Appropriate evaluation of and risk factors for radiation dermatitis in breast cancer patients receiving hypofractionated whole-breast irradiation after breast-conserving surgery.

BACKGROUND: In grading radiation-induced dermatitis (RID), there are not only inter-evaluator differences but also intra-evaluator variations. We retrospectively analyzed the advantages of establishing a more precise evaluation method using photographs to minimize intra-evaluator variations and RID risk factors. METHODS: We analyzed 301 breasts, including those of 3 patients with bilateral breast cancer who underwent hypofractionated whole-breast irradiation (WBI) after breast-conserving surgery. Four radiation oncologists (A, B, C and D) evaluated photographs taken before, during and after radiation therapy and graded RID using two methods. RESULTS: The percentages of maximum grades between the two methods varied widely. Kappa statistics revealed that the inter- and intra-evaluator agreements were mostly fair. In multivariate analysis, age (≤60 years old), boost irradiation, concurrent hormonal therapy and chemotherapy prior to WBI are statistically significant risk factors for ≥ grade 2 RID according to two evaluators (B and D), two evaluators (A and B), one evaluator (B) and one evaluator (D), respectively. CONCLUSIONS: The assessment of serial skin change in photographs is useful for judging RID. No risk factor was statistically significant for all evaluators because of wide intra-evaluator variations and large inter-evaluator differences. More objective criteria are needed for appropriate evaluation of RID.

Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase.

The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation­induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.

Bevacizumab treatment for symptomatic radiation necrosis diagnosed by amino acid PET.

Bevacizumab is effective in treating radiation necrosis; however, radiation necrosis was not definitively diagnosed in most previous reports. Here we used amino acid positron emission tomography to diagnose radiation necrosis for the application of bevacizumab in treating progressive radiation necrosis. Lesion/normal tissue ratios of <2.5 on (18)fluoride-labeled boronophenylalanine-positron emission tomography were defined as an indication of effective bevacizumab treatment. Thirteen patients were treated with bevacizumab at a dose of 5 mg/kg every 2 weeks. Two patients were excluded because of adverse events. The median reduction rate in perilesional edema was 65.5%. Karnofsky performance status improved in six patients after bevacizumab treatment. Lesion/normal tissue ratios on (18)fluoride-labeled boronophenylalanine-positron emission tomography (P = 0.0084) and improvement in Karnofsky performance status after bevacizumab treatment (P = 0.0228) were significantly associated with reduced rates of perilesional edema. Thus, (18)fluoride-labeled boronophenylalanine-positron emission tomography could be useful for diagnosing radiation necrosis and predicting the efficacy of bevacizumab in progressive radiation necrosis.

Extra-nodal natural killer/T cell lymphoma, nasal-type, treated by concurrent chemoradiotherapy.

The present study reports on a case of extra-nodal natural killer/T cell lymphoma, nasal-type (ENKL), stage IIEA, in a 50-year-old woman who presented with a white tumor on a refractory ulcer on the gum. Concurrent chemoradiotherapy was administered, and effected a partial response. However, tumor recurrence was observed 5 months after the final diagnosis, and the patient succumbed 1 month after recurrence. Although a definitive treatment for ENKL has yet to be established due to its rarity, radiation therapy (RT) is crucial to therapy, as ENKL is very sensitive to RT. However, treatment with radiation levels above 50 Gy with an extended RT field are required for a favorable outcome. The development of novel chemotherapy regimens may therefore be useful. Additionally, autologous or allogenic hematopoietic stem-cell transplantation may prove to be a promising approach.

Boron neutron capture therapy for newly diagnosed glioblastoma.

We evaluate the clinical results of a form of tumor selective particle radiation known as boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma (NDGB) patients, especially in combination with X-ray treatment (XRT). Between 2002 and 2006, we treated 21 patients of NDGB with BNCT utilizing sodium borocaptate and boronophenylalanine simultaneously. The first 10 were treated with only BNCT (protocol 1), and the last 11 were treated with BNCT followed by XRT of 20 to 30 Gy (protocol 2) to reduce the possibility of local tumor recurrence. No chemotherapy was applied until tumor progression was observed. The patients treated with BNCT (protocol 1 plus 2) showed a significant survival prolongation compared with the institutional historical controls. BNCT also showed favorable results in correspondence with the RTOG- and EORTC-RPA subclasses. The median survival time (MST) was 15.6 months for protocols 1 and 2 together. For protocol 2, the MST was 23.5 months. The main causes of death were cerebrospinal fluid dissemination as well as local recurrence. Our modified BNCT protocol showed favorable results of patients with NDGB not only for those with good prognoses but also for those with poor prognoses.

Patients' subjective evaluation of early and late sequelae in patients with breast cancer irradiated with short fractionation for breast conservation therapy: comparison with conventional fractionation.

BACKGROUND: To compare the frequency of "subjective" complications and their severity between conventional and short fractionation and to analyze the differences between the two groups. METHODS: Data from 350 patients with breast cancer who received breast conservation therapy between 1992 and 2003 were retrospectively analyzed. One hundred and ninety-six patients and 154 patients received 50 Gy in 25 fractions over 35 days (group C) and 44 Gy in 16 fractions over 22 days (group S), respectively. Early sequelae were evaluated at the end of radiation therapy (point A) and 7-10 days after the treatment (point B). Late sequelae were assessed at least 6 months after the end of radiation therapy (point C). RESULTS: The most commonly observed toxicity at point A was erythema, followed by heat sensation, sense of discomfort, and pain. There were no significant differences in these symptoms between the two groups. The frequency of these symptoms hardly changed between points A and B. At point C a sense of hardness more frequently appeared in group S than in group C with a significant difference. Other commonly noted symptoms had no significant difference between the two groups. CONCLUSIONS: Short fractionation results in acceptable patient "subjective" sequelae comparable to the sequelae experienced following conventional fractionation.

Effects of sivelestat sodium hydrate on the reduction of radiation pneumonitis.

In this study, we irradiated the murine lung and analyzed the inhibitory effects of sivelestat sodium hydrate, a neutrophil elastase (NE) inhibitor, on lung injury in mice. Sivelestat sodium hydrate (3 mg/kg) was administered by intraperitoneal injection immediately, 3, 6, and 12 h after irradiation in groups RE-0, RE-3, RE-6, and RE-12, respectively. A control group and a group receiving radiation without sivelestat (group R) were also used. NE activity was measured 24 and 48 h after irradiation. The lungs were simultaneously extirpated and stained with hematoxylin and eosin and a naphthol AS-D chloroacetate esterase stain (N-ASDCLA). NE activity increased in the groups in which the murine lungs were irradiated. There was no increase in NE activity in the control group. Among the sivelestat-administered groups, NE activity was slightly elevated in group RE-0 and was suppressed, compared to group R, in groups RE-3, RE-6, and RE-12 at 24 h after irradiation. In the irradiated groups, intra-alveolar neutrophil infiltration, perivascular edema, and alveolar wall thickness were observed, but these changes were mild in the sivelestat-administered groups. The number of N-ASDCLA-positive cells increased in the sivelestat-administered groups, while group R had low values. This indicated that sivelestat sodium hydrate blocked the release of NE from the neutrophils in the irradiated lungs. NE plays an important role in the development of radiation-induced lung injury. Sivelestat is thus expected to decrease radiation-induced lung toxicity by suppressing NE release from neutrophils.

Stereotactic radiosurgery (SRS) for multiple metastatic brain tumors: effects of the number of target tumors on exposure dose in normal brain tissues.

BACKGROUND: This study was carried out to clarify the practical limit of the number of stereotactic radiosurgery (SRS)-targeted tumors based on the irradiation dose of normal brain tissues. METHODS: Twenty-five patients with multiple brain metastases who received SRS from October 1998 to May 2002 were enrolled in the study. In each patient, the treatment options were thoroughly studied before deciding upon a course of treatment. The number of irradiated targets was increased one by one until all of the targets were included in a treatment plan. Given a surface dose of 25 Gy, we calculated the dose volume histogram (DVH) for the entire brain in each treatment plan and compared it with those of other treatment plans. Ultimately, only 5 of the 25 patients received irradiation for all of their tumors; the others received selective irradiation targeting only those tumors that were causing symptoms. RESULTS: When the number of targets increased, the DVH curve shifted to the right. The volume of the brain irradiated at a dose of 5 Gy or higher was 25.7% or less for 4 or fewer targets, 45.7% for 5-6 targets, 81.0% for 7-8 targets and 100% for 9-11 targets. When the number of the targets exceeded 8, more than 50% of the entire brain was irradiated at levels of at least 8.7 Gy. The dose distribution became very complex as the number of targets increased. Although the survival time of the group in which tumors were selectively targeted was longer than that in the group in which all tumors were irradiated, the difference between the two groups was not statistically significant ( P = 0.2537). CONCLUSION: In SRS for multiple brain metastases, risks of both acute and late sequelae may increase because the exposure dose to normal brain tissues increases with increased numbers of target tumors. Dose distribution becomes more complex according to the increase in the number of targets. Based on our DVH curves, we conclude that the exposure dose to normal brain tissues is acceptable when the number of targets is less than 7. Importantly, our study also reveals that it may not be necessary or desirable to irradiate all metastatic tumors.

[A case of effective bisphosphonate therapy for bone metastasis from breast cancer with multiorganic metastases].

A 50-year-old woman with a past history of breast cancer was referred to our department of radiology for detailed examination after abnormal shadows on chest x-ray were detected following a routine medical examination. After lung biopsy via thoracotomy, segmental resection of the lung was performed and mediastinal lymph nodes were dissected. A histopathological diagnosis of breast cancer with lung metastasis and mediastinal lymph-node metastases was made. Later, the patient complained of pain in the left lower extremity. A diagnosis of a left tibial metastasis was made according to bone scintigraphy and MRI. Radiation therapy at 50 Gy was then initiated. Chemotherapy and hormone therapy combined with bisphosphonate therapy (Bisphonal, once in 2 weeks), was also begun. During the treatment, the patient had multiple organ metastases including multiple brain metastases, and metastases to submental lymph nodes and the left adrenal gland. However, her bone metastasis was limited to the left tibial bone and no other bone lesions were detected by bone scintigraphy and MRI. She did not experience adverse effects from the bisphosphonate therapy. We consider that the inhibition of extension and further metastases of the tibial bone metastasis noted in this patient reflected the efficacy of bisphosphonate therapy, and that bisphosphonate therapy might become an essential treatment in patients with bone metastasis of breast cancer.