Common use of Toxicity Clause in Contracts

Toxicity. During radiotherapy, any kind of side effect was reported in 26% of all irradiated patients (Table 3). Nineteen percent was grade 1 toxicity, representing only minor complaints. In 7% of the patients there was a grade 2 or 3 complication. Acute transient neurological complaints were recorded in 53 patients, of which 35 had grade 1, not requiring any intervention. In 2 patients the shielding was adjusted and the upper border was lowered in 3 patients. In 13 patients treatment was interrupted due to serious pain in the gluteal region or legs. Remarkably, of these 13 patients, 6 patients were treated in one radiation institute. No relation with number of portals, upper border, treatment position or shielding could be found. Due to the fact that the neurotoxicity score was introduced in 1997, data about neurotoxicity are missing in 178 patients. In four (<1%) patients other grade 3 toxicity was reported, leading to postponement of the operation in two patients with thrombo-embolic complications. One patient required a catheter due to urinary retention after the radiotherapy. The last patient had anal blood loss 2 months after radiotherapy and proctoscopy confirmed a proctitis. Table 3. Number of patients with radiotherapy toxicity. ▇▇▇▇ ▇▇▇▇▇▇▇ ▇ ▇ ▇ ▇ Skin 685 8 2 0 Gastrointestinal 605 75 14 1 Genitourinary 676 16 2 1 Neurological 464 35 5 13 Other 655 31 7 2 Table 4. Surgery characteristics. RT+TME TME n=695 n=719 n % n % P Operation characteristics time (median, range) 180 65-390 180 70-380 ns blood loss (median, range) 1100 50-20000 1000 20-15000 <0.001 LAR 1025 800 <0.001 APR 1200 1300 ns hospital stay (median, range) 15.0 3-179 14.0 0-169 ns Operation type when LAR planned LAR 408 85 435 89 ns APR 45 9 35 7 ▇▇▇▇▇▇▇▇ 30 6 21 4 Stoma in LAR patients no stoma 176 36 216 43 0.05 stoma 263 64 249 57 Anastomosis in LAR patients side-end 261 60 278 60 ns end-end 54 12 50 11 pouch 122 28 132 29 missing 2 5 60 53 40 47 Operation time in minutes, blood loss in ml and hospital stay in days. ns=not significant To evaluate whether preoperative radiotherapy influences operation procedures, surgery characteristics are compared in Table 4. There was no significant difference in median operation time or median hospital stay between both treatment arms. Total blood loss was slightly increased (100 ml) in the irradiated (RT+) group (P<0.001). Subset analysis revealed that the difference in median blood loss was mainly present in the LAR patients: 1025 ml in the RT+ group vs. 800 ml in the non-irradiated (RT-) group (P<0.001), whereas median blood loss in the APR patients was not significantly different over the treatment arms. Of the patients planned to undergo a LAR operation, 9% in the RT+ group and 7% of the patients in the RT- group underwent an APR. In APR patients, conversion to a sphincter saving procedure took place in 20% of the irradiated patients and in 19% of the TME alone group. A pouch reconstruction was done in 28% of the irradiated patients undergoing a LAR vs. 29% of the non-irradiated patients. More RT+ patients received a temporary diverting stoma at the time of TME surgery than RT- patients did (64% vs. 57%, P=0.05). Postoperatively, slightly more RT- patients required a stoma due to complications, resulting in a not significantly different overall number of temporary stomas in both groups (68% vs. 63%, P=0.2), as is shown in Figure 1. There was no difference in the percentage of patients with complications during the operation. Bleeding during operation occurred in 13% of the patients in both groups. In 8% of the irradiated patients and in 7% of the non-irradiated patients, an unintended organ injury occurred. All reported postoperative complications are listed in Table 5. For most complications there was no difference between the two treatment arms. The overall postoperative complication rate was 48% in the irradiated group vs. 41% in the non-irradiated group (P=0.008). This difference was mainly attributable to the difference in perineal wound healing. In APR patients, perineal wound complications were significantly increased in the irradiated patients (29% vs. 18%, P=0.008), whereas there was no difference in the abdominal wound complications. Application of an omentoplasty did not lead to a reduction in perineal complications. In 40 irradiated APR patients the perineum was not included in the treatment field. Seven of these patients (18%) had perineal problems, vs. 54 (31%) of the 174 patients in which the perineum was included in the treatment field. The percentage of LAR patients showing clinical leakage postoperatively was 11% (n=105) and was not statistically different for irradiated and non-irradiated patients (11% vs. 12%). Leakage was less common in patients with a diverting stoma (8% vs. 16%, P=0.001). In patients with an end-end anastomosis leakage occurred in 16% of the LAR patients, whereas only 9% of the patients with a pouch reconstruction experienced anastomotic failure. In patients with a side-end anastomosis this percentage was 12%. There was no influence of the distance of the tumour from the anal verge or age on the occurrence of leakage. Twenty percent of the patients with leakage were treated conservatively, whereas 80% required a surgical reintervention. In total, 201 patients (14%) underwent one or more reinterventions with 103 patients in the RT+ group and 98 in the RT- group. Indications for reinterventions are listed in Table 6. No difference between the number of reinterventions in the LAR or APR patients was observed. Twenty-eight patients (4%) died in hospital in the RT+ group vs. 24 (3.3%) in the RT- group (P=0.49). Postoperative mortality (<30 days) was 3.5% in the RT+ group vs. 2.6% in the RT- group (P=0.38). There was a strong correlation between age and hospital death (P<0.001, Figure 2). Causes of hospital death are given in Table 7. In the RT+ group 10 patients died of cardiac problems versus 3 patients in the RT- group (P=0.04). Anastomotic leakage contributed to postoperative mortality in 12 patients (23% of all in-hospital mortalities).