Jj Feldmeier

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 patients 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.

Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury

Although hyperbaric oxygen is used to treat chronic radiation tissue injury, clinical evidence supporting its efficacy has been limited to date. The authors report prospectively collected patient outcomes from a single centers large experience using hyperbaric oxygen to treat chronic radiation injury.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy : A systematic review of randomised controlled trials

BACKGROUND Radiotherapy is a well-established treatment for some solid tumours. Hyperbaric oxygenation (HBO) may improve radiotherapeutic killing of hypoxic cancer cells, so the simultaneous administration of radiotherapy and HBO may reduce mortality and tumour recurrence. METHODS We performed a systematic search of the literature in September 2007 for randomised controlled trials, and made pooled analyses of pre-determined clinical outcomes. RESULTS Nineteen trials contributed to this review (2286 patients). There was a reduction in mortality for head and neck cancers at one and five years after therapy (at five years RR 0.82, P=0.03, NNT=5), and improved local tumour control at three months (RR 0.58, P=0.006, NNT=7). Any advantage is achieved at the cost of an increased rate of both severe radiation tissue injury (RR 2.35, P<0.0001, NNH=8) and the chance of seizures during therapy (RR 6.76, P=0.03, NNH=22). CONCLUSIONS There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe radiation tissue injury. The methodological and reporting inadequacies of the studies included in this review demand a cautious interpretation. More research is needed for head, neck and uterine cervical cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other sites.

Evidence Supporting the Use of Hyperbaric Oxygen in the Treatment of Osteoradionecrosis of the Jaw

a d l l a ( s fi e N i s yperbaric oxygen (HBO) is oxygen delivered at reater than 1 atmosphere of pressure in a chamber r pressure vessel with the intent to elevate tissue xygen partial pressure (PO2) beyond that attainable y breathing 100% oxygen at sea level. Chambers are ither monoplace for 1 patient or multiplace for sevral patients. Clinical HBO therapy is a medical treatent designed to exploit the physiologic changes ffected by elevated tissue PO2 to promote healing hrough a variety of molecular processes that reduce dema and inflammation, augment microbial killing, nd invoke stem cell mobilization, vasculogenesis, nd tissue repair. Elevated PO2 increases local conentrations of reactive nitrogen species by providing ubstrate for nitric oxide synthase (O2 and L-arginine) hile simultaneously producing reactive oxygen speies such as superoxide. Reactive nitrogen pecies and reactive oxygen species have dose-depenent actions on molecular processes through allosteic effects on regulatory enzymes, transcription facors, and genes that can be exploited to promote ealing in otherwise nonresponsive tissues. Animal tudies show that HBO increases vasculogenesis nd ameliorates the cytotoxic effects of radiation on ooth growth. It also increases salivary gland acini umber and lacunar osteoblast survival in the mandile in a dose-dependent fashion. The treatment of steoradionecrosis of the jaw (ORN) is among the 13

Salvage external beam radiotherapy for clinical failure after cryosurgery for prostate cancer.

PURPOSE To investigate the role of external beam radiotherapy (EBRT) as salvage treatment of prostate cancer after cryosurgery failure. METHODS AND MATERIALS Between 1993 and 1998, 6 patients underwent EBRT with curative intent for local recurrence of prostate cancer after cryosurgery. All 6 patients had biopsy-proven recurrence and palpable disease on digital rectal examination at the time of EBRT. The median follow-up was 34 months (range 8-46). The median prostate-specific antigen level was 2.3 ng/mL (range 0.8-4.1). No patient had evidence of metastatic disease. Two patients received hormonal therapy before beginning EBRT. No patient received hormonal therapy after EBRT completion. The median elapsed time between cryosurgery and EBRT was 3 years (range 1.5-4). The median delivered dose was 66 Gy (range 62-70.2) using a 10-MeV photon beam. An in-house-developed three-dimensional treatment planning system was used to plan delivery of the prescribed dose with conformal radiotherapy techniques. RESULTS After EBRT, all patients had complete resolution of palpable disease. Four patients (66%) were disease free at the time of the last follow-up. Two patients developed biochemical failure as defined by the American Society for Therapeutic Radiology and Oncology consensus definition. One of these patients had a prostate-specific antigen level of 97 ng/mL before cryosurgery. No patient developed distant metastasis during follow-up. Two patients (33%) developed proctitis; 1 case resolved with Rowasa suppositories and 1 required blood transfusion. CONCLUSIONS Our preliminary results suggest that EBRT can render a significant number of patients biochemically free of disease and can cause complete resolution of clinically palpable disease after initial cryosurgery. The results also showed that EBRT can be given without excessive morbidity. EBRT should be considered as a treatment option in these potentially curable cases.

Dosimetric characteristics of a linear array of γ or β-emitting seeds in intravascular irradiation: Monte Carlo studies for the AAPM TG-43/60 formalism

In principle, the AAPM TG-43/60 formalism for intravascular brachytherapy (IVBT) dosimetry of catheter-based sources is fully valid with a single seed of cylindrical symmetry and in the region comparable to or larger than the mean-free path of emitting radiation. However, for the geometry of a linear array of seeds within the few millimeter range of interest in IVBT, the suitability of the AAPM TG-43/60 formalism has not been fully addressed yet. We have meticulously investigated the dosimetric characteristics of catheter-based γ ( 192 Ir ) and β ( 90 Sr/Y ) sources using Monte Carlo methods before applying the AAPM TG-43/60 formalism. The dosimetric perturbation due to radiation interactions with neighboring seeds is at most 2% over the entire region of interest for the 192 Ir source, while it increases to about 5% for the 90 Sr/Y source. As the transaxial distance (y) increases beyond 3 mm, the sum of the dose contributions from neighboring seeds exceeds the dose contribution from the center seed for both sources. However, it continues to increase with the increasing y for 192 Ir but is saturated beyond y=5 mm for 90 Sr/Y . Even within a few millimeters from the seeds, the dose from the low-energy betas of 192 Ir is still less than 1% of the total dose. The radial dose and anisotropy functions are reformulated in reduced cylindrical coordinate with the reference point at y=2 mm . The dose rate constant of 192 Ir and the dose rate of 90 Sr/Y at the reference point showed a fairly good agreement ( within ±2%) with earlier studies and the NIST-traceable value, respectively. We conclude that the dosimetric perturbation caused by close proximity of neighboring seeds is nearly negligible so that the AAPM TG-43/60 formalism can be applied to a linear array of seeds.

Prophylactic hyperbaric oxygen treatment and rat spinal cord re-irradiation.

Normal tissue injury may lead to severe, life threatening, late side effects after therapeutic use of irradiation. Neurological complications caused by radiation of the spinal cord are ascribed to progressive, irreversible damage to the vasculature. Hyperbaric oxygen (HBO) is known to induce angiogenesis in irradiated tissue and has been proven to reduce late radiation injury in several normal tissues when applied during the latent period before complications become manifest. In the present study: (1). the prophylactic potential of HBO; (2). optimal timing of HBO therapy after spinal cord irradiation, i.e. during the latent period; and (3). effect of HBO on the re-irradiation tolerance of the spinal cord were investigated. The rat cervical spinal cord was locally X-ray irradiated with ten fractions of 6.5 Gy in 11 days. Five treatment groups (n=10) included: irradiation alone and irradiation followed by 30 HBO treatments (100% oxygen at 240 kPa for 90 min) during latency, with HBO starting either immediately, 5, 10 or 15 weeks after the primary irradiation course. One year after the primary treatment, the same spinal cord volume was re-irradiated with 20 Gy single dose. During life span, the animals were observed on the incidence of myelitis and the duration of the latent period. The actuarial analysis revealed no significant difference in neurological complications free survival between the irradiation alone and the irradiation+HBO treatment groups. A tendency towards radiosensitization was found in the group in which the primary irradiation course was immediately followed by the HBO treatment course. The data show that HBO applied during the latent period of progressively developing irradiation damage to the spinal cord does not increase the re-irradiation tolerance of this tissue.

Primary CNS lymphoplasmacytic lymphoma: a case report and review of literature.

Lymphoplasmacytic lymphoma is a chronic lymphoproliferative disorder characterized by a proliferation of plasma cells, small lymphocytes, plasmacytoid lymphocytes and the production of monoclonal IgM. Primary central nervous system lymphomas (PCNSL) are rare non-Hodgkin lymphomas (NHL) that can be found in the brain, leptomeninges, eyes or spinal cord, and are mostly intracerebral. PCNSLs constitute 3-4% of primary brain tumors, and in most cases are diffuse large B-cell lymphomas (DLBCL).(1) Low grade lymphomas as primary central nervous system (CNS) lymphoma are very rare. We present here a case report of a woman who presented with headache and was found to have primary intracranial lymphoplasmacytic lymphoma (LPL).

MO‐G‐BRA‐04: Advantages of Implementation of a Self‐Regulating Thermobrachy Seed for Solid Tumors

Introduction: The recently proposed thermobrachy seed combines a sealed radioactive source with a ferromagnetic core serving as a source for self‐ regulating hyperthermia when placed in an alternating electromagnetic field. This seed has the potential to address some shortcomings of other methods suggested for delivery of radiotherapy and hyperthermia, such as, as an inadequate temperature control due to complex invasive thermometry and feedback loops, temperature non‐uniformity, and prolonged time delay between hyperthermia and radiation treatments.Materials and Method: The thermobrachy seed consists of Ni‐Cu ferromagnetic alloy core coated with carbon containing I‐125 source and encapsulated in titanium capsule. The external dimension of the seed is the same as the BEST Model 2301 I125. In our modeling study, seeds are located in the central region of cylindrical water phantom. An alternating magnetic field was applied using an externally wrapped current carrying coil. The temperature distribution within the phantom due to the induction heating of the ferromagnetic seed was obtained using a finite element analysis method. This distribution was compared to radiationdose distribution from treatment planning system. Results: The thermoseed surface temperature rises rapidly and stays constant around the Curie temperature of the ferromagnetic material used. The temperature self‐regulation eliminates the need for invasive thermometry and simplifies the treatment procedure. The phantom volume reaching the therapeutic temperature range increases with increase of frequency or magnetic field strength. The temperature coverage over the target volume can be optimized by changing the magnetic field variables (intensity and frequency). Furthermore the tuning of the variables allows us achieving isothermal surfaces exactly similar to the radiation isodoses. Conclusion: The result shows that one can obtain the optimal isothermal distribution on the target volume to match with the prescribed radiation isodose distribution for the seed configuration by changing frequency and intensity of the alternating applied magnetic field.

SU‐FF‐T‐39: Investigating Thermal Properties of a Thermobrachytherapy Radioactive Seed for Concurrent Brachytherapy and Hyperthermia Treatments: Design Considerations

Purpose: Hyperthermia has been demonstrated to be one of the most effective radiation sensitizers. It offers significant improvement in both tumorcontrol and survival rate after radiation therapy without considerable increase in side effects. Previous studies show that the time interval between administrations of both modalities has to be rather short, preferably, within an hour. We propose a new Thermobrachytherapy radioactive seed model, serving as a heat source for concurrent administration of brachytherapy and hyperthermia. Method and Materials: A new combination seed is based on the BEST Model 2301‐ I 125 , where tungsten marker core is replaced with a ferromagnetic material, capable of producing heat when subjected to external alternating electro‐magnetic field. Such a replacement does not noticeably change the dose rate distribution, and has only minor effect on the radiographic properties of the seed. A finite‐element partial differential equation solver package “COMSOL Multiphysics” was used to evaluate thermal distribution of the heat induced in the ferromagnetic core. Results: The induction heat source has relatively low efficiency due to losses associated with a considerable distance between the ferromagnetic core and induction coil. However, the temperature distribution is tunable based on the number of seeds used during the treatment, their locations, coil diameter, and the frequency of the electro‐magnetic field. A model with a solid radiographic marker is preferable for the proposed application since it offers the highest heat output. We found that the implementation of the proposed seed will require only small changes in the internal structure of a standard commercial model, and will not affect significantly the dose rate and other TG43 factors characterizing radiation distribution. Conclusion: We will present the radiation and thermal properties of the new seed model which has high potential for implementation of concurrent brachytherapy and hyperthermia.