Late radiation sequelae as a consequence of breast-conserving therapy with cobalt irradiation aggravated by various risk factors.

This report deals with a 71-year-old female patient who developed cancer in her right breast 20 years ago, underwent breast-conserving surgery and received normofractionated radiotherapy with a 60Co unit. 19 years later, fibroids and calcified tissue appeared in her right mammary fold. Furthermore, a deep ulceration developed in this region during chemotherapy of bronchial carcinoma. Apart from being a Type 2 diabetic with arterial hypertension, she was also a habitual smoker. After extensive wound debridement and vacuum-assisted sealing therapy, the affected ribs were dissected and a latissimus dorsi flap was implanted. Our focus here is on the interaction of contributing risks for the development of late radiation sequelae, such as physical (especially unintended hot spots during 60Co irradiation) and pathophysiological factors (comorbidities and morbid affections). Fortunately, side-effects such as these are rare nowadays. As this case shows, however, they can be effectively handled by employing modern plastic surgery techniques.

Neuroprotection by oxygen in acute transient focal cerebral ischemia is dose dependent and shows superiority of hyperbaric oxygenation.

The neuroprotective effect of oxygen after acute stroke in rats has been shown previously. However, the question of optimal dosing still remains unanswered. Thus, we investigated the use of oxygen at different concentrations by either normobaric oxygenation (NBO) or hyperbaric oxygenation (HBO) at different pressures in a model of transient ischemia/reperfusion in rats. Animals underwent 90 min of middle cerebral artery occlusion (MCAO) followed by 90 min of reperfusion before oxygen treatment. Oxygen was applied either by NBO (100% O(2); 1.0 absolute atmosphere, ATA) or HBO (100% O(2); 1.5, 2.0, 2.5 or 3.0 ATA) for 1 h. Primary endpoints were infarct volume and clinical outcome measured 24 h and 7 days following the MCAO. A statistically significant and long-lasting reduction in infarct volume was seen in the HBO 2.5 ATA and 3.0 ATA groups over a period of 7 days. The reduced infarct volume was accompanied with a statistically significant improvement in clinical outcome in the high-dose oxygen-treated groups. The presented data indicate that oxygen is a highly neuroprotective molecule in transient focal cerebral ischemia in rats, when applied early and at high doses. The effect is dose dependent and shows a superiority of HBO over NBO, when the primary endpoints infarct volume reduction and clinical outcome are analyzed. These data are important for the development of new acute stroke treatment studies in humans.

Heterotopic calcification as a late radiation effect: report of 15 cases.

The LENT-SOMA scoring system for reporting late tissue effects following therapeutic radiation does not include heterotopic calcification as an end-point. Here we report on 15 long-term radiotherapy survivors with significant heterotopic calcifications. In all cases heterotopic calcification was linked to other radiation sequelae, e.g. ulceration, bone necrosis, nerve damage and fibrosis. The median time interval between radiotherapy and the occurrence of heterotopic calcification was 19 years (range 2-31 years). All patients received doses in excess of 40 Gy; overlap of adjacent fields played a role in some cases. It appears that heterotopic calcification can be regarded as end-stage damage following high dose radiotherapy. Heterotopic calcification in conjunction with local tissue breakdown is highly suggestive of previous radiation treatment.

Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H.

PURPOSE: Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. METHODS AND MATERIALS: Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO2) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. RESULTS: HBO but not carbogen significantly increased the median pO2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p = 0.044; air vs. HBO: p = 0.02; carbogen vs. HBO: p = 0.048). CONCLUSION: Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation.

Hyperbaric oxygen therapy for late sequelae in women receiving radiation after breast-conserving surgery.

PURPOSE: Persisting symptomatology after breast-conserving surgery and radiation is frequently reported. In most cases, symptoms in the breast resolve without further treatment. In some instances, however, pain, erythema, and edema can persist for years and can impact the patient's quality of life. Hyperbaric oxygen therapy was shown to be effective as treatment for late radiation sequelae. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment. PATIENTS AND METHODS: Forty-four patients with persisting symptomatology after breast-conservation therapy were prospectively observed. Thirty-two women received hyperbaric oxygen therapy in a multiplace chamber for a median of 25 sessions (range, 7-60). One hundred percent oxygen was delivered at 240 kPa for 90-min sessions, 5 times per week. Twelve control patients received no further treatment. Changes throughout the irradiated breast tissue were scored prior to and after hyperbaric oxygen therapy using modified LENT-SOMA criteria. RESULTS: Hyperbaric oxygen therapy patients showed a significant reduction of pain, edema, and erythema scores as compared to untreated controls (p < 0.001). Fibrosis and telangiectasia, however, were not significantly affected by hyperbaric oxygen therapy. Seven of 32 women were free of symptoms after hyperbaric oxygen therapy, whereas all 12 patients in the control group had persisting complaints. CONCLUSIONS: Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy.

Radiosensitizing effect of carbogen breathing during pulsed irradiation of the rat R1H tumor.

The objective of the present study was to investigate the radiosensitizing effect of carbogen breathing during pulsed x-ray irradiation in an experimental tumor model. Rat R1H rhabdomyosarcoma tumors were irradiated with 36 Gy total dose in 1 Gy high dose rate pulses, either hourly repeated, or in an 'office hours' protocol with irradiation-free overnight intervals. With the hourly, pulsed irradiation scheme, tumor growth delay (TGD) was significantly increased from 24.4+/-0.7 days in air-breathing animals to 29.0+/-0.9 days in animals breathing carbogen during irradiation. With irradiation during office hours, the TGD was shortened, and carbogen was less effective. The data show that carbogen acts as a radiosensitizer when applied during pulsed irradiation. Translation of the experimental data to clinical practice indicates that hyperoxygenation of the tumor during pulsed dose rate (PDR) or high dose rate (HDR) brachytherapy might enhance the tumor response of patients.

The influence of inspiratory hyperoxia on ischemia-reperfusion-induced tumour growth delay.

We investigated the ischemia-reperfusion-induced tumour growth delay as a function of ischemic time, tumour temperature, and the amount of inspired oxygen during reperfusion. The rhabdomyosarcoma R1H growing on the right flank of male WAG/Rij rats was clamped for 2 or 4 h at 20 degrees C or 37 degrees C. Five minutes prior to and 10 min during reperfusion the animals respired air, pure oxygen or carbogen (95% O2, 5% CO2). Comparison of single treatment modalities with untreated controls revealed significant tumour growth delays after clamping times of 4 h at 37 degrees C for air and pure oxygen, but not for carbogen.

[Changes in hemoglobin concentrations in combined radio- and chemotherapy in locally advanced ORL tumors]. / Anderungen der Hämoglobinkonzentration bei kombinierter Radio- und Chemotherapie lokal fortgeschrittener HNO-Tumoren.

BACKGROUND: Despite multimodality treatment strategies of locally advanced head and neck cancers long-term results leave much to be desired. There is evidence that oxygenation status of head and neck tumors is directly influenced by the hemoglobin concentration. The aim of this study was to verify changes in the hemoglobin level during combined radio-chemotherapy of locally advanced head and neck tumors. PATIENTS AND METHODS: Sixty-eight patients with locally advanced head and neck cancer had primary or adjuvant radiotherapy with doses of 60 to 74 Gy in combination with cisplatin- (+/- 5-FU) or carboplatin chemotherapy in the first and fifth week of treatment. Hemoglobin levels were analyzed before and at the end of radiotherapy. RESULTS: In 41% of all patients the initial hemoglobin concentration was below normal levels. The mean hemoglobin values in all patients dropped significantly from 12.9 +/- 1.7 g/dl before to 11.6 +/- 1.6 g/dl at the end of treatment. In 12 cases (18%) allogeneic erythrocytes had to be transfused during treatment. At the end of treatment 76% of all patients had anemic hemoglobin levels. In the groups of patients with cisplatin and carboplatin chemotherapy a significant decrease in hemoglobin levels was seen without meaningful statistical difference between these 2 groups. CONCLUSIONS: In patients with locally advanced head and neck cancer a high initial rate of anemia was registered (41%): This rate was nearly doubled during chemoradiation (76%). Since several studies have shown a correlation between hemoglobin levels and local tumor control, there is evidence, that this group might benefit from correcting anemia before combined radio-chemotherapy.

Pain palliation with rhenium-186 HEDP in breast cancer patients with disseminated bone metastases.

PURPOSE: For patients with metastatic prostate cancer, first results have shown that rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) is efficient in pain palliation of disseminated bone metastases. The aim of this study was to determine whether significant pain reduction can also be achieved in breast cancer patients with Re-186 HEDP. METHODS: Thirty patients with breast cancer who had multifocal painful bone metastases received a total of 38 intravenous Re-186 HEDP injections. Pain relief was assessed through daily documentation of the visual analog scale and analgesic consumption. A significant response to treatment was determined if the visual analog scale or analgesic consumption decreased significantly for at least 2 weeks. Blood counts were controlled at baseline and at weeks 4 and 8. RESULTS: A response to pain therapy was observed in 60% (18 of 30) of the patients. A reversible thrombocytopenia and leukopenia of grade 2 (according to World Health Organization criteria) was found in 4 and 2 patients, respectively. CONCLUSION: Patients with disseminated osseous metastases resulting from breast cancer can benefit from therapy with Re-186 HEDP.

Hyperbaric oxygen therapy in deep sternal wound infection after heart transplantation.

The results of orthotopic heart transplantation (OHTx) are still burdened with considerable early mortality due to graft rejection or infection. Sternum osteomyelitis is an infrequent postoperative complication. We report a case of deep sternal wound infection (2 months after OHTx) that was treated with hyperbaric oxygen therapy in addition to local surgical treatment.

The treatment of late radiation effects with hyperbaric oxygenation (HBO).

BACKGROUND: Late radiation injuries may impose a negative influence on the quality of life in the affected patients. In several entities, standardized treatment protocols are lacking. Hyperbaric oxygenation (HBO) has been shown to have beneficial effects in the treatment of late radiation sequelae. MATERIAL AND METHODS: The basic principles of HBO are reviewed as well as clinical issues. Current study protocols are presented. RESULTS: During HBO-therapy the patient breathes pure oxygen at pressures above 100 kPa. The oxygen solubility within the fluid phase of the blood is largely increased. Biological effects include an increased oxygen diffusibility, improved collagen synthesis and neoangiogenesis as well as an enhancement of antimicrobial defenses. By decreasing the capillary filtration pressure a reduction of edema becomes possible. HBO has been shown to prevent complications following surgery in irradiated tissues. Its efficacy as an adjunct in the treatment of osteonecroses in radiation patients could be demonstrated. In addition, the loss of osseointegrated implants in the maxillofacial bones of these patients could be significantly reduced. Further indications include soft tissue necroses, hemorrhagic cystitis and proctitis in tumor patients that have been treated by radiotherapy as part of a multimodality approach. CONCLUSIONS: HBO in the treatment of late radiation effects is still subject of investigation, but remarkable results have been reported. Optimized treatment protocols need to be determined in various entities. The rate of side effects is acceptable low.

Treatment of radiation proctitis with hyperbaric oxygen: what is the optimal number of HBO treatments?

AIM: Our objective was to investigate the effectiveness of hyperbaric oxygenation (HBO) in the treatment of radiation proctitis. The current literature was reviewed with regard to the necessary number of HBO treatments. PATIENTS AND METHODS: Two patients with proctitis after pelvic irradiation were treated with 40 and 38 HBO treatments, respectively. Hyperbaric oxygenation was delivered at 240 kPa over 90 min. RESULTS: In one patient, proctosigmoidoscopy showed a significant improvement after 40 HBO sessions. The other patient interrupted therapy after 38 HBO treatments without subjective change. The reported number of HBO sessions for a successful treatment of radiation proctitis ranges from 12 to 90. CONCLUSION: HBO should be considered before more invasive treatment modalities are performed for radiation proctitis.

Enhancement of radiosensitivity of rat rhabdomyosarcoma R1H with normobaric carbogen and hyperbaric oxygen (HBO) using conventionally fractionated irradiation.

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.

Combined modality treatment of bone metastases: response of the rhabdomyosarcoma R1H of the rat to postoperative irradiation combined with local release of daunorubicin from acrylic cement.

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.

Hyperbaric oxygen treatment for symptomatic breast edema after radiation therapy.

A 54-yr-old woman with a pT2pN0 breast cancer developed a long-standing symptomatic breast edema after lumpectomy and radiation therapy. The breast edema did not respond to non-steroidal anti-inflammatory drugs (NSAIDs) and manual lymph drainage of her arm. Three years after completion of radiation therapy, hyperbaric oxygen (HBO2) treatment was initiated. Fifteen HBO2 sessions were performed at a pressure of 240 kPa over 90 min in a multiplace chamber. At the end of treatment, breast discomfort had subsided completely, and 5 mo. after completing HBO2 therapy the patient is still free of complaints. We conclude from this observation that the value of HBO2 in the management of symptomatic radiation-induced breast edema should be investigated in a clinical study, because other effective treatment options are not available for this condition.

Post-Operative Radiotherapy of the Rhabdomyosarcoma R1H of the Rat.

Purpose. Post-operative radiotherapy (RT) is routinely applied in the treatment of several human tumours. The aim of the present study was to investigate the value of post-operative RT in a rat model.Methods. Experiments were performed using the rhabdomyosarcoma R1H of the WAG/Rij rat. Animals were randomized to different treatment schedules: surgery, RT or a combination of both. Tumours were excised at different sizes (0.1-4.5 g) aiming for complete macroscopic resection. RT (60 Gy in 30 daily fractions over 6 weeks) was applied either primarily or to the former turnout site from the third post-operative day. Tumour growth delay, time to recurrence and local tumour control were used as endpoints.Results. Pre-operative tumour size determined the time and rate of recurrence. The larger the tumour, the shorter the time to relapse and the higher the recurrence rate. The 50% local control rate (LCR(50)) for surgery was found in tumours with a mass of 0.8 g. For post-operative RT a LCR(50) was achieved for tumours with a mass of 1.1 g. For larger turnouts (> 1.1 g), however, the rate and time course of relapse were similar for both the group receiving RT alone and the group receiving post-operative RT.Discussion. In this model the tumour mass at excision governs the prognosis. Relatively small R1H turnouts may recur despite complete macroscopical resection. With regard to the LCR, the outcome for larger tumours is improved with post-operative RT (60 Gy/6 weeks) than compared with surgery alone. The factor is 1.3. Within a certain range of tumour sizes, combined treatment (surgery + RT) can improve the outcome considerably.

[Preoperative irradiation and interstitial radiotherapy-hyperthermia boost in breast tumors > or = 3 cm. The Düsseldorf experience]. / Präoperative Bestrahlung mit interstitiellem Radio-hyperthermie-Boost bei Mammatumoren > or = 3 cm. Düsseldorfer Ergebnisse.

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.

[Hyperbaric oxygenation (HBO) in the treatment of radiogenic side effects]. / Hyperbare Oxygenierung (HBO) zur Behandlung radiogener Nebenwirkungen.

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.