The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: Evidence suggestive of consequential late effect (CQLE)

Purpose: To correlate the acute toxicity during pelvic irradiation and the development of late rectal injury following radiation therapy for cervical carcinoma. Methods and Materials: Two hundred and twenty patients treated with curative-intent radiation therapy between November 1987 and January 1992 were analyzed. Patients were treated initially with external beam irradiation, 40-44 Gy/20-22 fractions to whole pelvis, followed by high dose rate intracavitary brachytherapy, 7.2 Gy to point. A for 3 fractions. Severity of diarrhea during radiation therapy was scored according to six criteria: fecal characteristics, frequency, onset, prescription of antidiarrheal agents, body weight loss during irradiation, and extramedical care needed. Patients were categorized as group ND (no obvious diarrhea), group MD (moderate diarrhea), and group SD (severe diarrhea) for sum score 0- 1, 2-5, and ≤6, respectively. The rate of radiation proctitis was expressed, analyzed, and compared with actuarial proctitis-free rate and prevalence. Results: 1) According to the score, 76 (35%), 89 (40%), and 55 (25%) patients were categorized as group ND, group MD, and group SD, respectively. Distribution of patients and treatment characteristics among the three groups appeared similar. Patients treated with a larger field size, ≤16.5 cm², tended to have increased severity of diarrhea. 2) Overall, 103 patients (47%, 103 of 220) developed radiation proctitis. Twenty-one patients were in group ND (28%, 21 of 76), 43 in group MD (48%, 43 of 89), and 39 in group SD (71%, 39 of 55). 3) The five-year actuarial proctitis-free rate was 72, 52, and 29% for group ND, MD, and SD, respectively (p < 0.005). 4) Taking time evolution and recoverability into account, the effect of diarrhea on the prevalence of radiation proctitis remained statistically significant at the first through the fourth year after irradiation. 5) Severity of radiation proctitis and severity of diarrhea were not correlated (Spearman's rank correlation coefficient r(s) = 0.229, p = 0.098). 6) Cox's multivariate analysis revealed that severity of diarrhea was the only factor that significantly correlated with the development of radiation proctitis. Conclusion: Patients with increased acute toxicity and diarrhea during radiation therapy of cervical carcinoma significantly increased the risk of late rectal injury. This result suggested that early excessive damage of acute-responding component of rectal wall may play an important role in the initiation of late rectal injury. Radiation proctitis can be accounted, in part, as a consequential late effect.