Su Ssan Kim

Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors

The aim of this study was to evaluate the treatment outcomes of stereotactic body radiation therapy for treating primary or metastatic thoracic tumors using a stereotactic body frame. Between January 1998 and February 2004, 101 lesions from 91 patients with thoracic tumors were prospectively reviewed. A dose of 10–12 Gy per fraction was given three to four times over consecutive days to a total dose of 30–48 Gy (median 40 Gy). The overall response rate was 82%, with 20 (22%) complete responses and 55 (60%) partial responses. The one- and two-year local progression free survival rates were 90% and 81%, respectively. The patients who received 48 Gy showed a better local tumor control than those who received less than 48 Gy (Fisher exact test; p = 0.004). No pulmonary complications greater than a RTOG toxicity criteria grade 2 were observed. The experience of stereotactic body frame based radiation therapy appears to be a safe and promising treatment modality for the local management of primary or metastatic lung tumors. The optimal total dose, fractionation schedule and treatment volume need to be determined after a further follow-up of these results.

Clinical prognostic factors and grading system for rib fracture following stereotactic body radiation therapy (SBRT) in patients with peripheral lung tumors.

BACKGROUND Several studies reported rib fractures following stereotactic body radiation therapy (SBRT) for peripheral lung tumors. We tried to investigate risk factors and grading system for rib fractures after SBRT. METHODS Of 375 primary or metastatic lung tumors (296 patients) which were treated with SBRT at the Asan Medical Center (2006-2009), 126 lesions (118 patients) were adjacent to the chest-wall (<1cm) and followed-up with chest computed tomography (CT) for >6 months; these were investigated in the present retrospective study. Three to four fractional doses of 10-20 Gy were delivered to 85-90% iso-dose volume of the isocenter dose. Rib fracture grade was defined from follow-up CT scans as the appearance of a fracture line (Gr1), dislocation of the fractured rib by more than half the rib diameter (Gr2), or the appearance of adjacent soft tissue edema (Gr3). Chest wall pain was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Correlations between dose-volume data and the development of rib fracture were then analyzed. The Kaplan-Meier method, log-rank tests, and chi-square tests were used for statistical analysis. RESULTS The median age of the patients was 69 years (range: 19-90). Over a median follow-up period of 22 months (range: 7-62), 48 cases of rib fracture were confirmed. Median time to rib fracture was 17 months (range: 4-52). The 2-year actuarial risk of rib fracture was 42.4%. Maximal grade was Gr1 (n=28), Gr2 (n=8), or Gr3 (n=15). The incidence of moderate to severe chest wall pain (CTCAE Gr ≥ 2) increased with maximal fracture grade (17.5% for Gr0-1 and 60.9% for Gr2-3; p<0.001). Multivariate analysis identified female gender, lateral location, and the dose to the 8cc of the chest wall as significant prognostic factors. CONCLUSIONS Female gender and lateral tumor location were clinical risk factors for rib fracture in the present study. Efforts to decrease chest wall dose should be made to reduce the risk of the rib fracture, particularly in high-risk patients.

Four-dimensional cone-beam computed tomography and digital tomosynthesis reconstructions using respiratory signals extracted from transcutaneously inserted metal markers for liver SBRT.

PURPOSE Respiration-induced intrafraction target motion is a concern in liver cancer radiotherapy, especially in stereotactic body radiotherapy (SBRT), and therefore, verification of its motion is necessary. An effective means to localize the liver cancer is to insert metal fiducial markers to or near the tumor with simultaneous imaging using cone-beam computed tomography (CBCT). Utilizing the fiducial markers, the authors have demonstrated a method to generate breath-induced motion signal of liver for reconstructing 4D digital tomosynthesis (4DDTS) and 4DCBCT images based on phasewise and/or amplitudewise sorting of projection data. METHODS The marker extraction algorithm is based on template matching of a prior known marker image and has been coded to optimally extract marker positions in CBCT projections from the On-Board Imager (Varian Medical Systems, Palo Alto, CA). To validate the algorithm, multiple projection images of moving thorax phantom and five patient cases were examined. Upon extraction of the motion signals from the markers, 4D image sorting and image reconstructions were subsequently performed. In the case of incomplete signals due to projections with missing markers, the authors have implemented signal profiling to replace the missing portion. RESULTS The proposed marker extraction algorithm was shown to be very robust and accurate in the phantom and patient cases examined. The maximum discrepancy of the algorithm predicted marker location versus operator selected location was < 1.2 mm, with the overall average of 0.51 +/- 0.15 mm, for 500 projections. The resulting 4DDTS and 4DCBCT images showed clear reduction in motion-induced blur of the markers and the anatomy for an effective image guidance. The signal profiling method was useful in replacing missing signals. CONCLUSIONS The authors have successfully demonstrated that motion tracking of fiducial markers and the subsequent 4D reconstruction of CBCT and DTS are possible. Due to the significant reduction in motion-induced image blur, it is anticipated that such technology will be useful in image-guided liver SBRT treatments.

The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: A multicenter, retrospective study (KROG 12-05)

PURPOSE The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. METHODS AND MATERIALS We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log-rank test and Cox proportional regression analysis. RESULTS Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. CONCLUSIONS PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

Phase II study of three-dimensional conformal radiotherapy and concurrent mitomycin-C, vinblastine, and cisplatin chemotherapy for Stage III locally advanced, unresectable, non–small-cell lung cancer

PURPOSE To evaluate the feasibility, treatment outcome, and toxicity of hyperfractionated three-dimensional conformal radiotherapy (CRT) and concurrent mitomycin-C, vinblastine, and cisplatin (MVP) chemotherapy in locally advanced, unresectable, Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Between August 1993 and December 1996, 161 patients with unresectable Stage III NSCLC were entered into this trial, and 146 (91%) completed the treatment. Hyperfractionated RT was given to a total dose of 64.8-70 Gy (1.2 Gy/fraction, b.i.d.) with two cycles of concurrent MVP chemotherapy (mitomycin-C 6 mg/m(2) on Days 2 and 29, vinblastine 6 mg/m(2) on Days 2 and 29, and cisplatin 60 mg/m(2) on Days 1 and 28). Of the 146 patients who completed the treatment, 78 received noncoplanar three-dimensional CRT using 4-6 fields and 17 received coplanar-segmented CRT. The clinical tumor response was assessed 1 month after RT completion by CT. Toxicity was graded using the Southwestern Oncology Group criteria. The normal tissue complication probability for the lung was calculated to determine the correlation with radiation pneumonitis, if any. Nineteen (13%) had Stage IIIA and 127 (87%) had IIIB disease, including 16 patients with pleural effusion and 20 with supraclavicular lymph node metastasis. RESULTS The response rate was 75%, composed of 22% complete responders and 53% partial responders. With a minimal follow-up of 45 months, the overall survival rate was 51.2% at 1 year, 25.1% at 2 years, and 14.8% at 5 years; the median survival was 12 months. Patients achieving a complete response (n = 32) had a 2-year overall survival rate of 49.8% and a 5-year survival rate of 39.2% compared with 22.5% and 11.4%, respectively, for the partial responders (n = 78; p = 0.0001). The actuarial local progression-free survival rate for all patients was 65.4% at 1 year, 42.1% at 2 years, and 36.3% at 4 years, and the actuarial distant-free survival rate was 65.4% at 1 year, 42.1% at 2 years, and 36.2% at 5 years. Severe weight loss (>10%) occurred in 20 (13.7%) of the 146 patients during treatment, 42 patients (29%) developed radiation pneumonitis (29 Grade 1 and 13 Grade 2). The average normal tissue complication probability value of the patients who had radiation pneumonitis was significantly greater than that of patients without pneumonitis (66.0% vs. 26.4%). Four patients died of treatment-related toxicity. CONCLUSION Hyperfractionated three-dimensional CRT and concurrent chemotherapy, as described here, is a well-tolerated regimen with acceptable toxicity. More effective treatment schemes are required to improve local disease control and overall survival.

Hyperuricemia in Kidney Transplant Recipients with Intact Graft Function

OBJECTIVES The aim of this study was to investigate the prevalence of hyperuricemia and factors predicting its occurrence, and to establish the relationship over time between serial changes in estimated glomerular filtration rate (eGFR) and uric acid (UR) concentration in kidney transplant (KT) recipients with eGFR >60 mL/min/1.73 m(2). METHODS Adult patients who underwent KT at the Asan Medical Center between 1990 and 2008 and maintained eGFR >60 mL/min/1.73 m(2) were retrospectively assessed. Clinical and laboratory data were obtained from inpatient and outpatient charts and from the hospital electronic database. RESULTS Of 356 patients, 301 (84.55%) had normal UR levels and 55 (15.45%) had hyperuricemia. After multivariate adjustment, transplant duration, male gender, eGFR, diabetes mellitus (DM), and calcium level were associated with higher mean UR levels. Mean UR level increased significantly and mean eGFR decreased significantly during the first year after transplantation, but there were no significant differences over the next 4 years. Serial UR and eGFR levels changed almost simultaneously. CONCLUSIONS Transplantation duration, male gender, eGFR level, DM, and serum calcium level were risk factors for hyperuricemia in kidney recipients with intact graft function. Increased uric acid after KT did not significantly affect graft function.

Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.

Diagnostic Value of Neck Node Status Using 18F-FDG PET for Salivary Duct Carcinoma of the Major Salivary Glands

18F-FDG PET and PET/CT have shown clinical usefulness in the initial staging and follow-up of patients with salivary malignancy. Therefore, we evaluated the utility of 18F-FDG PET in preoperative staging, determining the extent of neck node involvement, and surgical planning for patients with salivary duct carcinoma (SDC) of the major salivary gland. Methods: We evaluated 18 patients with SDC who were assessed by 18F-FDG PET and CT before surgery. The sensitivity, specificity, accuracy, and predictive values of CT and PET/CT for predicting the primary tumor site and determining the extent of neck node involvement at each dissected neck level were evaluated by comparing imaging findings with pathologic nodal stage. Results: The median maximum standardized uptake value of the primary lesions and cervical nodes were 4.7 (range, 1.8–12.1) and 5.8 (range, 1.7–13.0), respectively. The sensitivities of 18F-FDG PET and CT for predicting the primary tumor site were 100% (18/18) and 94.4% (17/18), respectively. In analyzing cervical lymph nodes at 73 dissected neck levels, 18F-FDG PET had a sensitivity of 76.1%, a specificity of 96.3%, a positive predictive value of 97.2%, and a negative predictive value of 70.3%; the corresponding values for CT were 39.1%, 92.6%, 90.0%, and 47.2%, respectively. The sensitivity and negative predictive value were significantly higher for 18F-FDG PET than for CT (P < 0.001 and P = 0.03, respectively).18F-FDG PET determination of the extent of neck node involvement changed the neck dissection regimen in 5 patients (27.8%). Conclusion: SDC of the major salivary gland is a highly metabolic tumor with high 18F-FDG uptake. 18F-FDG PET is useful for evaluating neck node status and for determining surgical planning in patients with major salivary gland SDC.

Postoperative radiation therapy following the incomplete resection of a non-small cell lung cancer

Purpose To review the results of postoperative radiation therapy (PORT) for residual non-small cell lung cancer (NSCLC) following surgical resection and evaluate multiple clinicopathologic prognostic factors. Materials and Methods A total of 58 patients, who completed scheduled PORT for positive resection margin, among 658 patients treated with PORT from January 2001 to November 2011 were retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after surgery. Chemotherapy was also administered to 35 patients, either sequentially or concurrently with PORT. Results The median age of patients was 63 years (range, 40 to 82 years). The postoperative pathological stage I NSCLC was diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10, large cell in 1, others in 4 patients. Microscopic residual disease (R1) was diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range, 50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year locoregional relapse-free survival and distant metastasis-free survival rates were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%. Chemotherapy did not influence the failure pattern or survival outcome. Conclusion PORT is an effective modality for improving local tumor control in incompletely resected NSCLC patients. Major failure pattern was distant metastasis despite chemotherapy.

Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report.

Purpose To assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer. Materials and Methods Patients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions. Results The study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity. Conclusion WP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings.