Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer.

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

Initial tumor volume as an important predictor for indication of intra-cavitary brachytherapy, intra-cavitary/interstitial brachytherapy, and multi-catheter sole interstitial brachytherapy in cervical cancer patients treated with chemoradiotherapy.

Purpose: Advances in three-dimensional image-guided brachytherapy technique allow for using intra-cavitary and interstitial brachytherapy (ICIS-BT), and sole interstitial brachytherapy (ISBT) in addition to conventional intra-cavitary brachytherapy (ICBT). However, no consensus has been reached regarding the choice of these techniques. The aim of this study was to propose the size criteria for indication of interstitial techniques. Material and methods: We examined initial gross tumor volume (GTV) at presentation and at each brachytherapy session. Also, dose volume histogram parameters for each modality were compared in 112 patients with cervical cancer treated with brachytherapy (ICBT, 54; ICIS-BT, 11; and ISBT, 47). Results: The average GTV at diagnosis was 80.9 cm3 (range, 4.4-343.2 cm3), which shrank to 20.6 cm3 (25.5% of initial volume, range, 0.0-124.8 cm3) at initial brachytherapy. GTV > 30 cm3 at brachytherapy and high-risk clinical target volume > 40 cm3 were good threshold values for indication of interstitial technique, and tumors with initial GTV > 150 cm3 could be candidates for ISBT. An ISBT dose of 89.10 Gy can be prescribed in equivalent dose in 2 Gy fractions (range, 65.5-107.6 Gy), which was higher than those of ICIS (73.94 Gy, range, 71.44-82.50 Gy) and ICBT (72.83 Gy, range, 62.50-82.27 Gy) (p < 0.0001). Conclusions: Initial tumor volume is an important predictor for indication of ICBT and ICIS-BT. ISBT or at least an interstitial technique is recommended for initial GTV > 150 cm3.

HDR-brachytherapy for accelerated partial breast irradiation: Long-term experience from a Japanese institution.

Purpose: We investigated the long-term oncological outcome of high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIB) for adjuvant accelerated partial breast irradiation (APBI) after breast conserving surgery in Japanese patients. Material and methods: Between June 2002 and October 2011, 86 breast cancer patients were treated at National Hospital Organization Osaka National Hospital (trial number of the local institutional review board, 0329). Median age was 48 years (range, 26-73 years). Eighty patients had invasive and 6 patients non-invasive ductal carcinoma. Tumor stage distribution was pT0 in 2, pTis in 6, pT1 in 55, pT2 in 22, and pT3 in one patient, respectively. Twenty-seven patients had close/positive resection margins. Total physical HDR dose was 36-42 Gy in 6-7 fractions. Results: At a median follow-up of 119 months (range, 13-189 months), the 10-year local control (LC) and overall survival rate was 93% and 88%, respectively. Concerning the 2009 Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology risk stratification scheme, the 10-year LC rate was 100%, 100%, and 91% for patients considered as low-risk, intermediate-risk, and high-risk, respectively. According to the 2018 American Brachytherapy Society risk stratification scheme, the 10-year LC rate was 100% and 90% for patients 'acceptable' and 'unacceptable' for APBI, respectively. Wound complications were observed in 7 patients (8%). Risk factors for wound complications were the omission of prophylactic antibiotics during MIB, open cavity implantation, and V100 ≥ 190 cc. No grade ≥ 3 late complications (CTCVE version 4.0) were observed. Conclusions: Adjuvant APBI using MIB is associated with favorable long-term oncological outcomes in Japanese patients for low-risk, intermediate-risk, and acceptable groups of patients.

Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer.

OBJECTIVE: Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. METHODS: The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). RESULTS: A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). CONCLUSION: It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.

＜Editors' Choice＞ Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Effect of a lead block on alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer: using model-based dose calculation algorithms to correct for inhomogeneity.

PURPOSE: The purpose of this study was to evaluate the effect of a lead block for alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer. MATERIAL AND METHODS: We treated 6 patients and delivered 5,400 cGy in 9 fractions using a lead block. Effects of lead block (median thickness, 4 mm) on dose attenuation by distance were visually examined using TG-43 formalism-based dose distribution curves to determine whether or not the area with the highest dose is located in the alveolar bone, where there is a high-risk of infection. Dose re-calculations were performed using TG-186 formalism with advanced collapsed cone engine (ACE) for inhomogeneity correction set to cortical bone density for the whole mandible and alveolar bone, water density for clinical target volume (CTV), air density for outside body and lead density, and silastic density for lead block and its' silicon replica, respectively. RESULTS: The highest dose was detected outside the alveolar bone in five of the six cases. For dose-volume histogram analysis, median minimum doses delivered per fraction to the 0.1 cm3 of alveolar bone (D0.1cm3 TG-43, ACE-silicon, and ACE-lead) were 344.3 (range, 262.9-427.4) cGy, 336.6 (253.3-425.0) cGy, and 169.7 (114.9-233.3) cGy, respectively. D0.1cm3 ACE-lead was significantly lower than other parameters. No significant difference was observed between CTV-related parameters. CONCLUSIONS: The results suggested that using a lead block for alveolar bone protection with a thickness of about 4 mm, can shift the highest dose area to non-alveolar regions. In addition, it reduced D0.1cm3 of alveolar bone to about half, without affecting tumor dose.

A successful approach for angiosarcoma of the scalp using helical tomotherapy and customized surface mold brachytherapy: A case report.

RATIONALE: Angiosarcoma of the scalp (ASS) is a rare solid tumor with a high risk of local recurrence. Effective treatment strategies are not currently available for angiosarcoma of the scalp (ASS). The aim of this study was to report the utility of high-dose-rate brachytherapy (HDRBT) as a boost treatment for ASS following total scalp irradiation using helical tomotherapy (HT). This is the first report of successful treatment of ASS using HT and HDRBT. PATIENT CONCERNS: An 81-year-old woman presented with hemorrhagic nodular skin tumors of the scalp. The patient first noticed the scalp mass 3 months before consultation, which became significantly enlarged within a short period. The tumor was positioned mostly in the parietal area, although the skin color change was widely spread to the surrounding scalp. DIAGNOSIS: The patient underwent biopsy of the skin lesion at the right parietal region, which revealed the presence of angiosarcoma on pathological examination. There was neither regional lymphadenopathy nor distant metastases on PET/CT. INTERVENTIONS: Considering the patient's old age and poor performance status because of a history of cerebral infarction, we considered that she was eligible for definitive chemoradiotherapy of the scalp. We adopted an individual surface mold HDRBT boost of 18 Gy in three fractions following total scalp irradiation with 50 Gy in 25 fractions delivered using HT. Docetaxel (40 mg/m2) was administered every 4 weeks, concurrently with radiotherapy. OUTCOMES: Treatment tolerance was good, and severe toxicity has not been observed to date. At 18 months after radiotherapy, the patient does not have any evidence of recurrence. CONCLUSION: Customized surface mold HDRBT following total scalp irradiation using HT resulted in excellent disease control and minimal toxicity; thus, it may be a promising therapeutic option for ASS.

Small bowel perforation caused by applicator implantation in high-dose-rate interstitial brachytherapy for recurrent pelvic tumor: a case report.

High-dose-rate interstitial brachytherapy (HDR-ISBT) is widely used for the treatment of pelvic tumors. However, there are a few reports on complications of applicator implantation in HDR-ISBT. We describe a case of small bowel perforation caused by applicator implantation in an 82-year-old male patient with recurrence tumor in the pelvis treated with HDR-ISBT. Eventually, the patient underwent laparotomy and partial intestinal resection. We recognized the site where the applicator was inserted into a part of the tumor on the mucosal surface. Pathological examination confirmed that the tumor had infiltrated the small intestine directly and that the infiltrated part had reached the submucosa. This is the first published report about small bowel perforation caused by applicator implantation. In cases where intestinal infiltration of the tumor is suspected, HDR-ISBT should be performed with maximum caution.

High dose rate interstitial brachytherapy for early stage lip cancer using customized dental spacer.

The present study aimed to report the efficacy and toxicity of our high-dose-rate (HDR) brachytherapy for early stage lip cancer (LC) using customized dental spacers. A retrospective analysis was performed among six patients with early stage LC treated with HDR interstitial brachytherapy between April 2015 and August 2019 using customized dental spacers. The total treatment dose was 49 Gy/7 fractions or 54 Gy/9 fractions. The median follow-up duration for the patients was 13 (range: 2-52) months. All patients completed the entire brachytherapy protocol safely and have experienced no local recurrence thus far. The CTV D100 and D90 values per fraction were median 100 (range: 98.3-100) % prescribed dose (PD) and median 133.4 (range: 129.3-138.9) % PD, respectively. The D2cc and D0.1cc values per fraction for the mandible were median 1.07 (range, 0.79-1.88) Gy and median 1.65 (range: 1.21-2.83) Gy, D2cc and D0.1cc values per fraction for oral cavity were median 1.48 (range, 1.31-1.72) Gy and median 2.73 (range: 1.79-2.88) Gy, respectively. Acute toxicities encountered were mucositis and lip edema limited to the irradiated area; none of them was beyond grade 2 and all were resolved within 1-2 months after treatment. We did not observe any late grade 2 adverse events or worse. This study shows that the adverse effects of HDR brachytherapy for early stage LC can be minimized using a dental spacer. Cooperation with the dentistry department is essential to make spacers that are individually customized for each patient.

Abscopal effect of high-dose-rate brachytherapy on pelvic bone metastases from renal cell carcinoma: a case report.

Radiation therapy is considered an optimal partner for immunotherapies. Several pre-clinical studies have demonstrated that regression of distant metastases, at remote non-irradiated sites of the body, termed the "abscopal effect", can be achieved by an appropriate timing and combination of radiation with immunotherapy. However, nearly all pre-clinical and clinical studies evaluating a combination of radiation and immunotherapies have used external beam radiation therapy. We present in this case report, the abscopal effect observed in a 30-year-old Japanese woman with metastatic renal cell carcinoma after the treatment with high-dose-rate interstitial brachytherapy combined with nivolumab. This is the first published report demonstrating an abscopal effect following brachytherapy for human malignancy. Our case indicates that immuno-oncology effects are not limited to external beam irradiation regimens as they can also be attained by brachytherapy.

An easy and novel method for safer brachytherapy: real-time fluoroscopic verification of high-dose-rate 192Ir source position using a flat-panel detector.

Real-time fluoroscopic verification of the active source position during actual treatment is the only established method to prevent high-dose-rate (HDR) brachytherapy events. The challenge is spurious signals from an HDR 192Ir source that result in image halation, making source positions indiscernible when using a non-modified image intensifier fluoroscope. We have previously reported a method for observing an HDR 192Ir source by using an elaborately modified image intensifier system. The newly developed flat-panel detector fluoroscope is, by contrast, inherently halation-free thanks to the wider dynamic range (12-14 bits), compared with image intensifier fluoroscopes (8 bits). To explore the feasibility, we applied a commercially available flat-panel detector fluoroscope without modification to actual treatment. We successfully observed source positions without halation for all 107 patients, with a total of 522 HDR treatment sessions during a 3-year period from 2014 to 2017. Actual source positions were compared with planned positions on the planning hard copy. With this method, we detected a total of 1 error (0.2%) among the 522 sessions, at a similar detection rate of 0.1% with our previous experience using a modified image intensifier fluoroscope. We found that a commercially available flat-panel detector fluoroscope is ready for use for real-time verification and outweighs the need for elaborate modifications of an image intensifier fluoroscope. A flat-panel detector fluoroscope will help the global radiation oncology community promote real-time verification programs, leading to safer HDR brachytherapy.

A new implant device to prevent edema-associated underdosage in high-dose-rate interstitial brachytherapy of mobile tongue cancer.

PURPOSE: Tongue edema is a potential cause of treatment target underdosage in high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To prevent such edema-associated alteration of dosimetry, we developed a special silicon device. In this report we communicate our initial experience with two mobile tongue cancer patients whom we treated using this new device. MATERIAL AND METHODS: The device consists of silicone tubes with a fixed width and scalable length depending on tongue size. These tubes are lined and fixed like a palisade, allowing the device to be used also as a template. The device is placed next to the lateral border of the tongue and on the floor of the mouth. In addition, a vinyl template can be placed on the dorsal tongue surface with both devices combined for implantation guidance. Between June and August 2012, two patients with locally confined tongue cancer were treated. RESULTS: Between June and August 2012, two mobile tongue cancer patients classified as cT2N0M0 were treated with HDR-ISBT using the silicone device. They underwent ISBT as monotherapy with fractional doses of 6.0 Gy up to a total physical dose of 54.0 Gy. The D90 (CTV) values of both patients were 6.3 Gy and 6.6 Gy and the D2cc (mandible) values were 3.4 Gy and 2.6 Gy, respectively. At present, both patients remain without local disease recurrence at 60 and 56 months after ISBT, respectively. CONCLUSIONS: The described silicone device has the potential to prevent underdosage to the treatment target related to tongue edema. It has been shown to be safe and easy to implement.

Correlation Between Dosimetric Parameters and Acute Dermatitis of Post-operative Radiotherapy in Breast Cancer Patients.

BACKGROUND/AIM: To examine the correlation between dosimetric parameters and acute radiation dermatitis in early breast cancer patients subjected to post-operative radiotherapy. PATIENTS AND METHODS: The data of 84 patients treated with post-operative radiotherapy were analyzed. The total prescribed dose was 50 Gy in 25 fractions over 5 weeks. Radiation dermatitis was assessed according to Common Terminology Criteria for Adverse Events v4.0. We set organ at risk whole body (from neck to abdomen examined by CT images) also as surrogate skin volume (3 mm thickness). RESULTS: A total of 28 patients showed radiation dermatitis grade equal or higher than 2 at the 50 Gy time point. These 28 patients were compared to 56 matched pair patients with grade 0-1 radiation dermatitis during the same treatment period. The mean of V5-20 and V40 in patient's whole volume and V40-50 in skin volume were significantly higher in patients who presented with acute radiation dermatitis Grades ≥2 than in the other patients who did not. The statistically most significant difference was observed for V40 for skin volume and V5 for patient whole volume. Rate of acute radiation dermatitis grade ≥2 was significantly higher for patients with V5 (whole body) >1,360 cm3 than those with V5 (whole body) <1,360 cm3 (47% vs. 27%, p=0.0353), as well as for patients with V40 (skin volume) >45 cm3 compared with those with V40 (skin volume) <45 cm3 (50% vs. 18%, p=0.0043). CONCLUSION: Dosimetric parameters were useful to predict radiation dermatitis grade ≥2. V5 (whole body) 1,360 cm3 and V40 (skin volume) 45 cm3 may be dose volume constrain for radiation dermatitis grade ≥2.

Radiotherapy for T1N0M0 Esophageal Cancer: Analyses of the Predictive Factors and the Role of Endoscopic Submucosal Dissection in the Local Control.

Several therapeutic options are available for clinical T1N0M0 thoracic esophageal squamous cell carcinoma (stage I ESCC); however, the studies on the treatment results are limited. This study assessed the outcomes of stage I ESCC treated with radiotherapy (RT), determined predictive factors, and evaluated the benefits of endoscopic submucosal dissection (ESD) combined with RT. We retrospectively analyzed the data of 50 patients (41 men, 9 women; median age, 66 years) with stage I ESCC treated with RT. The median total irradiation dose was 50 Gy. Elective nodal irradiation (ENI) was performed in 17 patients and ESD in 29 patients (ESD group). Forty-six patients concurrently received chemotherapy with RT. The median tumor length of ESD and non-ESD groups was 2.3 and 5 cm, respectively. The median follow-up was 33 months. The 3-year overall survival, disease-free survival (DFS), and local control (LC) rates were 77.3%, 61.1%, and 88.1%, respectively. Grade 3 adverse events occurred in 14 patients. T stage and tumor length were significant prognostic factors for 3-year DFS and 3-year LC, respectively. ESD appeared to be an important prognostic factor for LC. ENI and total irradiation dose above 50.4 Gy were not predictive factors. Our findings might help in treatment decisions for stage I ESCC.

Comparison of radiation dermatitis between hypofractionated and conventionally fractionated postoperative radiotherapy: objective, longitudinal assessment of skin color.

This study aimed to quantitatively compare radiation dermatitis due to hypofractionated (Hypo) and conventionally fractionated (Conv) external-beam radiotherapy in patients who underwent postoperative radiotherapy after breast-conserving surgery. Skin color changes, in terms of L* (brightness, white-black), a* (red-green), and b* (yellow-blue) values, due to external-beam radiotherapy were examined at alternate fractions using an objective method. Twenty-six patients were included in the Hypo group (42.56 Gy/16 fractions) and 46 in the Conv group (50 Gy/25 fractions). Radiotherapy decreased the L* value (darker) and increased the a* value (redder) gradually. These color alterations progressed linearly according to elapsed fractions and were similar between Hypo and Conv per fraction. The Hypo group showed significantly milder alterations in L* and a* values than the Conv group. The maximal dosage was significantly correlated to alterations in L* and a* values. Common Terminology Criteria for Adverse Events v4 assessment did not show a statistically significant difference between the Hypo (Grade 0:1:2 = 2:24:1) and Conv (1:39:6, p = 0.25) groups. The results of our objective analysis revealed that patients undergoing Hypo show milder color alteration than those undergoing Conv and that the maximal dosage is a useful predicator of color alteration.

Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23-4,993 days), and the median duration of patient follow-up was 256 days (range, 11-2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17-240 Gy2; α/ß = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.