A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Treated by Hepatic Arterial Infusion Chemotherapy and Radiotherapy

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Additionally, hepatic arterial infusion chemotherapy has been used as a treatment option for advanced HCC. Here, we report a case of sustained partial response in a patient with advanced HCC with PVT after hepatic arterial infusion chemotherapy and radiation therapy.

Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B. MATERIALS AND METHODS: We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy₁₀ (α/β = 10 Gy). A total of 184 patients were included in this study. RESULTS: Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy₁₀ (median, 56.0 Gy₁₀). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD. CONCLUSION: Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

Multicenter Planning Comparison of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis (KROG 16-17)

BACKGROUND/AIMS: To evaluate the technical feasibility of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) with the major portal vein tumor thrombosis (PVTT). METHODS: Ten institutions affiliated with the Korean Stereotactic Radiosurgery Group were provided the contours of four cases: the first case was the first branch PVTT with sufficient normal liver volume (NLV), the second was the first branch PVTT with insufficient NLV, the third was the main trunk PVTT at confluence level, and the fourth was the main trunk PVTT with entire length. The institutions were asked to make SBRT plans according to their current treatment protocols and to complete facility questionnaires. RESULTS: Based on institutional protocols, SBRT was feasible in nine institutions for the first case (32–60 Gy in 3–5 fractions), in eight institutions for the second case (32–50 Gy in 3–5 fractions), in seven institutions for the third case (35–60 Gy in 3–5 fractions), and in four institutions for the fourth case (35–42 Gy in 4–5 fractions). The other institutions recommended hypo- or conventional fractionation due to insufficient NLV or gastrointestinal organ proximity. With analysis of the SBRT dose to the central hepatobiliary tract, the major PVTT could theoretically be associated with a high risk of hepatobiliary toxicity. CONCLUSIONS: Although SBRT is a technically feasible option for HCC with the major PVTT, there was a variability among the participating institutions. Therefore, further studies will be necessary to standardize the practice of SBRT for the major PVTT.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: dosimetric comparison and risk assessment of solid secondary cancer

PURPOSE: To determine the optimal radiotherapy technique for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), we compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4_field), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT_co) and 7 coplanar and noncoplanar beams (IMRT_non). MATERIALS AND METHODS: We retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer. RESULTS: The best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4_field, 3D-CRT, IMRT_co, and IMRT_non. On the other hand, the mean liver dose was the highest with 4_field and the lowest with AP/PA. Compared with 4_field, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT_co and IMRT_non increased except the lungs. However, the absolute differences were much lower than <1%. CONCLUSION: Tailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity> or =grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV(5Gy)-rV(35Gy): normal liver volume receiving or =grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV(20Gy) was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores> or =6.

Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

PURPOSE: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the alpha/beta value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy10 (median, 55 Gy10). Nineteen lesions were treated with concurrent chemotherapy (CCRT). RESULTS: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV 48 Gy10 were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. CONCLUSION: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

A Survey of Stereotactic Body Radiotherapy in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate the current status of stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology (KROG 13-13). MATERIALS AND METHODS: SBRT was defined as radiotherapy with delivery of a high dose of radiation to an extracranial lesion in < or = 4 fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation oncology at 85 institutions in June 2013. RESULTS: All institutions (100%) responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47 institutions (55%) have not used SBRT. Regarding the treatment site, the lung (92%) and liver (76%) were the two most common sites. The most common schedules were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography (CT) was the most common method for planning CT (74%). During planning CT, the most common method of immobilization was the use of an alpha cradle/vacuum-lock (42%). CONCLUSION: Based on this survey, conduct of further prospective studies will be needed in order to determine the appropriate prescribed doses and to standardize the practice of SBRT.

Feasibility and Efficacy of Stereotactic Ablative Radiotherapy for Barcelona Clinic Liver Cancer-C Stage Hepatocellular Carcinoma

The purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 35 patients between 2003 and 2011. Vascular invasion was diagnosed in 32 patients, extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions. The median survival time was 14 months. The 1- and 3-yr overall survival (OS) rate was 52% and 21%, respectively. On univariate analysis, CP class A and biologically equivalent dose > or = 80 Gy10 were significant determinants of better OS. Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients. In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate. We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy10 is required for BCLC-C stage.

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

PURPOSE: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. MATERIALS AND METHODS: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. RESULTS: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. CONCLUSION: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

Radiation Treatment in Pathologic N0-N1 Patients Treated with Neoadjuvant Chemotherapy Followed by Surgery for Locally Advanced Breast Cancer / 한국유방암학회지

PURPOSE: This study evaluated the treatment results and the necessity to irradiate the supraclavicular lymph node (SCN) region in pathological N0-N1 (pN0-N1) patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery and radiotherapy (RT). METHODS: Between 1996 and 2008, 184 patients with initial tumor size >5 cm or clinically positive lymph nodes were treated with NAC followed by surgery and RT. Among these patients, we retrospectively reviewed 98 patients with pN0-N1. Mastectomy was performed in 55%. The pathological lymph node stage was N0 in 49% and N1 in 51%. All patients received adjuvant RT to chest wall or breast and 56 patients (57%) also received RT to the SCN region (SCNRT). RESULTS: At 5 years, locoregional recurrence (LRR)-free survival, distant metastasis-free survival, disease-free survival (DFS), and overall survival rates were 93%, 83%, 81%, and 91%, respectively. In pN0 patients, LRR was 7% in SCNRT- group and 5% in SCNRT+ group. In pN1 patients, LRR was 7% in SCNRT- group and 6% in SCNRT+ group. There was no significant difference of LRR, regardless of SCNRT. However, in pN1 patients, there were more patients with poor prognostic factors in the SCNRT+ group compared to SCNRT- group. These factors might be associated with worse DFS in the SCNRT+ group, even though RT was administered to the SCN region. CONCLUSION: Our study showed the similar LRR, regardless of SCNRT in pN0-pN1 breast cancer patients after NAC followed by surgery. Prospective randomized trial is called for to validate the role of SCNRT.

Incidence of Brain Metastasis and Related Subtypes in Patients with Breast Cancer Receiving Adjuvant Radiation Therapy after Surgery / 한국유방암학회지

PURPOSE: To assess the incidence of brain metastasis in patients with breast cancer receiving surgery and adjuvant radiotherapy (RT) and to evaluate subtypes associated with brain metastasis. METHODS: We retrospectively reviewed the medical records of 1,000 patients with breast cancer who were treated with surgery and adjuvant RT for a cure between January 2001 and July 2005 at Samsung Medical Center. Seventy-one patients received neoadjuvant chemotherapy before surgery. The pathological stage was I in 430 patients, II in 327, and III in 243. We divided the patients into three subtypes according to immunohistochemistry: triple negative (TN, 245 patients), human epidermal growth factor 2 (HER2) enriched (HE, 166 patients) and positive estrogen receptor or progesterone receptor without HER2 overexpression (EP, 589 patients). The median follow up time was 72 months after surgery. RESULTS: Locoregional failure-free survival rate and distant metastasis-free survival rate at 5 years were 92.8% and 86.1%, respectively. The disease free survival rate and overall survival rate at 5 years were 84.6% and 94.7%, respectively. Thirty-nine patients had brain metastasis, and the brain metastasis-free survival rate at 5 years was 97.2%. A univariate analysis showed that younger age, neoadjuvant chemotherapy, modified radical mastectomy, advanced pathological stage and the TN and HE subtypes were significant risk factors for brain metastasis. A multivariate analysis revealed that age, neoadjuvant chemotherapy, pathological stage and the TN and HE subtypes were statistically significant factors for brain metastasis. CONCLUSION: The cumulative incidence of brain metastasis was 3.9% after curative treatment. If patients have a clinically suspicious symptoms suggesting brain metastasis, clinicians should be aware that an early brain imaging work up and management are necessary. Because patients with the TN or HE subtypes accompanied by younger age and advanced pathological stage have increased brain metastasis (>10%), annual regular imaging follow-up may be recommended for these high risk patients.

Result of Neoadjuvant Chemotherapy, Surgery and Radiation Therapy in Locally Advanced Breast Cancer / 대한방사선종양학회지

PURPOSE: To evaluate the result of neoadjuvant chemotherapy, surgery, and radiation therapy in locally advanced breast cancer as well as analyze the prognostic factors affecting survival. MATERIALS AND METHODS: One hundred fifty-nine patients with breast cancer were treated by neoadjuvant chemotherapy between April 1995 and November 2006 at the Samsung Medical Center. Among these patients, we retrospectively reviewed 105 patients treated with neoadjuvant chemotherapy followed by surgery and radiation therapy for a cure with an initial tumor size >5 cm or clinically positive lymph nodes. All patients received anthracycline based chemotherapy except for 2 patients. According to clinical tumor stage, 3 patients (3%) were cT1, 26 (25%) were cT2, 39 (37%) were T3 and 37 (35%) were T4. Initially, 98 patients (93%) showed axillary lymph node metastasis. The follow-up periods ranged from 7~142 months (median, 41 months) after the beginning of neoadjuvant chemotherapy. RESULTS: Locoregional failure free survival rate and distant metastasis free survival rate at 5 years were 82.1% and 69.9%, respectively. Disease free survival rate and overall survival rate at 5 years were 66.1% and 77.1%, respectively. The results of a univariate analysis indicate that clinical tumor stage, pathologic tumor stage, pathologic nodal stage and pathologic TNM stage were statistically significant factors for disease free survival rate and overall survival rate. Whereas, a multivariate analysis indicated that only hormone therapy was a statistically significant factor for survival. CONCLUSION: The current study results were comparable to other published studies for neoadjuvant chemotherapy for breast cancer. Hormone therapy was a statistically significant prognostic factor. The patients with early clinical or pathologic stage had a tendency to improve their survival rate.

Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety / 대한방사선종양학회지

PURPOSE: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. MATERIALS AND METHODS: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. RESULTS: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. CONCLUSION: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.