Treatment of vascular soft tissue sarcomas with razoxane, vindesine, and radiation.

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.

Regional nodal recurrence in the management of breast cancer patients with one to three positive axillary lymph nodes. Outcome of patients following tangential irradiation without a separate nodal field.

PURPOSE: To examine the prognosis of breast cancer patients (T1-3, one to three positive axillary lymph nodes) and locoregional failure rate after breast-conserving therapy/modified radical mastectomy and adequate axillary dissection following tangential radiotherapy without irradiation of the regional lymph nodes. PATIENTS AND METHODS: From 1994 to 2002, the medical records of 183 breast cancer patients (T1-3, one to three involved axillary lymph nodes) were examined in order to identify those experiencing regional nodal recurrence, with or without local recurrence. The median age of the patient population was 58 years (range, 28-86 years). All patients underwent surgical treatment, either breast-conserving therapy (n = 146) or modified radical mastectomy (n = 37). The median number of lymph nodes removed was twelve (range, seven to 26 nodes). Irradiation was given to the breast through tangential fields. Chemotherapy was administered to 101 patients (55%), hormonal therapy to 124 (60%), and combined systemic treatment to 47 (26%). RESULTS: The median observation time was 44.4 months (range, 11-102 months). Of the 14 patients (7.7%) with a relapse, six (3.3%) had a local recurrence, five (2.8%) a regional relapse, and three (1.6%) a simultaneous recurrence. Nine out of 14 patients with locoregional relapse developed distant failure subsequently and seven of them (78%) died of the disease. CONCLUSION: Regional recurrence is uncommon among patients with one to three positive axillary lymph nodes treated with surgery, adequate axillary dissection, and tangential field irradiation only. The authors conclude that regional nodal irradiation should not routinely be given following adequate axillary dissection when only one to three lymph nodes are positive.

Patterns of care in radiotherapy of breast cancer in Austria 1985: data acquisition and comparison with data of US-PCS 1983.

PURPOSE: In Austria, a Patterns of Care Study (PCS) has been conducted to evaluate the standards of practice for breast cancer patients. The year 1985 was selected in order to establish a base data set. MATERIALS AND METHODS: At all nine radiation therapy facilities active in patient treatment in 1985, ten patients charts were randomly selected and reviewed. Evaluation of the radiotherapeutic standards was the principal purpose, however, surgical and histopathological parameters were also considered. RESULTS: Results of the Austrian PCS (including 90 patients) were compared with the "1983 Patterns of Care Process Survey for Definitive Breast Irradiation" performed in 1983 in the U.S. (including 191 patients). Documentation of pathologic tumour size (83% vs. 73%), histologic tumour subtype (99% vs. 97%) and microscopic margin analysis (60% vs. 51%) showed comparable results. Technical equipment was obviously quite different in the two countries, cobalt therapy was used in 25% in the US-PCS compared to 71% in the Austrian PCS. A clear difference also was obtained concerning the use of wedges for tangential breast/thoracic wall fields (64% vs. 21%) and the frequency of portal films (93% vs. 26%). CONCLUSIONS: Comparing both PCS studies, we found overall many similarities. Differences could be obtained in the quality level of radiation treatment, as for example use of wedges for tangential fields and the number of portal films. In a next step, a further Austrian PCS is planned to compare the Austrian base data from 1985 with quality standards from 1993 and 2001.

Phyllodes tumor: an unexpected tumor of the breast. A report on six patients.

BACKGROUND AND PURPOSE: To evaluate the role of adjuvant radiotherapy for an unexpected malignancy of the breast, known as phyllodes tumor, a retrospective study was undertaken. PATIENTS AND METHODS: Between 1994 and 2002, six female patients with a phyllodes tumor (borderline, n = 2; malignant, n = 4) were irradiated after modified radical mastectomy at our institution. No patient received adjuvant systemic therapy. RESULTS: Two patients experienced local failure, after 17 months (malignant) and 23 (borderline) months of observation. One of the patients with local relapse died intercurrently, the other because of multiple pulmonary metastases. Four patients are alive and show no evidence of disease. Median follow-up was 33.8 months (range 29-42 months). CONCLUSION: Based on the data from the literature and the authors' findings, it is concluded that surgery with wide negative margins is the preferred initial treatment option. There is no indication for axillary dissection, since these tumors rarely metastasize to regional lymph nodes. In patients with phyllodes tumors showing adverse prognostic factors, postoperative irradiation is recommended.

Long-term results after external radiotherapy in age-related macular degeneration. A prospective study.

PURPOSE: To prospectively evaluate the short- and long-term efficacy of external radiotherapy (RT) in patients with age-related macular degeneration (AMD) by comparing two different dose schedules. PATIENTS AND METHODS: In this prospective, nonrandomized, comparative study including 80 patients, the efficacy of external RT with a total dose of 14.4 Gy (group A, n = 40) and 25.2 Gy (group B, n = 40) was compared. Patients of group A were irradiated between September 1995 and July 1996, patients of group B between August 1996 and November 1997. 67 patients presented with occult choroidal neovascularization (CNV), 13 with classic subfoveal lesions. Complete ophthalmologic investigation was performed before RT, at intervals of 3 months during the 1st year after RT, and of 6 months thereafter. RESULTS: 12 months after RT, vision deteriorated in 85% (14.4 Gy) and 65% (25.2 Gy) of patients. Central visual field decreased with both dose schedules. There was no morphological benefit in neovascular changes. After 48 months, complete follow-up was possible in 46 patients who showed a significant loss of vision similar to the natural course of AMD. CONCLUSION: External RT of AMD with 14.4 Gy as well as with the escalated dose of 25.2 Gy showed a poor beneficial outcome after 6 and 12 months, respectively. After a follow-up of 4 years, visual outcome in irradiated patients was similar to the natural course of the disease. A conspicuous efficacy of RT in prevention of blindness could not be demonstrated.

Extracapsular extension in positive axillary lymph nodes in female breast cancer patients. Patterns of failure and indications for postoperative locoregional irradiation.

BACKGROUND AND PURPOSE: There has been little information regarding lymph node-positive breast cancer patients with extracapsular extension (ECE). The aim of this study was to evaluate the role of ECE in predicting survival and relapse rates. PATIENTS AND METHODS: From 1994-2002, 1,078 lymph node-positive women with breast carcinoma were treated at our institution, whereas 301 patients (27.9%) presented with ECE. 91 patients (30.2%) were identified as having three or less lymph nodes involved, 27.9% patients four to six, 15.6% patients seven to nine, and 26.2% patients ten or more nodes, respectively. The median age was 58.4 years (range: 28-84 years) and the median follow-up 34 months (range: 2-99 months). Nodal irradiation was given to patients with four or more positive lymph nodes. Chemotherapy was administered to 69.8%, hormonal therapy to 53.2%, and combined systemic treatment to 26% of patients. RESULTS: The 1-, 3-, and 5-year overall survival (OS) was 98%, 84%, and 73%, the 1-, 3-, and 5-year disease-free survival (DFS) 95%, 69%, and 58%, and the 1-, 3-, and 5-year metastasis-free survival (MFS) 96%, 73%, and 60%. The relapse rates were 6.6% (local), 0.3% (supraclavicular), 0.7% (isolated axillary), 1% (local + axillary), and 0.7% (local + supraclavicular), respectively. 81 patients (27%) developed distant metastases. In December 2002, 245 patients (81.4%) were alive, 202/245 without progression, 32/245 with distant metastases, 5/245 with local/locoregional recurrence, and 6/245 patients with local and distant failure. CONCLUSION: Isolated axillary nodal failure remains low in lymph node-positive patients with ECE. Balancing the risks and benefits of irradiation, we continue to recommend that complete axillary irradiation is not routinely indicated after adequate axillary dissection.

Analysis of competing risk parameters in irradiated prostate cancer patients.

PURPOSE: Retrospective competing risk analysis of prognostic factors in definitive-irradiated prostate cancer patients. PATIENTS AND METHODS: Data of 652 patients were analyzed according to three age subgroups (< 65, 65 < or = 75, > 75 years; Table 1). Pre-RT PSA values (median 13.4 ng/ml) were available for 340 patients. Adjuvant hormone therapy (n = 261) consisted either of orchiectomy (n = 151) or LHRH agonist with/without antiandrogen therapy or, in the early years, diethylstilbestrol. Neoadjuvant hormone therapy (n = 31) using LHRH agonists was given 6 months before and during radiotherapy. RESULTS: Biochemical failure was observed in 69/340 patients, 5 years after biochemical failure, 64.9% of them also had failed clinically. The cumulative incidence of local failure (LF) and distant metastases (DM) was 9.4% and 37.2%, respectively; LF and DM at the same time were seen in 18.2%. On multivariate analysis (Tables 2 and 3), advanced stage (relative risk [RR] 4.54), pre-RT PSA > 20 ng/ml (RR 2.79) and poorly differentiated tumors (RR 2.96) were significant predictors of biochemical failure. Advanced stage increased the risk of LF (RR 2.18), DM (RR 3.66), and prostate cancer death (PCD; RR 4.30). Hormone therapy decreased the risk of biochemical failure (RR 0.67), DM (RR 0.59), and PCD (RR 0.60) without reaching statistical significance. Median follow-up was 7.6 years. CONCLUSION: Risk of biochemical failure was predicted by pre-RT PSA, stage, and grade; in patients with biochemical failure, the cumulative incidence of death from intercurrent diseases and PCD was 25.0% and 29.2% after 5 years, respectively. The risk of DM and PCD was predicted by stage and grade. Higher age (> 75 years) decreased the relative risk of LF, DM, and PCD significantly.

Fractionated intraluminal HDR 192Ir brachytherapy as palliative treatment in patients with endobronchial metastases from non-bronchogenic primaries.

AIM: To evaluate the efficacy of iridium-192 high-dose rate (HDR) endobronchial brachytherapy for the palliation of symptoms caused by endobronchial metastases of non-bronchogenic primaries. PATIENTS AND METHOD: Between 1991 and 1998, eleven patients (female n = 3, male n = 8; age: median 66 years, range 44-81 years) underwent intraluminal HDR brachytherapy for histologically confirmed endobronchial metastases from non-pulmonary primary tumors of various sites like urogenital tract (n = 5), gastrointestinal tract (n = 3), ear/nose/throat (n = 2) and breast (n = 1). The median time between diagnosis of the primary non-bronchogenic tumor and histopathological diagnosis of the endobronchial metastases was 39 months, range 1-99 months. A total dose of 15-20 Gy was delivered in three to four fractions of 5-6 Gy once a week. No palliative chemotherapy was added. RESULTS: Median follow-up after palliative brachytherapy was 15 months (range 1.4-59 months). Objectively, complete endoscopic response was observed in three (27%) patients, and in five (46%) others partial opening of the initially obstructed airway was achieved. Treatment was judged unsuccessful in three (27%) patients. No patient showed up with local progression. At date of analysis five patients were alive with documented residual tumor (80%) or complete response (20%). Relief of symptoms occurred in the vast majority of patients (n = 8, 73%). CONCLUSION: HDR intraluminal brachytherapy palliates symptoms in patients suffering from endobronchial metastases of non-pulmonary primary tumors. The applied treatment is a safe, effective and well tolerated palliative procedure leading to an improved patient quality of life.

Radiation-induced osteosarcoma of the chest wall.

A case of radiation-induced sarcoma of the chest wall is reported. Twenty-seven years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old woman developed a radiation-induced osteosarcoma of the right thoracic wall. Initial diagnosis has been T-cell lymphoma of the skin. The right breast was irradiated with tangential fields and a total dose of 40 Gy, 2 Gy/day, 5 days a week. Orthovoltage treatment was performed in two courses of 20 Gy, 3 months apart. The clinical appearance of the secondary sarcoma was a diffuse infiltrated area in the irradiated breast which seemed to be fixed to the chest wall. Magnetic resonance imaging (MRI) demonstrated a mass in the right anterior thoracic wall which destroyed the fourth to the sixth rib. The tumor infiltrated the thoracic wall, including subcutaneous tissue and pericardium, as well as extending into the subphrenic space. Biopsy of the lesion revealed a poorly differentiated osteosarcoma. The patient's general condition precluded surgical or chemotherapeutic intervention; she died due to a cerebral stroke 6 months later. This case fulfilled all criteria for radiation-induced sarcoma, as there was a prior history of radiotherapy, latency period of several years, development of sarcoma within the irradiated field, and histologic confirmation of sarcoma.

Postprostatectomy radiotherapy for high-risk prostate cancer.

OBJECTIVES: To assess the biochemical and clinical results of postprostatectomy radiotherapy (RT) for high-risk, mostly non-rgan-confined prostate cancer. METHODS: After radical prostatectomy, 66 consecutive patients received either adjuvant (n = 29) or therapeutic (n = 37) postoperative RT. Therapeutic RT was given for persistently elevated postoperative prostate-specific antigen (PSA) levels (n = 14), gradually rising PSA levels (n = 6), or clinical local recurrence (n = 17). The selection of time and referral for RT was at the discretion of the treating urologists. RESULTS: The mean and median follow-up after surgery was 56.8 and 54.2 months, and after radiotherapy, it was 43.2 and 35.0 months, respectively. At 5 years, the actuarial biochemical control for the whole collective was 59.7% (95% confidence interval [CI] 43.3% to 72.8%). Patients treated with adjuvant RT had statistically improved biochemical control (85.2% versus 34.0%, P = 0.001), but not disease-free survival (91% versus 73%, P = 0.09). Advanced tumor stage (pT3b-4) (relative risk 16.6; 95% CI 0.9 to 313.3; P = 0.01), poorly differentiated histologic features (relative risk 4.63; 95% CI 1.8 to 12.2; P = 0.001), and pre-RT PSA (relative risk 1.15, 95% CI 1.06 to 1.25; P = 0.003) were associated with a statistically significant increased risk of biochemical failure. CONCLUSIONS: Although adjuvant postoperative RT resulted in improved biochemical control, no significant difference in disease-free survival has been obtained to date. It therefore remains to be determined whether the better biochemical control observed will ultimately translate into a survival benefit after longer follow-up and prospective trials.