Gemcitabine-Related Radiation Recall in a Patient with Metastatic Non-small Cell Lung Cancer

A sixty-seven year old male was treated with palliative radiation therapy due to his right hip joint pain, and the pain was caused by osteolytic right acetabular metastasis. He underwent 30 Gy irradiation and then his painful symptoms disappeared at the 1 month follow-up after radiation therapy. He next received received systemic chemotherapy with 3 cycles of gemcitabine plus cisplatin and then 6 cycles of docetaxel. He visited the emergency room at the time of 4 months after the completion of radiation therapy with complaints of relapsed right hip joint pain. On MRI, localized muscular swelling with infiltration and without contrast-enhancement was seen within the previous radiation field, and the clinical impression was radiation-recall myositis. We provided symptomatic treatment and his right hip joint pain with disability disappeared 2 weeks after the treatment. No relapse of the right hip joint pain developed during the patient's survival period. We experienced a case of radiation-recall myositis that was related to gemcitabine use after radiation therapy

Establishment of a Single Dose Radiation Model of Oral Mucositis in Mice / 대한방사선종양학회지

PURPOSE: Oral mucositis induced by radiotherapy to the head and neck area, is a common acute complication and is considered as the most severe symptom for cancer patients in the early stages of treatment. This study was proposed to establish the oral mucositis mouse model induced by a single dose of radiation for the facility of testing therapeutic candidates which can be used for the oral mucositis treatments. MATERIALS AND METHODS: Fifty-five BALB/c mice were divided into four groups: control, 16 Gy, 18 Gy, and 20 Gy. Oral mucositis was induced by a single dose of radiation to the head and neck using 6 MV x-Ray from linear accelerator. After irradiation, body weight and physical abnormalities were checked daily. Tongue tissues from all groups were taken on days 1, 2, 3, 5, 7, 9, and 14, respectively and H&E staining was conducted to examine morphological changes. RESULTS: Body weight dramatically decreased after day 5 in all irradiated mice. In the 16 Gy treatment group, body weight was recovered on day 14. The histology data showed that the thickness of the epithelial cell layer was decreased by the accumulated time after radiation treatment, up to day 9. Severe ulceration was revealed on day 9. CONCLUSION: A single dose of 16 Gy is sufficient dose to induce oral mucositis in Balb/C mice. Significant changes were observed in the Balb/C mice on days 7 and 9 after radiation. It is suggested that this mouse model might be a useful standard tool for studying oral mucositis induced by radiation.

Comparison of Skin dose Measurement Using Glass Dosimeter and Diode for Breast Cancer Patients / 의학물리

The purpose of this study was to measure the skin dose using the glass dosimeter and diode and to compare those measurements to the planned skin dose from the treatment planning system. For the reproducibility of the glass dosimeter (ASAHI TECHNO GLASS CIRPORATION, Japan), the same dose was irradiated to 40 glass dosimeters three times, among which 28 with the reproducibility within 3% were selected for the use of this study. For each of 27 breast cancer patients, the glass dosimeters and diodes were attached to 4 different locations on the skin to measure the dose during treatment. All the patients received one fraction of 180 cGy each. The maximum difference of measurements between the glass dosimeter and diode at the same location was 3.2%. Comparing with the planned skin dose from the treatment planning system (Eclipse v6.5, Varian, USA), the dose measured by the glass dosimeter and the diodeshowed on an average 3.4% and 2.3% difference, respectively. The measured doses were always less than the planned skin dose. This may be due to the specific errors of both detectors. Also, the difference may be caused by the fact that since the skin where the detectors were attached is pretty moveable, it was not fix the detectors on the skin.

Clinical Implementation of an Eye Fixing and Monitoring System with Head Mount Display / 의학물리

A system to non-invasively fix and monitor eye by a head mounted display (HMD) with a CCD camera for stereotactic radiotherapy (SRS) of uveal melanoma has been developed and implemented clinically. The eye fixing and monitoring system consists of a HMD showing patient a screen for fixing eyeball, a CCD camera monitoring patient' s eyeball, and an immobilization mask. At first, patient' s head was immobilized with a mask. Then, patient was instructed to wear HMD, to which CCD camera was attached, on the mask and see the given reference point on its screen. While patient stared at the given point in order to fix eyeball, the camera monitored its motion. Four volunteers and one patient of uveal melanoma for SRS came into this study. For the volunteers, setup errors and the motion of eyeball were analyzed. For the patient, CT scans were performed, with patient' s wearing HMD and fixing the eye to the given point. To treat patient under the same condition, daily CT scans were also performed before every treatment and the motion of lens was compared to the planning CT. Setup errors for four volunteers were within 1 mm and the motion of eyeball was fixed within the clinically acceptable ranges. For the patient with uveal melanoma, the motion of lens was fixed within 2 mm from daily CT scans. An eye fixing and monitoring system allowed immobilizing patient as well as monitoring eyeball and was successfully implemented in the treatment of uveal melanoma for SRS.

Optimal Timing for the Administration of Capecitabine with Preoperative Chemoradiation for Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer. MATERIALS AND METHODS: Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response. RESULTS: Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance. CONCLUSION: When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.

A Less Intensive Combination of Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer Patients who Have Aged 60 Years or More and Has a Poor Performance Status

BACKGROUND: The aim of this study was to evaluate the response, survival, and toxicities of a less intensive combination of paclitaxel and carboplatin, which is used in advanced non-small cell lung cancer (NSCLC) patients older than 60 years of age including those with a poor performance status. METHODS: Thirty patients received 135 mg/m2 of paclitaxel on day 1, and carboplatin was administered to the patients on day 1 every 4 weeks over an area under the concentration-time curve of 6. RESULTS: The response rate was 40%, the median overall survival was 9.1 months (95% CI, 4.2 to 14 months), and the 1 year survival rate was 31%. The median progression-free survival was 7.7 months (95% CI, 3.1 to 12.2 months). In addition, the toxicities were generally mild and reversible. CONCLUSION: This study demonstrates that a less intensive combination of paclitaxel/carboplatin is active and well tolerated in advanced NSCLC patients who are older than 60 years including those with a poor PS 3~4.

Ependymoma: a Retrospective Analysis of 25 Cases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the patterns of failure, survival rate, prognostic factors and treatment related complication in postoperative radiation treatment of patients with ependymoma. MATERIALS AND METHODS: We retrospectively analyzed 25 patients with histologically confirmed ependymoma treated between Jun. 1990 and Jun. 2001 with postoperative radiotherapy at Asan Medical Center. The study group comprised of 16 men and 9 women, with a median age of 23 years; including 6 supratentorial, 15 infratentorial and 4 spinal cord lesions. The extents of resection were ranked as either: gross total, near total, subtotal, partial resection or biopsy, with these types of surgical resection being performed in 13, 3, 6, 1 and 2 patients, respectively. Twelve of the patients had low grade ependymoma, and the other 13 a high grade tumor. The postoperative irradiation was administered using 4 MV or 6 MV photons, up to median dose of 55.0 Gy (range, 45.0~59.4 Gy), with the radiation field encompassing the preoperative tumor volume plus a 2 cm margin. Only 8 of the patients received either pre- or postoperative chemotherapy. The median follow-up period of survivors was 43 months. RESULTS: Ten of the 25 patients (40%) developed a recurrence, and 5 died. Of the 10 recurred patients, 6 showed an in-field recurrence, and one developed both an in-field and an out of field recurrence. The remaining 3 patients showed an out of field recurrence, including one case with a leptomeningeal recurrence. The 5-year overall survival, and progression-free, survival rates were 74.0 and 56.1%, respectively. The histological grades were statistically significant prognostic factors of the overall and progression-free survival rates. There were no significant treatment related complications, with the exception of one case of panhypopituitarism, which occurred 30 months after completion of the radiotherapy. CONCLUSION: The main pattern of recurrence was due to local failure. In order to improve the local control, and to reduce complications, advanced radiation treatment techniques, such as 3 dimensional radiotherapy, may be needed.

Preliminary Results of Paclitaxel, Cisplatin and Concurrent High-Dose Radiation Therapy for Locally Advanced Non-Small-Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To investigate the feasibility, toxicity and response rate, of concurrent chemoradiation therapy with paclitaxel/cisplatin in stage III locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between May 1999 and December 2000, 80 patients with stage III NSCLC were enrolled in a prospective protocol. Radiotherapy was given to a total dose of 70.2 Gy (daily fraction of 1.8 Gy for 5 days), over an 8 week period, on the gross tumor volume, combined with chemotherapy. The concurrent chemotherapy consisted of paclitaxel (40 mg/m2) and 20 mg/m2 cisplatin per week for 8 consecutive weeks. All patients received 3-D conformal radiotherapy using CT-simulated planning. Acute toxicities were evaluated by the RTOG scale. The median follow-up period was 16 months, ranging from 3 to 29 months. RESULTS: Of the 80 patients, 71 received treatment per protocol, with minor variation of protocol delivery. The median age of the patients was 60 years. Karnofsky Performance status were 100 and 90 in 62 patients, and 80 and 70 in 9, respectively. Weight loss of less than 5% for 6 months was observed in 22 patients. The response to treatment was evaluated from the radiological findings. Complete and partial responses were observed in 8 and 51 patients, respectively. Ultimately, 82% of patients (included complete responses: 8 cases) obtained more than a partial response. Although, radiation induced esophagitis was the most common treatment related toxicity, occurring in 44 patients (69%), severe radiation esophagitis like, grade 3, was observed in only 3 patients, and the most acute toxicities had completely recovered 1 month following treatment. The overall 2-year actuarial and progression free survivals were 56 and 45%, respectively. CONCLUSION: This combined modality has activity with manageable toxicity and 23 months in mean survival time in patients with stage III NSCLC. A longer follow up will be required to realise the expected higher survival of these results.

Efficacy of Neoadjuvant Chemotherapy and Radiotherapy for the Histology-confirmed Intracranial Germinoma: Preliminary Report / 대한방사선종양학회지

PURPOSE: We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. MATERIALS AND METHODS: Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP (bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. RESULTS: The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia in 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. CONCLUSION: A high response rate and disease control was experienced, which was the same as observed other studies and the morbidity from chemotherapy-induced toxicity was similar. With these results, the results from adjuvant chemotherapy and involved-field radiotherapy cannot be concluded to be equal to those from extended-field radiotherapy. The long term follow-up study on later complications are required in order to draw definite conclusions on the optimal management with minimum side effects.

Expression of TIMP1, TIMP2 Genes by Ionizing Radiation / 대한방사선종양학회지

PURPOSE: Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. MATERIALS AND METHODS: Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity (D0), radiation cytotoxicity and metastatic potential were measured by clonogenic assay, MTT assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promotor region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was performed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promotor. RESULTS: D0 of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. MTT assay confirmed cell viability, over 94% at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. CONCLUSIONS: We observed the difference of expresson and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

Immunohistochemical Studies for TIMP-1 and TIMP-2 Expression after Irradiation in Lung, Liver and Kidney of C57BL/6 Mouse / 대한방사선종양학회지

PURPOSE: Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. METHODS AND MATERIALS: Adult female mice of 10~12 weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was performed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. RESULTS: TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. In kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. CONCLUSIONS: Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

Individualized Determination of Lower Margin in Pelvic Radiation Field after Low Anterior Resection for Rectal Cancer Resulted in Equivalent Local Control and Radiation Volume Reduction Compared with Traditional Method / 대한방사선종양학회지

PURPOSE: When determining the lower margin of post-operative pelvic radiation therapy field according to the traditional method (recommended by Gunderson), the organs located in the low pelvic cavity and the perineum are vulnerable to unnecessary radiation. This study evaluated the effect of individualized determination of the lower margin at 2 cm to 3 cm below the anastomotic site on the failure patterns. MATERIALS AND METHODS: Authors included 88 patients with modified Astler-Coller (MAC) stages from B2 through C3, who received low anterior resection and post-operative pelvic radiation therapy from Sept. 1994 to May 1998 at Samsung Medical Center, Sungkyunkwan University. The numbers of male and female patients were 44 and 44, and the median age was 57 years (range: 32-81 years). Three field technique (posterior-anterior and bilateral portals) by 6, 10, 15 MV X-rays was used to deliver 4,500 cGy to the whole pelvis followed by 600 cGy's small field boost to the tumor bed over 5.5 weeks. Sixteen patients received radiation therapy by traditional field margin determination, and the lower margin was set either at the low margin of the obturator foramen or at 2 cm to 3 cm below the anastomotic site, whichever is lower. In 72 patients, the lower margin was set at 2 cm to 3 cm below the anastomotic site, irrespectively of the obturator foramen, by which the reduction of radiation volume was possible in 55 patients (76%). Authors evaluated and compared survival, local control, and disease-free survival rates of these two groups. RESULTS: The median follow-up period was 27 months (range : 7-58 months). MAC stages were B2 in 32 (36%), B3 in 2 (2%), C1 in 2 (2%), C2 in 50 (57%), and C3 in 2 (2%) patients, respectively. The entire patients' overall survival rates at 2 and 4 years were 94% and 68%, respectively, and disease-free survival rates at 2 and 4 years were 86% and 58%, respectively. The first failure sites were local only in 4, distant only in 14, and combined local and distant in 1 patient, respectively. There was no significant difference with respect to local control and disease-free survival rates ( p=0.42, p=0.68) between two groups of different lower margin determination policies. CONCLUSION: The new concept in the individualized determination of the lower margin depending on the anastomotic site has led to the equivalent local control and disease-free survival rates, and is expected to contribute to the reduction of unnecessary radiation-related morbidity by reduction of radiation volume, compared with the traditional method of lower margin determination.