Side Effects and Complications of Pelvic Radiation

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

Corn BW, J Clin Oncol 1994 Mar;12(3):510-5

Conjoint Department of Radiation Oncology, Fox Chase Cancer Center/Medical College of Pennsylvania, Philadelphia 19129.

Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial.

Creutzberg CL,  Int J Radiat Oncol Biol Phys 2001 Dec 1;51(5):1246-55   PORTEC Study Group. The Postoperative Radiation Therapy in Endometrial Carcinoma.

Department of Radiation Oncology, University Hospital Rotterdam-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. c.l.creutzberg@lumc.nl

The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French-Italian glossary. RESULTS: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1-4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3-4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1-2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p = 0.001). The 4-field box technique was associated with a lower risk of late complications (p = 0.06). CONCLUSION: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.

Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation.

Greven KM, Int J Radiat Oncol Biol Phys 1991 Sep;21(4):919-23
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA.

We analyzed the complications in 310 patients with pathologically documented endometrial carcinoma who received adjuvant radiation therapy (RT) at Fox Chase Cancer Center between 1970 and 1986. Variables included timing of treatment, technique, total dose, age, diabetes, previous abdominal surgery, hypertension, prior bowel pathology, and lymphadenectomy. According to the FIGO (1985) system, 258 patients had Stage I disease, 48 had Stage II, and one had Stage III. One hundred seventy patients received preoperative (preop) RT, 138 received postoperative (postop) RT, and 2 received preop and postop RT. A 4-field technique was used for 212 of 235 patients receiving external-beam (EX) RT, and 75 patients were treated with intracavitary (IC) RT only. Median follow-up was 5.5 years. Actuarial survival of all 310 patients was 78% at 5 years. Thirty-two complications occurred, involving the rectum, small bowel, femur, or lower extremity. Complications were graded according to the ECOG scoring system as grade 2 (mild) and grades 3, 4, or 5 (serious). One of 75 patients treated with IC RT only experienced a grade-2 complication (proctitis). Of 71 patients receiving 4-field EX RT only, 25 preop (16%) and 14 postop (14%) patients had complications. Of 139 patients treated with both EX and IC RT, grade-2 complications were seen in 5% of 87 preop patients and 12% of 52 postop patients (p = 0.17), whereas serious complications were observed in 4% of each group. Univariate analysis of the variables of interest revealed that the incidence of complications was associated with a lymphadenectomy (p = .03), use of external RT (p less than .01), and decreasing age (p = .04). Multivariate analysis confirmed that use of external RT was the most significant predictor for complications. In conclusion, similar complication rates were found in patients treated with either preop or postop 4-field EX RT. While pelvic RT clearly decreases pelvic relapse in patient with endometrial carcinoma, the risk benefit ratio for treatment of these patients should be carefully considered when recommending adjuvant RT for pelvic control.

Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer.

Jereczek-Fossa BA, Int J Radiat Oncol Biol Phys 2002 Feb 1;52(2):476-82Jassem J, Badzio A.

Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. barbara.fossa@ieo.it

PURPOSE: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). METHODS: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. RESULTS: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p = 0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p <0.001 and p = 0.47, respectively). The severity of acute bowel and bladder toxicity did not correlate with the time to occurrence of late toxicity in these locations (p = 0.34 and p = 0.47, respectively). CONCLUSION: Patients with increased acute bowel toxicity during postoperative RT for endometrial cancer have an increased risk of late bowel injury. A higher grade of acute bowel complications correlated with more severe late events, but was not predictive for its latency time. These findings suggest the possibility of an early indication of patients with an increased risk of late toxicity in whom preventive measures might be attempted.

Therapeutic outcome and relation of acute and late side effects in the adjuvant radiotherapy of endometrial carcinoma stage I and II.

Weiss E, Radiother Oncol 1999 Oct;53(1):37-44Hirnle P, Arnold-Bofinger H, Hess CF, Bamberg M.

Department of Radiation Oncology, University of Goettinigen, Germany.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy is the standard treatment for endometrial carcinoma. However, until now there has been no clear indication that radiotherapy in that setting improves survival. This calls for critical assessment of the relation between the expected benefit and the number and severity of postradiotherapeutic side effects. MATERIAL AND METHODS: In a retrospective study 159 consecutive patients with stage I and II endometrial carcinoma were treated with external radiotherapy and vaginal brachytherapy after hysterectomy and bilateral salpingoophorectomy (no surgical lymph node staging). Recurrence rates, survival and side effects were evaluated, in particular with regard to the relation of acute and late toxicity. RESULTS: Five percent of all patients developed a recurrence either in the abdomen or at distant locations. No pelvic relapses were diagnosed. Five-year relapse-free survival was 92% for stage IA + B, 84% for stage IC, and 79% for stage II disease. Acute toxicity was seen in 65.4% of patients, all grade 1 or 2, late toxicity grade 1 or 2 in 18.8%, grade 3 or 4 complications in 1.8%. The estimated 5-year freedom from late toxicity was 76.8%. Seventy-seven percent of all patients with treatment interruptions or premature end of therapy experienced late injury. In ten of 33 patients with late sequelae there was no free interval between early and late toxicity. No relation of radiation technique/fractionation and the rate of side effects was noticed. CONCLUSIONS: Adjuvant radiotherapy leads to excellent pelvic control, with few serious complications. Major acute toxicity shows significant correlation with the incidence of severe late injury, which we suggest to classify in part as consequential late effects.