Identification of Risk Factors for Sexual Dysfunction after Multimodal Therapy of Locally Advanced Rectal Cancer and Their Impact on Quality of Life: A Single-Center Trial.

PURPOSE: Sexual function is crucial for the quality of life and can be highly affected by preoperative therapy and surgery. The aim of this study was to identify potential risk factors for poor sexual function and quality of life. METHODS: Female patients were asked to complete the Female Sexual Function Index (FSFI-6). Male patients were demanded to answer the International Index of Erectile Function (IIEF-5). RESULTS: In total, 79 patients filled in the questionary, yielding a response rate of 41.57%. The proportion of women was represented by 32.91%, and the median age was 76.0 years (66.0-81.0). Sexual dysfunction appeared in 88.46% of female patients. Severe erectile dysfunction occurred in 52.83% of male patients. Univariate analysis showed female patients (OR: 0.17, 95%CI: 0.05-0.64, p = 0.01), older age (OR: 0.34, 95%CI 0.11-1.01, p = 0.05), tumor localization under 6cm from the anal verge (OR: 4.43, 95%CI: 1.44-13.67, p = 0.01) and extension of operation (APR and ISR) (OR: 0.13, 95%CI: 0.03-0.59, p = 0.01) as significant risk factors for poor outcome. Female patients (OR: 0.12, 95%CI: 0.03-0.62, p = 0.01) and tumors below 6 cm from the anal verge (OR: 4.64, 95%CI: 1.18-18.29, p = 0.03) were shown to be independent risk factors for sexual dysfunction after multimodal therapy in the multivariate analysis. Quality of life was only affected in the case of extensive surgery (p = 0.02). CONCLUSION: Higher Age, female sex, distal tumors and extensive surgery (APR, ISR) are revealed risk factors for SD in this study. Quality of life was only affected in the case of APR or ISR.

Are risk factors for anastomotic leakage influencing long-term oncological outcomes after low anterior resection of locally advanced rectal cancer with neoadjuvant therapy? A single-centre cohort study.

PURPOSE: Anastomotic leakage (AL) poses the most serious problem following low anterior resection in patients with rectal cancer independent of surgical approach or technique. The aim of this study was to evaluate risk factors for the occurrence of AL and how they affect the oncological long-term outcome of patients who received neoadjuvant therapy. METHODS: A single centre cohort study of 163 consecutive locally advanced rectal cancer patients (cT3, cT4, N +) that received neoadjuvant therapy followed by resection with primary anastomosis between January 1998 and December 2020 were included in this study. Short- and long-term findings were compared between patients with AL (Leakage +) and without AL (Leakage -). RESULTS: A complete follow-up was obtained from 163 patients; thereby, 33 patients (20%) developed an AL. We observed more patients with comorbidities (38% vs. 61%, p = 0.049) which developed a leakage in the course. Permanent stoma rate (36% vs. 18%, p = 0.03) was higher, and time between primary operation and stoma reversal was longer (219 days [172-309] vs. 93 days [50-182], p < 0.001) in this leakage group as well. Tumour distance lower than 6 cm from the anal verge (OR: 2.81 [95%CI: 1.08-7.29], p = 0.04) and comorbidities (OR: 2.22 [95%CI: 1.01-4.90], p = 0.049) was evaluated to be independent risk factors for developing an AL after rectal cancer surgery. Oncological outcome was not influenced by AL nor by other associated risk factors. CONCLUSION: We could clearly detect the distance of tumour from the anal verge and comorbidities independent risk factors for the occurrence of AL. Oncological findings and long-term outcome were not influenced by these particular risk factors.

Gamma Knife Radiosurgery in Recurrent Glioblastoma.

BACKGROUND: We evaluated Gamma Knife radiosurgery (GKRS) as a treatment option for patients with recurrent glioblastoma. PATIENTS AND METHODS: 42 patients with histopathologically diagnosed recurrent grade IV tumor were treated with GKRS. All patients had undergone standard multimodal first-line treatment. The average time from diagnosis to GKRS was 17.0 months. The median target volume was 5.1 cm3. The median margin dose was 10 Gy and the median central dose 20 Gy. In a subset of patients, O6-methylguanine methyltransferase (MGMT) promoter methylation analysis by pyrosequencing was performed. RESULTS: Most patients did not develop complications after GKRS. Time to radiological progression after initial GKRS was 4.4 months (95% CI: 3.1-5.7 months). Radiological progression mainly occurred beyond the GKRS-irradiated area. The median survival time after initial GKRS was 9.6 months (95% CI: 7.7-11.5 months). The median overall survival time from diagnosis was 25.6 months (95% CI: 21.8-29.3 months). Patients with MGMT promoter methylation survived significantly longer (33.4 months; 95% CI: 21.2-45.5 months) compared to patients without MGMT promoter methylation (16.0 months; 95% CI: 8.0-23.9 months). CONCLUSION: GKRS seems to be a relatively safe salvage treatment option for recurrent glioblastoma for highly selected patients but must be seen as part of a multimodal treatment algorithm.

Overall survival and extent of surgery in adult versus elderly glioblastoma patients: A population based retrospective study.

INTRODUCTION: The purpose of this retrospective population based study was to investigate the effect of the extent of surgery on overall survival in young versus adult glioblastoma patients in Vorarlberg/Austria during the last 4 years. METHODS: Forty-eight patients (median age 62.5 years, ranging from 25-82 years, 19 female and 29 male) with histologically proven glioblastoma received surgery (16 biopsies, 18 partial and 14 complete resections) and postoperative chemo-irradiation with concomitant and adjuvant temozolomide. The median follow up of the patient population was 11.7 months (ranging from 3 to 36 months). Postoperative temporary morbidity was found in 5 out of 48 (10.4%) patients, and no mortality or permanent morbidity occurred. One infection led to revision surgery. FINDINGS: Altogether, the 12/24 months overall survival was 54/20.2% with a median survival of 13.7 months. In younger patients (<65 yrs, median 57.5 yrs, 28 patients), the 12/24 months overall survival was 68.4/34.3% with 16.9 months median survival, in the elderly patients (>65 yrs, median 73 yrs, 20 patients) the 12/24 months overall survival was 28.8/5.8%, with 7.7 months median survival (Log-rank, p = 0.0005). Extent of surgery influenced overall survival of the adult group nearly significantly (biopsy versus complete resection: p = 0.06), but did not affect overall survival of the elderly (p = 0.5). CONCLUSIONS: Overall survival of elderly glioblastoma patients treated with surgery and chemo-irradiation with concomitant and adjuvant temozolomide is significantly reduced compared to the younger patients. In addition, in the elderly the extent of surgery did not influence the prognosis in our population.

Prostate cancer radiotherapy in Austria: overview on number of patients, intention to treat, and treatment techniques based on data from 2007.

PURPOSE: Aim of this analysis was to assess the current status of prostate cancer radiotherapy in Austria and compare these numbers to patients treated with surgery. MATERIAL AND METHODS: A questionnaire was sent to all 14 Austrian departments asking about numbers of prostate cancer patients treated and indication of treatment (primary, postoperative), as well as the treatment technique used (3D-CRT, IMRT, brachytherapy), treatment volumes (with/without pelvic irradiation), dose applied, and differences in treatment concepts. Data investigated were based on the year 2007. RESULTS: Of the 14 departments (65%), 9 departments decided to participate. A total of 1,191 prostate cancer patients were treated (847 primary, 344 postoperative). Primary patients were treated by external beam technique (91%) and permanent interstitial brachytherapy (9%). All postoperative patients were treated by 3D-CRT. Dose ranged from 70-78 Gy for primary patients and from 60-72 Gy for postoperative patients. A risk-adapted dose prescription was performed in 5 centers. Additional pelvic lymph node irradiation was based on signs of positive nodes in 4 departments and based on Roach formula/Partin table in 5 departments. CONCLUSION: About 25% of prostate cancer patients receive primary radiotherapy. This number reflects a high potential to conduct national studies. Treatment technique and dose applied was in all centers investigated in accordance with the German S3 guidelines.

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.

Combined vindesine and razoxane shows antimetastatic activity in advanced soft tissue sarcomas.

BACKGROUND: Razoxane and vindesine were shown to suppress distant metastasis in animal systems. Both drugs affect main steps of the metastatic cascade. Therefore, a pilot study was performed to study the influence of these drugs on the dynamics of metastasis in advanced soft tissue sarcomas (STS). This study was now updated. METHODS: Twenty-three patients with unresectable (n = 7) and oligometastatic STS (n = 16) received a basic treatment with razoxane and vindesine supported by radiotherapy and occasionally by surgery. Long-term treatment was intended in patients with metastatic disease. The cumulative number of new metastases after 6 and 9 months were determined. Thirty-six patients with comparable stages of STS treated with contemporary chemotherapy served as non-randomized, retrospective controls. The prognostic parameters of the groups were comparable. RESULTS: In patients receiving razoxane and vindesine, the median number of new metastases after 6 months was 0 (range, 0-40) and after 9 months likewise 0 (0-70). The corresponding numbers in the control group were 4.5 (range, 0-40) and 9 (0->100) (P < 0.001). The progression-free survival at 6 months was 74% in the study group and 23% in the controls. The median survival time from the occurrence of the first metastasis or the time of unresectability was 20+ months (range, 8-120+) versus 9 months (range, 2-252) (P < 0.001). The combined treatment was associated with a low to moderate toxicity. CONCLUSIONS: Trimodal treatment with razoxane, vindesine, and radiotherapy is feasible in patients with unresectable primaries and early metastatic STS. The combination inhibits the development of remote metastases in a majority of the patients and prolongs survival.

Razoxane and vindesine in advanced soft tissue sarcomas: impact on metastasis, survival and radiation response.

BACKGROUND: The treatment options in advanced soft tissue sarcomas (STS) are limited. In a pilot study, an antimetastatic and radiosensitizing treatment concept was explored. PATIENTS AND METHODS: Twenty-one patients with unresectable and/or oligometastatic STS received the drugs razoxane and vindesine supported by radiotherapy and surgery. Long-term treatment was intended in metastatic disease. Forty-one patients with comparable stages of STS treated with contemporary chemotherapy served as non-randomised controls. The prognostic parameters of the groups were comparable. RESULTS: In the study group, the median number of new metastases after 6 months was 0 (range, 0-40) and after 9 months likewise 0 (0-70). The corresponding numbers in the control group were 4.5 (range, 0-40) and 9 (0->100) (p<0.001). The progression-free survival at 6 months was 71% in the study group and 23% in the controls, and the median survival time from the occurrence of the first metastasis was 16 months versus 9 months. The rate of major responses under radiotherapy combined with razoxane and vindesine was 88%, and in the control group 62% (p=0.007). The combined treatment was associated with a low to moderate toxicity. CONCLUSION: The treatment combination inhibited the development of remote metastases in the majority of patients with STS and prolonged survival to some extent.

Irradiation with and without razoxane in the treatment of incompletely resected or inoperable recurrent rectal cancer. Results of a small randomized multicenter study.

BACKGROUND AND PURPOSE: In an earlier phase II study, irradiation together with razoxane was shown to improve local control in recurrent rectal cancer. Therefore, the Austrian Society of Radiooncology (OGRO) initiated a randomized controlled trial in 1992 to compare this combined treatment versus radiation therapy alone. PATIENTS AND METHODS: Between 1992 and 1999, 36 patients with localized recurrences of rectal cancer were randomized to receive radiotherapy without (group A) or with razoxane (group B). The prognostic variables of the two groups were similar except for a longer median latency period from initial surgery to local recurrence in group A. High-energy photons with daily fractions between 170 and 200 cGy were used. The median total radiation dose was 60 Gy in each group. The patients in group B received a median razoxane dose of 9.6 g (range, 5-12 g). Main outcome measures were local control, overall survival, and toxicity. RESULTS: The combined treatment with razoxane increased the local control rate compared to radiotherapy alone (39% vs. 8%; p = 0.05). The median survival time was not different between the groups (20 months each). No patient in arm A but four of 18 patients in arm B survived 5 years. Acute toxic effects were of moderate degree in both groups. There were no substantial differences as to late side effects. CONCLUSION: Radiotherapy together with razoxane is superior to radiation treatment alone in recurrent rectal cancer as far as local control is concerned. In some patients, long-term survival was achieved with razoxane and radiotherapy.

Combined radiotherapy and razoxane in the treatment of chondrosarcomas and chordomas.

BACKGROUND: Chondrosarcomas and chordomas are reported to have low radio-sensitivity. Therefore, a study was undertaken to explore the radioresponsiveness of these tumours using the sensitising agent razoxane. PATIENTS AND METHODS: Thirteen chondrosarcomas and five chordomas were irradiated with high-energy photons and razoxane in the period from 1984 to 2003. The median tumour dose was 60 Gy in the chondrosarcomas and 63 Gy in chordomas. Razoxane tablets were given at a dose of 125 mg twice daily starting 5 days before the first irradiation. The drug was continued on radiation days. RESULTS: Eight out of the 13 chondrosarcomas had unresectable or recurrent measurable disease. There were one complete and five partial responses, while two tumours remained unchanged (response rate 75%). The median duration of response was 22 months. Three out of four patients without clear surgical margins and one patient with clear margins had locally controlled disease. Overall, local control was achieved in seven out of twelve patients who were not radically resected. All five patients with chordomas survived 5 years and remained locally controlled at that time. Among four measurable tumours, two complete and one partial regression were noted. Razoxane was well tolerated; the dose limiting toxicity was leukopenia. CONCLUSION: Photon irradiation together with razoxane induces major responses in a majority of patients with chondrosarcomas and chordomas. This combination therapy seems to be more effective than photon irradiation alone.

Combined razoxane and radiotherapy for melanoma brain metastases. a retrospective analysis.

We retrospectively compared the efficacy of razoxane and radiotherapy with radiotherapy alone or in combination with a non-razoxane based medication in patients with melanoma brain metastases. From 19 assessable patients receiving whole brain irradiation with or without a boost (mean total dose 40.5 Gy) for measurable brain metastases, 8 patients underwent an additional razoxane therapy with 125 mg per os twice daily started 5 days before radiotherapy and given throughout the whole radiation period. The median razoxane dose was 6.25 g (range 3.2-8.0 g). Endpoints included radiation response rates, median survival time and 1-year survival rates. To generate reliable prognostic parameters for this non-randomized study population, the Score Index for Stereotactic Radiosurgery and the Radiation Therapy Oncology Group Recursive Partitioning Analysis score were applied. Radiotherapy with razoxane led to higher response rates (62% vs. 27%) and a lower percentage of progressive disease (12.5% vs. 36%) if compared with radiotherapy alone or with a non-razoxane based medication. This combination was associated with a longer median survival (5 months vs. 2.2 months; P=0.052) and a 1-year survival rate of 37.5% vs. 0% (P=0.027). Both treatment groups belonged to similar prognosis subsets. The treatment was well tolerated. Taken together our data support the therapeutic concept of a combined razoxane radiation therapy in melanoma patients with brain metastases. The favorable treatment effects are probably due to the radiosensitizing and the cytorallentaric mode of action of razoxane. Since the patient numbers are low, confirmatory studies are certainly necessary.

Radiotherapy and razoxane in advanced bile duct carcinomas.

OBJECTIVES: Little is known about the radiation sensitivity of bile duct carcinomas. The current study was undertaken to prospectively assess the objective response rates in bile duct carcinomas treated with radiotherapy and razoxane. MATERIALS AND METHODS: Twenty-three patients with advanced cancer of the biliary tree were irradiated together with the radiosensitizer razoxane at a dose of 125 mg twice daily by mouth. There were 16 females and 7 males, median age 68 years. They received a total tumor dose of 48 Gy (range 1.7-60) at the ICRU point with single fractions of 1.7 to 2 Gy. RESULTS: Among the 23 patients, 14 had measurable disease. Objective tumor responses were seen in 4/4 gallbladder carcinomas (1 CR, 3 PR), 4/5 extrahepatic cholangiocarcinomas (2 CR 2 PR), and 1/5 hepatobiliary cancers (1 PR), leading to an overall response rate of 64%. The tumors remained locally controlled in 12 out of 16 assessable patients (75%). On an intention-to-treat basis, all patients with different biliary cancer without distant metastases had a median-survival time of 10 months (range 1 to 48) from the start of the radiotherapy; the 1-year survival was 43%. No patient survived beyond 4 years. Tolerance to the treatment was fairly good. Nausea and vomiting of grade 1 and 2 (WHO) was noted in 61%, and reversible leukopenia of grade 3 and 4 in 9% of the cases. The rate of inherent complications was high. CONCLUSION: Combined radiotherapy and razoxane led to local response rates which are superior to data from the literature when radiotherapy alone is used. Obstacles to the treatment were complications of the disease and frequent metastasis.

Treatment options for malignant hemangioendotheliomas of the thyroid.

BACKGROUND: Malignant hemangioendotheliomas of the thyroid are rare tumors predominantly seen in areas with endemic goiter such as the Alpine regions. The estimated incidence of the disease is between 0.15 and 0.25 per 100.000 inhabitants annually for Western Austria. The tumor is regarded as radio-resistant, and its prognosis is reported to be dismal. PATIENTS AND METHODS: Between 1982 and 1999, 12 cases with immunohistochemically confirmed malignant hemangioendotheliomas of the thyroid were referred for postoperative or palliative treatment. There were 8 men and 4 women with a median age of 67 years (range, 55-81 years). With surgery, clear margins were achieved in 5, microscopic residues were left in 3, and gross residual disease in 3 patients. One patient had an inoperable primary tumor. Postoperative radiotherapy was given to 8 cases, 6 of them received the radiosensitizer razoxane on radiation days. Total tumor doses ranged between 54 and 65 Gy. Two patients with clear margins at surgery received no adjuvant radiotherapy and were observed only. RESULTS: Local tumor control was achieved in 11 of 12 patients; 5 lived longer than 5 years. The median survival time of all cases is presently 14 months (range, 0.5-196 months). If 3 cases with metastasis at diagnosis were left out of the analysis, the median survival is 70 months. Noteworthy is a complete regression of 2 lung metastases in a 72-year-old man treated with the combination of vindesine, razoxane, and radiotherapy; the patient is still in complete remission more than 94 months after 3-year maintenance therapy with vindesine and razoxane. Fibrinogen, factor VIII, and factor VIII-related antigen in the serum could serve as surrogate markers during the follow-up. The tolerance to the combined modality treatment was good to fair, local chemoradiation reactions of normal tissues have to be considered as the principal toxicity. It may also be of interest that 5 of 12 patients were exposed to vinyl chloride and other polymeric materials during their working life. CONCLUSIONS: This small series indicates that the course of the disease is not uniformly bleak and that the resistance to radiotherapy reported in the literature has to be questioned. It appears that adequate surgery together with rapid radiation therapy in combination with razoxane, a radiosensitizer and agent that can normalize tumor blood vessels, is able to improve the local control rate and thus perhaps to alter the natural history of this disease. In addition, the data offer new evidence of the occurrence of vinyl-chloride-induced angiosarcomas outside the liver, and support similar observations that have already been published in case reports.

Epidemiological aspects of hadron therapy: a prospective nationwide study of the Austrian project MedAustron and the Austrian Society of Radiooncology (OEGRO).

BACKGROUND: The planned MedAustron hadron therapy facility is designed to compare proton and carbon ion beam therapy under the same technical conditions. For the calculation of the number of potential patients for hadron therapy so far, only epidemiological estimations on cancer incidence are available without inclusion of the percentage of patients routinely referred to conventional radiotherapy. MATERIALS AND METHODS: Nationwide prospective survey to collect disease and treatment related data on patients receiving conventional radiotherapy at all 12 treatment facilities. Epidemiological cancer incidence (Statistic Austria 1999) were correlated with the number of patients receiving conventional radiotherapy. Based on published clinical and experimental results on proton and carbon ion therapy, a calculation of patient's subgroups suitable for hadron therapy was performed at five European University hospitals involved in the HICAT, CNAO, ETOILE and MEDAustron project. Using the mean values of the University specific percentages per tumour site, the number of potential patients was estimated. RESULTS: In Austria, a total of 3783 patients started radiotherapy during the study period of 3 months resulting in an approximated number of 15132 patients per year. The number of potential patients was estimated to 2044 per year, representing 5.6% of all newly diagnosed cancer patients and 13.5% of all irradiated cancer patients. CONCLUSION: There is a clear place for a hadron therapy facility in Austria, based on pattern of care in radiotherapy, cancer incidence and indications.

The med AUSTRON/OGRO patterns of care study on radiotherapy indications in Austria.

PURPOSE: In Austria a national survey was conducted by Med AUSTRON/Osterreichische Gesellschaft for Radio--Onkologie, Radiobiologie und Medizinische Radiophysik (OGRO) in order to estimate the indications, patient numbers and radiotherapy treatment planning procedures and performances at all Austrian radiotherapy institutes. Results were correlated with incidence rates (Austrian cancer registry) to determine patterns of radiotherapy practice in Austria. MATERIAL AND METHODS: At 12 radiotherapy departments of Austria data of all patients receiving irradiation within a 3 months (2002/2003) period were assessed. On the basis of a questionnaire number of treated patients, indications, and parameters of disease (stage, histology) and treatment modalities were evaluated. Results were analysed with regard to different tumour groups, according to academic and non academic hospitals, and correlated with epidemiological data on cancer incidence. RESULTS: In total, 3783 patients were registered within this period. According to the different tumour entities percentages of patients receiving radiotherapy within initial treatment varied from 3% to 90 % (e.g. brain tumours: 77%, breast cancer: 90%, prostate cancer: 35%). The most frequent indications to radiotherapy per radiotherapy department were breast cancer (range 22%-35%; mean 26%), urological tumours (range 6%-27%; mean 12%) and bone metastases (mean 10%, range 3%-17%). CONCLUSION: In Austria breast cancer, urological tumours and bone metastases are representing the most common indications to radiotherapy. Among the different departments variations in indications to radiotherapy were observed. Our study is the first evaluation of radiotherapeutic management in Austria.