Young Nam Kang

Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis

BackgroundThe objectives of this retrospective study was to evaluate the efficacy of stereotactic body radiation therapy (SBRT) for small non-resectable hepatocellular carcinoma (HCC) and SBRT combined with transarterial chemoembolization (TACE) for advanced HCC with portal vein tumor thrombosis (PVTT).MethodsThirty one patients with HCC who were treated with SBRT were used for the study. We studied 32 HCC lesions, where 23 lesions (22 patients) were treated targeting small non-resectable primary HCC, and 9 lesions (9 patients) targeting PVTT using the Cyberknife. All the 9 patients targeting PVTT received TACE for the advanced HCC. Tumor volume was 3.6–57.3 cc (median, 25.2 cc) and SBRT dose was 30–39 Gy (median, 36 Gy) in 3 fractions for consecutive days for 70–85% of the planned target volume.ResultsThe median follow up was 10.5 months. The overall response rate was 71.9% [small HCC: 82.6% (19/23), advanced HCC with PVTT: 44.4% (4/9)], with the complete and partial response rates of 31.3% [small HCC: 26.1% (6/23), advanced HCC with PVTT: 11.1% (1/9)], and 50.0% [small HCC: 56.5% (13/23), advanced HCC with PVTT: 33.3% (3/9)], respectively. The median survival period of small HCC and advanced HCC with PVTT patients was 12 months and 8 months, respectively. No patient experienced Grade 4 toxicity.ConclusionSBRT for small HCC and SBRT combined with TACE for advanced HCC with PVTT showed feasible treatment modalities with minimal side effects in selected patients with primary HCC.

STEREOTACTIC BODY RADIOTHERAPY FOR PATIENTS WITH UNRESECTABLE PRIMARY HEPATOCELLULAR CARCINOMA: DOSE-VOLUMETRIC PARAMETERS PREDICTING THE HEPATIC COMPLICATION

PURPOSE To identify the parameters that predict hepatic toxicity and deterioration of hepatic function. MATERIALS AND METHODS A total of 47 patients with small unresectable primary hepatocellular carcinoma received hypofractionated stereotactic body radiotherapy (SBRT) using the CyberKnife. Of those, 36 patients received no other local treatments that could influence hepatic toxicity at least for 3 months after the completion of SBRT. The gross tumor volume (GTV) was 18.3 ± 15.9 cm(3) (range, 3.0-81.3 cm(3)), and the total dose administered was 30-39 Gy (median, 36 Gy). To assess the deterioration of hepatic function, we evaluated the presence or absence of the progression of Child-Pugh class (CP class). To identify the parameters of predicting the radiation-induced hepatic toxicity and deterioration of the hepatic function, several clinical and dose-volumetric parameters were evaluated. RESULTS Of 36 patients, 12 (33%) developed Grade 2 or higher hepatic toxicity and 4 (11%) developed progression of CP class. The multivariate analysis showed that the only significant parameter associated with the progression of CP class was the total liver volume receiving a dose less than 18 Gy (<18 Gy). CONCLUSIONS The progression of CP class after SBRT limits other additional local treatments and also reflects the deterioration of hepatic function. Therefore, it would be important to note that the presence or absence of the progression of CP class is a dose-limiting factor. The total liver volume receiving <18 Gy should be greater than 800 cm(3) to reduce the risk of the deterioration of hepatic function.

Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer

Purpose Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ≥65 years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

Long-term clinical experience of high-dose ablative lung radiotherapy: High pre-treatment (18F)Fluorodeoxyglucose-positron emission tomography maximal standardized uptake value of the primary tumor adversely affects treatment outcome

PURPOSE The aim of this study was to report the long-term clinical experience with lung stereotactic ablative radiotherapy (SABR). METHODS Between April 2004 and December 2011, 58 of 92 consecutive lung SABR cases were treated with a curative purpose and were eligible for inclusion. Forty patients were treated for primary lung cancer, and eighteen were treated for locally confined recurrent tumors. The majority of the cases were medically inoperable (65.5%). A median five fractions with a total dose of 30-60Gy were prescribed to the planned target volume. We routinely performed an image-guided respiratory gating technique or four-dimensional computed tomography to minimize set-up errors and accurately determine target volumes. RESULTS The median follow-up was 23.8 (range, 1.5-77.2) months. The median age of the entire cohort was 73 (range, 48-90) years. The median gross tumor volume and maximal tumor diameter were 20 (range, 0.5-189.7) ml and 2.2 (range, 0.7-5.9) cm, respectively. The two-year local control (LC) rate was 92.1%, and the major pattern of failure was distant metastasis (25.9%). A high pre-treatment maximal standardized uptake value (mSUV) of the primary tumor significantly and adversely affected LC, local relapse-free survival, distant metastasis-free survival, cause-specific survival and overall survival. The toxicity rates (≥grade 2) were 34.5% and 35% for the central and peripheral tumors, respectively, and one grade 5 toxic event (death due to massive hemoptysis) occurred in a centrally located tumor at 16.7 months post-SABR. CONCLUSIONS Lung SABR remains an effective and safe local treatment modality. Pre-treatment mSUV may be a helpful parameter to select patients requiring higher radiation doses and adjuvant systemic therapy for lung SABR.

Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: the importance of boost volume assessment

BackgroundThe aim of this study was to report the long-term clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer.Materials and methodsBetween March 2004 and July 2007, 26 patients with locally advanced, medically inoperable head and neck cancer or gross residual tumors in close proximity to critical structures following head and neck surgery were treated with SBRT as a boost treatment. All patients were initially treated with standard external beam radiotherapy (EBRT). SBRT boost was prescribed to the median 80% isodose line with a median dose of 21 (range 10–25) Gy in 2–5 (median, 5) fractions.ResultsThe median follow-up after SBRT was 56 (range 27.6 − 80.2) months. The distribution of treatment sites in 26 patients was as follows: the nasopharynx, including the base of the skull in 10 (38.5%); nasal cavity or paranasal sinus in 8 (30.8%); periorbit in 4 (15.4%); tongue in 3 (11.5%); and oropharyngeal wall in 1 (3.8%). The median EBRT dose before SBRT was 50.4 Gy (range 39.6 − 70.2). The major response rate was 100% with 21 (80.8%) complete responses (CR). Severe (grade ≥ 3) late toxicities developed in 9 (34.6%) patients, and SBRT boost volume was a significant parameter predicting severe late complication.ConclusionsThe present study demonstrates that a modern SBRT boost is a highly efficient tool for local tumor control. However, we observed a high frequency of serious late complications. More optimized dose fractionation schedule and patient selection are required to achieve excellent local control without significant late morbidities in head and neck boost treatment.

The effect of metallic implants on radiation therapy in spinal tumor patients with metallic spinal implants

The aim of this study was to evaluate the effect of metallic implants on the dose calculation for radiation therapy in patients with metallic implants and to find a way to reduce the error of dose calculation. We made a phantom in which titanium implants were inserted into positions similar to the implant positions in spinal posterior/posterolateral fusion. We compared the calculated dose of the treatment planning systems with the measured dose in the treatment equipment. We used 3 kinds of computed tomography (CT) (kilovoltage CT, extended-scaled kilovoltage CT, and megavoltage CT) and 3 kinds of treatment equipment (ARTISTE, TomoTherapy Hi-Art, and Cyberknife). For measurement of doses, we used an ionization chamber and Gafchromic external beam therapy film. The absolute doses that were measured using an ionization chamber at the isocenter in the titanium phantom were on average 1.9% lower than those in the reference phantom (p = 0.002). There was no statistically significant difference according to the kinds of CT images, the treatment equipment, and the size of the targets. As the distance from the surface of the titanium implants became closer, the measured doses tended to decrease (p < 0.001), and this showed a statistically significant difference among the kinds of CT images: the effect of metallic implants was less in the megavoltage CT than in the kilovoltage CT or the extended-scaled kilovoltage CT. The error caused by the titanium implants was beyond a clinically acceptable range. To reduce the error of dose calculation, we suggest that the megavoltage CT be used for planning. In addition, it is necessary to consider the distance between the titanium implants and the targets or the organs at risk to prescribe the dose for the target and the dose constraint for the organs at risk.

Dosimetric parameter predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma

BackgroundThe purpose of this study was to identify parameters capable of predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma.MethodsBetween March 2006 and February 2012, 72 patients were eligible for this study. All patients received hypofractionated radiotherapy using the TomoTherapy Hi-Art (TomoTherapy, Madison, WI, USA) at Seoul St. Marys Hospital and Incheon St. Marys Hospital, the Catholic University of Korea. The radiation dose was a median 50 Gy (range: 40–50 Gy) in 10 fractions to 95% of the planning target volume. Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh (CP) score within 3 months after completion of helical tomotherapy.ResultsAn increase of at least 2 points in the CP score occurred in 32 of the 72 patients (44.4%). Multivariate logistic regression analysis revealed that pretreatment CP class and V15Gy were significant parameters associated with an increase in CP score (p = 0.009 and p < 0.001, respectively). The area under receiver operating characteristic curve was 0.863 for V15Gy (p < 0.001). For V15Gy, with a cutoff value of 43.2%, the accuracy was 0.806 (58/72) with a sensitivity of 0.938 and a specificity of 0.725.ConclusionsAn increase of at least 2 points in the CP score is a radiation dose-limiting factor, and the non-target normal liver receiving a dose more than 15 Gy (V15Gy) should be <43.2% to reduce the risk of the deterioration of hepatic function.

Determination of the α/β ratio for the normal liver on the basis of radiation-induced hepatic toxicities in patients with hepatocellular carcinoma

BackgroundThe purpose of this study was to determine the α/β ratio for normal liver with hepatitis by analyzing the toxicity data from patients with unresectable hepatocellular carcinoma treated with helical tomotherapy.MethodsBetween March 2006 and February 2012, 98 patients were eligible for this study. 66 patients received 45–50 Gy in 4.5-5 Gy fractions (Group A) and 32 patients received 36–60 Gy in 2.5-3 Gy fractions (Group B). Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh score within 4 months of completing helical tomotherapy. We attempted to find the statistically significant parameters in the 2 groups using α/β ratios of 2, 4, 6, 8, or 10, and compared the estimated probability curves of each significant parameter. We hypothesized that the α/β ratio associated with the best matches for the curves between the 2 groups would be equivalent to the α/β ratio for the normal liver.ResultsWhen using an α/β ratio of 2 or 4, different parameters were found to be statistically significant in a multivariate analysis (Group A: VBED30 for α/β ratio = 2 and VBED25 for α/β ratio = 4, Group B: VBED25 for α/β ratio = 2 and VBED20 for α/β ratio = 4). When using an α/β ratio of 6, 8, or 10, VBED20 was found to be a statistically significant parameter in both groups. Comparison of the estimated probability curve of each significant parameter between the groups revealed that an α/β ratio of 8 resulted in the best matches.ConclusionsWe suggest that the α/β ratio of the normal liver with hepatitis is 8. We hope that previously reported parameters and their values can be effectively used in different fractionation schemes by calculating the biologically effective dose using an α/β ratio of 8.

Supine linac treatment versus tomotherapy in craniospinal irradiation: planning comparison and dosimetric evaluation.

Craniospinal irradiation (CSI) is the standard treatment of primary intracranial tumour with risk of leptomeningeal dissemination. However, supine setup field-in-field technique does not need inter-fractional junction shift. Recently, the studies of CSI with tomotherapy showed excellent target coverage and tolerable normal organ dose in paediatric patients. The planning comparison and dosimetric difference between conventional radiotherapy and tomotherapy are presented. Three patients with central nervous system germinoma received supine CSI treatment. Normal tissue complication probability calculation was performed for parotid gland, kidney, lens, small bowel, ovary and testis. Homogenous vertebral body coverage for tomotherapy compared with conformal radiotherapy was found. The mean dose to each parotid gland decreased by 7.3 and 10 Gy, respectively, with tomotherapy. The volume of oesophagus and small bowel receiving >10 Gy was significantly lower. The V2, V5, V10 and V20 of the lungs are 81.6, 12.4, 2.3 and 0 % with tomotherapy. Tomotherapy showed excellent homogenous dose distribution through the craniospinal axis (PTV) and higher conformity index.

The technical feasibility of an image-guided intensity-modulated radiotherapy (IG-IMRT) to perform a hypofractionated schedule in terms of toxicity and local control for patients with locally advanced or recurrent pancreatic cancer

BackgroundThe purpose of this study was to evaluate the technical feasibility of an image-guided intensity modulated radiotherapy (IG-IMRT) using involved-field technique to perform a hypofractionated schedule for patients with locally advanced or recurrent pancreatic cancer.MethodsFrom May 2009 to November 2011, 12 patients with locally advanced or locally recurrent pancreatic cancer received hypofractionated CCRT using TomoTherapy Hi-Art with concurrent and sequential chemotherapy at Seoul St. Mary’s Hospital, the Catholic University of Korea. The total dose delivered was 45 Gy in 15 fractions or 50 Gy in 20 fractions. The target volume did not include the uninvolved regional lymph nodes. Treatment planning and delivery were performed using the IG-IMRT technique. The follow-up duration was a median of 31.1 months (range: 5.7-36.3 months).ResultsGrade 2 or worse acute toxicities developed in 7 patients (58%). Grade 3 or worse gastrointestinal and hematologic toxicity occurred in 0% and 17% of patients, respectively. In the response evaluation, the rates of partial response and stable disease were 58% and 42%, respectively. The rate of local failure was 8% and no regional failure was observed. Distant failure was the main cause of treatment failure. The progression-free survival and overall survival durations were 7.6 and 12.1 months, respectively.ConclusionThe involved-field technique and IG-IMRT delivered via a hypofractionated schedule are feasible for patients with locally advanced or recurrent pancreatic cancer.