Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38-90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8-82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient's condition. The median follow-up of surviving patients was 63 months (range, 1-126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.

Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging.

BACKGROUND: Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. MATERIAL AND METHODS: Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. RESULTS: FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/ß = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. CONCLUSION: This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

Utility of an initial adaptive bladder volume control with ultrasonography for proton-beam irradiation for prostate cancer.

PURPOSE: Our purpose was to evaluate the utility of time-fixed bladder volume control and adaptive bladder volume control with ultrasonography (US). MATERIALS AND METHODS: Seventy-five patients with prostate cancer treated with proton-beam therapy were enrolled. Treatment plans were created using computed tomography (CT) images obtained 60 min after urination with usual water intake. Just before each irradiation, bladder volume was measured with US at the directed urine collection time. Bladder volume was calculated according to orthogonal diameters. A bladder volume of <50 ml was considered to reflect a collapsed bladder. The percentage of collapsed bladders was examined in total and from the first to fifth irradiations. RESULTS: In total, 1,439 US confirmations (51 %) in 2,821 fractions were obtained and analyzed. A collapsed bladder was observed 152 of 1,439 times (11 %) in total, and the percentages of collapsed bladders from the first to fifth irradiations were 32 %, 18 %, 16 %, 12 %, and 7 %, respectively. CONCLUSION: Time-fixed bladder control is associated with a risk of bladder volume insufficiency. Adaptive bladder volume control with initial US feedback could decrease the risk of bladder volume insufficiency.

Basaloid squamous cell carcinoma in the nasal cavity treated with proton beam therapy concurrent with cisplatin: a case report.

INTRODUCTION: Basaloid squamous cell carcinoma is a rare and aggressive variant of squamous cell carcinoma. Basaloid squamous cell carcinoma is mostly seen in the upper aerodigestive tract and has a propensity for lymph node spread and systemic metastases. Various treatment modalities have been reported, including surgical excision supplemented with radiotherapy/adjuvant chemotherapy. To the best of our knowledge, treatment of nasal basaloid squamous cell carcinoma with proton beam therapy and cisplatin has not been described in the literature. CASE PRESENTATION: We report the case of a 56-year-old Japanese man with locally invasive basaloid squamous cell carcinoma in his right nasal cavity with invasion of the orbit, paranasal sinus, and buccal subcutaneous tissue. He underwent proton beam therapy concurrent with cisplatin. Acute and late side effects did not exceed grade 3. At 24-month follow up, he remains in complete remission. CONCLUSION: Proton beam therapy concurrent with cisplatin may be one choice for locally invasive basaloid squamous cell carcinoma.

Noninvasive monitoring of radiation-induced early therapeutic response using high-resolution MR imaging and proton MR spectroscopy in VX2 carcinoma.

The purpose of this study was to evaluate the usefulness of high-resolution MRI (HR-MRI) and proton MR spectroscopy ((1)H-MRS) for monitoring the early therapeutic response to radiotherapy. Twenty rabbits with VX2 carcinoma were divided into control (n = 8) and irradiation (n = 12) groups. The irradiation group underwent HR-MRI and (1)H-MRS using a microscopy coil at 1, 3, 7 or 14 days after irradiation. Rabbits in the control group were subjected to HR-MRI and (1)H-MRS at the same time intervals. All rabbits were killed after imaging and subjected to histopathologic examinations. The diameter of necrosis by HR-MRI was then compared to that on the gross specimens. The ratios of choline/creatine (Cho/Cr) and lactate/creatine (Lac/Cr) on the tumor and necrotic area detected by in vivo (1)H-MRS were compared between the control and irradiation groups, respectively. In addition, the ratios of Cho/Cr and Lac/Cr were compared between the tumor and necrotic area in each irradiation group. A significant correlation was found between the diameter of necrosis in each sequence of HR-MRI and that in the gross specimens (r = 0.84-0.91, p = 0.03- < 0.003). The ratios of Lac/Cr in the tumors of the irradiation groups were significantly higher than those in the control groups after 1 day and 3 days of irradiation (p = 0.04, and p = 0.02). Histological analysis showed necrosis and swelling of the endothelia of capillaries and arterioles at 1 day and 3 days after irradiation. It was suggested that HR-MRI and (1)H-MRS are useful methods for monitoring the early therapeutic response to radiotherapy.

Depiction of hypervascular hepatocellular carcinoma with 64-MDCT: comparison of moderate- and high-concentration contrast material with and without saline flush.

OBJECTIVE: The purpose of this study was to evaluate prospectively the depiction of hypervascular hepatocellular carcinoma on 64-MDCT scans obtained with contrast agents of varying iodine concentrations administered with and without saline flush. SUBJECTS AND METHODS: The study included 149 patients, among whom 36 patients with hypervascular hepatocellular carcinoma were identified. Patients were randomly assigned to one of three protocols: A, contrast material of 300 mg I/mL; B, 370 mg I/mL; C, 370 mg I/mL plus saline flush. In all protocols, the same iodine load per kilogram of body weight (516 mg/kg) was administered for the same injection duration (30 seconds). Enhancement values in the aorta, liver, and portal vein and tumor-liver contrast were measured at multiphase CT. RESULTS: Aortic enhancement was significantly different between protocols A and B (p = 0.04, p < 0.0001) and protocols B and C (p = 0.02, p < 0.001) in the first and second phases. Portal venous enhancement was significantly different between protocols B and C (p = 0.02) in the first phase and between protocols B and C and protocols A and C (p < 0.01, p = 0.02) in the second phase. Tumor-liver contrast was significantly different between protocols A and B (p = 0.03, p = 0.02) and protocols B and C (p = 0.03, p = 0.04) in the first and second phases but not between protocols A and C. There was no significant difference in hepatic enhancement among the three protocols. CONCLUSION: Use of moderate concentration was more effective than use of a high concentration of contrast material for depiction of hepatocellular carcinoma. Adding a saline flush to the high-concentration protocol eliminated the difference in depiction of hepatocellular carcinoma between the moderate- and high-concentration protocols.

Lung carcinoma: diffusion-weighted mr imaging--preliminary evaluation with apparent diffusion coefficient.

PURPOSE: To prospectively evaluate diffusion-weighted (DW) magnetic resonance (MR) imaging with a split acquisition of fast spin-echo signals for diffusion imaging (SPLICE) sequence for tissue characterization of lung carcinomas by using apparent diffusion coefficients (ADCs). MATERIALS AND METHODS: An institutional review board approved this study; informed consent was obtained from patients. Thirty patients (nine women, 21 men; mean age, 68.0 years) with lung carcinoma underwent DW MR imaging with the SPLICE sequence. ADC of each lung carcinoma was calculated from DW MR images obtained with low and high b values. ADCs of lung carcinomas were statistically compared among histologic types. Nine surgically excised lung carcinomas were evaluated for correlation between ADCs and tumor cellularities. Analysis of variance was used to determine changes in ADCs and histologic lung carcinoma types. Spearman rank correlation was calculated between ADCs and tumor cellularities. RESULTS: ADCs for lung carcinomas were 1.63 x 10(-3) mm(2)/sec +/- 0.5 (mean +/- standard deviation) for squamous cell carcinoma, 2.12 x 10(-3) mm(2)/sec +/- 0.6 for adenocarcinoma, 1.30 x 10(-3) mm(2)/sec +/- 0.4 for large-cell carcinoma, and 2.09 x 10(-3) mm(2)/sec +/- 0.3 for small-cell carcinoma. ADC of adenocarcinoma was significantly higher than that of squamous cell carcinoma and large-cell carcinoma (P < .05). ADCs were 1.59 x 10(-3) mm(2)/sec +/- 0.5 and 1.70 x 10(-3) mm(2)/sec +/- 0.4 for moderately and poorly differentiated squamous cell carcinoma, respectively. ADCs were 2.52 x 10(-3) mm(2)/sec +/- 0.4 and 1.44 x 10(-3) mm(2)/sec +/- 0.3 for well- and poorly differentiated adenocarcinoma, respectively. ADC of well-differentiated adenocarcinoma was significantly higher than that of moderately and poorly differentiated squamous cell carcinoma and poorly differentiated adenocarcinoma (P < .05). With the Spearman rank test, ADCs of lung carcinomas correlated well with tumor cellularities (Spearman coefficient, -0.75; P < .02). CONCLUSION: ADCs of lung carcinomas overlap, but ADCs of well-differentiated adenocarcinoma appear to be higher than those of other histologic lung carcinoma types.

Usefulness of a saline flush for intravenous 3-dimensional computed tomography portography using multidetector-row helical computed tomography.

PURPOSE: To evaluate the clinical usefulness of a saline flush technique in improving the imaging quality of 3-dimensional computed tomography portography (3D-CTP). METHODS: To evaluate liver metastases, 58 patients were divided into 2 groups undergoing 3D-CTP with or without a saline flush. The computed tomography (CT) values of the right portal vein (RPV), left portal vein (LPV), main portal vein (MPV), and right hepatic parenchyma (RHP) were assessed. Maximum intensity projection (MIP) 3D-CTP images were evaluated by vessel visualization. RESULTS: Higher mean CT attenuation values in the RPV, LPV, MPV, and RPV-RHP were observed in the saline flush group and were statistically significant (P = 0.04, P = 0.03, P = 0.01, and P = 0.04, respectively). The difference in imaging quality between 2 groups was statistically significant (P = 0.04). In segment VIII, the ability to depict the segmental branches was significantly higher when the saline flush technique was used (P = 0.03). CONCLUSIONS: The saline flush technique increases the CT attenuation values of the portal vein and the difference in values between the portal vein and the tissue around it and improves the MIP imaging quality of 3D-CTP.