Limited effects of selenium substitution in the prevention of radiation-associated toxicities. results of a randomized study in head and neck cancer patients.

OBJECTIVE: The substitution of selenium activates the selenium-dependent enzyme glutathione peroxidase, which is important for scavenging free radicals. To date, only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies, e.g. irradiation or chemotherapy, and therefore the objective of this study was to investigate the clinical impact of selenium in such therapies. PATIENTS AND METHODS: 39 patients (8 female, 31 male) with advanced head and neck cancer were included in a randomised phase II study. The mean age was 63.52+/-9.31 years. Tumour localizations: oral cavity 15 patients, oropharynx 19 patients, hypopharynx 5 patients, carcinoma of unknown primary 1 patient. Group A (n=22) received 500 microg sodium selenite on the days of radiotherapy and 300 microg sodium selenite on days without radiotherapy. Group B (17) was irradiated without any selenium substitution. Both groups were well balanced according to age, gender, localization and stage of the tumour. The RTOG grade of radiation-associated toxicities was evaluated once per week. RESULTS: The following serious toxicities were observed (group A vs. group B): dysphagia 22.7% vs. 35.3%, loss of taste 22.7% vs. 47.1%, dry mouth 22.7% vs. 23.5%, and stomatitis 36.4% vs. 23.5%. A statistical trend (Fisher's exact test) was only seen for the loss of taste (p=0.172). The weekly patient analysis (Student's t-test) showed a significant reduction of dysphagia in the selenium group (Group 1) at the last week of irradiation. CONCLUSION: This small randomised trial showed limited effects of selenium in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy of head and neck cancer.

Selenium in the treatment of head and neck lymphedema.

OBJECTIVE: To investigate the impact of selenium in the treatment of lymphedema of the head and neck region after radiotherapy alone or in combination with surgery. SUBJECTS AND MATERIALS: Between June 1996 and June 2001 a total of 36 cancer patients (29 male, 7 female; median age 61 years) were treated with selenium for persistent, extensive or progressive lymphedema of the head and neck region. Twenty had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received 350 microg/m(2) body surface sodium selenite medication p.o. daily (total dose 50 microg per day) for a period of 4-6 weeks after radiotherapy. The optimal effect of the selenium treatment was assessed after 4 weeks of therapy using the Miller score system. A visual analogue scale on a scale of 0-10 was used to assess the patient's quality of life prior to and after selenium. RESULTS: 75% of the patients had an improvement of the Miller score of one stage or more. The self-assessment of quality of life using the visual analogue scale improved significantly after selenium treatment with a reduction of 4.4 points (p < 0.05). Of the 20 patients with endolaryngeal edema tracheostomy was not necessary in 13 patients (65%), but 5 and 2 received a temporary or permanent tracheostomy, respectively. No episode of erysipelas was observed in all study patients. CONCLUSION: Our results suggest a short positive effect of sodium selenite on secondary head and neck lymphedema caused by radiotherapy alone or in combination with surgery.

[Use of complementary/alternative therapy methods by patients with breast cancer]. / Anwendung komplementärer/alternativer Therapiemassnahmen bei Patientinnen mit Brustkrebs.

BACKGROUND: Complementary/alternative medicine (CAM) is gaining increasing importance especially in the treatment of patients with breast carcinoma. The purpose of this analysis was to investigate the prevalence of CAM in patients with breast carcinoma, to statistically describe the preparations and therapies used, and to determine the reasons for their use, the source of information and the individual perception. PATIENTS AND METHODS: The statements of 203 patients with breast carcinoma who underwent radiotherapy were analyzed. The median age was 54 years (range 38-77 years). All patients underwent surgery as first therapy. 36 patients received a second-line radiotherapy because of metastases (27 patients) or local recurrence (9 patients). RESULTS: 159 patients (78%) stated to carry out an additional treatment. 31 out of the 36 patients with metastases or local recurrence used CAM. Vitamin preparations (67%), mistletoe therapy (59%), and mineral preparations (33%) were used most frequently. 70% of the patients used a combination of two or more preparations/therapies. The most cited reason for using CAM was the aim of increasing quality of life (28%) and improving the immune system (27%). 72% stated an improvement of their individual perception. The main source of information was the general practitioner or the gynecologist. CONCLUSION: The radiotherapist has to take these complementary/alternative therapies into consideration; their importance should be evaluated in further studies.

A new administration schedule for amifostine as a radioprotector in cancer therapy.

Thus far, amifostine, a new radioprotective substance, had been given as short infusion 30 minutes before radiotherapy. In our investigation for the first time we have administered the substance as bolus injection (200 mg/m2 dissolved in 10 ml sodium chloride 0.9%). 42 patients with malignancies of the head and neck region, recurrences of rectal carcinomas and bronchial carcinomas had been treated with different solution volumes over different time periods. Using amifostine as a bolus injection had led to a statistically significant decrease in acute toxicity (p = 0.012). In comparison to short infusion (15 minutes) we have documented the same radioprotective impact. Hence, bolus injection of amifostine is feasible and can spare manpower and time in the department of radiotherapy.

Radiotherapy on adult patients with soft tissue sarcoma with fast neutrons or photons.

Through adjuvant photon radiotherapy, it is possible to improve tumor control as well as avoid ultra radical surgery in patients with soft tissue sarcoma. Similar results have been obtained in cases of incomplete resected G1/G2 sarcoma after applying neutron radiotherapy. We compared the results of a group of patients with soft tissue sarcoma treated with those having received photon therapy (100 patients) or neutron therapy (61 patients). The median dose in the photon treated group was 60 Gy (range 45 to 65 Gy). The neutron therapy group received a median dose of 14.1 Gy (range 5.0 to 18.57 Gy). Patients treated with mixed-beam irradiation received an average dose of 36.5 Gy photon and 8.5 Gy neutrons. The 5-year survival rate of the photon group rated 43.1%. In the neutron group we found 42.5%, respectively. In both groups the results of surgical resection and grading were of high significance according to survival. 4% of the patients belonging to the photon group developed grade III/IV WHO side effects. In the neutron group side effects grade III/IV WHO were observed in 11% of the cases. Comparing treatment results of neutron and photon therapy we demonstrated that incompletely resected G1 and G2 tumor patients show greater benefit in the case of neutron radiotherapy.

[Combined radiochemotherapy of an irresectable carcinoma of the pancreas]. / Simultane Radio-chemotherapie eines lokal inoperablen Pankreaskarzinoms.

Local irresectable carcinoma of the pancreas was diagnosed by explorative laparotomy of a 62-years old patient. At this stage (T3 N1 M0), a curative surgical therapy was not possible. The prognosis in these cases is bad. Medium survival time is less than half a year. In order to improve prognosis a combined radiochemotherapy has been applied. The total tumor dose of 44.8 Gy was applied in 2 daily fractions of 1.6 Gy. On the first 3 days of radiotherapy 600 mg/m2 5-FU and 300 mg/m2 folinic acid were given i.v.. Chemotherapy was repeated each 28 days. After 45 months of observation and application of 20 courses chemotherapy no local or systemical progress can be proven in this patient. His health status is good. A combined radio-chemotherapy improves prognosis in locally irresectable carcinoma of the pancreas. In particular cases survival time is surprisingly long.

Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study.

Between July 1990 and September 1993, 32 patients with locally advanced irresectable adenocarcinoma of the pancreas, histologically proven by laparotomy, were involved in our study. Patients were treated with hyperfractionated, accelerated radiotherapy and simultaneous application of 5-fluorouracil and folinic acid. Chemotherapy was given on days 1,2 and 3. Determination of the target volume for radiotherapy was carried out by computerized axial tomography. The total tumour dose of 44.8 Gy was applied relative to the 90% isodose in two daily fractions of 1.6 Gy, resulting in ten fractions per week. On the first three days of radiotherapy, 600 mg m-3 of 5-fluorouracil and 300 mg m-3 of folinic acid were given i.v. According to response, chemotherapy was repeated in 4-week intervals. The median survival time for all patients was 12.7 months, compared with 3-7 months after palliative surgery (historical control). The median progression-free interval was 6.6 months. Toxicity and therapy-induced morbidity were recorded according to WHO criteria. Nausea and vomiting of WHO grade I and II occurred in 72.1% and of grade III and IV in 27.9% of the patients. WHO grade I and II diarrhoea was seen in 11 patients. The overall incidence of leucopenia and thrombocytopenia was 37.4%; severe side-effects (WHO III-IV) occurred in 9.3% of all patients. One patient experienced a severe mucositis (WHO III). This combined modality treatment consisting of accelerated hyperfractionated radiotherapy and chemotherapy turned out to be feasible for patients with locally advanced, irresectable pancreatic cancer. The therapy could be applied in a short period of time, approximately half the time used in conventional therapy schemes.

[High-dose multimodal radiotherapy of confluent destructively growing aggregated keratoacanthoma. 2 case reports]. / Hochdosierte multimodale Radiotherapie konfluierend-destruierend wachsender, aggregierter Keratoakanthome, Zwei Falldarstellungen.

BACKGROUND: Keratoacanthoma is a fairly common, benign, usually self-resolving skin lesion that arises from the hair follicle. This nodular lesion shows a predilection for areas exposed to light, mainly for the face. We report on the intensive radiation therapy of 2 cases of a rare subset of keratoacanthoma which showed a locally aggressive, seriously destructive growth. PATIENTS AND METHODS: Two female patients with previously treated, confluent-destructive growing keratoacanthoma were treated by multimodal, high-dose radiotherapy. Patient 1 showed a rapid progress of midfacial tumor with destructive infiltration of the left cheek, nasal cartilage, the cribriform plate of ethmoid and congestion of the conjunctiva close to the lacrimal caruncle. This could be shown in clinical and histopathological investigations and CT-scans. The coexistence of cutaneous and conjunctival lesions in locally rapidly enlarging keratoacanthoma of the face is unusual and unreported to our knowledge. One case of simultaneous conjunctival and multiple, eruptive keratoacanthoma of the body has been reported. Patient 2 had received soft X-ray pretreatment because of a large, relapsing keratoacanthoma of the left cheek. RESULTS: Patient 1 underwent a parallel, intensive treatment of the conjunctiva with 90Sr-contact therapy, percutaneous high-dose 60Co-gamma- and megavoltage electron treatment (10 and 18 MeV) of the midfacial lesions. Conjunctiva and caruncle showed a complete remission of keratoacanthoma. In the other facial areas no long-term regression could be reached, despite giving a fully cancericidal, total dose of more than 100 Gy in some regions. Patient 2: Further high dose radiotherapy using megavoltage electron treatment with a total dose of 50 Gy showed a complete remission of the lesion for 5 months. Another relapse of this keratoacanthoma could be operated successfully. There was no more relapse established in follow-up checks. CONCLUSIONS: The 2 case reports show that in treatment of locally destructive growing subsets of keratoacanthoma a sufficient therapy should be initiated in time. Keratoacanthoma and subsets of this lesion that do not respond well to initial treatment, recur early or show seriously aggressive growth should be treated early by combined therapy that takes previous experiences into consideration.