Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer.

We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3-4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.

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.

Erratum: Shibata S.; et al. Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas. Cancers 2018, 10, 71.

The authors wish to make the following corrections to this paper [...].

Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas.

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66-80.5 CGE in 10-32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child-Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.

Respiratory-gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract without Fiducial Markers.

The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38-87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2-72.3 months). The median tumor size was 36.5 mm (range, 11-124 mm). Kaplan-Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract.

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.

Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET.

PURPOSE: Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHODS: Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method. RESULTS: The means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively). CONCLUSION: Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.

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.

The usefulness of vinyl polysiloxane dental impression material as a proton beam stopper to save normal tissue during irradiation of the oral cavity: basic and clinical verifications.

PURPOSE: To evaluate the feasibility and usefulness of vinyl polysiloxane (VPS) dental impression material as a proton beam stopper for oral cavity irradiation. METHODS: VPS compounds with different base-catalyst mixture ratios were created, and the relative linear stopping power (RLSP) of each VPS compound was measured to compare with the RLSPs obtained from converted CT data. Then, a model plan was created to simulate oral cancer, and depth-dose distributions that were calculated using radiation treatment planning (RTP) were investigated by comparing the distribution with the measurements. The radioactivation of the VPS material was also measured after 2-Gy proton beam irradiations. For clinical use, a T4 gingival squamous cell carcinoma was treated using proton beam therapy with a VPS bite block. Treatment plans with and without the VPS bite block were created, and the dose-volume histograms (DVH) of the tongues were compared. RESULTS: Both the RLSPs and the CT numbers were constant of the ratio of VPS mixtures. The measured RLSP of the VPS was 1.51±0.01, which was approximately 4% greater than the CT-converted RLSP. In a model simulation, the measured depth-dose distribution inside the VPS dropped steeply compared to the RTP calculation, and the dose behind the VPS bite block was less than 0.1% of the prescribed dose. The equivalent dose rates for VPS immediately after irradiation were below 1 µSv∕h and reached background levels within 30 min. In clinical use, VPS reduced a 10 cc local overdose region as well as the mean dose in the tongue compared to the plan without VPS, while the DVH of the planning target volume was maintained. The onset of severe mucositis was not observed behind the VPS bite block. CONCLUSIONS: VPS is easy to shape and reproducible. The authors succeeded in demonstrating its safety and accuracy as a proton beam stopper.

Kikuchi-Fujimoto disease: PET/CT assessment of a rare cause of cervical lymphadenopathy.

PURPOSE: Kikuchi-Fujimoto disease (KFD), formerly called subacute necrotizing lymphadenitis, is a rare cause of cervical lymphadenopathy. The purpose of this study was to evaluate the usefulness of FDG PET/CT for distinguishing KFD from non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: Twenty-two patients with cervical lymphadenopathy (8 with KFD and 14 with NHL) underwent CT and FDG PET/CT scans to examine the cervical lymphadenopathy. Regional values of FDG uptake were evaluated using the standardized uptake value (SUV) and partial volume corrected SUV (corSUV) based on the count recovery coefficient. Tumor size (mm), SUV, and corSUV were compared among KFD, indolent NHL, and aggressive NHL. RESULTS: KFD lesions tended to be smaller (13.8 ± 5.4 mm) than those of indolent (25.4 ± 11.8) and aggressive (29.7 ± 18.8) NHL, whereas there were no significant differences in size. As for SUV, a significant difference was observed only between indolent and aggressive (6.4 ± 1.5 and 17.3 ± 9.3, P < 0.05) NHL; however, KFD showed a significantly greater corSUV (23.8 ± 10.6) as compared with indolent NHL (9.2 ± 5.1, P < 0.05), which did not show a significant difference from aggressive NHL (21.4 ± 10.2). FDG PET/CT detected thoracoabdominal lesions in 2 patients (25%) with KFD. CONCLUSIONS: KFD shows high FDG uptake for size, which may reflect the pathologic characteristics, including necrotizing lymphocytes and numerous histiocytes (macrophages) surrounding small necrotic foci. FDG PET/CT will be useful for detecting noncervical lesions of KFD and distinguishing KFD from NHLs using both SUV and corSUV.