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.

[Short-term hypofractionated radiotherapy followed by total mesorectal excision]. / Kleinvolumige hypofraktionierte Radiotherapie vor totaler mesorektaler Exzision.

PURPOSE: Is preoperative short-term radiotherapy of operable rectal carcinoma feasible with regard to early side effects and perioperative complications? PATIENTS AND METHODS: As of December 1996 to March 1999, 34 patients with locally advanced rectal cancer have been irradiated preoperatively with 5 times 5 Gy. After CT-planning, radiotherapy was administered using a 3-field or 4-field box technique with 2 anterior-posterior fields or a posterior field of 9 +/- 2 cm x 11.5 +/- 2.4 cm and 2 opposed bilateral fields of 9 +/- 1.5 cm x 11.5 +/- 2 cm with 6- to 25-MV photons. Surgery was performed 14 +/- 6 days after irradiation in 33/34 patients (82% anterior resection with total mesorectal excision, 18% abdomino-perineal resection). Patients with a positive lymph node status or pT3/4 lesions underwent adjuvant chemotherapy with 5-Fluorouracil (5-FU). The median follow-up period is 189 days (range: 15 to 548 days). RESULTS: The following early side reactions were registered: increased bowel movements (4/34), fatigue (2/34), pain in the groins (1/34), nausea and perianal smart (1/34), vertigo (1/34), temporary urinary obstruction (1/34). One patient with heart failure NYHA Grade III died of a heart attack after 21 days. Preoperative T and N categories showed a distribution of 3, 29 and 2 for T4, T3 and unknown and 20, 11 and 3 for N+, N- and unknown; postoperative T and N categories showed a distribution of 3, 19 and 11 for T4, T3 and T2 and 19 and 14 for N+ and N-. In 32 of 33 patients tumor-free margins were achieved. One patient with peritoneal metastases had a R1 resection. In 3 patients metastases were detected intraoperatively. Perioperative complications were: 2 cases of leaking anastomosis and postoperative bowel atonia, 1 case with bowel obstruction, delayed wound healing, wound dehiscence and temporary renal dysfunction. CONCLUSION: Preoperative radiotherapy is feasible with moderate toxicity and is able to induce down staging despite the short time interval between radiotherapy and surgery.

[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.

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.

Induction chemotherapy and radiotherapy to avoid mastectomy in stage IIA-IIIA breast cancer.

The aim of the presented protocol was to investigate tumour remission and breast conservation rates with and without flap supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. 101 patients with stage IIA-IIIA breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. 96 patients underwent salvage surgery. Complete pathologic response was not related to tumour diameter at diagnosis, the applied chemotherapy regime, number of chemotherapy cycles, overall radiation treatment time and time interval between radiotherapy and surgery. A breast conserving approach was possible in 55 patients (54%). After a median follow-up of 18 months no patient developed an isolated local recurrence.

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.

[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.