1558 patients reported a significant higher risk if paracentral dose is superior to 75 Gy. Perez109 reported 4% of rectosigmoideal complications with dose lower than 75 Gy and 9% with higher doses. Logsdon125 found a risk of major complication greater for patients with FIGO III B cervical carcinoma treated with dose superior to 52 Gy of external beam irradiation to the central pelvis, followed by brachytherapy. For Roeske120, the point A and external beam irradiation doses were the most significant treatment related factors.

Major rectal complications are more frequent when the total rectal dose and the HWT (Height, Width, Thickness) volume (volume enclosed by the 60 Gy isodose for combined irradiation) are higher96,126-128.

Several authors have studied the role of dose rate. Haie-meder129 in a prospective randomised trial comparing 0.4 Gy/h and 0.8 Gy/h reported more complications with the higher dose rate. In a randomized trial of preoperative brachytherapy, the patients treated with the higher dose rate (0.73 Gy/h versus 0.38 Gy/h) showed a two fold increase in surgical difficulties130. Perez109 found an increased rectal morbidity with dose rate higher than 0.8 Gy/h too.

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