AIM:To investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours. BACKGROUND:In the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment. MATERIALS AND METHODS:Data were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment. RESULTS:The mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes. CONCLUSIONS:More caution and an additional safety margins are required when tracking a single fiducial marker.

Background: The treatment efficacy after CyberKnife stereotactic body radiotherapy (SBRT) have not been adequately addressed. The purpose of this study was to investigate pattern of recurrence according to irradiation field after CyberKnife SBRT for early-stage non-small cell lung cancer (NSCLC). Methods: This retrospective study included patients with peripheral cTl/2N0M0 NSCLC that was treated with SBRT using a CyberKnife between May 2013 and March 2016 at single institute and followed up by more than two imaging examinations. Both operable and inoperable patients were included. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method with 95% confidence intervals (CI). Cumulative incidence curves of recurrence were calculated and compared using the Gray's test. Results: Total 71 patients were included and analyzed in this study. The median follow-up period for surviving patients was 34 months (range, 7-64 months). The 2-year OS and PFS rate were 93% (95% Cl: 83-97%) and 77% (95% CI: 65-86%), respectively. The 2-year cumulative incidence rate of infield recurrence and out-of-field recurrence were 6% (95% CI: 2-14%) and 17% (95% CI: 9-27%), respectively. Gross tumor volume (GTV) >= 9mL and diagnosis-to-treatment interval (DTI) >= 290 days were significantly associated with infield recurrence (P<0.001 and P=0.007), and epidermal growth factor receptor (EGFR) mutation was significantly associated with out-of-field recurrence (P=0.014). Conclusions: Treatment efficacy after CyberKnife SBRT for peripheral early-stage NSCLC was identical to previous conventional linac-based SBRT reports. With short follow-up period, it was found that GTV and DTI were the significant predictive factor of infield recurrence, and EGFR mutation was the significant predictive factor of out-of-field recurrence.

OBJECTIVEStereotactic body radiotherapy has emerged as an attractive alternative to conventional radiotherapy for spinal metastases. However, it has limitations, including the need for advanced techniques and specific adverse effects. The present trial aimed to validate the feasibility and safety of stereotactic body radiotherapy in Japanese patients with spinal metastases.METHODSPatients with one or two spinal metastases received stereotactic body radiotherapy of 24 Gy in two fractions. The primary endpoint was the proportion of severe adverse effects (≥ grade 3) in patients within 6 months after spine stereotactic body radiotherapy. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The treatment protocol was considered feasible and tolerable if the proportion of severe adverse effects was 10% or less.RESULTSOverall, 20 spinal segments in 20 patients who registered between March 2014 and October 2015 were included. Minor and major deviations were observed in the planning of 2 and 0 cases, respectively. The treatment completion rate was 100%. The median follow-up after registration was 24.5 (range: 1-61) months. Although four patients experienced acute grade 2 adverse effects, no grade 3 or higher adverse effects were observed within 6 months after spine stereotactic body radiotherapy. Vertebral compression fractures were observed in two patients (14 and 16 months after stereotactic body radiotherapy). The local control and pain response rates at 6 months were 100 and 83%, respectively.CONCLUSIONThis study demonstrated the feasibility and safety of spine stereotactic body radiotherapy in Japanese patients with spinal metastases.

Oligo-recurrence has been considered to confer improved prognosis than other oligometastatic conditions, and stereotactic body radiation therapy (SBRT) is considered as an option of local therapy for lung or liver metastases. The purpose of this study was to investigate the efficacy and safety of SBRT for lung and liver oligo-recurrent lesions and evaluate predictive factors for local control and prognosis.

PURPOSE:This study aimed to assess the effectiveness of multiple dose-volume specifications in minimizing interinstitutional, target-prescribed, dose variations for spine stereotactic body radiation therapy (SBRT).METHODS AND MATERIALS:Seven institutions with a total of 10 treatment apparatuses participated in this study. SBRT plans for 3 representative spinal metastases were generated using 2 different protocols (Protocols 1 and 2) for target dose. While using just 2 target dose objectives (doses delivered to 95% and maximum point dose) in Protocol 1, 3 target dose constraints (doses delivered to 95% and 50% and maximum point dose) were defined in Protocol 2 with the intent to decrease target dose variation. A dose-volume histogram analysis was performed for the evaluated planning target volume (PTVevl) and critical neural structures such as the spinal cord and cauda equina.RESULTS:Doses to the organs at risk were all maintained at the maximal tolerance in both protocols; however, the interinstitutional variation of the PTVevl dose-volume histograms was significantly decreased with Protocol 2. Furthermore, the mean PTVevl covered by the prescription dose was increased from 73.0% in Protocol 1 to 85.8% in Protocol 2. There were no differences in the mean values of the nearly maximum dose of the critical neural structures between 2 protocols.CONCLUSIONS:In spine SBRT with the emphasis on preservation of critical neural structures, the target prescribed dose should be defined by using multiple dose-volume objectives to minimize user and apparatus-dependent dose variabilities for the spinal metastases that are adjacent to the critical neural structures.

The treatment of brainstem metastases remains a challenge as the brainstem itself is considered a neurological organ at risk. We aimed to investigate the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy (HFSRT) for brainstem metastases, and to examine the balance between efficacy and safety for the management of neurological symptoms. A total of 26 lesions [pons (n = 18), medulla (n = 4) and midbrain (n = 4)] in 20 patients treated with CyberKnife hypofractionated stereotactic radiotherapy were retrospectively analyzed. The total radiation doses (18-30 Gy) were delivered in 3 or 5 equal fractions. The median follow-up was 6.5 (range, 0.5-38.0) months. The 6- and 12-month local control rates were 100% and 90%, respectively. Symptomatic failures, defined as the worsening and appearance of neurological symptoms due to the brainstem lesion after CyberKnife HFSRT, were observed in 6 patients [local failure (n = 1) and adverse events (n = 5). The symptomatic control and overall survival rates were 90% and 72% (after 6 months), respectively, and 76% and 53% (after 12 months), respectively. Longer symptomatic control was associated with site of lesion origin, and longer overall survival was associated with a graded prognostic assessment score of > 2. To our knowledge, this is the second study to investigate the efficacy and safety of CyberKnife HFSRT for brainstem metastases. The local control rate was comparable with that of prior stereotactic radiosurgery studies. We propose a new evaluation criterion-'symptomatic control'-to evaluate the efficacy and safety of brainstem radiotherapy.

PURPOSE:The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data.METHODS AND MATERIALS:Data from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters.RESULTS:The overall means ± standard deviations (SDs) of the correlation errors were 0.70 ± 0.43 mm, 0.36 ± 0.16 mm, 0.44 ± 0.22 mm, and 0.95 ± 0.43 mm for the superoinferior (SI), left-right (LR), anteroposterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13 ± 0.11 mm, 0.03 ± 0.02 mm, 0.03 ± 0.02 mm, and 0.14 ± 0.11 mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions.CONCLUSIONS:Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination.

Stereotactic body radiation therapy (SBRT) is an option for local therapy for lung or liver oligometastases. The purpose of this study was to investigate safety and efficacy of SBRT using the robotic radiosurgery system for lung and liver oligometastases and evaluate which dosimetric parameters predict local failure (LF). In total, 76 patients with 114 lesions (lung: 70, liver: 44) were treated with SBRT using the robotic radiosurgery system between May 2013 and July 2016 at our institute. The study cohort included patients with 1–3 synchronous lung/liver metastases and a controlled primary lesion. Patients with less than 6 months of follow-up or Eastern Cooperative Oncology Group performance status (PS) >2 were excluded. Total radiation dose range was 48–64 Gy in 3, 4, or 8 equal fractions. The radiation dose delivered to the planning target volume (PTV) was prescribed to the 75–85% isodose line, covering ≥95% of the PTV. Median follow-up and age were 19 months (range, 7–43) and 69 years (range, 37–91), respectively. Forty-four patients (57.9%) were male and 32 patients (42.1%) were female. Four patients (5.3%) had a PS of 2. Primary tumors were observed in colorectum (n = 73 lesions; 64.0%), gastric region (n = 6 lesions; 5.3%), ovary (n = 6 lesions; 5.3%), esophagus (n = 5 lesions; 4.4%), and others (n = 24 lesions; 21.0%). Eighty-three lesions (72.8%) were treated with chemotherapy before SBRT. At SBRT consultation, 46 patients (60.5%) had one, 22 (29.0%) patients had two, and 8 (10.5%) patients had three metastatic lesions. The median maximum tumor diameter (MTD) was 19 mm (range, 5–57) and median gross tumor volume (GTV) was 3.2 mL (range, 0.2–106.8). The median PTV biological effective dose (BED10), mean GTV BED10, and minimum GTV BED10 were 122.0 Gy (range, 43.3–181.0), 178.0 Gy (range, 92.6–239.0), and 144.5 Gy (range, 36.6–208.5), respectively. Nine lesions (7.9%) were treated with 3 fractions, 80 lesions (70.2%) with 4 fractions, and 25 lesions (21.9%) with 8 fractions. Thirty lesions (26.3%) were treated with chemotherapy after SBRT. The 1- and 2-year LC rates were 88.8% and 78.0%, respectively. Absence of post SBRT chemotherapy (p=0.006), MTD >20 mm (p=0.016) and minimum GTV BED10 <112.5 Gy (p=0.038) were significant predictors of LF. Histology of colorectal cancer (p=0.542) was not a significant predictive factor of LF. The 2- and 3-year overall survival rates were 76.0% and 51.2%, respectively. Grade 3, grade 2, and grade 1 adverse events were observed in 1, 2 and 53 patients, respectively. SBRT with the robotic radiosurgery system is a safe and effective treatment for lung or liver oligometastases. Among dosimetric parameters, minimum GTV BED10 <112.5 Gy was a significant predictive factor for LF. A larger patient cohort or a prospective study is needed to validate our results.

The purpose of this study is to identify the suitable leaf margin for liver stereotactic body radiotherapy (SBRT) with flattening filter-free (FFF) beams, as compared with that with flattening filter (FF) beams. SBRT treatment planning for 10 patients with liver cancer was performed using 10-MV FFF and FF beams obtained from a Varian TrueBeam (Varian Medical Systems, Palo Alto, CA) linear accelerator. Each plan was generated with the leaf margin to the planning target volume (PTV) ranging from -3 to 5 mm. The prescription dose at D95 (dose covering 95% of the volume) was 48 Gy in 4 fractions to the PTV. The following dosimetric parameters were evaluated quantitatively: homogeneity index (HI), conformity index (CI), gradient index (GI), the normal liver receiving a dose greater than or equal to 20 Gy (V20), and the mean normal liver dose. The HI for FFF and FF beams increased as the leaf margin decreased. The leaf margins that achieved the best CI and GI were 0.1 and -0.3 mm for FFF beams, and 0.1 and -0.9 mm for FF beams. The liver V20 and the mean liver dose reached their minimum values at leaf margins of -0.8 and 0.0 mm for FFF beams, and -0.8 and 0.0 mm for FF beams. The suitable leaf margin for SBRT planning did not differ significantly for FFF and FF beams. Our data showed that, for both FFF and FF beams, a leaf margin of 0 or -1 mm was optimal for liver SBRT planning in terms of both target coverage and normal tissue sparing. (C) 2017 American Association of Medical Dosimetrists.

Purpose or ObjectiveNew technologies, as IMRT, VMAT and Helical Tomotherapy (HT) is one of the most emerging aspect of radiation therapy, especially regarding brain tumors management; glioblastoma (GBM), for its radio-resistance and high rate of local recurrence, is a challenging field of application of new technologies.In this retrospective study we evaluated the impact of altered fractionation, administered with HT, associated with temozolomide (TMZ) in the treatment of GBM. Material and MethodsFrom 2010 to 2014, 23 patients with primary diagnosis of GBM were treated at our Institution.Median age was 57 (range 26-75) and all patients had histologically proven diagnosis of GBM; 15 patients (65%) had a radiological proven residual disease after surgery.Bio-molecular markers profiling was not routinely analyzed; molecular genetic profile, using FISH test, was assessed in 11 (48%) of the 23 patients; evaluation of MGMT promoter was performed in 10 patients: 7 presented an unmethylated profile, and 3 a methylated status.In 6 patients mutations of IDH1 were tested and only in 2 patients they are present.Considering extent of the disease and its location, patients were treated with two different radiation therapy schedules.In 16 patients (70%) two different volumes were identified: PTV1, encompassing surgical bed and/or residual disease (GTV1) with a margin of 0.5 cm, treated with a total dose of 59.8 Gy in 23 fractions of 2.6 Gy, and PTV2, obtained expanding the PTV1 of 1 cm all around, treated with a total dose of 46 Gy in 23 fractions of 2 Gy (Simultaneous Integrated Boost SIB technique).In the remaining 7 patients (30%) it was possible treated a single volume (PTV1) with a total dose of 59.8 Gy in 23 fractions of 2.6 Gy.According to the EORTC regimen, concomitant daily TMZ dose of 75 mg/mg was administered for the entire period of radiation therapy followed by adjuvant schedule at a dose of 150-200 mg/mq daily for 5 consecutive days every 4 weeks. ResultsAll patients completed the combined therapy without grade ≥3 acute toxicity.Complete blood count every 2 weeks, and contrast-enhancement brain MR every 3 months were performed during follow up.At the time of the present study, 12 patients (52%) were died, 2 patients (9%) had disease progression, two patients (9%) had a radiological evidence of stable disease (SD) and 7 (30%) were free from disease.The average follow-up was 12 months (range 2-46) and median overall survival (OS) was 12 months with a progression free survival (PFS) average time of 7.6 months. ConclusionOur results, in terms of OS and PFS, are similar to the literature ones; but it is remarkable that about 65% of patients had a subtotal resection and therefore a poor prognosis and poor expected outcome as well documented in large previous studies.Altered fractionation that we used achieved similar results of standard schedule of treatment of 60 Gy in 30 fractions, without increasing acute and late toxicity, and reducing total time of about 25%.

Background: The purpose of this study was to compare the dose distributions and treatment delivery efficiency of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams (FFF-VMAT) against VMAT with flattening filter (FF) beams (FF-VMAT) and Helical TomoTherapy (HT) for head and neck cancer. Methods: Ten patients with nasopharyngeal and oropharyngeal cancer were chosen for this planning comparison study. Three treatment plans (dual arc FFF-VMAT, dual arc FF-VMAT, and HT) were created for each patient. The three prescription dose levels of the planning target volumes were 69.96, 60, and 54 Gy in 33 fractions, using the simultaneous integrated boost technique. Comparisons of the plan quality were performed by analyzing the homogeneity, conformity, dose to the organs at risk (OARs), the number of monitor units (MUs), and beam-on time (BOT) necessary for delivering the plans. Results: The target coverage and sparing of the OARs for FFF-VMAT were almost equivalent to those for FFVMAT and HT. Compared to FF-VMAT, FFF-VMAT and HT significantly increased the number of MUs. The BOTs were the same for FFF-VMAT and FF-VMAT but significantly increased for HT. Conclusion: We here present the first report of FFF-VMAT achieving a comparable plan quality with less delivery time to that of FF-VMAT and HT in head and neck cancer. FFF-VMAT is a highly efficient and feasible option for the treatment of head and neck cancer in clinical practice.

AIM:To evaluate the treatment results of radiotherapy (RT) in children and adults with brainstem gliomas (BSGs) and review the previous literature.METHODS:Thirty patients (14 children, 16 adults) with BSG treated using RT were retrospectively evaluated. The median ages of the children and adults were 8 years (range: 2-16 years) and 49 years (range: 19-75 years), respectively. A histological diagnosis was obtained in 11 patients. The median total radiation dose was 56 Gy (range: 50-70 Gy) with a single fraction size of 1.8-2.0 Gy. Temozolomide was administered concurrently with RT in 14 patients.RESULTS:Tumor progression after RT occurred in 26 patients (14 children and 12 adults). Four adults survived without tumor progression. The median survival times for children and adults were 8.5 and 39 months, respectively. The 1-, 2- and 3-year overall survival rates for children/adults were 29%/75%, 14%/68% and 0%/53%, respectively (P = 0.001), and the 1-, 2- and 3-year progression-free survival rates for children/adults were 14%/69%, 0%/49% and 0%/35%, respectively (P < 0.001). Grade 3 or higher acute and late toxicities did not occur.CONCLUSION:In this study, the prognosis of children with BSGs was considerably poorer than that of adults, and our results are consistent with those of previous studies. Efforts should be made to improve the survival outcomes of patients with BSGs, especially children.

Introduction: Oral supportive care including oral and dental care and management of oral complications is important for the cancer patients undergoing anti-cancer therapy. Objectives: This retrospective study evaluated the relationship between oral complications and dental conditions of the patients undergoing chemotherapy or radiotherapy. Methods: Clinical records for 600 consecutive patients from March 2014 to October 2015 were analyzed. Patients' dental conditions (the number of remaining, decayed and fixed teeth, the severity of periodontal disease, and oral hygiene status) were checked before starting anti-cancer therapy. Oral supportive care was continued to maintain good oral hygiene, and to detect and manage oral complications early. Results: Patients were 348 males and 252 females aged 17-94 years. Primary site of cancer were: head and neck in 104, lung in 100, esophagus in 67, colon in 59, hematological cancer in 57, breast in 48, and others in 165. The treatments were chemotherapy in 221, radiotherapy in 216, and concurrent chemoradiotherapy in 163. NCI CTC-AE grade 3-4 oral complications occurred in 125 patients, which were oral mucositis, dental infections, and medication-related osteonecrosis of the jaw. The patients with G3-4 oral complications had worse oral hygiene and less number of remaining teeth compared to the patients with G1-2 oral complications. Rates of improved oral hygiene status 3 months after starting anti-cancer therapy was better in the patients with G1-2 oral complications. Conclusions: Oral supportive care for cancer patients receiving anticancer therapy should begin before the start of treatment and continue until the successful completion of treatment, especially for the patients with poor oral hygiene or a small number of remaining teeth.

Objective: The aims of this study were to investigate the frequency of symptomatic radiation pneumonitis (RP) after CyberKnife lung stereotactic body radiotherapy (SBRT) and to evaluate predictive factors of symptomatic RP. Methods: 56 patients with peripheral non-small-cell lung cancer were treated using the CyberKnife® VSI™ System (Accuracy Inc., Sunnyvale, CA) between May 2013 and September 2015. Total radiation doses ranged from 48 to 56 Gy, as delivered in four equal fractions. Symptomatic RP was defined as a grade of ≥2. Predictive factors for symptomatic RP were evaluated using univariate and multivariate analyses. Results: With a median follow-up duration of 12.5 months (range, 3–27 months), symptomatic RP was observed in 6 (10.7%) of the 56 patients. In the univariate analysis, percent vital capacity (p < 0.05), maximum tumour diameter (p < 0.05), gross tumour volume (p < 0.05), planning target volume (p < 0.01), mean lung dose (p < 0.01) and a normal lung volume receiving 5–50 Gy of radiation (V5–50) (p < 0.01) were identified as significant predictive factors for symptomatic RP. In the multivariate analysis, only a V25 >3.4% (p = 0.011) was identified as a significant predictive factor of symptomatic RP. Conclusion: The incidence of symptomatic RP after CyberKnife SBRT was almost identical to the incidences reported in the linear accelerator-based SBRT. A significant association was observed between a V25 >3.4% and the risk of developing symptomatic RP. Advances in knowledge: This is the first report that has investigated prognostic factors for symptomatic RP after CyberKnife SBRT for lung cancer. The newly developed scoring system may help to predict symptomatic RP.

This study aimed to evaluate the efficacy of stereotactic body radiotherapy (SBRT) compared with three-dimensional conformal radiotherapy (3DCRT). Forty-three patients with portal vein tumor thrombosis (PVTT)/inferior vena cava tumor thrombosis (IVCTT) treated with SBRT (27 with CyberKnife (CK) and 16 with TrueBeam (TB)) from April 2013 to December 2014, and 54 treated with 3DCRT from June 2008 to March 2013 were evaluated. Dosimetric parameters, response to radiotherapy (RT) and survival outcomes were compared in total SBRT vs. 3DCRT, CK vs. 3DCRT and TB vs. 3DCRT, respectively. The median biologically effective dose 10 (BED10) values in total SBRT, CK, TB and 3DCRT were 73.4 Gy10, 75.0 Gy10, 60.5 Gy10 and 58.5 Gy10, respectively (P < 0.001 in total SBRT vs. 3DCRT, P < 0.001 in CK vs. 3DCRT, P = 0.004 in TB vs. 3DCRT). The tumor response rates were 67%, 70%, 62% and 46%, respectively (P = 0.04, P = 0.04, P = 0.25). The 1-year overall survival rates were 49.3%, 56.7%, 38.1% and 29.3%, respectively (P = 0.02, P = 0.02, P = 0.30), and the 1-year local progression rates were 20.4%, 21.9%, 18.8% and 43.6%, respectively (P = 0.01, P = 0.04, P = 0.10). The use of SBRT made it possible to achieve a higher BED10 compared with the use of 3DCRT. Improvements in local control and survival were achieved in the CK group and the total SBRT group. Our results suggest that SBRT may have the potential to be the standard RT technique for the treatment of PVTT/IVCTT.

目的：再発・転移頭頸部がんに対するドセタキセル・シスプラチン（DC）療法の安全性および効果について後方視的に検討する。対象および方法：2006年7月から2012年10月までにDC療法を実施した再発・転移頭頸部がん患者24例。結果：扁平上皮癌（上咽頭がん3例を除く）17例を対象とする有効性に関する検討では，奏効割合47%（完全奏効 18%，部分奏効 29%），生存期間中央値390日，無増悪生存期間中央値188日であった。全24例を対象とする安全性に関する検討では，有害事象は発熱性好中球減少が8例（33%）にみられ，そのうち5例は1コース目で発症していた。有害事象のために減量が必要となった，または治療を中止した症例はそれぞれ12例（50%），2例（8%）であった。治療関連死亡は認めなかった。結論：再発・転移頭頸部扁平上皮癌に対するDC療法は既報と同程度の治療効果を示した。実施にあたっては発熱性好中球減少に対する適切な対応が必要と考えられた。

Purpose/Objective(s): The objective of this study is to improve tumorselectivity and enhance the radiotherapeutic efficacy using doxorubicinloaded hollow gold nanoparticles (Dox@HAuNP)-mediated hyperthermia, radiation and chemotherapy. Gold nanoparticles have gained interest as a novel platform for cancer therapy due to their efficient light to heat conversion and radiosensitization. Previous investigations for utilizing HAuNPs have focused on hyperthermia or radiation therapy alone. In this study, we demonstrate the combination of hyperthermia, radiation therapy and chemotherapy using doxorubicin-loaded HAuNPs. Materials/Methods: Dox@HAuNP was synthesized by the seed-mediated method and coated with polyethylene glycol (PEG) for an extended blood circulation. Their size, shape, and zetapotential were confirmed by Zetasizer and TEM. Their absorption spectrum, amount of doxorubicin loaded into HAuNPs and doxorubicin release were measured by a UV-Vis spectrophotometer. The concentration of HAuNPs was determined using ICPMS. In vitro cytotoxicity was measured using CCK-8 assay with A549 cells (human non-small cell lung carcinoma), and in vivo antitumor activity was evaluated using xenograft mouse model. Results: Dox@HAuNPs were produced with low polydispersity and mean diameters of 52 nm 4 nm, and NIR-triggered doxorubicin release from Dox@HAuNP was clearly demonstrated. The maximum accumulation in tumor was observed at 24 hours post-administration. The ability of Dox@HAuNPs to enhance cytotoxicity in vitro in response to radiation and hyperthermia was evaluated using CCK-8 assay. It was found that the combination of photothermal, radiation and chemo-therapy using Dox@HAuNP markedly enhanced antitumor effect. The combination of Dox@HAuNP, hyperthermia and radiation delayed tumor growth by a factor of 4.3, and made tumors’ weight to be 6.8 fold lighter than control tumors. Conclusions: This work presents that combination of Dox@HAuNP, hyperthermia and radiation had significantly greater antitumor activity than chemotherapy, radiation or hyperthermia alone. This combination strategy is expected to dramatically increase the likelihood of cell killing and potentially overcome resistance to chemotherapeutic agents or radiation. Author Disclosure: S. Jeong: None.