Acute Gastrointestinal and Genitourinary Toxicity in Women with Gynecologic Malignancies Treated with Intensity-Modulated Radiotherapy Regiane S. Andrade 1 ; George Voynov 1 ; Ron Lalonde 2 ; Chyongchiou J. Lin 3 ; Shalom Kalnicki 1 ; Kristina Gerszten 1 ; Dwight E. Heron 1 1. Radiation Oncology, 2. D3 Advanced Radiation Planning, 3. Health Policy and Management University of Pittsburgh Medical Center, Pittsburgh, PA 26% 60% 60% 34% 14% 1.8% 0 10 20 30 40 50 60 G0 G1-2 G3-4 Grade GI (SB) Toxicity Historical GI UPMC GI 70% 78% 28% 20% 2% 0% 0 10 20 30 40 50 60 70 80 G0 G1-2 G3-4 Grade GU Toxicity Historical GU UPMC GU 0 0 0 G5 0 0 0 G4 2 0 0 G3 7 6 3 G2 32 17 16 G1 66 84 88 G0 SMALL BOWEL BLADDER RECTUM RTOG TOXICITY RTOG Toxicity Scale 0 1 2 3 4 UPPER G. I. No change Anorexia w ith <=5% w eight loss from pretreatment baseline/ nausea not requir ing antiemetics/ abdominal discomfort not requiring parasympatholyticdrugs or analgesics Anorexia w ith <=15% w eight loss from pretreatment baseline/nausea &/ or vomiting requiring antiemetics/ abdominal pain requiring analgesics Anorexia w ith >15% w eight loss from pretreatment baseline or requiring N-G tube or parenteral support. Nausea &/or vomiting requiring tube or parenteral support/abdominal pain, severe despite medication/hematemesis or melena/ abdominal distention (flat plate radiograph demonstrates distended bow el loops Ileus, subacute or acute obstruction, perforation, GI bleeding requiring transfusion/abdominal pain requiring tube decompression or bow el diversion LOWER G. I. INCLUDING PELVIS No change Increased frequency or change in quality of bow el habits not requiring medication/ rectal discomfort not requiring analgesics Diarrhea requir ing parasympatholyticdrugs (e.g., Lomotil)/ mucous discharge not necessitating sanitary pads/ rectal or abdominal pain requiring analgesics Diarrhea requir ing parenteral support/ severe mucous or blood discharge necessitating sanitary pags/abdominal distention (flat plate radiograph demonstrates distended bow el loops) Acute or subacute obstruction, fistula or perforation; GI bleeding requiring transfusion; abdominal pain or tenesmus requiring tube decompression or bow el diversion GENITOURINA RY No change Frequency of urination or nocturia tw ice pretreatment habit/ dysuria, urgency not requiring medication Frequency of urination or nocturia w hich is less frequent than every hour. Dysuria, urgency, bladder spasm requiring local anesthetic (e.g., Pyrid iu m) Frequency w ith urgency and nocturia hourly or more frequently/ dysuria, pelvis pain or bladder spasm requiring regular, frequent narcotic/gross hematuria w ith/ w ithout clot passage Hematuria requiring transfusion/ acute bladder obstruction not secondary to clot passage, ulceration or necrosis Acute Toxicities in Patients Treated with IMRT Introduction: Radiation Therapy plays an important role in the treatment of a number of gynecologic malignancies. However, GI complications of treatment remain problematic, and considerable attention has been focused on reducing the risk of these sequelae. Recently, major advances in conformal therapies such as IMRT has demonstrated the ability to reduce the volume of normal tissue irradiated while concentrating the prescribed dose to the target volume thus resulting in greater conformity. We evaluated the acute GI and GU toxicities in patients with gynecologic malignances treated with IMRT. Material and Methods Between June 2001 and December 2003, 107 women with gynecologic malignancies were treated with IMRT in the Department of Radiation Oncology at the University of Pittsburgh Medical Center. There were 54 uterine, 34 cervical, 11 ovarian, 7vulvar, and 1 vaginal malignancies treated with definitive or adjuvant therapy. Target volumes were contoured on a planning contrast-enhanced CT scan, and a 1-cm margin was added to obtain the planning target volume (PTV). A 5-9 field IMRT plan was developed, and dose-volume histograms were created which included the PTV, rectum, small bowel, and bladder. We determined the incidence of acute toxicity and whether a correlation existed between acute toxicity and the volumes (in percent) of rectum, small bowel, and bladder receiving 30 Gy (V30), 40 Gy (V40), 45 Gy (V45), and 50 Gy (V50). Normal organ toxicities were scored according to the 5-point RTOG Acute Radiation Morbidity Scoring Criteria scale. Kolmogorov-Smirnov Z test and histogram were used to evaluate the normality of the variables of interest. Pearson’s correlation coefficients were calculated for variables with normal distribution while Spearman’s correlation coefficients were calculated for variables with skewed distribution. Results: • In all patients, the PTV received at least 92% of the prescribed dose. • Sixty-six patients experienced Grade 0, 32 with Grade 1, 7 with Grade 2, and 2 with Grade 3 acute small bowel toxicities. There were no Grade 4, or 5 toxicities. • For bladder, 84 patients developed Grade 0, 17 with Grade 1, 6 with Grade 2, and none of the patients had Grade 3, 4, or 5 acute toxicities. • For rectum, 88 patients developed Grade 0, 16 with Grade 1, 3 with Grade 2, and there were no Grade 3, 4, or 5 acute toxicities. • The analysis showed a positive correlation only between V50 and the presence of acute toxicity for small bowel. • There was no correlation for rectum and bladder acute toxicities and the doses (V30,V40, V45, and V50). Conclusions: • The acute GI and GU toxicities of pelvic IMRT are relatively low. IMRT was well tolerated, with no patient developing toxicity higher than Grade 2 for rectum and bladder. The frequency of Grade 3 and Grade 1 and 2 (combined) for SB was lower compared to historical controls (1) with a higher incidence of patients that presented Grade 0 acute toxicities (1.8% vs. 14% for G1, 34% vs.60% for G1-2 and 60% vs. 26% for G3-4). For GU, the same tendency was observed (graph). • The acute toxicity appeared to correlate with V50 only (although the significance was borderline). The lack of correlation for rectum and bladder toxicities and dose include the low incidence of Grade 2 or higher toxicities, and a larger sample may be necessary. • This overall reduction in acute toxicity is translated by the reduction of normal tissue irradiated. We believe that this reduction in severe toxicity will result in fewer severe late GI /GU toxicities commonly seen with pelvic radiotherapy. Reference: 1- Keys HM, et al. N Engl J Med. 1999 340(15): 1154-61.