Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas.

PURPOSE: To evaluate the clinical outcome of combination of carbon-ion radiotherapy with separation surgery (CIRT-SS) in patients with primary spinal/paraspinal sarcoma (PSPS) and epidural spinal cord compression (ESCC). METHODS: CIRT-SS was performed in 11 consecutive patients. Patients treated in the primary and salvage settings were categorized into Group A (n = 8) and Group B (n = 3), respectively. Clinical results and imaging findings were collected, with a particular focus on ESCC grade, treatment-associated adverse events (AEs), and the locoregional control (LRC) rate and overall survival (OS). RESULTS: The median follow-up period from the start of CIRT-SS was 25 months (7-57 months). ESCC was improved by SS in all cases. No patients exhibited radiation-induced myelopathy (RIM), but three developed Grade 3 vertebral compression fracture (VCF) during follow-up. Locoregional recurrences were observed in four patients [Group A: 1 (12.5%), Group B: 3 (100%)]. Over the entire follow-up period, three patients developed distant metastases and two patients died. The 2-year LRC rate and OS were 70% and 80%, respectively. CONCLUSION: CIRT-SS in the primary setting achieved acceptable LRC and OS without RIM in patients with PSPS and with ESCC. VCF was the most frequent AE associated with CIRT-SS.

[The timing of the appearance of oral mucositis induced by concurrent chemoradiotherapy with S-1 for head and neck cancer].

Oral mucositis is a frequent adverse event in patients receiving concurrent chemoradiotherapy for head and neck cancer. Although the management of oral mucositis is essential to improve treatment completion rates, no detailed studies on the time of oral mucositis appearance have been reported. We conducted a retrospective study on the timing of the appearance of oral mucositis induced by concurrent chemoradiotherapy with S-1 for head and neck cancer. A total of 11 patients with head and neck cancer who received concurrent chemoradiotherapy with S-1 were examined. All patients developed oral mucositis within 13.8 ± 5.6 days after the initiation of radiotherapy (20.4 ± 8.1 Gy). In addition, the effects of pain-associated symptoms caused by oral mucositis on the patients' nutritional status, including reduction in caloric intake (24.4% ± 31.1%), weight loss (5.2% ± 5.2%), and duration of a regular diet (24.5 ± 17.1 days), were observed and lasted until the completion of radiation therapy. The delineation of the timing of oral mucositis appearance has become a key motivator for the patients to perform oral care proactively to limit severity and serves as a necessary index for monitoring oral health and managing pain and nutrition.

Limb salvage using radical combined hyperthermia and radiotherapy for myxofibrosarcoma of the lower leg in an elderly patient.

Soft tissue sarcomas account for only 1.5% of malignant tumors in adults and are therefore challenging to treat. We present a case of myxofibrosarcoma of the lower leg in an 88-year-old woman who successfully responded to combined hyperthermia and radiotherapy. We proposed a below-knee amputation because of the spread of the lesion, but the patient opted for hyperthermia with radiotherapy. One and a half years later, the tumor partially regrew, and the regrown mass was resected with an R0 margin. Unfortunately, the patient developed a surgical site infection immediately after the resection, and a skin ulcer formed. It took about 2 years for conservative treatment to result in complete ulcer epithelization. The patient has been ambulant, and has not experienced any symptoms of local recurrence or metastasis in the two and a half years since the surgery. Although adverse events related to combined hyperthermia and radiotherapy, such as delayed wound healing, should be considered, it could be an option for the treatment of localized soft-tissue sarcoma, especially in elderly patients.

Successful Management of Radiation-Associated Insufficiency Fracture of the Tibial Plateau with Low-Intensity Pulsed Ultrasound.

BACKGROUND Clinical management of radiation-associated pathological fracture is challenging because of a high nonunion rate and potential for morbidity. We report a case of radiation-associated insufficiency fracture of the tibial plateau after surgery, perioperative chemotherapy, and adjuvant radiation therapy for synovial sarcoma of the proximal calf that was successfully treated with low-intensity pulsed ultrasound (LIPUS). CASE REPORT A healthy 52-year-old Japanese woman presented with a slowly growing, painful soft tissue mass over her proximal calf. Histological examination of core needle biopsy specimens led to a pathological diagnosis of synovial sarcoma. After perioperative ifosfamide and doxorubicin chemotherapy and surgical resection, adjuvant radiation therapy was administered, with a total of 60 Gy in 30 fractions. At 5 months after surgery and 2 months after the completion of radiation therapy, she developed an insufficiency pathological fracture of the proximal tibia without any apparent trauma. The patient was treated with LIPUS for 1 year. There was no collapse or deformity of the knee joint. The patient remained free of symptoms and had no recurrences for 2 years after surgery. CONCLUSIONS This is the first report of radiation-associated pathological fracture that was successfully treated with LIPUS. LIPUS could be a safe and effective treatment option in the management of radiation-associated pathological fractures.

Malignant myoepithelioma in the maxillary sinus: case report and review of the literature.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

Retrospective analysis: concurrent chemoradiotherapy and adjuvant chemotherapy for T2N0 glottic squamous cell carcinoma.

This study aimed to evaluate the efficacy and toxicity of concurrent chemoradiotherapy and adjuvant chemotherapy for T2N0 glottic squamous cell carcinoma. Between May 1993 and March 2004, 32 patients with T2N0 glottic squamous cell carcinoma received concurrent chemoradiotherapy as the primary treatment modality for larynx preservation. Radiotherapy was delivered five days a week using a once-daily fractionation of 2.0 Gy (median total dose: 70 Gy). The chemotherapy regimen comprised carboplatin in 4 patients, carboplatin and tegafur and uracil in 7, carboplatin and futraful in 2, and futraful in 19 patients. Twenty-four patients received adjuvant chemotherapy with tegafur and uracil. Initial local tumor control was achieved in 30 patients (94%). The 5-year overall survival and 5-year local control rates were 97% and 70%, respectively. Univariate analysis revealed adjuvant chemotherapy as a significant prognostic factor for the local control rate (P = 0.038). The 5-year local control rate in patients treated or not treated with adjuvant chemotherapy was 82% and 42%, respectively. No significant differences in the local control rate were noted in overall treatment time, total radiation dose, age, and disease extension to the subglottis. With regard to adverse reactions, grade 3 neutropenia and grade 3 hepatotoxicity were observed in 1 and 2 patients, respectively. We observed no severe late complications (RTOG/EORTC criteria Grade 3-4) related to this combination therapy. Concurrent chemoradiotherapy and adjuvant chemotherapy was effective but with mild toxicity, and adjuvant chemotherapy significantly improved local control. We suggest the use of this combination therapy for achieving a local control of T2N0 glottic squamous cell carcinoma.

Preliminary results of radiation therapy for locally advanced or recurrent adenoid cystic carcinomas of the head and neck using combined conventional radiation therapy and hypofractionated inverse planned stereotactic radiation therapy.

PURPOSE: To investigate the clinical outcomes and feasibility of combined conventional radiation therapy (RT) and hypofractionated inverse planned stereotactic radiation therapy (SRT) for locally advanced or recurrent adenoid cystic carcinomas (ACCs) of the head and neck. PATIENTS AND METHODS: Five patients with ACCs of the head and neck were treated with combined conventional RT and inverse planned SRT. Radiation doses of 40 to 50 Gy were delivered with 20 to 25 fractions using conventional RT, and then an additional 20 to 25 Gy was delivered by 4 to 5 fractions of SRT. RESULTS: Median follow-up was 12 months. Local control was obtained in all 5 patients, PR in 2 patients and SD in 3 patients. According to the Radiation Therapy Oncology Group (RTOG) late-radiation morbidity scoring criteria, adverse effects included Grade 2 xerostomia in 1 patient, Grade 2 trismus in 1 patient, and Grade 4 mucosal ulceration in 1 patient. CONCLUSION: Combined treatment with conventional RT and hypofractionated inverse planned SRT may be effective for short-term local control in patients with locally advanced or recurrent ACCs. Further evaluation is needed for long-term follow-up.

Breath-hold monitoring and visual feedback for radiotherapy using a charge-coupled device camera and a head-mounted display: system development and feasibility.

PURPOSE: The aim of this study was to present the technical aspects of the breath-hold technique with respiratory monitoring and visual feedback and to evaluate the feasibility of this system in healthy volunteers. METHODS AND MATERIALS: To monitor respiration, the vertical position of the fiducial marker placed on the patient's abdomen was tracked by a machine vision system with a charge-coupled device camera. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. Five healthy male volunteers were enrolled in this study. They held their breath at the end-inspiration and the end-expiration phases. They performed five repetitions of the same type of 15-s breath-holds with and without a head-mounted display, respectively. A standard deviation of five mean positions of the fiducial marker during a 15-s breath-hold in each breath-hold type was used as the reproducibility value of breath-hold. RESULTS: All five volunteers well tolerated the breath-hold maneuver. For the inspiration breath-hold, the standard deviations with and without visual feedback were 1.74 mm and 0.84 mm, respectively (P = 0.20). For the expiration breath-hold, the standard deviations with and without visual feedback were 0.63 mm and 0.96 mm, respectively (P = 0.025). CONCLUSION: Our newly developed system might help the patient achieve improved breath-hold reproducibility.

Radiation therapy for recurrent esophageal cancer after surgery: clinical results and prognostic factors.

OBJECTIVE: To evaluate the outcome of radiotherapy for recurrent esophageal cancer after surgery and to determine the prognostic factors. METHODS: From 1987 through 2002, 82 patients treated with radiotherapy for loco-regional recurrences of esophageal cancer after surgery were retrospectively reviewed. The stage at initial surgery was I in 16, II in 41, III or higher in 24 and unknown in 1. The median size of recurrent tumors was 3.5 cm in diameter. Fifty-two patients were treated with radiotherapy alone, and 30 were treated with radiotherapy combined with chemotherapy. The median total dose of external radiotherapy given was 50.4 Gy in 28 fractions. RESULTS: The median survival period after recurrence was 7.0 months. The 2- and 5-year overall survival rate for all patients was 22 and 11%, respectively. In univariate analysis, the patients with performance status (PS) = 0-1, or tumor size <3.5 cm, and those treated with total dose >/=50 Gy showed a better survival outcome than each the other groups. The patients with a history of previous radiotherapy showed a poorer survival outcome in univariate analysis than each the other groups. In multivariate analysis, tumor size, PS and radiation dose were independent prognostic factors for overall survival. CONCLUSION: The prognosis of patients with post-operative loco-regional recurrence of esophageal cancer is poor. However, a long-term survival may be expected by definitive radiotherapy for the patients with small-size tumors and with a good PS.

Long-term local control of recurrent adenoid cystic carcinoma in the parotid gland with radiotherapy and intraarterial infusion chemotherapy.

We report a case of postoperative recurrence of adenoid cystic carcinoma in the left parotid gland treated with radiotherapy and arterial infusion chemotherapy. A 52-year-old woman had a history of surgical resection for an adenoid cystic carcinoma arising from the left parotid gland 25 years before. Despite two reoperations for local recurrence after the initial surgery, she had a third local recurrence in the remnant of the left parotid gland. The patient was treated with a concurrent combination of radiotherapy (60 Gy/30F) and intraarterial infusion chemotherapy with carboplatin (750 mg/30 days) from which she obtained a complete response. The patient has remained free of local progression 54 months after treatment. Radiotherapy and arterial infusion chemotherapy is effective treatment for local recurrence of adenoid cystic carcinoma in the head and neck.

Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy.

PURPOSE: To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp. METHODS AND MATERIALS: The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 +/- 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients. RESULTS: The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05). CONCLUSION: Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined with systemic administration of rIL-2 may prolong survival. Additional studies with detailed treatment protocols are recommended.

Adult rhabdomyosarcoma in the nasal and paranasal sinuses showing complete local response to a combination of chemotherapy and radiotherapy using 3D-CRT and IMRT.

We report on a 69-year-old woman with rhabdomyosarcoma arising from the nasal and paranasal sinuses. She was referred to our hospital with a reduced ability to smell and impaired bilateral vision, narrowing of the visual field, and left facial pain. Computed tomography (CT) revealed a large tumor in the nasal and left paranasal sinuses invading the left orbital cavity and anterior skull base, and lymph node swellings in the submental and left accessory nerve areas. A biopsy specimen from the nasal tumor was diagnosed histologically as a rhabdomyosarcoma, alveolar type. Because the intracranial direct invasion and distant metastases to the thoracic spine were suspected by pretreatment examination, our case was determined to be inoperable by a head and neck surgeon. Radiotherapy with a total dose of 60 Gy was carried out to control the primary disease. The three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques were used in order to reduce the doses to risk organs. Combined with radiotherapy, chemotherapy was also performed for the treatment of lymph-node metastases and distant diseases. After the treatment was completed, the primary tumor and lymph-node metastases disappeared completely; there was no sign of re-growth during the follow-up period. Chemoradiotherapy may be an effective treatment also for inoperable adult rhabdomyosarcoma in the head and neck region. Furthermore, the 3D-CRT and IMRT techniques are both useful methods of radiotherapy for this disease.

Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy.

We describe a 68-year-old man who underwent hyperbaric oxygen (HBO) therapy to manage radiation necrosis of the brain, which developed after two treatments with stereotactic radiosurgery (SRS) to the same lesion. The necrosis was subsequently treated with steroids alone for 2 months; however, he progressed clinically and radiographically. Improvement again was noted with the reinstitution of HBO therapy. This case suggests that HBO therapy is an important therapeutic option in the treatment of brain radiation necrosis caused by SRS.

Oestrogen causes G2/M arrest and apoptosis in breast cancer cells MDA-MB-231.

Flavonoids have been shown to exert many biological activities within cancer cells, and oestrogen is known to be structurally related to flavonoids. We investigated the effects of oestrogen in cancer cells to determine if its activities would be similar to those of flavonoids. When 50 microM 17 beta-oestradiol (oestradiol) was added to the oestrogen receptor (ER) alpha-negative breast cancer cell line MDA-MB-231, growth arrest was apparent, similar to that observed with genistein and daidzein. Oestradiol exhibited a dose response curve for the growth arrest similar to those of genistein and daidzein. Apoptosis occurred in the breast cancer cells after treatment with 50 microM oestradiol, genistein, or daidzein, with similar profiles. Flow cytometry analysis revealed that oestradiol treatment caused G2/M arrest and apoptosis. Cell-cycle arrest at G2/M began at 6 h after treatment, and apoptosis began within 24 h. Because MDA-MB-231 cells are ER alpha negative, these results suggest that oestradiol induces cell-cycle arrest and apoptosis through an ER alpha-independent pathway.

Acute exposure to cobalt induces transient methemoglobinuria in rats.

We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological examinations of these samples were conducted. Obvious macroscopic and biochemical methemoglobinuria was observed just after injection of cobalt, but the level of urinary methemoglobin decreased gradually, almost disappearing by 24 h. The levels of cobalt in peripheral blood and urine showed a very similar pattern to that of methemoglobinuria. Neither anemia nor bilirubinemia was observed, indicating no extrarenal intravascular hemolysis. Pathological examination of the kidneys revealed that the glomerular capillaries were filled with red blood cells at 1 h after injection. Electron microscopy showed deformed red blood cells in the glomerular capillaries and condensed hemoglobin in Bowman's capsule that passed through the basement membrane. There were no trends toward increases in plasma levels of creatinine or blood urea nitrogen. These results indicate that exposure to cobalt induces transient methemoglobinuria through the lysis of red blood cells and oxidation of iron in hemoglobin at the glomerular capillaries without causing renal dysfunction.

[Effect of Cepharanthin to prevent radiation induced xerostomia in head and neck cancer].

We retrospectively examined the effect of Cepharanthin to prevent radiation xerostomia in 37 cases of head and neck cancer. In the Cepharanthin group, the degree of xerostomia was milder than in the non-Cepharanthin group in spite of higher normal tissue complication probability (NTCP) and mean dose (MD) of parotid glands. In the non-Cepharanthin group, the degree of xerostomia was significantly correlated with NTCP and MD of parotid glands. MD of parotid glands and use of Cepharanthin were significantly related to more severe xerostomia by multivariate analysis with logistic regression. Cepharanthin may prevent radiation xerostomia after radiotherapy for head and neck cancer.

[Effect of Cepharanthin in preventing radiation induced normal tissue damage in prostate cancer].

A total of 97 patients with prostate cancer who underwent radiotherapy were retrospectively reviewed to analyze the protective efficacy of Cepharanthin for acute or late toxicity to the bladder/urethra and rectum. Cepharanthin administrations were divided into 3 groups: intravenous, oral, and non-administration. Acute urinary toxicity was significantly milder for the intravenous group than for the oral and non-administration groups. The protective efficacy of Cepharanthin was not approved for acute rectal toxicity, but late rectal toxicity was significantly milder for the intravenous group than for the oral group. Intravenous Cepharanthin administration may prevent acute or late toxicity by radiotherapy for prostate cancer.

Advantage of early induction of opioid to control pain induced by irradiation in head and neck cancer patients.

OBJECTIVE: Although radiotherapy is effective for head and neck cancer patients, the local pain evoked by the irradiation itself reduces food intake and frequently halts the treatment. Thus, pain control is an important problem in radiotherapy for head and neck cancer. We performed to examine whether early induction of low-dose, opioid from mild pain improves dietary and caloric intake, while reducing weight loss. METHODS: The subjects were 43 patients who were hospitalized for head and neck cancer from 2004 to 2008. They were patients who underwent radiation treatment but those who did not undergo preoperative treatment. They were divided into two groups, depending on whether the pain was mild or moderate when an opioid was introduced (MILD and MODERATE, N=23 and 20, respectively). RESULTS: The visual analog scale scores for pain were significantly lower in the MILD than in the MODERATE group at between 25 and 50 Gy. The amount of oxycodone used for pain was significantly lower in the MILD than the MODERATE group. A regular diet was maintained for significantly longer in the MILD group. Caloric intake was significantly higher in the MILD group at over 20 Gy. Weight loss was significantly lower in the MILD group at over 20 Gy. The incidence of side effects was equal in both groups. CONCLUSION: Our results indicated that the introduction of opioids for mild pain during radiotherapy controls the level of pain, improving food intake in head and neck cancer patients.