Izumi Koike

Quantification of circulating cell-free DNA in the plasma of cancer patients during radiation therapy.

Cell‐free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell‐free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human‐specific and mouse‐specific cell‐free DNA. Human‐specific DNA was detectable only in plasma from tumor‐bearing mice. However, mouse‐specific plasma DNA was significantly higher in tumor‐bearing mice than in normal mice, suggesting that cell‐free plasma DNA originated from both tumor and normal cells. We measured the total cell‐free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell‐free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell‐free plasma DNA concentrations only decreased over the course of the treatment. The total cell‐free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell‐free plasma DNA during radiation therapy. (Cancer Sci 2009; 100: 303–309)

FDG-PET scanning after radiation can predict tumor regrowth three months later.

PURPOSE Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) is well known for providing excellent clinical information regarding malignant tumors. We investigated whether dual-time FDG-PET performed immediately post radiation could predict early regrowth of malignant tumors. MATERIALS AND METHODS Twenty patients with malignant tumors were included in this study. All patients received radiation, and each underwent FDG-PET before the initiation of therapy and within 10 days of completing their course of irradiation. PET images after irradiation were obtained at 60 min and 180 min post FDG injection. For 26 lesions in 20 patients, standardized uptake value (SUV) before and after treatment was calculated and then correlated with postradiation tumor response and outcome at 3 months status post irradiation. RESULTS Retention index [RI = (SUV on delayed image - SUV on early image)/SUV on early image] after irradiation showed a significant difference between patients with residual tumor and those without residual tumor at 3 months status post irradiation (p < 0.0025). All 9 lesions in 6 patients with residual tumors showed more than 0.1 of RI, whereas none of the lesions with less than 0.1 of RI revealed residual tumors. CONCLUSIONS Dual-time FDG-PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors.

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases

PURPOSE To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. MATERIALS AND METHODS One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60mg/m(2), cisplatin, total 150mg/m(2)) and daily concurrent radiotherapy (total of 60Gy) for 6 weeks. RESULTS The median follow-up for all patients was 46.2 months (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients. CONCLUSION Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.

Role of Radiotherapy as Curative Treatment of Extramammary Paget’s Disease

PURPOSE Extramammary Pagets disease (EMPD) is a relatively rare malignancy that usually arises in the genital areas. Wide surgical excision remains the standard and most reliable curative treatment of EMPD. However, surgery is sometimes not possible, because many patients are elderly, and complete excision can be difficult owing to the tumor location. We, therefore, performed a review to determine the role of radiotherapy (RT) for EMPD. METHODS AND MATERIALS A total of 22 patients with EMPD in their external genitalia (4 men and 18 women, age 52-94 years at RT) underwent RT with curative intent. Nine patients had regional lymph node metastases. A total dose of 45-70.2 Gy (median, 60) was delivered to the pelvis, including the tumors, in 25-39 fractions (median, 33). RESULTS In all but 3 patients, the irradiated tumors were controlled during a follow-up period of 8-133 months (median, 42). Of the 22 patients, 13 developed recurrences, including local progression within the radiation field in 3 and lymph node and/or distant metastases outside the radiation field in 10, at 3-43 months after treatment. The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Of the 22 patients, 7 patients had died at 33-73 months after RT. The cause of death was tumor progression in 4, infectious pneumonia in 2, and renal failure in 1 patient. The overall and cause-specific survival rates were 100% for both at 2 years and 53% and 73% at 5 years, respectively. No therapy-related Grade 3 or greater toxicity was observed. CONCLUSIONS RT is safe and effective for patients with EMPD. It appears to contribute to prolonged survival as a result of good tumor control.

Noninvasive and Curative Radiation Therapy for Sebaceous Carcinoma of the Eyelid

PURPOSE Sebaceous carcinoma of the eyelid is a rare malignancy. Surgical excision remains the standard and most reliable curative treatment. However, surgery is sometimes not possible because many patients are elderly, and it frequently causes functional and cosmetic impairment of the eyelid. We therefore carried out a study to determine the role of radiation therapy in relation to sebaceous carcinoma of the eyelid. METHODS AND MATERIALS Thirteen patients with sebaceous carcinoma of the eyelid underwent radiation therapy with curative intent. There were 6 men and 7 women, and their ages at irradiation ranged from 60 to 85 years (median, 78 years). Only 1 patient had cervical lymph node metastasis, and none of the patients had distant metastasis. A total dose of 50 to 66.6 Gy (median, 60 Gy) was delivered to tumor sites in 22 to 37 fractions. RESULTS All irradiated tumors were controlled at a median follow-up period of 55 months. Only 1 patient had recurrence of cervical lymph node metastasis outside the radiation field, at 22 months after irradiation. The 5-year local progression-free and disease-free rates were 100% and 89%, respectively. The overall and disease-free survival rates at 5 years were 100% and 89%, respectively. Although acute and transient therapy-related reactions of Grade 2 or less were observed, there were no severe toxicities of Grade 3 or greater. CONCLUSIONS Radiation therapy is a safe and effective treatment for patients with sebaceous carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.

Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

PURPOSE Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. METHODS AND MATERIALS Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage IEA in 29 patients and stage IIEA in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. RESULTS All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. CONCLUSIONS Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

Postoperative radiation therapy for extramammary Paget's disease

Extramammary Pagets disease (EMPD) is a rare cutaneous malignancy that is usually treated with surgery. Patients with positive surgical margins require adjuvant therapy, but there have been few reports on the use of radiation therapy.

Development of system using beam's eye view images to measure respiratory motion tracking errors in image‐guided robotic radiosurgery system

The accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS) is considered to be patient‐dependent because the SRTS relies on an individual correlation between the internal tumor position (ITP) and the external marker position (EMP), as well as a prediction method to compensate for the delay incurred to adjust the position of the linear accelerator (linac). We aimed to develop a system for obtaining pretreatment statistical measurements of the SRTS tracking error by using beams eye view (BEV) images, to enable the prediction of the patient‐specific accuracy. The respiratory motion data for the ITP and the EMP were derived from cine MR images obtained from 23 patients. The dynamic motion phantom was used to reproduce both the ITP and EMP motions. The CyberKnife was subsequently operated with the SRTS, with a CCD camera mounted on the head of the linac. BEV images from the CCD camera were recorded during the tracking of a ball target by the linac. The tracking error was measured at 15 Hz using in‐house software. To assess the precision of the position detection using an MR image, the positions of test tubes (determined from MR images) were compared with their actual positions. To assess the precision of the position detection of the ball, ball positions measured from BEV images were compared with values measured using a Vernier caliper. The SRTS accuracy was evaluated by determining the tracking error that could be identified with a probability of more than 95% (Ep95). The detection precision of the tumor position (determined from cine MR images) was <0.2 mm. The detection precision of the tracking error when using the BEV images was <0.2 mm. These two detection precisions were derived from our measurement system and were not obtained from the SRTS. The median of Ep95 was found to be 1.5 (range, 1.0–3.5) mm. The difference between the minimum and maximum Ep95 was 2.5 mm, indicating that this provides a better means of evaluating patient‐specific SRTS accuracy. A suitable margin, based on the predicted patient‐specific SRTS accuracy, can be added to the clinical target volume. PACS number: 87.53.Ly

Radiation therapy for lymph node metastasis from extramammary Paget's disease

Inoperable patients with lymph node metastasis from extramammary Pagets disease (EMPD) have limited curative treatment options.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors

BACKGROUND Extramammary Pagets disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.