[Comment. Hyperbaric oxygenation (HBO) in the treatment of radiogenic side effects. Clinical experiences are decisive!].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to U M Carl.
Explore the source record for details and available documents.
Reconstruction techniques for pathological fractures caused by bone metastases often include acrylic cement to stabilise defects. The aim of this study was to test in a rodent model, whether outcome could be improved by local chemotherapy from an anticancer drug added to the acrylic cement. Tumour excision 17 days after transplantation into the femur was followed by fractionated irradiation. Supplementation of acrylic cement with daunorubicin led to a considerable reduction of TCD37% from 72.9 Gy (62.2-82.8) to 29.3 Gy (21.8-37.5) (P = 0.0007). Local chemotherapy diffusing from bone cement combined with postoperative radiotherapy was highly effective in the experimental system studied.
Hypoxic clonogenic cells are an important contributory factor in tumour radioresistance. The objective of the present study was to evaluate whether hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally fractionated irradiation schedule, and whether the radiosensitizing potential is different from carbogen. Experiments were performed using the rhabdomyosarcoma R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30 X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/- 4.1 days for air, normobaric carbogen and HBO, respectively. The differences between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were significant. Use of carbogen and HBO produced the same local control probability at 150 days and this was significantly higher than local control under ambient conditions (p < 0.0001). It was concluded that the time to achieve complete remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore, both HBO and carbogen give higher local control probabilities than treatment under ambient conditions when used with a conventionally fractionated radiation schedule.
AIM: The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. PATIENTS AND METHODS: One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy 192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 x 2 Gy/week. Local hyperthermia with 43.5-44.5 degrees C over 60 minutes was delivered immediately before interstitial radiotherapy. RESULTS: One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases. CONCLUSION: In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
AIM: Many reports show that late complications of radiotherapy can be successfully treated by hyperbaric oxygen (HBO). This synopsis attempts to review the literature to identify areas of clinical use and further research. PATIENTS AND METHODS: Clinical and experimental data about HBO treatment of radiation late effects are analysed. Mechanisms of hyperbaric oxygen in the treatment of late radiation side effects are discussed. RESULTS: There is evidence in the literature that HBO is beneficial in the treatment of radiation cystitis, osteoradionecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits. The prophylactic use of HBO has shown to prevent the development of osteoradionecrosis after tooth removal and the loss of titanium implants in irradiated facial bones. The physiologic basis of HBO can be referred to induction of neoangiogenesis and revascularisation. CONCLUSIONS: Clinicians can be encouraged to use hyperbaric oxygen for the treatment of radiation cystitis, osteonecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits following radiation therapy.
Patients with adenocarcinoma of the prostate with positive surgical margins and/or seminal vesicle invasion after radical prostatectomy (RP) have a high risk of local recurrence or distant spread of disease. Several investigators reported increased local control rates following adjuvant radiotherapy (RT). However, it is unclear whether this procedure, with or without hormonal therapy (HT), improves the outcome. From 1975 to 1987, 56 patients with adenocarcinoma of the prostate underwent adjuvant RT following RP (pathological stage C1, n = 19; stage C2, n = 17; stage D1, n = 20). In 27 of 56 patients an additional immediate orchiectomy was performed. 48 patients received 4000-5000 cGy to the pelvic lymphatics, including the prostatic fossa, followed by a boost to the prostatic fossa to complete 6400-7000 cGy, whereas 8 patients were treated to the prostatic fossa only. With a median follow-up of 89 months, the overall survival rate of patients with stages C1, C2 and D1 did not differ significantly (10-year overall survival rate 84, 74 and 71, respectively). The local control rate for 5- and 10-years was 96 and 90%, respectively. A significant advantage in overall survival (5- and 10-year rate: 92 versus 93% and 92 versus 63%; P < 0.05, respectively) and clinical disease-free survival (5- and 10-year rate: 92 versus 72% and 92 versus 49%; P < 0.05, respectively) was seen in 27 patients with orchiectomy compared with 29 patients without HT. A total of 15 patients (26%) developed at least one form of late toxicity, in most cases a mild proctitis, cystitis, or penile or leg oedema. However, 6 patients (11%) had severe grade 3 or 4 side-effects that necessitated a cystectomy in 2 cases as well as a colostomy in 2 cases. In all patients with grade 3 or 4 side-effects, 70 Gy as a tumour-encompassing isodose were applied. Adjuvant RT, following RP in stage C and D1 prostate cancer with positive surgical margins and/or seminal vesicle invasion increases local control. Whether immediate HT influences the outcome, as seen in this study, should be proven in prospective clinical trials.
PURPOSE: The incidence of endometrial cancer has increased considerably within the last decades. Due to early symptoms more than 88% of all patients present initially with FIGO stage I or II disease. PATIENTS AND METHODS: One hundred and forty-four patients out of 192 patients with stage I endometrial cancers received surgical treatment alone. Like the remaining 48 patients 39 out of 65 patients with stage II tumors received adjuvant radiation therapy with 50 Gy to the true pelvis. RESULTS: Independent on the chosen treatment results in stage I were influenced by the depth of myometrial invasion (p = 0.023). With a crude 5-year survival rate of 88% patients with less than 33% reached life expectation of matched healthy women. With deeper infiltration crude survival rates were as low as 77%. In stage II tumors 5-year crude survival was elevated 60 to 80% independent on the depth of myometrial infiltration by adjuvant radiation therapy (p = 0.11). CONCLUSIONS: Despite its potential curability and the general knowledge that the prognosis of endometrial carcinomas is governed by a number of factors there are no generally accepted standard treatment modalities available Thus there is great demand for randomized clinical trials.
Explore the source record for details and available documents.
PURPOSE: Divergent opinions exist on the value of adjuvant treatment in endometrial cancer. This paper aims at clarifying the indications for adjuvant radiotherapy by reviewing the literature and presenting own data. METHODS: For endometrial cancer 5-year survival data are analysed with respect to the value of adjuvant radiotherapy and/or chemo-/hormone therapy. RESULTS: Adjuvant radiotherapy in FIGO stage I and II tumors reduces pelvic recurrence rates from 15 to 20% to 1 to 5%. In high risk stage I patients the 5-year survival rate is increased by 30 to 40% using pre-operative high dose endocavitary brachytherapy or postoperative external beam therapy. In stage II disease the 5-year survival rate is increased to 60 to 80% when applying 50 to 60 Gy post surgery. In stage III and IV tumors primary radiotherapy results in 5-year survival rates of 16 to 40%. CONCLUSIONS: In stage I and II endometrial cancer primary treatment consists of surgery followed by radiotherapy in eligible cases. In stage III and IV tumors primary radiotherapy is generally advocated. No properly randomized trials are available to date on the value of adjuvant treatment. There is a great demand for such trials in order to confirm the available data. According to the extent of the disease and the discrimination of certain risk groups these trials should include external beam pelvic irradiation, brachytherapy, para-aortic irradiation as well as systemic chemo-or hormone therapy.
The magnitude of the delay of cells in the phases of the cell cycle after irradiation may be related to the radioresponsiveness of tumor cell populations. In this study we have quantified division delay in two mouse tumors in vivo after single and fractionated doses of X rays and single doses of neutrons. The incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and quantitative method to detect cell cycle perturbations after radiation treatment. The more rapidly growing SAF tumor showed less G2-phase delay per gray than a more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF tumor failed to show any G1/S-phase delay while the Rh tumor experienced a longer G1-phase delay than that measured for G2 phase (3.1 vs 1.8 h). There was a trend in both tumors for lower doses to be more effective in producing cell cycle delays. Neutrons caused longer G2-phase delays on a unit dose basis, 2.5 and 5.4 h for the SAF and Rh tumors, respectively. The RBE for neutrons for division delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction in division delay at higher total doses (10 or 12 Gy) but was without effect at the lower dose studied (6 Gy). These studies show the feasibility of measuring cell cycle delays in vivo, and future developments are suggested for a possible predictive test in patients receiving radiotherapy.
From 1965 to 1986, 173 patients with gynaecological cancer received para-aortic radiation treatment using a biaxial-four-segmental-rotating field technique. Seventy-five patients with cervical cancer and proven lymph node involvement were eligible for analysis. Crude survival and disease-free survival in 37 patients with FIGO III and 15 patients with FIGO IVA, receiving initial para-aortic treatment were compared with the corresponding data from patients in whom para-aortic treatment was secondary applied when para-aortic metastases became clinically symptomatic. Five-year survival rates of 37.5% (FIGO III) and 27.3% (FIGO IVA) were encouraging as none of the patients in the secondary group survived for more than 16 months. The number of complications induced by the described method of survived for more than 16 months. The number of complications induced by the described method of para-aortic irradiation appears to be substantially lower than with other methods using equal doses. Five cases of severe but not life-threatening side-effects were observed among 173 treated patients.
A number of experimental investigations has demonstrated, that tumor growth delay due to a mixed fractionated treatment schedule with photons and neutrons can be prolonged compared to pure photon treatment. That question after the mechanisms remains undissolved. In the presented study of the R1H tumor of the rat 30 fractions using 2 Gy of photons in 39 days are compared to results of mixed fractionated treatment schedules with neutrons and photons. Neither a prolonged net growth delay (NGD) was found nor does the sequence in which neutrons and photons are given influence the outcome when replacing photons by neutrons in twelve of 30 fractions (RBE 2.5). In contrast, hypofractionated schedules (five fractions/total dose 40 Gy/four days) have a considerable longer NGD when replacing two fractions of photons by neutrons (RBE 2.5) (p < 0.01). This could be explained if 8 Gy photons/fraction destroyed all euoxic tumor cells, a 24 hour interval was too short for reoxygenation and thus make hypoxia to a major problem in 8 Gy/fraction photon treatment.
Data from previous animal experiments were analyzed retrospectively with a view to the induction of secondary tumors. The skin of 86 rats was exposed locally to multiple fractions of 200 kV p X rays at doses of 60 to 82 Gy applied in 30 or 35 fractions in 6 weeks, i.e., in the clinically relevant range of 1.9 to 2.7 Gy per fraction. The course of the early skin reaction was scored and compared to the late carcinogenic effects of the treatment using Kaplan-Meier data analysis. With increasing total dose the median duration of the early skin reaction increased, while median latency of tumor induction in the irradiated area of skin decreased from 381 days after 60 Gy to 274 days after 82 Gy. Independent of the total dose, number of fractions, and operative intervention, 84 to 100% of the animals cured by irradiation developed a secondary neoplasm inside the treated area. The majority of induced tumors were squamous cell carcinomas. In the skin covering the thorax, which had received a dose of 15 Gy in 10 fractions for elective irradiation of the lungs, no tumors were induced.
The value of follow-up investigations depends on the therapeutic consequences of early detection of recurrences and metastatic disease. After breast conservation early detection of recurrent disease by physical and apparative examinations has to be aimed for due to a possible curation by salvage surgery. Also in recurrences of the chest wall a great deal of local controls can be achieved when detected early and at smaller sizes. While axillary recurrences can be controlled by surgery and radiation therapy the prognosis is poor in the case of a supraclavicular and retrosternal lymph node involvement. Diagnostic and therapeutic options will be discussed for these five types of recurrences.
Studies were carried out to investigate proliferative changes in two murine experimental tumours in response to radiation. Results were generated using bromodeoxyuridine labelling and flow cytometry. This study demonstrates the possible ambiguity of previous studies using tritiated thymidine in which inability to discriminate normal and tumour cell components in murine tumours may lead to different values for cell kinetic parameters. In particular, the sarcoma F appeared to have a growth fraction of 0.62 when all cells were considered; in reality the growth fraction of the tumour cells only (based on DNA content discrimination) was close to unity. Radiation, administered either as single or fractionated doses, caused little change in the proliferative characteristics of the sarcoma F tumour but had profound effects on the adenocarcinoma Rhodesia tumour. Major changes were the accumulation of cells in G2 for several days after the end of the radiation treatment in both tumours and a dramatic drop in labelling index of the Rhodesia tumour. In neither tumour was there any evidence to suggest an increase in tumour cell proliferation during or after the irradiations. The diploid cells within the sarcoma F tumour showed an initial depression of labelling index followed by a rapid increase overshooting the control labelling index at higher radiation doses. Much of the effects could be attributed to cell cycle delays.