Dongryul Oh

Pelvic Bone Complications After Radiation Therapy of Uterine Cervical Cancer: Evaluation with MRI

OBJECTIVE The purpose of this study was to assess the prevalence and distribution of radiation-induced insufficiency fractures and to investigate other bony complications of the female pelvis associated with radiation therapy using MR images. MATERIALS AND METHODS Two radiologists retrospectively evaluated pelvic MR images of 510 patients (mean age, 54.7 years) who underwent pelvic irradiation for uterine cervical cancer for the presence and location of insufficiency fractures by consensus. We calculated the cumulative prevalence of pelvic insufficiency fractures on the basis of their results. In addition, we identified other associated bony complications of the female pelvis by reviewing the MR images. RESULTS Insufficiency fractures were diagnosed in 100 patients; the 5-year cumulative prevalence was 45.2%. An insufficiency fracture was diagnosed a median of 16.9 months after radiation therapy. The fracture sites were the sacrum body and alae, medial side of the iliac bone, the roof of the acetabulum, superior rami of the pubic bone, femoral heads, and L5 vertebra. Sixty-one patients (61%) developed multiple fractures, and among them, 40 (40%) had bilateral symmetric lesions of the sacral alae. Other complications associated with the radiation therapy, as determined by evaluation of the MR images, were osteolysis and avascular necrosis of the femoral head. CONCLUSION Radiation-induced pelvic insufficiency fractures are a frequent complication of radiation therapy for uterine cervical cancer. Osteolysis and avascular necrosis of the femoral head were also diagnosed using MRI after radiation therapy.

Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity.

Purpose:We prospectively evaluated the efficacy and toxicity of early 3-dimensional conformal radiotherapy (3D-CRT) for patients with unresectable hepatocellular carcinoma (HCC) after incomplete transcatheter arterial chemoembolization (TACE). Methods:Patients with unresectable HCC who failed 1 or 2 courses of TACE were eligible for this study. Three dimensional-CRT was added for HCC with incomplete uptake of iodized oil. Between January 2006 and February 2007, 40 patients (43 lesions) were enrolled. TACE was performed by using Lipiodol and adriamycin, followed by Gelfoam embolization. Two cycles of TACE were performed in 24 patients (60%), whereas 16 patients (40%) underwent one cycle. The median dose of 54 Gy (3 Gy daily) was delivered with 3D-CRT. Tumor response was evaluated by changes in tumor size on serial computed tomography scans and toxicity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results:An objective response was achieved in 27 of 43 lesions (62.8%), with a complete response in 9 lesions (20.9%) and partial response in 18 lesions (41.9%). The overall survival rate was 72.0% at 1 year and 45.6% at 2 years. There was no grade 3 or greater acute toxicity. Nine patients (22.5%) showed progression of the disease within the irradiated field during the follow-up and intrahepatic metastases developed in 16 patients (40.0%). Conclusion:Early 3D-CRT for HCC unresponsive to 1 or 2 cycles of TACE resulted in a 62.8% tumor response rate and relatively high complete response rates (20.9%) with acceptable toxicity. This study shows that the application of 3D-CRT could be considered for patients with incomplete TACE.

Potentially curative stereotactic body radiation therapy (SBRT) for single or oligometastasis to the lung

Abstract Background. To analyze the treatment outcomes of a potentially curative therapy, stereotactic body radiation therapy (SBRT), for patients with single or oligometastasis to the lungs. Material and methods. Sixty-seven metastatic lung lesions in 57 patients were treated with SBRT between September 2001 and November 2010. All patients had single or oligo-metastasis to the lungs following a meticulous clinical work-up, including PET-CT scans. The lungs were the most common primary organ (33 lesions, 49.3%), followed by the head and neck (11 lesions, 16.4%), the liver (nine lesions, 13.5%), the colorectum (seven lesions, 10.4%), and other organs (seven lesions, 10.4%). Three different fractionation schedules were used: 50 Gy/5 fractions to four lesions (6.0%); 60 Gy/5 fractions to 44 lesions (65.7%); and 60 Gy/4 fractions to 19 lesions (28.3%). Results. Local tumor progression occurred in three lesions (4.5%). The three-year actuarial local control rate was 94.5%. Tumors larger than or equal to 2.5 cm showed poorer local control (98.3% vs. 77.8%, p <0.01). Metastatic tumors from the liver and colorectum showed lower local control rates than those from other organs (77.8%, 85.7%, and 100%, p =0.04). The two-year overall survival rate was 57.2%. Patients with tumors smaller than 2.5 cm had more favorable survival rates (64.0% vs. 38.9% at two-year, p =0.032). Patients with extrathoracic disease had poorer survival rates (66.1% vs. 0% at two-year, p =0.003). Patients with disease-free intervals longer than two years showed a trend toward good prognosis (71.1% vs. 51.1% at two-year, p =0.106). Grade 2 lung toxicity occurred in four patients (6.0%). One patient experienced Grade 5 lung toxicity following SBRT. Conclusion. SBRT for single or oligo-metastasis to the lung seems quite effective and safe. Tumor size, disease-free interval, and presence of extrathoracic disease are prognosticators for survival.

Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma, nasal type: a multicentre, retrospective analysis

BACKGROUND Assessment of tumour viability after treatment is essential for prediction of treatment failure in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We aimed to assess the use of the post-treatment Deauville score on PET-CT and Epstein-Barr virus DNA as a predictor of residual tumour, to establish the risk of treatment failure in patients with newly diagnosed ENKTL. METHODS In a retrospective analysis of patient data we assessed the prognostic relevance of the Deauville score (five-point scale) on PET-CT and circulating Epstein-Barr virus DNA after completion of treatment in consecutive patients with ENKTL who met eligibility criteria (newly diagnosed and received non-anthracycline-based chemotherapy, concurrent chemoradiotherapy, or both together) diagnosed at the Samsung Medical Center in Seoul, South Korea. The primary aim was to assess the association between progression-free survival and risk stratification based on post-treatment Deauville score and Epstein-Barr virus DNA. With an independent cohort from two different hospitals (Hong Kong and Singapore), we validated the prognostic value of our risk model. FINDINGS We included 102 patients diagnosed with ENKTL between Jan 6, 2005, and Nov 18, 2013, in the study cohort, and 38 patients diagnosed with ENKTL between Jan 7, 2009, and June 27, 2013, in the validation cohort. In the study cohort after a median follow-up of 47·2 months (IQR 30·0-65·5), 45 (44%) patients had treatment failure and 33 (32%) had died. Post-treatment Deauville score and Epstein-Barr virus DNA positivity were independently associated with progression-free and overall survival in the multivariable analysis (for post-treatment Deauville score of 3-4, progression-free survival hazard ratio [HR] 3·607, 95% CI 1·772-7·341, univariable p<0·0001; for post-treatment Epstein-Barr virus DNA positivity, progression-free survival HR 3·595, 95% CI 1·598-8·089, univariable p<0·0001). We stratified patients into three groups based on risk of treatment failure: a low-risk group (post-treatment Epstein-Barr virus negativity and post-treatment Deauville score of 1-2), a high-risk group (post-treatment Epstein-Barr virus negativity with a Deauville score 3-4, or post-treatment Epstein-Barr virus positivity with a Deauville score 1-2), and treatment failure (Deauville score of 5 or post-treatment Epstein-Barr positivity with a Deauville of score 3-4). This risk model showed a significant association with progression-free survival (for low risk vs high risk, HR 7·761, 95% CI 2·592-23·233, p<0·0001; for low risk vs failure, HR 18·546, 95% CI 5·997-57·353, p<0·0001). The validation cohort showed the same associations (for low risk vs high risk, HR 22·909, 95% CI 2·850-184·162, p=0·003; for low risk vs failure, HR 50·652, 95% CI 6·114-419·610, p<0·0001). INTERPRETATION Post-treatment Deauville score on PET-CT scan and the presence of Epstein-Barr virus DNA can predict the risk of treatment failure in patients with ENKTL. Our results might be able to help guide clinical practice. FUNDING Samsung Biomedical Research Institute.

The role of adjuvant radiotherapy in microscopic tumor control after extrahepatic bile duct cancer surgery.

Objectives:To evaluate effects of radiotherapy (RT) after surgery for extrahepatic bile duct (EHBD) cancer. Methods:There were 60 patients with EHBD cancer treated with postoperative RT. Surgical extents were R0 in 24 patients, R1 in 23, and R2 in 13. The indications for adjuvant RT were positive resection margin, lymph node metastasis, or more than pT2. Radiation was delivered to tumor bed and regional lymphatics, and for R1 or R2 patients, boost RT was planned. Overall survival (OS) and progression-free survival (PFS) was calculated and survival in the R0 and R1 patients with negative lymph nodes was compared. The pattern of treatment failures and prognostic factors were analyzed. Results:The 2- and 5-year survival rates were 36.6% and 12.3% for OS, and 31.2% and 16.2% for PFS. In comparison of R0 with R1 patients who had negative lymph node, 2-year OS and PFS were 53.0% and 55.0% in R0, and 40.7% and 36.7% in R1 (P = ns). The first site of failure was loco-regional in 29 patients. The lymph node metastasis was a significant prognostic factor in OS (P = 0.04) and PFS (P = 0.02). Conclusions:Lymph node metastasis was a poor prognostic factor and adjuvant RT may be useful in patients with microscopic residual tumor. However, because there were high loco-regional recurrences, additional study is needed to determine more effective RT such as increased RT dose or use of radiosensitizers.

Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer

BACKGROUND Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. PATIENTS AND METHODS Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. RESULTS Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT (P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy (P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥ 20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). CONCLUSIONS PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.

Prognostic Significance of Tumor Response as Assessed by Sequential 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography During Concurrent Chemoradiation Therapy for Cervical Cancer

PURPOSE To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). METHODS AND MATERIALS A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUV(max)%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV(max)% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. RESULTS During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUV(max) in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUV(max)% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV(max)% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. CONCLUSION Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUV(max)% ≥60% at 4 weeks of CCRT may predict CR response on 1-month post-CCRT PET/CT and also PFS.

Prediction of radiation pneumonitis following high-dose thoracic radiation therapy by 3 Gy/fraction for non-small cell lung cancer: analysis of clinical and dosimetric factors.

OBJECTIVE This study was undertaken to identify the factors predictive of radiation pneumonitis (RP) in 69 non-small cell lung cancer patients treated with thoracic radiation therapy only by 3 Gy fractions. METHODS A total of 69 patients who received only RT in daily 3 Gy were included in this study. Grade > or =3 RP was defined as an RP event. The cumulative incidence of RP was estimated and the correlations of the development of RP with the potential predictors were determined. RESULTS The cumulative incidence of events was 17.1% at 12 months. By univariate analysis, all clinical factors [age, performance status, weight loss, pre-RT forced expiratory volume in 1 s, tumour location, stage, RT dose and clinical target volume] were not associated with the risk of Grade > or =3 RP; however, all dosimetric factors [V5-50 and mean lung dose (MLD)] closely correlated with the development of RP. The receiver-operative characteristics (ROC) analysis revealed that MLD was the best predictors of Grade > or =3 RP (area under curve ROC = 0.937). By multivariate analysis, MLD was the only significant factor to be predictive of RP risk: the probability of Grade > or =3 RP was 3.7% when MLD < or = 16.1 Gy and 78.4% when MLD > 16.1 Gy. CONCLUSIONS Dosimetric parameters were valuable in predicting the development of RP.

Scheduled Interval Trans-Catheter Arterial Chemoembolization Followed by Radiation Therapy in Patients with Unresectable Hepatocellular Carcinoma

Combination treatment of trans-catheter arterial chemoembolization (TACE) and conformal radiation therapy (RT) reported promising results in patients with hepatocellular carcinoma (HCC), but, optimal interval was not determined. We hypothesized that a two-week interval between TACE and RT would be optimal. Therefore, we designed this study to evaluate the safety and efficacy of scheduled interval TACE followed by RT. HCC patients who were not eligible for standard therapies were enrolled for scheduled interval TACE followed by RT (START). Patients received TACE on the first day of treatment, and then RT was delivered after 14 days. The entire course of treatment took between four and five weeks. In 81 patients (96.4%), START was completed in the planned treatment period. RT was delayed in the remaining three patients because of decreased liver function or poor performance status after TACE. Of the 81 patients, objective response was observed in 57 patients (70.4%). One unexpected death occurred after START due to hepatic failure. Other toxicities were manageable. The median survival was 14.7 months. There was a significant difference in overall survival according to the response to START (P < 0.001). In conclusion, START is safe and feasible.

Transcatheter arterial chemoembolization and radiation therapy for treatment-naive patients with locally advanced hepatocellular carcinoma.

Purpose To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naïve patients with locally advanced hepatocellular carcinoma (HCC). Materials and Methods Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10). Results At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). Conclusion The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naïve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.