Photon and electron backscatter dose and energy spectrum analysis around Lipiodol using flattened and unflattened beams.

PURPOSE: The aim of the current study was to evaluate the backscatter dose and energy spectrum from the Lipiodol with flattening filter (FF) and flattening filter-free (FFF) beams. Moreover, the backscatter range, that was defined as the backscatter distance (BD) are revealed. METHODS: 6 MVX FF and FFF beams were delivered by TrueBeam. Two dose calculation methods with Monte Carlo calculation were used with a virtual phantom in which the Lipiodol (3 × 3 × 3 cm3 ) was located at a depth of 5.0 cm in a water-equivalent phantom (20 × 20 × 20 cm3 ). The first dose calculation was an analysis of the dose and energy spectrum with the complete scattering of photons and electrons, and the other was a specified dose analysis only with scattering from a specified region. The specified dose analysis was divided into a scattering of primary photons and a scattering of electrons. RESULTS: The lower-energy photons contributed to the backscatter, while the high-energy photons contributed the difference of the backscatter dose between the FF and FFF beams. Although the difference in the dose from the scattered electrons between the FF and FFF beams was within 1%, the difference of the dose from the scattered photons between the FF and FFF beams was 5.4% at a depth of 4.98 cm. CONCLUSIONS: The backscatter range from the Lipiodol was within 3 mm and depended on the Compton scatter from the primary photons. The backscatter dose from the Lipiodol can be useful in clinical applications in cases where the backscatter region is located within a tumor.

Long-term results of neoadjuvant chemoradiotherapy using cisplatin and 5-fluorouracil followed by esophagectomy for resectable, locally advanced esophageal squamous cell carcinoma.

This study retrospectively evaluated the long-term results of neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy for the patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC). Altogether, 49 patients treated from 2008 to 2012 were analyzed. Chemotherapy consisted of 5-fluorouracil and cisplatin. Radiotherapy was performed with a total dose of 40 Gy in 20 fractions for primary tumor, metastatic lymph nodes, and elective nodal area. Subsequently, transthoracic esophagectomy with extensive lymphadenectomy was performed. The median follow-up time for the survivors was 86 (range, 55-111) months. Pathological complete response from NCRT was observed in 17 (35%) patients. The 5-year overall survival and relapse-free survival rates were 56% [95% confidence interval (CI): 43-71%] and 55% (95% CI: 41-69%), respectively. The 5-year locoregional control rate was 84% (95% CI: 74-95%). Multivariate analyses revealed body mass index, N-factor, and %ΔSUVmax as significant factors for overall survival. Recurrences and within-irradiation field failure were observed in 16 (31%) and 4 (8%) patients, respectively. Toxicities of NCRT were generally mild. Postoperative Grade IIIb or worse complications were seen in 14% of patients, including one Grade V case (2%). The 5-year incidence rate of late complications of Grade 3 or worse was 22% (95% CI: 7-36%). The cumulative 5-year incidence rate of metachronous malignancies was 13% (95% CI: 1-26%). NCRT followed by esophagectomy for patients with resectable, locally advanced ESCC showed favorable locoregional control and overall survival, with acceptable postoperative complications. Long-term careful follow-up for late complications and metachronous malignancies is needed.

Relative biological effectiveness study of Lipiodol based on microdosimetric-kinetic model.

OBJECTIVES: We examine the contrast agent Lipiodol effect on the relative biological effectiveness (RBE) values for flattening filter free (FFF) and flattening filter (FF) beams of 6 MV-Xray (6 MVX) and 10 MVX. METHODS: Lipiodol was placed at 5 cm depth in water. According to the microdosimetric kinetic model, the RBE values for killing the human liver hepatocellular cells were calculated from dose and lineal energy (yd(y)) from Monte Carlo simulations. RBE200kVX and RBECo were defined as the ratios of dose using reference radiation (200 kVX, Co-ɤ) to the dose of test radiation (FFF and FF beams for 6 MV and 10 MV) to produce the same biological effects. The dose enhancement RBE (RBEDE) was defined as the ratios of a dose without Lipiodol to with Lipiodol using to produce the same biological effects. The dose needed to achieve 10% (D10%) and 1% cell survival (D1%) was evaluated by cell surviving fraction (SF) formula. RESULTS: The deviation of mean y‾D values with and without Lipiodol were 3.9-4.8% for 6 MVX and 3.5-3.6% for 10 MVX. The RBE200kVX and RBECo with Lipiodol were larger than that without Lipiodol. The RBEDE was larger for FFF beam than for FF beam. The deviation of RBEDE for FFF and FF beams of 6 MVX was larger than that of 10 MVX. CONCLUSION: The presence of Lipiodol seemed to locally increase the absorbed dose and to also cause an enhancement of the relative biological effectiveness.

Effect of secondary electron generation on dose enhancement in Lipiodol with and without a flattening filter.

PURPOSE: Lipiodol, which was used in transcatheter arterial chemoembolization before liver stereotactic body radiation therapy (SBRT), remains in SBRT. Previous we reported the dose enhancement in Lipiodol using 10 MV (10×) FFF beam. In this study, we compared the dose enhancement in Lipiodol and evaluated the probability of electron generation (PEG) for the dose enhancement using flattening filter (FF) and flattening filter free (FFF) beams. METHODS: FF and FFF for 6 MV (6×) and 10× beams were delivered by TrueBeam. The dose enhancement factor (DEF), energy spectrum, and PEG was calculated using Monte Carlo (MC) code BEAMnrc and heavy ion transport code system (PHITS). RESULTS: DEFs for FF and FFF 6× beams were 7.0% and 17.0% at the center of Lipiodol (depth, 6.5 cm). DEFs for FF and FFF 10× beams were 8.2% and 10.5% at the center of Lipiodol. Spectral analysis revealed that the FFF beams contained more low-energy (0-0.3 MeV) electrons than the FF beams, and the FF beams contained more high-energy (>0.3 MeV) electrons than the FFF beams in Lipiodol. The difference between FFF and FF beam DEFs was larger for 6× than for 10×. This occurred because the 10× beams contained more high-energy electrons. The PEGs for photoelectric absorption and Compton scattering for the FFF beams were higher than those for the FF beams. The PEG for the photoelectric absorption was higher than that for Compton scattering. CONCLUSIONS: FFF beam contained more low-energy photons and it contributed to the dose enhancement. Energy spectra and PEGs are useful for analyzing the mechanisms of dose enhancement.

Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy Combined with Radiotherapy and Sorafenib for Advanced Hepatocellular Carcinoma Patients with Major Portal Vein Tumor Thrombosis.

OBJECTIVE: To compare the outcome of hepatic arterial infusion chemotherapy combined with radiotherapy (HAIC + RT) versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombosis (PVTT). METHODS: This retrospective study included 108 HCC patients with PVTT of the main trunk or first branch and Child-Pugh ≤7. Sixty-eight received HAIC + RT and 40 received sorafenib. Patients were then assigned to the HAIC + RT group (n = 36) and the sorafenib group (n = 36) through case-control matching. The decision to treat with HAIC + RT or sorafenib was left to the attending physician. RESULTS: The median overall, progression-free, and postprogression survival were significantly longer in the HAIC + RT group than in the sorafenib group (9.9 vs. 5.3, p = 0.002; 3.9 vs. 2.1, p = 0.048; and 3.7 vs. 1.9 months, p = 0.02, respectively). Multivariate analysis identified HAIC + RT (hazard ratio = 2.02; 95% confidence interval, 1.14-3.57; p = 0.01) as a significant and independent determinant of overall survival. CONCLUSIONS: In patients with advanced HCC and major PVTT, survival was significantly longer in those treated with HAIC + RT than with sorafenib.

Dosimetric impact of Lipiodol in stereotactic body radiation therapy on liver after trans-arterial chemoembolization.

PURPOSE: Stereotactic body radiation therapy (SBRT) combining trans-arterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study is aimed to estimate the dose enhancement in Lipiodol's proximity and to evaluate the dose calculation accuracy of the Acuros XB (AXB) algorithm and anisotropic analytical algorithm (AAA) in the Eclipse treatment planning system (TPS) (ver. 11, Varian Medical Systems, Palo Alto, USA), compared with that of the Monte Carlo (MC) calculation (using BEAMnrc/DOSXYZnrc code) for a virtual phantom and a treatment plan for liver SBRT after TACE. METHODS: The MC calculation accuracy was validated by comparing its results with the percent depth dose (PDD) and the off-axis ratio (OAR) measured using a water-equivalent phantom containing Lipiodol. The dose difference in Lipiodol's proximity and the inhomogeneity correction accuracies of the AAA, AXB algorithm, and MC calculation were evaluated by calculating the PDDs and OARs for the virtual phantom with Lipiodol and the lateral profile for the clinical plan data. RESULTS: The measured data and the MC results agreed within 3%. The average dose in the Lipiodol uptake region was higher by 8.1% for the virtual phantom and 6.0% for the clinical case compared to that in regions without Lipiodol uptake. For the virtual phantom, compared with the MC calculation, the AAA and the AXB algorithm underestimated the doses immediately upstream of the Lipiodol region by 5.0% and 4.2%, in the Lipiodol region by 7.4% and 9.8%, and downstream of the Lipiodol region by 5.5% and 3.9% respectively. These discrepancy between the AXB and MC calculations were due to the incorrect assignment of Lipiodol material properties. Namely, the bone material was assigned automatically by the AXB algorithm as the materials for the AXB algorithm do not contain iodine, which is the main constituent of Lipiodol. CONCLUSIONS: The MC calculation indicated a larger and more accurate dose increase in Lipiodol compared with the TPS algorithms. The observed dose enhancement in the tumor area could be clinically significant.

Availability of applying diaphragm matching with the breath-holding technique in stereotactic body radiation therapy for liver tumors.

PURPOSE: Image-guided radiotherapy (IGRT) based on bone matching can produce large target-positioning errors because of expiration breath-hold reproducibility during stereotactic body radiation therapy (SBRT) for liver tumors. Therefore, the feasibility of diaphragm-based 3D image matching between planning computed tomography (CT) and pretreatment cone-beam CT was investigated. METHODS: In 59 liver SBRT cases, Lipiodol uptake after transarterial chemoembolization was defined as a tumor marker. Further, the relative isocenter coordinate that was obtained by Lipiodol matching was defined as the reference coordinate. The distance between the relative isocenter coordinate and reference coordinate, which was obtained from diaphragm matching and bone matching techniques, was defined as the target positioning error. Furthermore, the target positioning error between liver matching and Lipiodol matching was evaluated. RESULTS: The positioning errors in all directions by the diaphragm matching were significantly smaller than those obtained by using by the bone matching technique (p < 0.05). Further, the positioning errors in the A-P and C-C directions that were obtained by using liver matching were significantly smaller than those obtained by using bone matching (p < 0.05). The estimated PTV margins calculated by the formula proposed by van Herk for diaphragm matching, liver matching, and bone matching were 5.0 mm, 5.0 mm, and 11.6 mm in the C-C direction; 3.6 mm, 2.4 mm, and 6.9 mm in the A-P direction; and 2.6 mm, 4.1 mm, and 4.6 mm in the L-R direction, respectively. CONCLUSIONS: Diaphragm matching-based IGRT may be an alternative image matching technique for determining liver tumor positions in patients.

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer.

BACKGROUND: Esophageal cancer is most frequently treated with platinum-based chemoradiotherapy (CRT). We previously described a phase I study of definitive CRT with docetaxel (DOC) and 5-fluorouracil (5FU) in patients with advanced esophageal cancer. This regimen had low toxicity and was effective without platinating agents. The present study aims to determine the antitumor effects of neoadjuvant CRT with DOC and 5FU and surgical outcomes. METHODS: We reviewed data from 38 patients with locally advanced cancer of the esophagus or esophagogastric junction who underwent trimodality therapy comprising neoadjuvant CRT with DOC and 5FU followed by esophagectomy between 2003 and 2008. RESULTS: Esophagitis was the most common toxicity associated with neoadjuvant CRT (grade 3; 26.3%), and hematologic toxicity was mild. Transthoracic esophagectomy and pharyngolaryngoesophagectomy proceeded in 36 (94.7%) and 2 (5.3%) patients, respectively, and 35 (92.1%) underwent R0 resection. Five (13.2%) patients had complete pathologic responses (pCR) of the primary tumor, and 23 (60.5%) had pathologic reductions of over two-thirds of the primary tumor. The T or N status was also down-staged in 26 (68.4%) patients. Overall postoperative morbidity developed in 21 (55.3%) patients, and mortality due to postoperative morbidity was zero. The 5-year recurrence-free and overall survival rates were 39.5% and 44.7%, respectively. CONCLUSIONS: The rates of neoadjuvant CRT toxicity and postoperative complications were acceptable, and the complete resection rate and survival data were favorable. This regimen is promising as neoadjuvant CRT for esophageal cancer and very useful as an alternative regimen for treating patients with esophageal cancer who cannot tolerate cisplatin.

[Availability of using diaphragm matching in stereotactic body radiotherapy (SBRT) at the time in breath-holding SBRT for liver cancer].

PURPOSE: Liver image guided radiation therapy (IGRT) based on bone matching risks generating serious target positioning errors for reasons of lack of reproducibility of expiration breath hold. We therefore investigated the feasibility of 3D image matching between planning CT images and pretreatment cone-beam computed tomography (CBCT) images based on diaphragm surface matching. METHOD: 27 liver stereotactic body radiotherapy (SBRT) cases in whom trancecatheter arterial chemoembolization (TACE) had been performed in advance of radiotherapy were manually image-matched based on contrast, Lipiodol used in the TACE as the marker of the tumor, and the relative coordinates of the isocenter obtained by contrast matching, defined as the reference coordinate. The target positioning difference between diaphragm matching and bone matching were evaluated by using relative coordinates of the isocenter from the reference obtained for each matching technique. RESULTS: The target positioning error using diaphragm matching and bone matching was 1.31±0.83 and 3.10±2.80 mm in the cranial-caudal (C-C) direction, 1.04±0.95 and 1.62±1.02 mm in the anterior-posterior (A-P) direction, and 0.93±1.19 and 1.12±0.94 mm in the left-right (L-R) direction, respectively. The positioning error due to diaphragm matching was significantly smaller than for bone matching in the C-C direction (p<0.05). CONCLUSION: IGRT based on diaphragm matching has potential as an alternative image matching technique for the positioning of liver patients.

Local hyperthermia combined with external irradiation for regional recurrent breast carcinoma.

BACKGROUND: The purpose of this study was to evaluate the therapeutic effects of hyperthermia in combination with radiotherapy for locoregional recurrence of breast cancer, and to assess the factors related to subsequent local tumor control. METHODS: Between March 1981 and February 2001, 85 lesions in 73 patients were treated with local hyperthermia combined with external irradiation. Of 75 evaluable lesions, 41 were previously irradiated. Mean radiation dose to the previously unirradiated area was 59.5 +/- 6.8 Gy (range, 40-70 Gy), while a total dose of 43.0 +/- 12.4 Gy (range, 12-74.4 Gy) was administered to previously irradiated tumors. Hyperthermia was administered once or twice per week. The average number of hyperthermia sessions was 4.5 (2-9). RESULTS: Complete responses (CRs) were achieved in 56% (23/41) of previously irradiated and 47% (16/34) of unirradiated tumors. There was no significant difference in the CR rate between the two groups. Compared with the response of bulky/nodular tumors, diffuse/multiple small nodular tumors showed a higher CR rate at 4 weeks after treatment. However, at 6 months after treatment, they showed a significantly lower local control rate. CONCLUSIONS: The present findings suggested a significant benefit of local hyperthermia combined with radiotherapy in the treatment of locally recurrent breast cancer, especially for previously irradiated recurrence, by reducing the total irradiation dose. Diffuse/multiple small nodular tumors respond earlier than bulky/large nodular tumors; however, they tend to recur within the treatment field. The purpose of this study was to evaluate the therapeutic effects of hyperthermia in combination with radiotherapy for locoregional recurrence of breast cancer, and to assess the factors related to subsequent local tumor control.