[en] Purpose: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. Materials and methods: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). Results: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. Conclusions: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve

[en] Purpose: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. Methods and Materials: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). Results: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, ≥ 3 < 6, ≥ 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels ≤ 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes ≥ 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p 0.0210) and DM (p = 0.0011). Conclusion: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications

[en] Purpose: Because of the often expressed concern with the potential for an increase of late toxicity in patients treated with HDR regimens, a detailed analysis was undertaken to determine the incidence, severity, and factors associated with late sequelae in a series of patients whose treatment included high-dose rate intracavitary placements (HDR-ICP). Materials and Methods: Between 1985 and March 1991, 144 consecutive patients with inoperable cancer of the cervix (FIGO stage I: 25 patients, II: 46 patients, III: 58 patients, IV: 15 patients) underwent external beam radiation therapy (EBRT) to the pelvis followed by Ir-192 HDR-ICP. EBRT was delivered with 23 MeV photons through shaped portals using AP/PA or 4-field technique. Maximum doses to the pelvis ranged from 33.3-60 Gy (median 48.4 Gy), minimum doses from 30-54 Gy (median 46 Gy) for AP/PA fields, with maximum doses from 25.3-56 Gy (median 52.6), and minimum doses from 24-50.4 Gy (median 50) for the 4-field technique. HDR-ICP were performed after completion of EBRT in 1-6 fractions (mean 2.6) with total doses ranging from 8.5-38.7 Gy (median 19 Gy). In all cases doses to the bladder base, bladder neck, and anterior wall of the rectum were calculated at the time of HDR-ICP, and the dose of each fraction was adjusted in an attempt to optimize the tumor to normal tissue ratios. Results: The mean follow-up time and percentage of patients remaining free of disease were 51.2 mo, 92%; 41.7 mo, 67.4%; 41.3 mo, 44.8%; 14.5 mo, 6.7% for stages I, II, III, and IV, respectively. Overall 3 year survival rates were 87.6%, 67%, 55.3% and 10% for stages I, II, III, and IV, respectively. Four patients developed five serious radiation induced late sequelae. These included one recto-vaginal fistula (0.7%), two vesico-vaginal fistulas (1.4%), one small bowel obstruction requiring surgery (0.7%), and one patient with necrosis of both ureters and bilateral hydronephrosis. In addition, 14 patients (9.7%) had a total of 19 less severe complications not requiring hospitalization or surgery. These included three partial bowel obstructions, one sigmoidal stenosis, three patients with colitis, three patients with proctitis, three asymtomatic rectal ulcers, two asymtomatic vaginal ulcers, three patients with cystitis and one case of low abdominal subcutaneous induration. Analysis of pretreatment and dosimetric parameters failed to reveal any statistically significant correlations with the development of late sequelae. Conclusion: The stage for stage survival and tumor control rates obtained in this series are comparable with these reported following either low-dose-rate treatment regimens or HDR regimens employing a higher (>5) number of treatment fractions. The relatively low treatment related morbidity and the patient convenience of treatment using EBRT with 2-4 fractions of HDR suggest that further study of this approach is indicated. Careful monitoring of doses to bladder base, bladder neck, and anterior wall of the rectum is necessary to assure optimal tumor control and low normal tissue toxicity

[en] Objective: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been well characterized. However, despite the increasing use of high-dose-rate (HDR) brachytherapy few studies with adequate patient numbers and follow-up have analysed prognostic factors. This current study investigates pretreatment and treatment factors for their correlation with disease-free survival (DFS) and pelvic control. Materials and Methods: Between September 1985 and December 1994, 181 patients with primary carcinoma of the cervix FIGO stages IB (32), II (65), IIIB (78), and IV (6) received EBR to the whole pelvis (median dose: 48 Gy) followed by 1-6 HDR placements (median: 3). The median brachytherapy dose delivered to point A was 17,5 Gy. Hemoglobin levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Parameters analysed to assess their impact on survival, DSF, and pelvic control included patient age, FIGO stage, tumor size (<3 vs ≥3<6 vs ≥6 cm maximum diameter), tumor grade, pretreatment hemoglobin level (< 11 g/dl), total dose to point A, number of HDR fractions, and overall treatment time. Also evaluated was the prognostic significance of enlarged pelvic lymph nodes (≥ 2 cm) noted on pretreatment pelvic CAT-scan. Results: At 5 years actuarial survival, DFS, and pelvic control rates for all patients were 60%, 58% and 67%. The DFS by stage was for IB: 94%, II: 63%, IIIB: 43% and IV:0%; the pelvic control rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified were FIGO stage (p<0.0003), tumor size (p<0.0001), pretreatment hemoglobin level (p<0.0001), and enlarged pelvic nodes (p<0.0001). Five-year DFS rates for tumors <3, ≥3<6, and ≥6 cm were 97%, 65%, and 24%; patients with initial hemoglobin levels < 11g/dl had a DFS of 26% vs 69% for patients with levels > 11g/dl; and those with enlarged pelvic nodes had a survival of 30% vs 66% for patients without enlarged nodes. The same factors were also prognostically significant for pelvic control. Age, grade, dose, number of HDR placements, and overall treatment time were not of prognostic significance for either DFS or pelvic control. Conclusions: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy and demonstrated the significance of tumor size, pretreatment hemoglobin, and enlarged pelvic nodes in addition to FIGO stage of disease. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications

[en] Objective: Despite multimodality treatment regimens the survival rates for patients with stage III epithelial ovarian cancer have shown minor improvement in the last decade and remain poor. An analysis of the results of our trimodality treatment regimens was undertaken to identify prognostic factors for progression-free survival (PFS) and to correlate these with patterns of failure. Materials and Methods: Between May 1985 and December 1994, 52 patients with FIGO stage III ovarian cancer underwent maximum cytoreductive surgery, followed by chemotherapy (1-10 cycles, median: 6) and external beam irradiation. Radiation treatment consisted of whole abdominal irradiation (30 Gy), pelvic boosts (21,6 Gy), diaphragmatic boosts (12 Gy) and paraaortic nodal boosts (12 Gy) if the latter were involved. Patient age ranged from 31-79 years (median: 59). Follow-up for all patients was from 1-127 months (median: 25) and 38-127 months (median: 76) for patients at risk. Factors analysed for their impact on PFS and patterns of failure included postsurgical size and site of residual tumor, age, tumor grade, unilateral or bilateral ovarian involvement, presence of ascites, number of cycles of chemotherapy, and completion of radiotherapy. Results: Actuarial survival and PFS rates at 5 years were 30% and 29%. The presence of localized miliary seeding at the dome of the right diaphragm (MDS; 14 patients) as well as residual disease >2 cm after surgical debulking (6 patients) strongly influenced PFS. Patients with MDS or >2 cm residual disease had a PFS of 0% with a median survival of 6 and 8 months, respectively. These results were significantly worse (p=0.0006) than those obtained for the 16 patients with no macroscopic tumor or the 15 patients with macroscopic residuals <2 cm who had PFS rates of 47% and 46% and median survivals of 21 and 39 months, respectively. Patterns of failure showed significantly higher rates of distant metastases in patients with MDS (64%) or in patients with > 2 cm residual (67%) compared with patients who had no or < 2 cm macroscopic residual. None of the other parameters tested were of prognostic significance. Conclusions: Localized MDS as well as gross residual disease (> 2 cm) were found to be strongly prognostic and are associated with a high incidence of distant failure. If our finding of the prognostic significance of MDS can be confirmed, it is suggested that Taxol containing chemotherapy regimens be employed in the treatment of such patients as are now being utilized in the treatment of patients with suboptimal debulked disease

[en] Purpose: In previous studies, razoxane and vindesine together with radiotherapy was proved to be effective in soft tissue sarcomas (STS). Because razoxane leads to a redifferentiation of pathological tumor blood vessels, it was of particular interest to study the influence of this drug combination in vascular soft tissue sarcomas. Methods and Materials: This open multicenter Phase II study was performed by the Austrian Society of Radiooncology. Among 13 evaluable patients (10 angiosarcomas and 3 hemangio-pericytomas), 9 had unresectable measurable disease, 3 showed microscopic residuals, and 1 had a resection with clear margins. They received a basic treatment with razoxane and vindesine supported by radiation therapy. Outcome measures were objective response rates, survival time, and the incidence of distant metastases. Results: In nine patients with measurable vascular soft tissue sarcomas (eight angiosarcomas and one hemangiopericytoma), 6 complete remissions, 2 partial remissions, and 1 minor remission were achieved, corresponding to a major response rate of 89%. A maintenance therapy with razoxane and vindesine of 1 year or longer led to a suppression of distant metastases. The median survival time from the start of the treatment is 23+ months (range, 3-120+) for 12 patients with macroscopic and microscopic residual disease. The progression-free survival at 6 months was 75%. The combined treatment was associated with a low general toxicity, but attention must be given to increased normal tissue reactions. Conclusions: This trimodal treatment leads to excellent response rates, and it suppresses distant metastases when given as maintenance therapy.

[en] Background and purpose: There is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This retrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications. Material and methods: Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave. max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG). Results: Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P=0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae. Conclusion: In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis