Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma

PURPOSE: Stereotactic body radiotherapy (SBRT) takes advantage of low α/β ratio of prostate cancer to deliver a large dose in few fractions. We examined clinical outcomes of SBRT using CyberKnife for the treatment of low- and intermediate-risk prostate cancer. MATERIALS AND METHODS: This study was based on a retrospective analysis of the 33 patients treated with SBRT using CyberKnife for localized prostate cancer (27.3% in low-risk and 72.7% in intermediate-risk). Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. RESULTS: Thirty-three patients with a median 51 months (range, 6 to 71 months) follow-up were analyzed. There was no biochemical failure. Median PSA nadir was 0.27 ng/mL at median 33 months and PSA bounce occurred in 30.3% (n = 10) of patients at median at median 10.5 months after SBRT. No grade 3 acute toxicity was noted. The 18.2% of the patients had acute grade 2 genitourinary (GU) toxicities and 21.2% had acute grade 2 gastrointestinal (GI) toxicities. After follow-up of 2 months, most complications had returned to baseline. There was no grade 3 late GU and GI toxicity. CONCLUSION: Our experience with SBRT using CyberKnife in low- and intermediate-risk prostate cancer demonstrates favorable efficacy and toxicity. Further studies with more patients and longer follow-up duration are required.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.

Method of tumor volume evaluation using magnetic resonance imaging for outcome prediction in cervical cancer treated with concurrent chemotherapy and radiotherapy

PURPOSE: To evaluate the patterns of tumor shape and to compare tumor volume derived from simple diameter-based ellipsoid measurement with that derived from tracing the entire tumor contour using region of interest (ROI)-based 3D volumetry with respect to the prediction outcome in cervical cancer patients treated with concurrent chemotherapy and radiotherapy. MATERIALS AND METHODS: Magnetic resonance imaging was performed in 98 patients with cervical cancer (stage IB-IIIB). The tumor shape was classified into two categories: ellipsoid and non-ellipsoid shape. ROI-based volumetry was derived from each magnetic resonance slice on the work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters were measured to calculate volume as an ellipsoid. RESULTS: The more than half of tumor (55.1%) had a non-ellipsoid configuration. The predictions for outcome were consistent between two volume groups, with overall survival of 93.6% and 87.7% for small tumor ( or =40 mL) using ROI and diameter based measurement, respectively. Disease-free survival was 93.8% and 90.6% for small tumor, 54.3% and 62.7% for intermediate-size tumor, and 13.7% and 10.3% for large tumor using ROI and diameter based method, respectively. Differences in outcome between size groups were statistically significant, and the differences in outcome predicted by the tumor volume by two different methods. CONCLUSION: Our data suggested that large numbers of cervical cancers are not ellipsoid. However, simple diameter-based tumor volume measurement appears to be useful in comparison with ROI-based volumetry for predicting outcome in cervical cancer patients.

Treatment Results of CyberKnife Radiosurgery for Patients with Primary or Recurrent Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. MATERIALS AND METHODS: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. RESULTS: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage I, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 Gy10. Among 20 lesions that received above 100 Gy10, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. CONCLUSION: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 Gy10 for peripheral T1 stage patients with NSCLC is recommended.

Comparing Concurrent Chemoradiotherapy to Chemotherapy Alone for Locally Advanced Unresectable Pancreatic Cancer / 대한방사선종양학회지

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. MATERIALS AND METHODS: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/m2). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/m2) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. RESULTS: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. CONCLUSION: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

Survival Analysis of Patients with Brain Metastsis by Weighting According to the Primary Tumor Oncotype / 대한방사선종양학회지

PURPOSE: This study was performed to retrospectively analyze patient survival by weighting according to the primary tumor oncotype in 160 patients with brain metastasis and who underwent whole brain radiotherapy. MATERIALS AND METHODS: A total of 160 metastatic brain cancer patients who were treated with whole brain radiotherapy of 30 Gy between 2002 and 2008 were retrospectively analyzed. The primary tumor oncotype of 20 patients was breast cancer, and that of 103 patients was lung cancer. Except for 18 patients with leptomeningeal seeding, a total of 142 patients were analyzed according to the prognostic factors and the Recursive Partitioning Analysis (RPA) class. Weighted Partitioning Analysis (WPA), with the weighting being done according to the primary tumor oncotype, was performed and the results were correlated with survival and then compared with the RPA Class. RESULTS: The median survival of the patients in RPA Class I (8 patients) was 20.0 months, that for Class II (76 patients) was 10.0 months and that for Class III (58 patients) was 3.0 months (p<0.003). The median survival of patients in WPA Class I (3 patients) was 36 months, that for the patients in Class II (9 patients) was 23.7 months, that for the patients in Class III (70 patients) was 10.9 months and that for the patients in Class IV (60 patients) was 8.6 months (p<0.001). The WPA Class might have more accuracy in assessing survival, and it may be superior to the RPA Class for assessing survival. CONCLUSION: A new prognostic index, the WPA Class, has more prognostic value than the RPA Class for the treatment of patients with metastatic brain cancer. This WPA Class may be useful to guide the appropriate treatment of metastatic brain lesions.

The Analysis of Dose in a Rectum by Multipurpose Brachytherapy Phantom / 대한방사선종양학회지

PURPOSE: In this work we designed and made MPBP (Multi Purpose Brachytherapy Phantom). The MPBP enables one to reproduce the same patient set-up in MPBP as the treatment of the patient and we tried to get an exact analysis of rectal doses in the phantom without need of in-vivo dosimetry. MATERIALS AND METHODS: Dose measurements were tried at a point of rectum 1, the reference point of rectum, with a diode detector for 4 patients treated with tandem and ovoid for a brachytherapy of a cervix cancer. Total 20 times of rectal dose measurements were made with 5 times a patient. The set-up variation of the diode detector was analyzed. The same patient set-ups were reproduced in self-made MPBP and then rectal doses were measured with TLD. RESULTS: The measurement results of the diode detector showed that the set-up variation of the diode detector was the maximum 11.25+/-0.95 mm in the y-direction for Patient 1 and the maximum 9.90+/-2.40 mm, 20.85+/-4.50 mm, and 19.15+/-3.33 mm in the z-direction for Patient 2, 3, and 4, respectively. In analyzing the degree of variation in 3 directions the more variation was showed in the z-direction than x- and y-direction except Patient 1. The results of TLD measurements in MPBP showed the relative maximum error of 8.6% and 7.7% at a point of rectum 1 for Patient 1 and 4, respectively and 1.7% and 1.2% for Patient 2 and 3, respectively. The doses measured at R1 and R2 were higher than those calculated except R point of Patient 2. This can be thought to related to the algorithm of dose calculation, whcih corrects for air and water but is guessed not to consider the correction for the scattered rays, but by considering the self-error (+/-5%) TLD has the relative error of values measured and calculated was analyzed to be in a good agreement within 15%. CONCLUSION: The reproducibility of dose measurements under the same condition as the treatment could be achieved owing to the self-made MPMP and the dose at the point of interest could be analyzed accurately. If a treatment is performed after achieving dose optimization using the data obtained in the phantom, dose will be able to be minimized to important organs.

Role of Glycogen Synthase Kinase-3 in Motor Neuronal Cell Death Mechanism of in Vitro Familial ALS Model (G94A, A4V mutant motoneuron)

BACKGROUND: G93A or A4V mutations in the human Cu/Zn- superoxide dismutase gene (hSOD1) cause familial amyotrophic lateral sclerosis (fALS). However, it has not yet clearly understood how these bring about fALS. We investigated the effects of the G93A or A4V mutations in hSOD1 on the phosphatydilinositol-3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway, and effects of GSK-3 inhibitor on the G93A- or A4V-mutant cells. METHODS: To evaluate those effects, VSC4.1 motoneuron cells were transfected with G93A- or A4V-mutant types of hSOD1 (G93A and A4V cells, respectively) with/without GSK-3 inhibitor were compared with them transfected with wild type (wild cells) in cell viability and intracellular signals, including PI3K/Akt, GSK-3, and caspase-3, 24 hours after neuronal differentiation. RESULTS: Compared with wild cells, MTT assay revealed a greatly reduced viability in G93A and A4V cells without GSK-3 inhibitor. However, treatment with GSK-3 inhibitor increased the viability of G93A and A4V cells. Western blotting showed that PI3K and pAkt were decreased, and GSK-3 and caspase-3 were increased in G93A and A4V cells, and that GSK-3 inhibitor treatment reduced caspase-3 but did not affected PI3K, Akt and GSK-3. CONCLUSIONS: These results suggest that the G93A or A4V mutations induce inhibition of PI3K/Akt and activation of GSK-3 and caspase-3 resulting the vulnerability to oxidative stress, and that GSK-3 mediated cell death mechanism is important in G93A and A4V cell death.

Comparison of the Result of Radiation Alone and Radiation with Daily Low Dose Cisplatin in Management of Locally Advanced Cervical Cancer / 대한방사선종양학회지

PURPOSE: An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. MATERIALS AND METHODS: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900~1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000~3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. RESULTS: The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiatoin groups, respectively (p=0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (p=0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (> or =3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. CONCLUSION: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates in locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

The Role of Postoperative Radiation Therapy in Extrahepatic Bile Duct Cancers / 대한방사선종양학회지

PURPOSE: The goal of this study was to determine the role of postoperative radiation therapy in extrahepatic bile duct cancers. MATERIALS AND METHODS: Between 1997 and 2001, 41 patients with extrahepatic bile duct cancer having undergone surgical resection were retrospectively analyzed. Of the 41 patients, 22 were treated by surgery alone (Group I) with remaining 19 treated by surgery and postoperative radiation therapy (Group II). A gross total surgical resection with pathologically negative margins was performed in 11 of the patients (50%) in Group I, and in 7 of the patients (36.8%) in Group II. There were no significant differences in the disease stage, surgical procedure or pathological characteristics of the two groups. The patients in group II received 45~54 Gy (median: 50.4 Gy) of external beam radiation therapy to the tumor bed and draining nodal area. RESULTS: The local failure rate was significantly higher in group I (54.5%) than in group II (15.8%)(p=0.010). Of the 12 failed patients in Group I and the 3 failed patients in group II, 7 and 3 had a positive resection margin. The overall 3-year survival rates were 38.3 and 38.9% and the 3-year disease free survival rates were 18.8 and 26.3% in groups I and II, respectively. However, the patients with positive resection margins who received adjuvant radiation therapy had higher 3-year overall survival rates than those with surgery alone (36.4% vs. 24.2%, p=0.06), and 3-year disease free survival rate was significantly higher in the group II patients who had positive margins compared with those in group I (25.0% vs. 18.2%, p=0.04). CONCLUSION: Postoperative adjuvant radiation therapy appeared to reduce the incidence of local failure in patients with extrahepatic bile duct cancer, and might improve the survival rate in the patients with positive resection margins.

Correction Method on Mismatched Posterior Edge of Medial and Lateral Tangential Fields for Three Fields Techniques in Breast Cancer / 대한방사선종양학회지

PURPOSE: The target volume for the three field technique in breast cancer include the breast tangential and supraclavicular areas. The techniques rotating the gantry and couch angles, to match these two areas, will geometrically produce mismatching of the posterior edge between the medial and lateral tangential beams. This mismatch was confirmed by film dosimetry and three-dimensional computer planning. The correction methods of this mismatching were studied in this article. MATERIALS AND METHODS: After the supraclavicular field was simulated using a half beam block and the medial and lateral tangential fields, by the rotation of the couch and gantry, we compared the following two methods to correct the mismatch. The first method was the rotation of collimator until a line drawn on the posterior edge of tangential beams before the rotation of couch aligned the line drawn on the posterior edge after the rotation. The second method was the rotation of collimator according to the formula developed by the author as follows; Co=2sin(-1){sin angle x sin (C/2)} (Co: collimator angle, angle: angle between tangential beam and table, C: couch angle) RESULTS: The film dosimetry showed the mismatching of posterior edges of the medial and lateral tangential fields prior to the rotation of collimator, while the posterior edges matched well after the rotation of collimator according to the formula. The three-dimensional computer plan also showed that the posterior edges matched well after the rotation of collimator accordingly. The DVH of the ipsilateral lung with the proper rotation of collimator angle was better than that without the rotation of collimator angle. CONCLUSION: The mismatching of the posterior edges of the medial and lateral tangential fields can be recognized on the three field technique in breast irradiation when the gantry and couch are simultaneously rotated and can be corrected with the proper rotation of the collimator angle. The radiation dose to the ipsilateral lung could be lowered with this technique.

Intravenous Regional Anesthesia Using Mepivacaine and Tramadol / 대한마취과학회지

BACKGROUND: Tramadol, an opioid n receptor agonist and monoaminergic reuptake inhibitor, has been studied as an adjunct to general and regional anesthesia. Tramadol has been added to local anesthetic regimens for various peripheral nerve blocks, resulting in prolonged anesthesia and analgesia. The purpose of this study was to evaluate the effectiveness of using tramadol as a component of intravenous regional anesthesia (IVRA) to enhance postoperative analgesia. METHODS: Thirty-six patients undergoing hand surgery received IVRA with mepivacaine 0.5%, and were assigned randomly and blindly to one of the following groups: Group I (n = 12) received only 0.5% mepivacaine 40 ml, Group II (n = 12) was given 0.5% mepivacaine 40 ml and 50 mg tramadol, and Group III (n = 12) received 0.5% mepivacaine 40 ml and 100 mg tramadol. After the completion of the operations, analgesic effects were evaluated by using the visual analogue scale (0 - 10). Sedation scores (0 - 3), supplemental analgesic use, and side effects were also evaluated. RESULTS: Patients who received IVRA with 100 mg tramadol reported a significantly lower pain score after tourniquet deflation compared with other groups, and a decreased need for analgesics in the postanesthesia care unit. No significant postoperative sedation, nausea, vomiting, or headache developed in any of the patients. CONCLUSIONS: The addition of 100 mg tramadol to 0.5% mepivacaine for IVRA provided improved analgesia in the postanesthesia care unit after the operation and decreased the need for analgesic supplements after the operation.

The Correlation between DNA Ploidy and the Clinicohistologic Findings in Colorectal Cancer / 대한방사선종양학회지

PURPOSE: DNA ploidy pattern was shown to correlate with several clinicohistologic findings in several tumors. Aim of this study was to evaluate the correlation of the clinicohistologic findings in colorectal cancer and the failure pattern in rectosigmoid cancer with DNA ploidy. MATERIALS AND METHODS: DNA flow cytometry using the Hedley methods on paraffin embedded specimen from 117 patients with colorectal cancers after curative resection was performed. We tried to find the correlation between DNA ploidy and various clinicohistologic findings. And then the correlation DNA ploidy and the failure pattern in 75 patients of rectosigmoid cancer was analized. RESULTS: Forty samples (34.2%) from tumors gave aneuploidy histogram. There was no significant difference in the frequency of DNA aneuploidy in terms of age, sex, depth of invasion, location and Dukes stage. But there was a significant correlation between DNA ploidy and the failure rates in Dukes stage B rectosigmoid cancer ( p=0.048). CONCLUSIONS: These findings suggest that DNA ploidy pattern shows the correlation with the treatment failure rates in Dukes stage B rectosigmoid, but not with many other clinicohistologic findings. However, more patients will be needed to disclose these findings.