GYNECOLOGIC ONCOLOGY 39, 47-55 (1990)
Radiation Therapy in Stage III Ovarian Cancer following Surgery and Chemotherapy: Prognostic Factors, Patterns of Relapse, and Toxicity:
A Preliminary Report
KARIN S. ARIAN-SCHAD, M.D.,, DANIEL S. KAPP, PH.D., M.D.,t ARNULF HACKL, M.D. ,* FREYJA M. JUETTNER, M.D. .* HUBERT LEITNER, PH.D. ,* G~NTER PORSCH, M.D. ,* MANFRED LAHOUSEN, M.D. ,$
AND HELLMUTH PICKEL, M.D.+
*University Clinic of Radiology/Department of Radiotherapy; #University Clinic of Gynecology and Obstetrics, Graz, Austria; and TStanford University, Department of Radiation Oncology, Stanford, California
Received January 3 1, 1990
Twenty patients with FIG0 stage III epithelial ovarian cancer who had undergone maximum cytoreductive surgery (including pelvic and paraaortic lymph node dissection) and combination chemotherapy (4-10 cycles, median 6) were treated with irra- diation to the abdomen and pelvis with 30 Gy followed by dia- phragmatic/paraaortic and pelvis boost fields to 42 and 51.6 Gy, respectively. Second-look laparotomy was not performed. Sev- enteen of 20 patients completed the planned course of radiation. In 2 cases, failure to complete treatment was related to acute hematologic toxity, and 1 patient refused further treatment. Five patients (29%) required treatment breaks ranging from 8 to 16 days (median, 12 days) due to pancytopenia. Actuarial overall survival and relapse-free survival at 3 years for the 17 patients who completed radiation was 69 and 47%, respectively, with follow-up ranging from 19 to 53 months (median: 24, mean: 27.6 months). Seven patients (41%) relapsed within the abdomen alone and 2 patients developed extraabdominal lymph node metastasis as their sole site of failure. The prognostic factors evaluated for correlation with relapse-free survival included histologic subtype, grade, amount of residual disease at the time of surgery, and nodal involvement; only residual tumor at surgery (none vs ~2 cm or >2 cm) was found to be statistically significant (P < 0.01). Three-year overall survival correlated with amount of residual disease following the initial cytoreductive surgery. It was 100% for patients with no residual disease, 66.7% for s2 cm, and 26.7% for those with >2 cm residual disease, respectively. Radiation treatment was well tolerated, with only one patient developing treatment-related bowel obstruction 7 months after radiation ther- apy. The results of this planned trimodality treatment approach compare favorably with those reported following surgery and
To whom reprint requests should be addressed at University Clinic of Radiology, Department of Radiotherapy, Auenbruggerplatz, A-8036 Graz, Austria.
chemotherapy, particularly in patients who have been maximally cytoreduced. 0 1990 Academic Press, Inc.
Despite combined treatment approaches, the survival rates in advanced stage ovarian cancer have shown little improvement in the last decade. Management with more radical surgery [l-3], new chemotherapy combinations utilizing cis-platinum [4,5], second-look operations, and varying radiation treatment techniques have been eval- uated [6-101. Several prognostic factors including stage, histological subtype, grade, and extent of residual tumor after debulking surgery have been shown to be predictive for recurrence of disease and survival [8,10-221.
The benefit of radiation therapy as an adjuvant to chemotherapy in advanced stage ovarian cancer has not yet been clearly defined but its curative potential as post- operative first-line therapy has been demonstrated in a selected subgroup of patients [23,24]. Poor tolerance to large-field radiation in patients previously treated with combined chemotherapy regimens including c&platinum has been documented in literature [8,18,20,25-281. We retrospectively reviewed 20 patients with FIG0 stage III epithelial ovarian cancer, who had been treated in a uni- form manner with radical surgery, multidrug chemo- therapy, and whole abdominal pelvic radiation (WAP) with additional boost to the subdiaphragmatic area, the paraaortic lymph nodes, and the true pelvis. The aims of this study were to evaluate pretreatment and treatment factors predictive of recurrence-free survival; sites of recurrent disease; treatment-related toxicities; and com- plications due to the addition of radiotherapy.
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MATERIAL AND METHODS was initiated. The radiation therapy fields employed were similar to those described previously by Schray et al.
Between May 1985 and December 1987, 20 patients [81, but the sequence of treatment of the various fields ages 43-68 years (median, 59 years), with FIG0 stage differed. WAP radiation was delivered with an 8-MeV III epithelial ovarian cancers, were treated with maxi- photon beam through open AP/PA fields. The daily frac- mum cytoreductive surgery followed by chemotherapy tion was 1.5 Gy, five times a week, both fields treated and, if no measurable disease progression was docu- daily to a total dose of 30 Gy. After a scheduled 2-week mented, with external beam radiation therapy. Patient break, a diaphragmatic boost field at a daily dose of 1.5 selection criteria for surgery and chemotherapy included Gy at the midplane was employed up to a total of 42 Gy age ~70 years; Karnofsky performance status ~80%; no through individually shaped fields with the patient treated radiologic evidence of extraperitoneal metastases; nor- in the prone position. If either positive pelvic or para- mal renal and hepatic functions (serum creatinine co.15 aortic lymph nodes were found at surgery, the diaphrag- nmole liter or 1.5 mg/lOO ml, serum bilirubin ~20 mi- matic field was extended to include the paraaortic lymph cromole/liter or 1.5 mg/lOO ml); normal blood counts (WBC *4000/mm3, platelets 2 100,000/mm3); no history
nodes. An AP/PA shaped true pelvic field was added to the diaphragmatic or diaphragmatic/paraaortic field and
of previous malignant disease, aside from basal or squa- simultaneously treated with 23-MeV photons with a daily mous cell carcinoma of the skin; and no serious con- fraction of 1.8 Gy to a total of 5 1.6 Gy. current medical illness. Pretreatment evaluation included Other modifications to the method described by Schray full history and physical examination. Radiological et al.  included enlargement of the width of the upper workup consisted of chest X-ray, CT scan of the ab- portion of the diaphragmatic boost fields to 18 to 20 cm domen and pelvis, and intravenous pyelogram (IVP). In and shielding of both kidneys and liver from both the selected cases, ultrasound of the liver was performed to AP and the PA fields with 3% cerrobend transmission help rule out hepatic metastases. blocks placed at 15 and 19.5 Gy, respectively. Using a
Surgery included hysterectomy, bilateral salpingo- CT-aided treatment planning system, calculations in oophorectomy, omentectomy, exploration of the dia- three defined planes were obtained for every treatment phragmatic surfaces, pelvic and abdominal washings, and field. Special care was taken to cover the entire peri- attempted radical pelvic and paraaortic lymph node dis- toneal surface. Blood counts were obtained once a week, section with maximum tumor debulking. If infiltration or more frequently if indicated. If WBC fell to into adjacent organs was confirmed intraoperatively, low
TABLE 1 1 oo- Patient Parameters
80 overall survival
No. of patients Percentage
Stage III 20 100
Histologic subtype 20 t
Serous 12 60 Endometroid 3 15 Mutinous 2 10 Clear-cell 2 10 FIG. 1. Overall and recurrence-free survival from date of surgery Undifferentiated I 5 for 17 patients, FIG0 stage III, who completed the planned course of
Histologic grades radiation.
Well differentiated 5 25 Moderately differentiated 7 35 Poorly differentiated 7 35 differentiated, 7 moderately differentiated, 7 poorly dif- Undifferentiated I 5 ferentiated, and 1 undifferentiated carcinoma. No mac-
Residual at initial surgery roscopic residual disease was present in 40% (8/20) of No visible disease 8 40 the patients, and residual disease ~2 cm was present in Residual ~2 cm 3 15 Residual >2 cm 9 45
15% (3/20) and >2 cm in 45% (9/20) of the patients. Radiation therapy was well tolerated. Seventeen of 20
Nodal involvement None 5 25
patients were able to complete the planned course of
Pelvic nodes only 3 15 radiation. Two patients could not complete their radia-
Paraaortic nodes only 1 5 tion treatments because of persistent bone marrow de- Pelvic and paraaortic nodes II 55 pletion and 1 patient refused to continue treatment.
Overall and relapse-free-3-year survival from date of surgery (Fig. 1) for the 17/20 patients who have com-
tologic subtype (serous, mutinous, endometroid, clear- pleted the full course of irradiation was 69% (median: cell, undifferentiated), tumor grade (well vs moderate vs 24, mean: 27.6 months) and 47% (median: 22, mean: poorly vs undifferentiated), and lymph node status (none 25.3), respectively, with a follow-up from 19 to 53 months vs pelvic vs paraaortic vs pelvic plus paraaortic for overall survival. Time to recurrence ranged from 17 involvement). to 37 months (median: 20, mean: 22.1). The overall and
relapse-free survival from onset ofradiation (Fig. 2) was
RESULTS 71.8% (median: 16, mean: 19.6, range: lo-45 months) and 23.8%, respectively, with recurrences observed be-
Radical surgery, including pelvic and paraaortic lymph tween 9 and 29 months after initiation of radiation node dissection, was carried out in all but two patients, therapy. in whom only retroperitoneal samplin