Does HCC Etiology Impact the Efficacy of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma? An Asian Liver Radiation Therapy Group Study.

Background/Purpose: The Asian Liver Radiation Therapy Study Group has formed a large and detailed multinational database of outcomes following stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Here, we explored the potential impact of HCC etiology on SBRT efficacy. Tumor control probability (TCP) models were established to estimate the likelihood of local control (LC). Methods: Data from 415 patients who were treated with SBRT for HCC were reviewed. Cox proportional hazards models were used to identify key predictors of LC. TCP models accounting for biologic effective dose (BED) and tumor diameter were generated to quantify associations between etiology and LC. Results: Cox models demonstrated that hepatitis C virus (HCV) infection was associated with favorable LC following SBRT (HR=0.52, 95% CI 0.04-0.96, p=0.036). The 2-year LC rate for patients with HCV etiology was 88%, compared to 78% for other patients. Small tumor and high BED were also associated with favorable LC. TCP models demonstrated a 10-20% absolute increase in predicted LC across the range of SBRT doses and tumor sizes. Conclusion: We found a novel association between HCV status and LC after SBRT for HCC that warrants further exploration. If validated in other datasets, our findings could help clinicians tailor SBRT schedules.

The effect of adjuvant chemotherapy and early tumor regression on the outcome of nasopharyngeal cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVES: We assessed the role of adjuvant chemotherapy (ACT) in patients with advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy (CCRT) and investigated the prognostic factors for recurrence and survival. MATERIALS AND METHODS: Between January 2008 and January 2018, 88 non-metastatic nasopharyngeal carcinoma patients treated with CCRT and with or without ACT in two institutions were retrospectively reviewed. The initial tumor response evaluation was performed 1 month after CCRT completion. Survival analysis was performed for factors such as initial tumor regression, ACT and other clinical factors. Subgroup analysis was performed for the four-group categorized according to tumor regression and ACT (CR with/without ACT, non-CR with/without ACT). RESULTS: Complete response (CR) 1 month after CCRT was a favorable prognosticator for progression-free survival (PFS) (hazard ratio [HR] 3.16, 95% confidence interval [CI] 1.02-9.85, p = 0.046) and overall survival (OS) (HR 3.19, 95% CI 1.14-8.93, p = 0.027). Also, ACT was an independent factor for PFS (HR 0.38, 95% CI 0.15-0.98, p = 0.047) and OS (HR 0.37, 95% CI 0.13-0.99, p = 0.047). In subgroup analysis, the CR after CCRT followed by ACT group showed significantly higher locoregional recurrence-free survival (p = 0.02), OS (p = 0.003), distant-metastasis free survival (p = 0.07), and PFS (p = 0.01) than the other three groups. CONCLUSION: Tumor regression 1 month after CCRT, and administration of ACT identified as an independent prognosticator for PFS and OS in this study. Even patients who show early tumor regression after CCRT may benefit from ACT. Further randomized trials should define the role of ACT in patients with nasopharyngeal cancer who achieved CR after CCRT.

Dose-Response Relationship in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: A Pooled Analysis of an Asian Liver Radiation Therapy Group Study.

PURPOSE: Despite the worldwide implementation of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC), there is a lack of consensus guideline on prescription dose. Herein, this multinational study aimed to investigate the effects of the prescribed radiation dose on oncologic outcomes of SBRT for HCC. METHODS AND MATERIALS: The multi-institutional retrospective cohort included 510 patients treated with SBRT between 2010 and 2016. All relevant clinical factors and factors related to SBRT were analyzed to evaluate freedom from local progression (FFLP) and overall survival (OS). Based on a biologically effective dose (BED) cutoff value of 100 Gy, 198 tumors were selected from each group in propensity score matching (PSM). RESULTS: Baseline characteristics in the BED <100 Gy group were unfavorable (Child-Pugh class B, 19%; advanced stage, 72%; median tumor size was 4 cm) compared with the BED ≥100 Gy group. With a median follow-up of 22 (interquartile range, 9.8-37.6) months, the 2-year FFLP and OS rates were 77% and 73%, respectively. Patients treated with a BED ≥100 Gy showed better rates of 2-year FFLP and OS than patients treated with a BED <100 Gy (FFLP, 89% vs 69%; OS, 80% vs 67%; P < .001). In the multivariable analysis before and after PSM, BED ≥100 Gy was identified as the main prognostic factor for both FFLP and OS (P < .01). Additionally, a dose-response relationship was observed between FFLP and BED (odds ratio, 0.92 per 5 Gy, P = .048). CONCLUSIONS: A BED ≥100 Gy was significantly associated with outcomes, and a dose-response relationship was observed between local tumor progression and BED. Given that SBRT is being increasingly used in HCC, detailed consensus guidelines regarding SBRT dose prescription should be established.

Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

Image similarity evaluation of the bulk-density-assigned synthetic CT derived from MRI of intracranial regions for radiation treatment.

OBJECTIVE: Various methods for radiation-dose calculation have been investigated over previous decades, focusing on the use of magnetic resonance imaging (MRI) only. The bulk-density-assignment method based on manual segmentation has exhibited promising results compared to dose-calculation with computed tomography (CT). However, this method cannot be easily implemented in clinical practice due to its time-consuming nature. Therefore, we investigated an automatic anatomy segmentation method with the intention of providing the proper methodology to evaluate synthetic CT images for a radiation-dose calculation based on MR images. METHODS: CT images of 20 brain cancer patients were selected, and their MR images including T1-weighted, T2-weighted, and PETRA were retrospectively collected. Eight anatomies of the patients, such as the body, air, eyeball, lens, cavity, ventricle, brainstem, and bone, were segmented for bulk-density-assigned CT image (BCT) generation. In addition, water-equivalent CT images (WCT) with only two anatomies-body and air-were generated for a comparison with BCT. Histogram comparison and gamma analysis were performed by comparison with the original CT images, after the evaluation of automatic segmentation performance with the dice similarity coefficient (DSC), false negative dice (FND) coefficient, and false positive dice (FPD) coefficient. RESULTS: The highest DSC value was 99.34 for air segmentation, and the lowest DSC value was 73.50 for bone segmentation. For lens segmentation, relatively high FND and FPD values were measured. The cavity and bone were measured as over-segmented anatomies having higher FPD values than FND. The measured histogram comparison results of BCT were better than those of WCT in all cases. In gamma analysis, the averaged improvement of BCT compared to WCT was measured. All the measured results of BCT were better than those of WCT. Therefore, the results of this study show that the introduced methods, such as histogram comparison and gamma analysis, are valid for the evaluation of the synthetic CT generation from MR images. CONCLUSIONS: The image similarity results showed that BCT has superior results compared to WCT for all measurements performed in this study. Consequently, more accurate radiation treatment for the intracranial regions can be expected when the proper image similarity evaluation introduced in this study is performed.

Intensity-modulated radiotherapy reduces gastrointestinal toxicity in pelvic radiation therapy with moderate dose.

This retrospective study was performed to evaluate and compare gastrointestinal (GI) toxicities caused by conventional radiotherapy (cRT) and intensity modulated radiotherapy (IMRT) in 136 cancer patients treated with pelvic radiotherapy (RT) with moderate radiation dose in a single institution. A matched-pair analysis of the two groups was performed; each group included 68 patients. Conventional RT was delivered using the four-field box technique and IMRT was delivered with helical tomotherapy. The median daily dose was 1.8 Gy and the median total dose was 50.4 Gy (range 25.2-56 Gy). Primary end point was GI toxicity during and after RT. Secondary end point was factors that affect toxicity. Patients treated with IMRT had lower incidence of grade ≥ 2 acute GI toxicity compared to the patients treated with cRT (p = 0.003). The difference remained significant in multivariate analysis (p = 0.01). The incidence of chronic GI toxicity was not statistically different between the two groups, but the cRT group had higher incidence of grade 3 chronic GI toxicity. Based on our results, IMRT can reduce GI toxicity compared to cRT in the treatment of pelvic radiotherapy even with moderate radiation dose and this will enhance patients' quality of life and treatment compliance.

Prognostic value of tumor volume and radiation dose in moderate-sized hepatocellular carcinoma: A multicenter analysis in Korea (KROG 14-17).

The purpose of this study is to investigate the prognostic value of tumor volume and radiation dose for predicting treatment outcomes in moderate-sized hepatocellular carcinoma (HCC).A total of 72 patients with unresectable HCC ranging in size from 5 to 10 cm were treated with high-dose radiotherapy including hypofractionated radiotherapy (HRT) and stereotactic body radiotherapy (SBRT), in 3 institutions from 2003 to 2013. The HRT doses ranged from 33 to 60 Gy in 3 to 10 fractions. The primary endpoint was local progression-free survival (PFS); the secondary endpoints were overall PFS, overall survival (OS), and treatment toxicity.The median follow-up period after radiotherapy was 12.8 months. The local PFS rates at 1 and 2 years were 57.0% and 39.0%, respectively, with a median of 13.6 months. The OS rates at 1 and 2 years were 70.1% and 45.2%, respectively, with a median of 21.1 months. A gross tumor volume (GTV) of 214 cm and a total dose of 105 Gy10 were identified as the optimal cutoff values of radiotherapeutic factors for local PFS. Patients with GTV ≤ 214 cm and total dose >105 Gy10 had significant higher 2-year local PFS and OS than patients with GTV >214 cm and total dose ≤ 105 Gy10 (P = .020 for local PFS, P = .009 for OS).The optimal cutoff values of GTV ≤ 214 cm and total dose >105 Gy10 may be useful for predicting survival outcomes when treating moderate-sized HCC with high-dose radiotherapy.

Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy.

PURPOSE: The neutrophil-lymphocyte ratio (NLR) has been suggested as an inflammation-related factor, but also as an indicator of systemic anti-tumor immunity. We aimed to evaluate the prognostic value of the NLR and to propose a proper cut-off value in patients with locally advanced rectal cancer who received preoperative chemoradiation (CRT) followed by curative total mesorectal excision (TME). METHODS: A total of 110 rectal cancer patients with clinical T3-4 or node-positive disease were retrospectively analyzed. The NLR value before preoperative CRT (pre-CRT NLR) and the NLR value between preoperative CRT and surgery (post-CRT NLR) were obtained. Using a maximally selected log-rank test, cut-off values were determined as 1.75 for the pre-CRT NLR and 5.14 for the post-CRT NLR. RESULTS: Patients were grouped as follows: group A, pre-CRT NLR ≤ 1.75 and post-CRT NLR ≤ 5.14 (n = 29); group B, pre-CRT NLR > 1.75 and post-CRT NLR ≤ 5.14, or pre-CRT NLR ≤ 1.75 and post-CRT NLR > 5.14 (n = 61); group C, pre-CRT NLR > 1.75 and post-CRT NLR > 5.14 (n = 20). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) and overall survival (OS) rates showed significant differences between the NLR groups (3-year DFS rate: 92.7% vs. 73.0% vs. 47.3%, for group A, B, and C, respectively, p = 0.018; 3-year OS rate: 96.0% vs. 85.5% vs. 59.8%, p = 0.034). Multivariate analysis revealed that the NLR was an independent prognostic factor for DFS (p = 0.028). CONCLUSION: Both the pre-CRT NLR and the post-CRT NLR have a predictive value for the prognosis of patients with locally advanced rectal cancer treated with preoperative CRT followed by curative TME and adjuvant chemotherapy. A persistently elevated post-CRT NLR may be an indicator of an increased risk of distant metastasis.

Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy.

We aimed to investigate the pre-radiotherapy neutrophil-to-lymphocyte ratio (prNLR) as a prognostic factor in patients with locally advanced hepatocellular carcinoma (HCC) treated with radiotherapy (RT), and to determine the optimal cut-off value for prNLR. We retrospectively evaluated 56 patients with locally advanced HCC treated with RT (helical tomotherapy) between March 2006 and February 2012. The optimal cut-off value was determined by using a maximally selected log-rank test. Prognostic factors that influence the local progression-free survival (PFS) and overall survival (OS) were evaluated. A prNLR of 2.1 was determined to be the optimal cut-off value. In a comparison between the high-prNLR group and the low-prNLR group, there was a 13.1-month difference in the median OS (10.3 vs. 23.4 months, p = 0.003) and a 10.4-month difference in the median local PFS (7.1 vs. 17.5 months, p = 0.001). On multivariate analysis of prognostic factors for local PFS and OS, the prNLR was identified as an independent prognostic factor, and the hazard ratio was 4.2 and 2.5, respectively. We demonstrated that a low prNLR was significantly associated with better PFS and OS in patients with locally advanced HCC treated with RT, and the prNLR should be considered as an independent prognostic factor in these patients.

Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07).

PURPOSE: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). MATERIALS AND METHODS: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. RESULTS: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. CONCLUSION: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.

Interobserver variability in gross tumor volume delineation for hepatocellular carcinoma : Results of Korean Radiation Oncology Group 1207 study.

PURPOSE: There has been increasing use of external beam radiotherapy for localized treatment of hepatocellular carcinoma (HCC) with both palliative and curative intent. Quality control of target delineation in primary HCC is essential to deliver adequate doses of radiation to the primary tumor while preserving adjacent healthy organs. We analyzed interobserver variability in gross tumor volume (GTV) delineation for HCC. PATIENTS AND METHODS: Twelve radiation oncologists specializing in liver malignancy participated in a multi-institutional contouring dummy-run study of nine HCC cases and independently delineated GTV on the same set of provided computed tomography images. Quantitative analysis was performed using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE) with kappa statistics calculating agreement between physicians. To quantify the interobserver variability of GTV delineations, the ratio of the actual delineated volume to the estimated consensus volume (STAPLE), the ratio of the common and encompassing volumes, and the coefficient of variation were calculated. RESULTS: The median kappa agreement level was 0.71 (range 0.28-0.86). The ratio of the actual delineated volume to the estimated consensus volume ranged from 0.19 to 1.93 (median 0.94) for all cases. The ratio of the common and encompassing volumes ranged from 0.001 to 0.56 (median 0.25). The coefficient of variation for GTV delineation ranged from 8 to 57 % (median 26 %). CONCLUSION: The interobserver variability in target delineation of HCC GTV in this study is noteworthy. Multi-institution studies involving radiotherapy for HCC require appropriate quality assurance programs for target delineation.

Hypofractionated intensity-modulated radiotherapy in patients with localized prostate cancer: a preliminary study.

PURPOSE: The aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer. MATERIALS AND METHODS: Thirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the α/ß ratio is 1.5 Gy. RESULTS: The median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ≥3 acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed. CONCLUSION: Favorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer.

Prognosis Can Be Predicted More Accurately Using Pre- and Postchemoradiotherapy Carcinoembryonic Antigen Levels Compared to Only Prechemoradiotherapy Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer Patients Who Received Neoadjuvant Chemoradiotherapy.

We aimed to evaluate the prognostic value of a change in the carcinoembryonic antigen (CEA) level during neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. A total of 110 patients with clinical T3/T4 or node-positive disease underwent nCRT and curative total mesorectal resection from February 2006 to December 2013. Serum CEA level was measured before nCRT, after nCRT, and then again after surgery. A cut-off value for CEA level to predict prognosis was determined using the maximally selected log-rank test. According to the test, patients were classified into 3 groups, based on their CEA levels (Group A: pre-CRT CEA ≤3.2; Group B: pre-CRT CEA level >3.2 and post-CRT CEA ≤2.8; and Group C: pre-CRT CEA >3.2 and post-CRT CEA >2.8). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) rates of Group A and Group B were similar, while Group C showed a significantly lower 3-year DFS rate (82.5% vs. 89.5% vs. 55.1%, respectively, P = 0.001). Other clinicopathological factors that showed statistical significance on univariate analysis were pre-CRT CEA, post-CRT CEA, tumor distance from the anal verge, surgery type, downstage, pathologic N stage, margin status and perineural invasion. The CEA group (P = 0.001) and tumor distance from the anal verge (P = 0.044) were significant prognostic factors for DFS on multivariate analysis. Post-CRT CEA level may be a useful prognostic factor in patients whose prognosis cannot be predicted exactly by pre-CRT CEA levels alone in the neoadjuvant treatment era. Combined pre-CRT CEA and post-CRT CEA levels enable us to predict prognosis more accurately and determine treatment and follow-up policies. Further large-scale studies are necessary to validate the prognostic value of CEA levels.

Distinctive Patterns of Initially Presenting Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer.

This study was designed to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV non-small cell lung cancer (NSCLC).Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes.The enrolled study cohort comprised 81% (n = 346) Adenoca patients and 19% (n = 81) SQ patients. The median age of the study population was 65 years (range, 30-94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age ≥65 years (69.1% vs 50.6%; P = 0.003) and male sex (84% vs 56.4%; P < 0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P < 0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P = 0.001), and brain metastasis (35% vs 16%; P = 0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3-6) were more frequently found to have Adenoca (91.6% vs 73.4%; P < 0.001). In multivariate prognostic evaluation, sex (P = 0.001), age (P < 0.001), histology (P < 0.001), LN status (P = 0.032), pleural/pericardial metastasis (P = 0.003), abdomen/pelvis metastasis (P < 0.001), axilla/neck metastasis (P = 0.006), and treatment factors (P < 0.001) remained independent prognostic factors affecting overall survival.We observed distinctive patterns of primary metastases and clinical outcomes according to the histological subtypes in stage IV NSCLC. Future studies need to disclose the underlying mechanism of these unique metastatic features and tumor biologies.

Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group.

OBJECTIVE: To investigate practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea. METHODS: In June 2013, the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology conducted a national patterns-of-care survey about stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma, consisting of 19 questions and 2 clinical scenarios. RESULTS: All 208 radiation oncologists (100%), who are regular members of Korean Society for Radiation Oncology, responded to this survey. Among these, 95 radiation oncologists were specialists for hepatology; 64 physicians did not use stereotactic body radiotherapy for hepatocellular carcinoma, and 31 physicians used stereotactic body radiotherapy. Most physicians (52%) performed stereotactic body radiotherapy to hepatocellular carcinoma in ≤5 cases per year. Physicians applied stereotactic body radiotherapy according to tumour size and baseline Child-Pugh class. All physicians agreed the use of stereotactic body radiotherapy to 2.8-cm hepatocellular carcinoma with Child-Pugh class of A, while 23 physicians (74%) selected stereotactic body radiotherapy for Child-Pugh class of B. Nineteen physicians (61%) selected stereotactic body radiotherapy to 5-cm hepatocellular carcinoma with Child-Pugh class of A, and only 14 physicians (45%) selected stereotactic body radiotherapy for Child-Pugh class of B. On the other hand, the preferred dose scheme was same as 60 Gy in three fractions. CONCLUSIONS: Among radiation oncologists in Korea, there was diversity in the practice for stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma. Additional prospective studies are necessary to standardize the practice and establish Korea-specific practice guidelines for hepatocellular carcinoma stereotactic body radiotherapy.

The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis.

PURPOSE: We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). MATERIALS AND METHODS: A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. RESULTS: After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). CONCLUSION: This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Identifying the optimal criteria of radiotherapeutic parameters for patients with unresectable locally advanced hepatocellular carcinoma.

The purpose of this study is to identify the optimal criteria of the radiotherapeutic parameters in patients with unresectable locally advanced hepatocellular carcinoma (HCC). 103 patients were enrolled in this study. All patients received RT delivered using the TomoTherapy Hi-Art system between March 2006 and February 2012. We evaluated the planning target volume (PTV), total dose (Gy10), and NTNL-V(BED20) (non-target normal liver volume receiving more than a biologically effective dose of 20 Gy8) as significant radiotherapeutic parameters associated with hepatic function deterioration and local progression-free survival (PFS). A PTV of 279 cm3 or 304 cm3, a total dose of 60 Gy10, and a NTNL-V(BED20) of 40.8% were identified as the optimal cut-off values of radiotherapeutic parameters to prevent hepatic function deterioration and prolong local PFS. Based on these findings, patients were divided in a favorable and an unfavorable prognosis group. The differences in median local PFS, overall survival, and incidence of deteriorated hepatic function between the two groups were 11.2 months, 11.1 months, and 71.7%, respectively (p < 0.001 in each case). In conclusion, we suggest that the optimal criteria of the radiotherapeutic parameters for patients with unresectable locally advanced HCC are: PTV ≤ 279 cm3, total dose > 60 Gy10, and NTNL-V(BED20) ≤ 40.8%.

Identification of Biologically Effective Dose-Volumetric Parameters That Predict Radiation-Induced Hepatic Toxicity in Patients Treated With Helical Tomotherapy for Unresectable Locally Advanced Hepatocellular Carcinoma.

The purpose of this study is to identify dose-volumetric parameters that predict radiation-induced hepatic toxicity (RIHT) by analyzing the relationship between the biologically effective dose (BED) delivered to the normal liver and RIHT.The clinical and dosimetric data from 123 patients with unresectable hepatocellular carcinoma (HCC) treated with helical tomotherapy were analyzed. The median radiation dose was a 50 Gy in 4.5 Gy fractions (range, 30-60 Gy in 1.8-5.0 Gy fractions) to 95% of the planning target volume. RIHT was defined as a Child-Pugh score increase of at least 2 points within 3 months of helical tomotherapy completion.RIHT developed in 60 patients (48.7%). Multivariate logistic regression analysis showed that VBED20 (percentage of nontarget normal liver volume that received more than a BED of 20 Gy) was a significant parameter (P < 0.001), and the cut-off value was 40.8% with a sensitivity and specificity of 0.833 and 0.698, respectively, according to the receiver operating characteristic curve (P < 0.001).Maintaining a VBED20 below 40.8% will reduce the risk of RIHT, and the proposed normal liver tolerance curve could be a useful guideline when treating unresectable HCC patients with various radiotherapy dose schedules.

Prognostic value of pretreatment (18)F-FDG PET-CT in radiotherapy for patients with hepatocellular carcinoma.

PURPOSE: The purpose of this study was to investigate the predictable value of pretreatment (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in radiotherapy (RT) for patients with hepatocellular carcinoma (HCC) or portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: We conducted a retrospective analysis of 36 stage I-IV HCC patients treated with RT. (18)F-FDG PET-CT was performed before RT. Treatment target was determined HCC or PVTT lesions by treatment aim. They were irradiated at a median prescription dose of 50 Gy. The response was evaluated within 3 months after completion of RT using the Response Evaluation Criteria in Solid Tumors (RECIST). Response rate, overall survival (OS), and the pattern of failure (POF) were analyzed. RESULTS: The response rate was 61.1%. The statistically significant prognostic factor affecting response in RT field was maximal standardized uptake value (maxSUV) only. The high SUV group (maxSUV ≥ 5.1) showed the better radiologic response than the low SUV group (maxSUV < 5.1). The median OS were 996.0 days in definitive group and 144.0 days in palliative group. Factors affecting OS were the %reduction of alpha-fetoprotein (AFP) level in the definitive group and Child-Pugh class in the palliative group. To predict the POF, maxSUV based on the cutoff value of 5.1 was the only significant factor in distant metastasis group. CONCLUSION: The results of this study suggest that the maxSUV of (18)F-FDG PET-CT may be a prognostic factor for treatment outcome and the POF after RT. A %reduction of AFP level and Child-Pugh class could be used to predict OS in HCC.