Conjunctival Lymphoma: Retrospective Analysis of the Treatment Result and Complications with Radiation Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In order to evaluate the response to radiation therapy and to analyze the patterns of failure, survival and complications, we performed a retrospective analysis of patients with conjunctival lymphoma. MATERIALS AND METHODS: From November 1991 to March 1999, 11 patients were diagnosed as conjunctival lymphoma at Asan Medical Center. Five patients had bilateral involvements, and a total of 16 eyes received radiation therapy. Using 6 to 9 MeV electrons or 4 MV photon beams, all patients were treated with a single anterior field to total doses ranging from 30 Gy to 45 Gy delivered in 10 to 25 fractions. The median follow up period was 57 Months. RESULTS: All patients achieved a complete response with radiation therapy. Two of 16 eyes that were treated (12.5%) developed local recurrence after radiation therapy, however they were salvaged with 30 Gy of reirradiation. The five-year local control was 88.9%. One out of 11 patients (9.9%) developed lung metastasis and received chest irradiation. At the last follow up, one had died of pneumonia and 10 patients were alive without disease evidence. The five-year overall survival rate was 77.8% and 5-year disease free survival was 77.8%. Cataract and dry eye occurred in one patient (9.9%) respectively. CONCLUSION: Radiation therapy is a very effective and safe treatment modality for conjunctival lymphoma. The local control rate of radiotherapy was excellent and complications were acceptable. Radiation therapy is also an effective treatment modality for recurrent conjunctival lymphoma. It generally requires more than three months to achieve complete response following radiation therapy, thus we recommend evaluating the response to radiation therapy at three months after completion of treatment.

Retrospective Analysis of the Results of Adjuvant Chemotherapy in Breast Cancer Patients with 10 or More Positive Nodes: Nonrandomized Comparison of Adriamycin-Containing Regimens / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the results of adriamycin-based adjuvant chemotherapy with or without high dose chemotherapy (HDC) with stem cell transplantation (SCT) in breast cancer with 10 or more positive axillary nodes. MATERIALS AND METHODS: Seventy-one breast cancer patients who had undergone surgery and had 10 or more positive axillary nodes were included in this study held between January 1997 and December 1999. The pathologic and clinical records were reviewed retrospectively. RESULTS: Twenty-nine patients were treated with adriamycin followed by 8 courses of CMF (group I); 22 patients received 4 courses of adriamycin and 7 patients received 3 courses of adriamycin. Twenty-six patients received median 6 courses of CAF (group II) and 16 patients underwent HDC and autologous SCT (group III). With a median follow-up of 27.1 months, relapses were observed in 24 patients (33.8%) and the 3-year disease-free survival (DFS) rate was 57.1%; group I/II 55.4%, and group III 62.7%. The three-year overall survival (OS) rate was 86.1%; group I/II 83.0%, group III 93.8%. There were no difference in the 3-year DFSs or in the OSs of group I and group II. However, patients who received only 3 courses of the sequential adriamycin in group I showed a significantly poorer 3-year OS than those that received 4 courses of adriamycin (42.9% vs. 95.5%). CONCLUSION: Our study shows that adriamycin-containing combination chemotherapy is as effective as HDC with SCT in patients with 10 or more positive axillary lymph nodes judging by 3-year DFS and OS, and shows that three courses of adriamycin seems to be inadequate.

Treatment Results of Postoperative Radiation Therapy for Malignant and Atypical Meningioma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the survival rate, prognostic factors and patterns of failure in malignant and atypical meningiomas, and investigated the role of radiation therapy in the treatment of these tumors. MATERIALS AND METHODS: We retrospectively reviewed nineteen patients treated at Asan Medical Center between Mar. 1994 and Jun. 2000 with histologically confirmed malignant or atypical meningiomas. The median patient age was 52 years. The extent of surgery prior to radiation was gross total resection in 13 and subtotal resection in 6. Eleven patients were referred for radiation immediately after diagnosis and the remainder after at least one recurrence. All patients received megavoltage radiation to a median dose of 55.8 Gy. The median follow-up period was 41 months. RESULTS: Eleven patients (57.9%) showed no evidence of disease, five patients died of meningioma and three were alive with disease. The 5-year overall and relapse-free survivals were 75.9 and 50.6%, respectively. There were no statistically significant prognostic factors found to be associated with relapse-free survival by univariate or multivariate analysis. During the follow-up period, no significant treatment-related complications were detected. CONCLUSION: The major patterns of failure were in-field recurrence. In order to reduce local failure, a higher radiation dose may be needed and a high precision therapy should be considered.

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.

A CT Simulator Phantom for Geometrical Test / 대한방사선종양학회지

PURPOSE: To design and test the CT simulator phantom for geometrical test. MATERIAL AND METHODS: The PMMA phantom was designed as a cylinder which is 20 cm in diameter and 24 cm in length, along with a 25x25x31 cm3 rectangular parallelepiped. Radio-opaque wires of which diameter is 0.8 mm are attached on the other surface of the phantom as a spiral. The rectangular phantom was made of four 24x24x0.5 cm3 square plates and each plate had a 24x24 cm2, 12x12 cm2, 6x6 cm2 square line. The squares were placed to face the cylinder at angles 0degrees, 15degrees, 30degrees, respectively. The rectangular phantom made it possible to measure the field size, couch angle, the collimator angle, the isocenter shift and the SSD, the measurements of the gantry angle from the cylindrical part. A virtual simulation software, AcQSimTM, offered various conditions to perform virtual simulations and these results were used to perform the geometrical quality assurance of CT simulator. RESULTS: A 0.3~0.5 mm difference was found on the 24 cm field size which was created with the DRR measurements obtained by scanning of the rectangular phantom. The isocenter shift, the collimator rotation, the couch rotation, and the gantry rotation test showed 0.5~1 mm, 0.5~1degrees0.5~1degrees, and 0.5~ 1degreesdifferences, respectively. We could not find any significant differences between the results from the two scanning methods. CONCLUSION: The geometrical test phantom developed in the study showed less than 1 mm (or 1degrees) differences. The phantom could be used as a routine geometrical QC/QA tools, since the differences are within clinically acceptable ranges.

A Prospective Randomized Trial Comparing the Sequence of Adjuvant Chemotherapy and Radiotherapy following Curative Resection of Stage II, III Rectal Cancer / 대한방사선종양학회지

PURPOSE: To evaluate the side effects, pattern of failure, and survival rate according to the sequence of postoperative adjuvant radiotherapy and chemotherapy, patients with stages II and lll rectal cancer who had undergone curative resection were randomized to early radiotherapy group (arm I) or 'late radiotherapy group (arm II)', then we intend to determine the most effective sequence of the radiotherapy and chemotherapy. MATERIALS AND METHODS: From January 1996 to March 1999, 3 13 patients with curatively resected stages II and III rectal cancer have been randomized to early' or late radiation therapy group and recei ved combined chemotherapy (5-FU 375 mg/m/day, leucovorin 20 mg/m, IV bolus daily D1-5, 8 cycles) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Arm I received radiation therapy from day 1 with first cycle of chemotherapy and arm II received radiation therapy from day 57 with third cycle of chemotherapy after completion of first two cycles. Preliminary analysis was performed with 228 patients registered up to Jun 1998. Two out of the 228 patients were excluded because of double primary cancer. Median follow-up period was 23 months. RESULTS: Local recurrence occurred in 11 patients (9.7%) for arm I and 9 patients (8%) for arm II. There was no significant difference between both groups (p=0.64). However, distant metastasis was found in 22 patients (19.5%) for arm I and 35 patients (31.0%) for arm II and which showed statistically significant difference between the two groups (p=0.046). And neither 3-year disease-free survival (70.2% vs 59.2%, p=0.2) nor overall survival (89.4% vs 88.0%, p=0.47) showed significant differences. The incidence of leukopenia during radiation therapy and chemotherapy was 78.3% and 79.9% respectively but leukopenia more than RTOG grade 3 was only 2.1% and 6.0% respectively. The incidence of diarrhea more than 10 times per day was significantly higher in the patients for arm I than for arm II (71.2% vs 4 1.6%, p=0.02) but this complication was controlled with supportive cares. CONCLUSION: Regardless of the sequence of postoperative adjuvant radiation therapy and chemotherapy a fter curative resection for rectal cancer, local recurrence rate was low with combined chemoradiotherapy. But distant metastasis rate was lower in early radiation therapy group than in late radiation therapy group and the reason is unclear. Most patients completed these treatments without severe complication, so these were thought to be safe treatments but the treatment compliance should be improved.

Postoperative Adjuvant Radiation Therapy in Endometrial Carcinoma / 대한방사선종양학회지

PURPOSE: To evaluate the histopathological prognostic factors, relapse pattern and survival in patients with endometrial carcinoma who were treated with surgery and postoperative adjuvant radiotherapy (RT). METHODS AND MATERIALS: From September 1991 to December 1997, 27 patients with endometrial carcinoma treated with surgery and postoperative adjuvant RT at Asan Medical Center were entered in this study. Surgery was performed with total abdominal hysterectomy in six, total abdominal hysterectomy with pelvic lymph node dissection in eight and radical hysterectomy in 13 patients. External RT of 50.4 Gy was done to all patients and among these, additional high dose rate vaginal vault irradiation of 20-25 Gy with fractional dose of 4-5 Gy was boosted in 16 patients. The patients were followed for 6-95 months (median 30). RESULTS: The number of patients according to FIGO stage were I 18 (67%), II 1 (4%) and III 7 (26%). Patients with poor histologic grade, deep myometrial invasion, adnexal involvement, lymphovascular invasion showed more pelvic lymph node involvement, but no statistical significance was indicated. The 5year overall and disease free survival were 100% and 76.8%, respectively. Relapse sites were pelvic, para-aortic lymph node, and multiple metastases including lung, and no vaginal relapse was developed. Factors that were associated with disease free survival were FIGO stage (p=0.01), lymphovascular invasion (p=0.03), pelvic lymph node involvement (p=0.000 1). There was only one Grade 1 rectal bleeding without moderate to severe complications. CONCLUSION: Postoperative adjuvant RT is considered to reduce the loco-regional failure, resulting the improvement of survival. The group of patients with the risk of vaginal failure without vaginal vault irradiation should be investigated according to stage and grade.

Preliminary Results of Stereotactic Radiosurgery Using Stereotactic Body Frame / 대한방사선종양학회지

PURPOSE: To evaluate efficacy and complication of stereotactic radiosurgery using stereotactic body frame. METHODS AND MATERIALS: From December 1997 to June 1999, 11 patients with primary and metastatic tumors were treated with stereotactic radiosurgery using stereotactic body frame(Precision Therapy(TM)). Three patients were treated with primary hepatoma and seven with metastatic tumor from liver, lung, breast, trachea and one with arteriovenous malformation on neck. We used vacuum pillow for immobilization and made skin marker on sternum and tibia area with chest marker and leg marker. Diaphragm control was used for reducing movement by respiration. CT-simulation and treatment planning were performed. Set-up error was checked by CT-Simulator before each treatment. Dose were calculated on the 80~90% isodose of isocenter dose and given consecutive 3 fractions for total dose of 30 Gy (10 Gy/fraction). RESULTS: Median follow-up was 12 months. One patient (9%) showed complete response and four patients (36%) showed partial response and others showed stable disease. Planning target volumes (PTV) ranged from 3 to 111 cc (mean 18.4 cc). Set-up error was within 5 mm in all directions (X, Y, Z axis). There was no complication in all patients. CONCLUSION: In primary and metastatic tumors, stereotactic radiosurgery using stereotactic body frame is very safe, accurate and effective treatment modality.

Outcome of Surgical Excision for Isolated Locoregional Recurrence of Breast Cancer

PURPOSE: Locoregional recurrence of breast cancer after surgery has been regarded as a harbinger of distant metastases. The present study was undertaken to determine survival following surgical excision of isolated locoregional recurrence and to analyze prognostic factors for their impact on survival after locoregional recurrence. Also, this study may provide information on the group that benefits from surgical management. METHODS: From March 1993 to December 1998, of 43 patients with isolated locoregional recurrence after breast cancer surgery, 26 patients were treated with surgical excision with or without irradiation. Survival was retrospectively analyzed according to prognostic factors. RESULTS: The median follow-up was 15 months. The 3-year disease-free survival rates were 50% for locoregional recurrences treated with surgical resection and 6% for patients treated without surgery (p=0.04), and the overall survival rates were 63% and 14%, respectively (p=0.07). Univariative analysis demonstrated that the initial axillary node status and the disease-free interval were significant prognostic factors for overall survival (p=0.04 and p=0.06, respectively). The disease-free interval from surgery to recurrence was also a significant prognostic factor for disease-free survival (p=0.03). CONCLUSION: These results suggest that patients suffering from isolated locoregional recurrence of breast cancer after a long disease-free interval and an initial node negative status may survive for long periods of time with aggressive surgical treatment.

Outcome of Surgical Excision for Isolated Locoregional Recurrence of Breast Cancer / 한국유방암학회지

PURPOSE: Locoregional recurrence of breast cancer after surgery has been regarded as a harbinger of distant metastases. The present study was undertaken to determine survival following surgical excision of isolated locoregional recurrence and to analyze prognostic factors for impact on survival after locoregional recurrence. Also, this study may provide information on the benefit group from surgical management. METHODS: From March 1993 to December 1998, of 43 patients with isolated locoregional recurrence after breast cancer surgery, 26 patients were treated with surgical excision with or without irradiation. Survival was analyzed according to prognostic factors retrospectively. RESULTS: The median follow-up was 15 months. the 3-year disease-free and overall survival was 50% and 63% for locoregional recurrences treated with surgical resection, and 6% and 14% for patients without surgery, respectively(p=0.04, p=0.07). Univariative analysis demonstrated that the initial axillary node status and the disease-free interval were found to be significant prognostic factors for overall survival(p=0.04, p=0.06). The disease-free interval from surgery to recurrence was also a significant prognostic factor for disease-free survival(p=0.03). CONCLUSION: These results suggest that isolated locoregional recurrence of breast cancer with a long disease-free interval and an initial node negative status may survived for long periods of time with aggressive surgical treatment.

Effect of Adjuvant Chemotherapy of Operable Breast Cancer : Survival and Prognostic Factor Analysis / 대한암학회지

PURPOSE: Though the therapy using regimens similar to western countries has been done by medical oncologists in several different centers in Korea, there is no large scale study about the results of those adjuvant chemotherapy as in western country and it is not clear whether the results are same in Korean population as in western countries not only in overall outcome but also depending on various prognostic categories. It is important to review whether Korean patients would have equivalent results as in western countries or not when they were treated with the same standardized regimens. We examined the effect of adjuvant systemic chemotherapy on survival and analyzed prognostic factors. MATERIALS AND METHODS: A retrospective analysis of survival and prognostic factors was done in 341 consecutive breast cancer patients who received curative operation followed by systemic conventional adjuvant chemotherapy between 1989 and 1996. The survival rate was compared using Kaplan-Meier method and Log-rank method. To evaluate an independent prognostic factors, Cox proportional hazard model was used. RESULTS: After median follow up of 56 months (range 28 118 months), the mean disease-free survival (DFS) and overall survival (OS) was 81.0+/-2.7 and 91.5+/-2.6 months respectively. The 5-year DFS and OS rate was 61% and 77%, respectively. On univariate analysis, prognostic factors significant for DFS were tumor size ( 2 cm), hormonal receptor status, and histologic grade. Prognostic factors affecting both DFS and OS are as follows: age ((pound)40 vs 41-50 vs. (3)51), number of axillary node involvement, .and stage. Multivariate analysis showed that the number of axillary node involvement was the strongest adverse predictor. CONCLUSION: The effect of adjuvant chemotherapy in Korean patients is not different from western countries and this report emphasizes the prognostic importance of number of axillary node involvement in breast cancer patients and necessity of intensive management of those with four or more positive nodes.

Effect of Protein Kinase C Inhibitor (PKCI) on Radiation Sensitivity and c-fos Transcription Activity / 대한방사선종양학회지

PURPOSE: The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. The recent identification of the gene mutated in AT, ATM, and the demonstration that it encodes a homologous domain of phosphatidylinositol 3-kinase (PI3-K), the catalytic subunit of an enzyme involved in transmitting signals from the cell surface to the nucleus, provide support for a role of this gene in signal transduction. Although ionizing radiation was known to induce c-fos transcription, nothing is known about how ATM or PKCI mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKCI on radiation sensitivity and c-fos transcription in normal and AT cells. MATERIALS AND METHODS: Normal (LM217) and AT (AT5BIVA) cells were transfected with PKCI expression plasmid and the overexpression and integration of PKCI was evaluated by northern blotting and polymerase chain reaction, respectively. 5 Gy of radiation was exposed to LM and AT cells transfected with PKCI expression plasmid and cells were harvested 48 hours after radiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing CAT assay of reporter gene after transfection of c-fos CAT plasmid into AT and LM cells. RESULTS: Our results demonstrate for the first time a role of PKCI on the radiation sensitivity and c-fos expression in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells but reduced apoptosis in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than that in LM cells. The c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells CONCLUSION: Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells. The results may be a reason of increased radiation sensitivity of AT cells. PKCI may be involved in an ionizing radiation induced signal transduction pathway responsible for radiation sensitivity and c-fos transcription. The data also provided evidence for novel transcriptional difference between LM and AT cells.

Breast Cancer during Pregnancy and Lactation

BACKGROUND: The clinical features of breast cancer associated with pregnancy and lactation remain unknown in many aspects, partly because the incidence is relatively low. The purpose of this study was to evaluate clinicopathologic characteristics and the survival rate of pregnancy-associated breast cancer patients. METHODS: Among 1,265 breast cancer patients treated at the Breast Clinic of Asan Medical Center from July 1989 to December 1998, 13 subjects with breast cancer diagnosed during pregnancy (2 cases) and lactation (11 cases) were evaluated retrospectively. RESULTS: The incidence of pregnancy-associated breast cancer was 1.03% of all breast cancer patients. The mean age and the symptom duration of the subjects was 31.2 years and 8.8 months, repectively. As for surgical procedure, a modified radical mastectomy and breast-conserving surgery were carried out in 10 cases (76.9%) and 2 cases (15.4%), respectively. The median tumor size was 4.0 cm. Lymph node metastases were found in 7 cases (61.5%). According to the TNM classification, all of the patients showed stage II or above tumors. Invasive ductal carcinoma (10 cases, 76.9%) was the most common histopathologic type of tumor. The positive rate of ER and PR in the subjects were 63.6% and 50.0%, respectively. The 3-year overall survival rate and disease-free survival rate were 69.9% and 44.4%, respectively. CONCLUSIONS: This study shows that most of the patients with breast cancer during pregnancy and lactation are in a more advanced stage with a delay in detection and diagnosis, and hence have a unfavorable prognosis.

Primary Central Nervous System Lymphoma / 대한암학회지

PURPOSE: Primary central nervous system lymphoma (PCNSL) is defined as lymphoma limited to the cranial-spinal axis without evidence of systemic disease and its incidence has risen threefold during the last fifteen years among apparantly healthy population. This study was intended to analyze the clinicopathologic features and treatment outcome of the patient with PCNSL. MATERIALS AND METHODS: Twenty one patients were diagnosed and treated for the PCNSL limited to brain parenchyme at Asan Medical Center between March 1989 and December 1996. We reviewed clinical records of these patients and analyzed clinicopathologic features, treatment response, survival time and prognostic factors. RESULTS: The ratio of male to female was 1.3: 1 and the most prevalent age group was the 4th decade. Most patients had diffuse large cell (19/21) and B-cell type (8/8). Seventeen (94.4%) among 18 evaluable patients achieved complete remission (CR) as initial response, but 53% of patients showed recurence of the disease. Median times of disease-free and overall survival were 40 and 50 months, respectively and 5 year overall survival rate was 35.3 %. Prognostic factors such as age and performance status, had a statistically significant influence on the overall survival but not on disease-free survival. CONCLUSION: CR rate of the patients with PCNSL was high, but relapses were frequent. There fore further studies are needed to define the pmgnostic factors and to decrease relapse rate.

Radiotherapy in Incompletely Resected Gastric Cancers / 대한방사선종양학회지

PURPOSE: Although local recurrence rates of stomach cancer after radical surgery have been eported in the range of 30-70%, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. MATERIALS AND METHODS: From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiomyosarcoma. The numbers of patients with stage IB, II, IIIA, IIIB, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion. Minimum and median follow-up periods were 12 months and 18 months, respectively. RESULTS: Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than 15% of their pretreatment weight. But hematemesis, melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/ remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient. Peritoneal seeding occurred in 6, liver metastases in 2, and distant nodes in 2 patients. Four year disease specific survival rate was 40% and disease free survival was 48%. Median survival was 35 months and median disease free survival time was 26 months. Stages and radiation dose were not significant prognostic factors for locoregional failures. CONCLUSION: Although all patients in this study had positive surgical margins, locoregional failure rate was 28%, and 4 year disease specific survival rate was 40%. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences, but we could find a possibility of the role of postoperative radiotherapy in patients with high risk factors.

Postoperative Sequential Mitomycin-C, Vinblastine, and Cisplatin (MVP) Chemotherapy and Radiotherapy for Resected Stage II-IIIA Non-small Cell Lung Cancer / 대한내과학회지

OBJECTIVES: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. METHODS: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m2, Vinblastine 6 mg/m2, Cisplatin 60 mg/m2) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. RESULTS: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis. CONCLUSION: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity.

Clinical Experience of Three Dimensional Conformal Radiation Therapy for Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aim of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. MATERIALS AND METHODS: Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial. Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy. Seventy eight patients (82.1%) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication probabilities (NTCP). RESULTS: Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100% of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range ; 0.17-0.43) was 68% of the mean NTCP with 2D treatment planning (range ; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79%), showed major response including 25 (26%) with complete responses and 50 (53%) with partial responses. One and two year overall survivals of stage lll patients were 62.6% and 35.2% respectively. Twenty percent (19/95) of patients had pneumonitis ; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for patients without complication was 62% of those with complications. CONCLUSIONS: This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.

Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of The Uterine Cervix : A Phase I/II Prospective Study / 대한방사선종양학회지

PURPOSE: Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. METHODS AND MATERIALS: From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m2/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m2/day intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of RT. RESULTS: The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol; The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and III+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB andIII+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. CONCLUSION: Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

Radiation Therapy of Intracranial Germinoma / 대한치료방사선과학회지

PURPOSE: Intracranial germinoma is the most radiocurable tumor of the primary intracranial neoplasm. But, the optimum radiation dose and target volume remain controversial. In this retrospective study, we analysed the spreading pattern at presentation and the pattern of the failure and survival of intracranial germinoma. MATERIALS AND METHODS: From 1989 to 1996, 23 patients were treated for intracranial germinoma at Department of Radiation Oncology. Twenty-one patients were treated at their initial presentation and 2 patients were treated for recurrent disease. Six patients had multiple tumor masses on MRI and 7 patients had ventricular seeding on MRI. The examination of cerebrospinal fluid cytology was done in 15 patients and 3 out of 15 patients had positive cerebrospinal cytology. In tumor marker study of alpha-FP and beta-hCG, 6 patients had mildly elevated beta-hCG in serum or cerebrospinal fluid. Twenty-one patients were treated with whole craniospinal axis irradiation and 2 patients were given whole ventricular radiation therapy. The total dose was ranged between 4500cGy and 5600cGy to primary tumor site (median 5580 cGy). Dose to the entire ventricular system ranged from 1980cGy to 3960 cGy (median 2700cGy) and dose to the spinal axis ranged from 2160cGy to 3900cGy (median 2700cGy). RESULTS: Of 23 patients, 21 patients are alive without evidence of disease for median 4 years follow-up. One patient who had markedly elevated alpha-FP and beta-hCG suffered from persistent disease after radiation therapy and received 2 cycles of chemotherapy. She died 9 months after chemotherapy. One patient who developed ventricular seeding after gamma-knife was treated with whole craniospinal irradiation, he died after 1 year due to probably brain necrosis. The hematologic toxicity of 3 or 4 grade were seen in 7 patients, and patient's endocrinologic dysfunction was not deteriorated after radiation therapy. One patient had been treated with growth hormone replacement due to short stature. CONCLUSIONS: This retrospective study has confirmed the excellent result of radiation therapy in intracranial germinoma. The complication rate during or after radiation therapy is considered within acceptable range. It is necessary to further investigate the optimal dose and treatment volume of radiation therapy. The role of chemotherapy in the treatment of intracranial germinoma should be further investigated.