Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries.

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2-6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9-105.9), 77.7 Gy EQD2 (range, 56.9-99.1), 68.0 Gy EQD2 (range, 48.6-90.7) and 62.0 Gy EQD2 (range, 39.6-83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Clinical utilization of radiation therapy in Korea, 2016.

Radiotherapy (RT) is one of the primary cancer treatment modalities. To estimate the actual utilization of RT and infrastructure in Korea, the current study was performed. Data from 2012 to 2016 were extracted from the Health Insurance Review and Assessment Service. In addition, a nationwide survey was conducted to collect the statistics of RT facilities, equipment and human resources in Korea. The total number of patients treated with RT was 72 563 in 2016. The five cancers that were most commonly treated with RT in 2016 were breast, lung, colorectal, liver and prostate cancer. According to analyses of specific treatment modalities, the number of patients treated with intensity-modulated radiotherapy (IMRT), stereotactic radiation therapy (SRT) and proton therapy increased from 6670, 6306 and 50 in 2012 to 21584, 9048 and 703 in 2016, respectively. Ninety radiation oncology centers were working in 2015 and there were a total of 213 megavoltage teletherapy machines. In 2015, 310 patients were treated per megavoltage RT machine, 246 patients per radiation oncologist, 501 patients per medical physicist and 111 patients per radiotherapy technologist. In conclusion, the number of patients who underwent RT in Korea has increased steadily from 2012 to 2016. The IMRT utilization rate remarkably increased in 2016, and the number of patients treated with advanced treatment modalities such as IMRT, SRT and proton therapy is expected to increase.

Multi-institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiation Therapy Using Weekly Cisplatin for Patients With Pelvic Node-Positive Cervical Cancer in East and Southeast Asia.

PURPOSE: This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer. METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course. RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Feasibility of using stereotactic body radiation therapy for unresectable soft tissue tumors of the trunk.

PURPOSE: To evaluate the feasibility of stereotactic body radiation therapy (SBRT) for unresectable soft tissue tumors of the trunk. MATERIALS AND METHODS: Between January 2002 and December 2008, 23 patients with 36 lesions of soft tissue tumors, which were located in the trunk and not suitable for resection, underwent SBRT. Among the 36 lesions, 31 were malignant and 5 were benign. The median tumor volume was 24 cm3 (range, 2.6-213 cm3). SBRT doses ranged from 20 to 48 Gy in 1-5 fractions. RESULTS: With a median follow-up of 73 months, the overall survival (OS) and local control (LC) rates at 5 years were 39% and 52%, respectively. For malignant tumors, the OS and LC rates at 5 years were 28% and 47%, respectively. For benign tumors, the OS and LC rates at 5 years were 80% and 100%, respectively. There was no acute toxicity of grade ≥3. One case of grade 3 late skin toxicity was reported 10 months after SBRT. CONCLUSION: SBRT may be an effective and safe treatment modality for the local control of unresectable soft tissue tumors of the trunk including tumors of a benign nature.

Feasibility of split-course stereotactic ablative radiotherapy for oligometastases.

BACKGROUND: There is growing interest in the use of stereotactic ablative radiotherapy (SABR) for oligometastases. However, extreme caution should be exercised in treating tumors closely located to organs at risk (OARs) with SABR. To reduce complications, we have applied split-course SABR to oligometastases closely located to OARs or to those being retreated with radiotherapy. METHODS: We retrospectively reviewed the records of patients with oligometastases who were treated with planned split-course SABR between January 2012 and December 2016. RESULTS: A total of 23 patients with 29 oligometastatic lesions were enrolled. The primary diagnoses were bone and soft tissue cancers in 13 lesions, liver cancers in 12 lesions, and colorectal cancers in four lesions. The median tumor volume was 78 cm3 (range, 4-1781 cm3). The lesions were treated with 1-3 fractions in the first stage of SABR (first SABR), and one or two fractions in the second stage of SABR (second SABR). The time interval between the two stages was about 4 weeks. A partial response was noted in 16 lesions (55%) after the first SABR, and practical reductions in the doses to OARs were observed in the second SABR compared with the first SABR. The 1-, 2- and 3-year local control rates were 92%, 65% and 43%, respectively. No Grade 4 or 5 toxicities were observed during or after treatment. CONCLUSION: Split-course SABR appeared to be feasible for the treatment of oligometastases closely located to OARs.

The Clinical Utilization of Radiation Therapy in Korea between 2011 and 2015.

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2011 and 2015. MATERIALS AND METHODS: We analyzed the claims data from the Health Insurance Review and Assessment Service to estimate the clinical utilization of RT. The source population consisted of all patients who had any of the International Classification of Diseases 10th revision cancer diagnoses (C00-C97) and those with diagnostic codes D00-D48, who were also associated with at least one of the procedure codes related to RT. RESULTS: The total number of patients who received RT in 2011, 2012, 2013, 2014, and 2015 were 54,810, 59,435, 61,839, 64,062, and 66,183, respectively. Among them, the total numbers of male and female patients were 24,946/29,864 in 2011, 27,211/32,224 in 2012, 28,111/33,728 in 2013, 29,312/34,750 in 2014, and 30,266/35,917 in 2015. The utilization rate of RT in cancer patients has also increased steadily over the same period from 25% to 30%. The five cancers that were most frequently treated with RT between 2011 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. More than half of cancer patients (64%) were treated with RT in the capital area (Seoul, Gyeonggi, and Incheon). CONCLUSION: The total number of patients who underwent RT increased steadily from 2011 to 2015 in Korea. The utilization rate of RT in cancer patients is also increasing.

Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors.

PURPOSE: To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. MATERIALS AND METHODS: Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3-4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1-2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. CONCLUSION: SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

Prognostic Importance of the Site of Recurrence in Patients With Metastatic Recurrent Cervical Cancer.

PURPOSE: The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. METHODS AND MATERIALS: Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board. RESULTS: Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group). CONCLUSIONS: We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.

Multicentre dose audit for clinical trials of radiation therapy in Asia.

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy.

The clinical utilization of radiation therapy in Korea between 2009 and 2013.

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2009 and 2013. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service. The subjects were patients who had diagnostic codes C00-C97 or D00-D48 according to the 10th revision of the International Classification of Diseases, with procedure codes indicating RT treatment. RESULTS: The total number of patients who received RT in 2009, 2010, 2011, 2012, and 2013 were 45,571, 49,593, 54,671, 59,172, and 61,485, respectively. Among them, the total numbers of male and female patients were 20,780/24,791 in 2009, 22,711/26,882 in 2010, 24,872/29,799 in 2011, 27,101/32,071 in 2012, and 27,941/33,544 in 2013. The five cancers that were most frequently treated with RT between 2009 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. The three leading types of cancer among the male patients were lung, colorectal, and liver cancers, whereas in female patients, they were breast, uterine cervical, and lung cancers. The type of cancer most commonly treated by RT was cancer of the central nervous system in patients aged 20 years or less, breast cancer in patients aged 30-50 years, and lung cancer in patients aged 60 years or more. CONCLUSION: Data from this study provided the clinical utilization of RT in Korea between 2009 and 2013.

Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: This study aimed to evaluate the effect of stereotactic ablative radiotherapy (SABR) after incomplete transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients. METHODS: The study enrolled 178 HCC patients initially treated with TACE between 2006 and 2011. Patients were included if they had Barcelona Clinic Liver Cancer stage 0 or A, ≤3 nodules with a total sum of longest diameter ≤10 cm, Child-Turcotte-Pugh score of ≤7, no major vessel invasion, and no extra-hepatic metastases. RESULTS: Twenty-four patients achieved a complete response to TACE (group 1). Among those with incomplete response, 47 patients received other curative treatments (group 2), 37 received SABR (group 3), and 70 received non-curative treatments (group 4). The 2-year overall survival (OS) rates for groups 1, 2, 3, and 4 were 88 %, 81 %, 73 %, and 54 %, respectively. The corresponding 5-year OS rates were 50 %, 58 %, 53 %, and 28 %, respectively. CONCLUSIONS: Patients treated with SABR after incomplete TACE had similar survival outcomes to those achieving complete response to TACE or receiving curative treatments. However, patients receiving non-curative treatments had significantly lower survival rates than the other groups. Therefore, if SABR was indicated at the initial diagnosis, it might be recommended after TACE failure.

Concurrent chemoradiotherapy for T3-4 and N0-1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia.

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3-4 and N0-1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3-4 N0-1 M0, World Health Organization Type 2-3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m(2)). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3-4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis-free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

AIMS: To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. METHODS: We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). RESULTS: The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. CONCLUSION: SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.

The Clinical Status of Radiation Therapy in Korea in 2009 and 2013.

PURPOSE: The purpose of this study is to estimate the clinical status of radiation therapy (RT) in Korea. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service (HIRA). The subjects were patients with malignant neoplasms who had procedure codes concerning RT in 2009 and 2013. RESULTS: The total numbers of patients who underwent RT in 2009 and 2013 were 42,483 and 56,850, respectively. The numbers of men and women were 20,012 and 22,471 in 2009 and 26,936 and 29,914 in 2013, respectively. The five most frequent RT sites were metastatic, breast, gastrointestinal, thoracic, and gynecologic cancers in 2009, and metastatic, breast, gastrointestinal, thoracic and head and neck cancers in 2013. The three leading types of cancer among men were metastatic, gastrointestinal, and thoracic, and breast, metastatic, and gynecologic among women. According to age, the most common treatment site was the central nervous system for those aged 20 years or less, the breast for those in their 30s to 50s, and metastatic sites for those in their 60s or older. CONCLUSION: Data from this study provide an overview of the clinical status of RT in Korea.

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≥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 (rV5Gy-rV35Gy: normal liver volume receiving

Stereotactic Body Radiotherapy for Recurrent or Oligometastatic Uterine Cervix Cancer: A Cooperative Study of the Korean Radiation Oncology Group (KROG 14-11).

AIM: To evaluate local control and patient survival for recurrent or oligometastatic uterine cervical cancer treated with stereotactic body radiotherapy (SBRT) using CyberKnife, and to demonstrate the safety of SBRT. PATIENTS AND METHODS: Between 2002 and 2013, 100 recurrent or oligometastatic lesions in 85 patients were treated with SBRT at three Institutions. SBRT sites were within the previous RT field in 59 and partially overlapped in nine. SBRT sites included three local recurrences, 89 lymph node metastases, and eight distant metastases. Patients were treated with a median dose of 39 Gy in three fractions, which was equivalent to a biologically effective dose (BED) of 90 Gy. RESULTS: The median follow-up period was 20.4 months. Local failure occurred in 17 out of 100 SBRT-treated sites. The 2-year and 5-year local progression-free survival rates were 82.5% and 78.8%, respectively. Eleven local failures occurred within the previous RT field. The 2-year and 5-year overall survival rates were 57.5% and 32.9%, respectively. BED >90 Gy (p=0.072) and >69 Gy (p=0.059) and longer disease-free interval (p=0.065) predicted marginally superior local control. Re-irradiation appeared to be related to inferior local control (p<0.001), but the SBRT BED in this group was much lower than the dose in the other group (median BED, 79 Gy vs. 90 Gy). Chronic toxicities of grade 3 or more occurred in five cases. CONCLUSION: SBRT for recurrent or oligometastatic cervical cancer resulted in excellent local control, especially with a long disease-free interval and high BED treatment, with acceptable toxicities. Therefore, SBRT can be considered a therapeutic option for these patients.

Stereotactic body radiotherapy for oligometastases confined to the para-aortic region: clinical outcomes and the significance of radiotherapy field and dose.

We retrospectively reviewed 88 patients with oligometases in the para-aortic region from any controlled primary tumor site who were treated with stereotactic body radiotherapy (SBRT). The 5-year local control, disease-free survival, and overall survival rates were 83%, 31%, and 41%, respectively. A 90% tumor-control probability was predicted at a biological effective dose of 90 Gy. Severe gastrointestinal toxicities (grade ≥3) were observed in 2 of 88 patients (1%). The results of this study are limited by the retrospective nature of the study but could serve as the background and rationale for future prospective trials on SBRT-based treatment for oligometastses.

Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma.

PURPOSE: To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma. MATERIALS AND METHODS: From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL). RESULTS: The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume (<50 vs. ≥50 mL), and pre-SBRT CEA level (<5 vs. ≥5 ng/mL) were significant in overall survival rate. In multivariate analysis, ECOG score (p = 0.037) and tumor volume (p = 0.030) were statistically significant. In the recurrent tumor group, patients with >12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with ≤12 months (p = 0.026). Six patients (10%) experienced ≥grade 3 complications. CONCLUSION: SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.

Low and high linear energy transfer radiation sensitization of HCC cells by metformin.

The purpose of this study was to investigate the efficacy of metformin as a radiosensitizer for use in combination therapy for human hepatocellular carcinoma (HCC). Three human HCC cell lines (Huh7, HepG2, Hep3B) and a normal human hepatocyte cell line were treated with metformin alone or with radiation followed by metformin. In vitro tests were evaluated by clonogenic survival assay, FACS analysis, western blotting, immunofluorescence and comet assay. Metformin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, metformin abrogated G2/M arrest and increased the cell population in the sub-G1 phase and the ROS level, ultimately increasing HCC cellular apoptosis. Metformin inhibits the repair of DNA damage caused by radiation. The radiosensitizing effects of metformin are much higher in neutron (high LET)-irradiated cell lines than in γ (low LET)-irradiated cell lines. Metformin only had a moderate effect in normal hepatocytes. Metformin enhances the radiosensitivity of HCC, suggesting it may have clinical utility in combination cancer treatment with high-LET radiation.

High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma.

BACKGROUND: Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. METHODS: Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy). RESULTS: LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. CONCLUSIONS: This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.