A method for delivering the required neutron fluence in an accelerator-based boron neutron capture therapy system employing a lithium target.

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

Gynecological technical notes for appropriate spacer injections.

BACKGROUND: Despite its efficacy, if adherence to dose constraints for surrounding normal tissues proves unattainable, the risk of late radiation-related adverse events after primary radiotherapy involving brachytherapy remains a noteworthy concern. Some studies suggest that similar to prostate radiotherapy, spacers may potentially reduce doses to surrounding healthy rectal or bladder tissues. However, guidance on spacer injections for gynecologic brachytherapy is scarce, and the optimal anatomical location for spacer placement remains undefined. We discuss maximizing the effects of spacers from an anatomical perspective. FINDINGS: As vesicovaginal and rectovaginal septa form part of the endopelvic fascia and are not uniform tissues, spacer injection resistance varies. In pelvic organ prolapse surgery, saline is injected into the anterior and posterior vaginal walls as a spacer, and the vagina, vesicovaginal septum, and bladder can be fluidly dissected. Relatively firm vesicovaginal septum tissue is used as a reconstructive organ, whereas rectovaginal septum tissue is less dense. Cervical cancer is invasive, involving surrounding fascia and ligaments. Ideally, the vesicovaginal and rectovaginal septa should be resected in radical hysterectomy. Here, spacer adaptation and the technical details of injection are described. When using ultrasound guidance for spacer injection, the target site should be adequately magnified, and the spacer ideally injected into the incision layer during radical hysterectomy. Finally, posthysterectomy, the intestinal tract may adhere to the vaginal cuffs. Therefore, artificial ascites may be useful; however, the spread depends on perioperative manipulation. CONCLUSIONS: Anatomical and surgical viewpoints are advantageous for safe, therapeutic, and replicable spacer injection administration.

Acral cutaneous malignant melanoma treated with linear accelerator-based boron neutron capture therapy system: a case report of first patient.

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.

Relative biological effectiveness for epithermal neutron beam contaminated with fast neutrons in the linear accelerator-based boron neutron capture therapy system coupled to a solid-state lithium target.

This study aimed to quantify the relative biological effectiveness (RBE) for epithermal neutron beam contaminated with fast neutrons in the accelerator-based boron neutron capture therapy (BNCT) system coupled to a solid-state lithium target. The experiments were performed in National Cancer Center Hospital (NCCH), Tokyo, Japan. Neutron irradiation with the system provided by Cancer Intelligence Care Systems (CICS), Inc. was performed. X-ray irradiation, which was assigned as the reference group, was also performed using a medical linear accelerator (LINAC) equipped in NCCH. The four cell lines (SAS, SCCVII, U87-MG and NB1RGB) were utilized to quantify RBE value for the neutron beam. Before both of those irradiations, all cells were collected and dispensed into vials. The doses of 10% cell surviving fraction (SF) (D10) were calculated by LQ model fitting. All cell experiments were conducted in triplicate at least. Because the system provides not only neutrons, but gamma-rays, the contribution from the gamma-rays to the survival fraction were subtracted in this study. D10 value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was 4.26, 4.08, 5.81 and 2.72 Gy, respectively, while that acquired by the X-ray irradiation was 6.34, 7.21, 7.12 and 5.49 Gy, respectively. Comparison of both of the D10 values, RBE value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was calculated as 1.7, 2.2, 1.3 and 2.5, respectively, and the average RBE value was 1.9. This study investigated RBE of the epithermal neutron beam contaminated with fast neutrons in the accelerator-based BNCT system coupled to a solid-state lithium target.

Salvage high-dose rate brachytherapy for myxofibrosarcoma of the brachium: a technical report.

An 80-year-old male presented with T1N0M0 myxofibrosarcoma in or next to the humeral canal, which is located between the biceps and triceps of the right upper arm. Because the tumor was close to critical anatomical structures such as the brachial artery, median nerve and ulnar nerve, it was deemed impossible to perform limb-sparing surgery with an adequate resection margin. Therefore, preoperative external beam radiation therapy (EBRT) followed by limb-sparing surgery was offered. Magnetic resonance imaging taken after 40 Gy/20 fractions of EBRT showed an inadequate response, and limb-sparing surgery was not deemed possible at this point. Amputation of the right arm was offered, but the patient refused. Therefore, salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) was offered. Under local anesthesia and sedation, 14 plastic needles were inserted, and 36 Gy in 6 fractions of HDR-ISBT was performed. Although radiation-induced incomplete paralysis of the median nerve was noted, no local progression or distant metastasis was found on the CT that was taken 2 years after the treatment.

Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (CCRT) has been the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). BACKGROUND AND PURPOSE: The results of the PACIFIC trial established the use of consolidative durvalumab after concurrent chemoradiotherapy (CCRT) as the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). A subgroup analysis of the PACIFIC trial reported a better progression-free survival (PFS) in Asians. Although real-world data on LA-NSCLC patients who received CCRT plus durvalumab have been reported, there have been few large-scale reports on Asians. In this study, we investigated prognostic factors in the largest real-world data set in Asia of only Japanese LA-NSCLC patients treated with CCRT plus durvalumab. MATERIALS AND METHODS: One hundred and thirteen LA-NSCLC patients who received definitive CCRT and consolidative durvalumab at our institution between May 2018 and April 2021 were analyzed. Overall survival (OS), cause-specific survival (CSS), PFS, distant metastasis-free survival (DMFS), and in-field progression-free survival (IFPFS) were investigated as treatment outcomes using competing risk analyses. RESULTS: During a median follow-up of 24 months (range, 5-47) after the initiation of durvalumab therapy, 31 patients died, of whom 23 died of lung cancer. In the multivariate analysis, the pretreatment factors that correlated with OS were ILA scores, adenocarcinoma, and performance status at the initiation of durvalumab. Furthermore, ILA score and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 1 % were significantly correlated with CSS, and PD-L1 TPS ≥ 1 % was significantly correlated with PFS and IFPFS. CONCLUSION: Pretreatment ILA, adenocarcinoma, and performance status may have an impact on OS of LA-NSCLC patients receiving CCRT plus durvalumab.

Failure modes and effects analysis study for accelerator-based Boron Neutron Capture Therapy.

BACKGROUND: Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail. PURPOSE: The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system. METHODS: In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived. RESULTS: The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities. CONCLUSIONS: This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

Hydrogel spacer injection to the meso-sigmoid to protect the sigmoid colon in cervical cancer brachytherapy: A technical report.

Purpose: The use of a hydrogel spacer inserted into recto-vaginal fossa is a valuable strategy to mitigate radiation exposure to the rectum during radiation therapy for female pelvic malignancies. However, when the sigmoid colon is in proximity to the cervix, radiation exposure to the sigmoid colon cannot be adequately mitigated with a hydrogel spacer injected into the recto-vaginal fossa. Here, we presented a case, in which a hydrogel spacer was injected into the meso-sigmoid to protect the sigmoid colon. Material and methods: A 73-year-old female diagnosed with T3b stage IIIC2r uterine cervical cancer (FIGO 2018) underwent high-dose-rate interstitial brachytherapy consisting of 24 Gy in 4 fractions, following concurrent chemoradiotherapy with external beam radiation therapy of 50 Gy in 25 fractions of whole pelvic radiation therapy. In the initial brachytherapy, the sigmoid colon was in close contact with the uterine cervix. In the second brachytherapy, attempts to create a space between the sigmoid colon and uterine cervix using injected artificial ascites were unsuccessful due to rapid absorption of fluid. In the third and fourth brachytherapy fractions, 5 mL of hydrogel was injected into the meso-sigmoid through a pouch of Douglas under trans-rectal ultrasonography guidance. Dose ratio of sigmoid colon D2cc and high-risk clinical target volume (HR-CTV) D90 of each brachytherapy were evaluated. Results: Dose ratio of the sigmoid colon D2cc to HR-CTV D90 was 1.03, 0.43, 0.56, and 0.47 in each respective brachytherapy session, indicating dose escalation to HR-CTV whilst achieving acceptable sigmoid dose with hydrogel spacer injected into the meso-sigmoid. Conclusions: The dose ratio of the sigmoid colon to HR-CTV D90 was decreased by introducing a hydrogel spacer into the meso-sigmoid. In cases where the sigmoid colon is in proximity to the cervical tumor, this novel technique can be considered to achieve better clinical outcomes.

Analyzing spatial distribution between 18F-fluorodeoxyglucose and 18F-boronophenylalanine positron emission tomography to investigate selection indicators for boron neutron capture therapy.

BACKGROUND: 18F-FDG PET is often utilized to determine BNCT selection due to the limited availability of 18F-BPA PET, which is performed by synthesizing 18F into the boron drug used for BNCT, although the uptake mechanisms between those are different. Additionally, only a few non-spatial point parameters, such as maximum SUV (SUVmax), have reported a correlation between those in previous studies. This study aimed to investigate the spatial accumulation pattern between those PET images in tumors, which would be expected to either show higher uptake on 18F-BPA PET or be utilized in clinical, to verify whether 18F-FDG PET could be used as a selection indicator for BNCT. METHODS: A total of 27 patients with 30 lesions (11 squamous cell carcinoma, 9 melanoma, and 10 rhabdomyosarcoma) who received 18F-FDG and 18F-BPA PET within 2 weeks were enrolled in this study. The ratio of metabolic tumor volumes (MTVs) to GTV, histogram indices (skewness/kurtosis), and the correlation of total lesion activity (TLA) and non-spatial point parameters (SUVmax, SUVpeak, SUVmin, maximum tumor-to-normal tissue ratio (Tmax/N), and Tmin/N) were evaluated. After local rigid registration between those images, distances of locations at SUVmax and the center of mass with MTVs on each image and similarity indices were also assessed along its coordinate. RESULTS: In addition to SUVmax, SUVpeak, and Tmax/N, significant correlations were found in TLA. The mean distance in SUVmax was [Formula: see text] and significantly longer than that in the center of mass with MTVs. The ratio of MTVs to GTV, skewness, and kurtosis were not significantly different. However, the similarities of MTVs were considerably low. The similarity indices of Dice similarity coefficient, Jaccard coefficient, and mean distance to agreement for MTV40 were [Formula: see text], [Formula: see text], and [Formula: see text] cm, respectively. Furthermore, it was worse in MTV50. In addition, spatial accumulation patterns varied in cancer types. CONCLUSIONS: Spatial accumulation patterns in tumors showed low similarity between 18F-FDG and 18F-BPA PET, although the various non-spatial point parameters were correlated. In addition, the spatial accumulation patterns were considerably different in cancer types. Therefore, the selection for BNCT using 18F-FDG PET should be compared carefully with using 18F-FBPA PET.

Clinical impact of p16 positivity in nasopharyngeal carcinoma.

Purpose: The clinical characteristics and prognosis of HPV-related nasopharyngeal cancer (NPC) remain controversial. The relationship between p16 status and outcome was retrospectively investigated in the NPC patients. Materials and Methods: Between May 2009 and May 2019, 81 NPC patients who received definitive radiation therapy, in a hospital in Japan, were identified and the prognosis was investigated. p16, p53, and Epstein-Barr virus (EBV) status were assessed. Also, circumferential tumor extent in the nasopharyngeal cavity was assessed on a 5-point scale. Results: Nine and 72 patients were p16-positive and p16-negative, respectively. Fewer patients were EBV-encoded RNA in situ hybridization (EBER-ISH)-positive in the p16-positive group than in the p16-negative group (p < .01). Seventy-five patients were nonkeratinizing NPCs, and six patients were keratinizing NPCs. There were two p16-positive patients among the keratinizing NPCs.The mean circumferential tumor extent scores of 16-positive and p16-negative NPCs were 4.2 and 3.2, respectively with a statistically significant difference (p = .02). Two-year progression-free survival (PFS) of p16-positive and p16-negative patients undergoing chemoradiation therapy were 100% and 69%, respectively (p = .13). Conclusion: In this study conducted in Japan, p16-positive NPC patients are minor but not very low, and the proportion of keratinizing NPCs was small. p16-positive NPCs were seen both in keratinizing and nonkeratinizing NPCs. P16-positive NPC had a tendency of better PFS than p16-negative NPC. This better prognosis might be due to the higher radiosensitivity of the p16-positive cell. Additionally, p16-positive NPCs seemed to spread more extensively in circumference along the nasopharyngeal mucosa than p16-negative NPCs.

Evaluation of breast cosmetic changes with a computer-software; the breast cancer conservative treatment cosmetic results (BCCT. core) in hypofractionated whole breast irradiation after breast-conserving surgery-supplementary analysis of multicenter single-arm confirmatory trial: JCOG0906.

BACKGROUND: A good cosmetic outcome has been defined as an important endpoint in breast-conserving therapy (BCT). Various evaluation methods have been studied, but the optimal method has yet to be identified. The present supplementary analysis of JCOG0906 focused on comparing evaluation methods for breast cosmetic outcomes following hypofractionated whole breast irradiation (HFWBI) to examine whether a computer-software (the Breast Cancer Conservative Treatment cosmetic results [BCCT. core])-based program evaluation (CE) can be used for Asian women in clinical trials of BCT. METHODS: Of 306 women, 292 underwent institutional evaluation (IE) for breast cosmetic outcomes before (pre) and 3 years after (post) HFWBI using a 4-point scale (excellent/good/fair/poor), and they were evaluated by CE and a central panel evaluation (PE) on the same scale using 292 pairs of pre/post-HFWBI photographs. PE was performed twice by consensus of the same two experts with a 3-year interval. CE was assessed individually by two radiation oncologists, an expert and a non-expert. Intra-observer variability and inter-observer variability were calculated using the kappa (k) and weighted kappa (wk) statistics. RESULTS: The agreement between the first and second PE using pre/post-HFWBI photographs was moderate (k = 0.60, wk = 0.64. k = 0.53, wk = 0.60). The agreement between the expert and non-expert on CE was substantial (k = 0.72, wk = 0.76. k = 0.72, wk = 0.77). The inter-observer variability of CE was smaller than the intra-observer variability of PE. CONCLUSION: CE with BCCT. core was considered a reproducible and an appropriate evaluation method for Asian women in clinical trials of BCT, when breast cosmetic changes were compared between pre/post therapy.

Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer.

Purpose: Hyaluronate gel has been injected as a spacer into the rectovaginal fossa and vesicouterine fossa during brachytherapy for patients with cervical cancer at our institution. The effect of hyaluronate gel injection (HGI) on dose-volume parameters was investigated in this study. Methods and Materials: Between July 2008 to January 2020, a total of 104 patients (non-HGI group: 52 patients; HGI group: 52 patients) who underwent curative radiation therapy for cervical cancer were selected. The total doses of external beam radiation therapy and brachytherapy for high-risk clinical target volume (CTVHR) D90, bladder D2cc, and rectal D2cc were converted to the equivalent dose in 2 Gy fractions (EQD2) and were analyzed for association with HGI. Results: Median CTVHR D90 (EQD2) in the non-HGI group was 76.0 Gy (63.7-99.5 Gy), and in the HGI group it was 79.4 Gy (52.6-97.5 Gy) (P = .017). The median bladder D2cc and rectal D2cc (EQD2) were 62.9 Gy and 56.0 Gy in the non-HGI group and 63.7 Gy and 54.8 Gy in the HGI group, which had no significant difference. Conclusions: In cases with HGI, a significant CTVHR D90 dose increase was obtained with sufficient bladder and rectal doses suppression.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies.

PURPOSE: Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. METHODS AND MATERIALS: We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. RESULTS: The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). CONCLUSIONS: Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Non-Robustness of Ang's Risk Classification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma in Japanese Patients.

BACKGROUND: Validity of the risk classification by Ang for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains to be studied in the patients treated by modalities other than chemoradiotherapy and in Japanese patients. MATERIALS AND METHODS: Between 2010 and 2018, 122 patients with HPV-related OPSCC in stages III and IV by the TNM classification 7th edition (TNM-7) were treated curatively at a single institution in Japan. The median age was 62.7 years. Over 50% of the patients underwent surgery with or without adjuvant therapy. The influence of multiple factors on survival was analyzed. RESULTS: The amount of smoking dichotomized at 10 pack-year, which was used in Ang's risk classification, was not predictive of prognosis, and Ang's risk classification was not significantly influential on prognosis in multivariate analysis. In the patients treated with definitive radiation therapy, Ang's risk classification was not predictive of the prognosis in univariate analysis. The impact of smoking was significant only in the patients undergoing the definitive operation. CONCLUSIONS: Ang's risk classification was not robust in predicting the prognosis of general Japanese HPV-related OPSCC patients. The amount of smoking might have different prognostic influences depending on the therapeutic method.

Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients.

PURPOSE: This study reports the first-in-human use of a linear accelerator-based boron neutron capture therapy (BNCT) system and the first treatment of patients with scalp-angiosarcoma with accelerator-based BNCT. PATIENTS AND METHODS: A single-center open-label phase I clinical trial has been conducted using the system since November 2019. Patients with a localized node-negative scalp-angiosarcoma along with the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy were enrolled. After administration of boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose delivered to the skin being 12 Gy-Eq was performed. The safety and effectiveness of accelerator-based BNCT therapy for localized scalp angiosarcoma were evaluated. RESULTS: Scalp-angiosarcoma of the two patients did not develop the dose-limiting toxicity in the clinical trial. They reached CR within half a year and did not exhibit in-field failure 20 months after BNCT without any severe treatment-related adverse events. Although a grade 3 adverse event of an asymptomatic but increased serum amylase level was noted in both patients, it relieved without any treatment. Additionally, no severe acute dermatitis was observed for both patients, which is typically seen with conventional primary radiotherapy. CONCLUSIONS: It was suggested that BNCT would be a promising treatment modality for scalp-angiosarcoma, which is difficult to treat.

Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas.

Cutaneous angiosarcomas is a rare cancer with poor prognoses. The common radiotherapy techniques that have been reported so far are two pairs of lateral X-ray and electron fields. However, it is quite difficult to irradiate scalp angiosarcomas (SAs) homogeneously with this technique. In this study, safety, effectiveness, and risk factors were assessed for localized SAs ≥ 5 cm treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with boluses. Sixty-eight angiosarcoma patients who had received radiotherapy in our institution between January 2007 and November 2020 were retrieved from our radiotherapy database. Of these patients, 27 localized SA patients were included in the retrospective analysis. The 2-year overall survival, local progression-free rate, and distant metastases-free survival were 41.8%, 48.4%, and 33.1%. All the patients experienced acute radiation dermatitis ≥ grade 2, with18 (66.7%) ≥ grade 3. No nodule lesion was a significant unfavorable predictive factor of acute radiation dermatitis ≥ grade 3. Tumor bleeding at the initiation of radiotherapy and tumor invasion to the face were significant predictive factors of overall survival, and tumor bleeding at the initiation of radiotherapy was also a significant predictive factor of local progression-free rate.

Bevacizumab increases late toxicity in re-irradiation with image-guided high-dose-rate brachytherapy for gynecologic malignancies.

INTRODUCTION: Patients with recurrent gynecologic malignancies having had pelvic irradiation, generally have limited salvage options. This study investigated patients with gynecologic malignancies, who had a history of pelvic irradiation and received salvage re-irradiation using image-guided high-dose-rate brachytherapy (IG-HDR-BT). MATERIAL AND METHODS: Patients with gynecologic malignancies, who had a history of previous irradiation and received re-irradiation using IG-HDR-BT for disease recurrences from June 2014 to March 2020 were included in this study. RESULTS: A total of 37 patients were included in this retrospective analysis. Primary tumor was uterine cervical cancer in 31 patients, endometrial cancer in 5 patients, and vaginal cancer in 1 patient. Median follow-up period of patients who were alive at the time of analysis was 15.4 months (range, 4.1-61.4 months). Two-year overall survival, progression-free survival, and local control were 68.9%, 49.3%, and 67.5%, respectively. Severe late toxicities ≥ grade 3, which were related to re-irradiation, were observed in 9 patients (24.3%). Usage of bevacizumab in the entire course of treatment was associated with development of late ≥ grade 3 fistula formation, bowel perforation, or vaginal ulcer (50% vs. 6.9%, p = 0.013). Tumor size ≥ 2.5 cm was associated with development of late ≥ grade 3 of rectum, bladder, or vaginal toxicities (0% vs. 28%, p = 0.047). CONCLUSIONS: If the recurrent disease was found in small size and there was no history of bevacizumab usage, re-irradiation with IG-HDR-BT could be considered, even in patients with a previous history of pelvic irradiation.

Monte Carlo simulation of tilted contact plaque brachytherapy placement for juxtapapillary retinoblastoma.

BACKGROUND: The 106-Ruthenium contact plaque applicator is utilized for the treatment of intraocular tumor within a thickness of less than 6 mm. If anything obstructs the placement of the plaque applicator, the treatment is generally difficult because the applicator has to be temporarily located just on the opposite side of the retinal tumor. Furthermore, the plaque applicator edge of approximately 1 mm does not contain 106Ru, estimating the delivered radiation dose for eccentric tumor is challenging because the lateral dose profile is inadequately provided by the manufacture's certification. This study aims to simulate tumor coverage of the tilted applicator placement for treating an infant with juxtapapillary retinoblastoma and to achieve the effective treatment. CASE PRESENTATION: We present an infant with retinoblastoma whose tumor involved macular and was invading just temporal side of the optic disc. Additionally, posterior staphyloma was induced by a series of previous treatments, making it more difficult to treat the standard plaque placement. Thus, the applicator type of CCA was intentionally tilted to the eyeball and the distance between the posterior edge of the applicator and the eyeball had to be then equal to or more than 2 mm based on the dose distribution of the applicator calculated using Monte Carlo simulation to minimize damage to surrounding tissues while covering the tumor. It was then comparable to the certification and previous reports. Based on the acquired dose distribution, the optimal placement of the applicator was derived from varying the distance between the applicator's edge and the eyeball, and the distance was then determined to be 2 mm. In this case, the minimum dose rate in the tumor was 25.5 mGy/min, and the time required to deliver the prescribed dose was 26.2 h. Therefore, the tilted 106Ru plaque applicator placement could deliver the required dose for the treatment. The physical examination revealed no active tumor as a result of the treatment. CONCLUSIONS: Optimizing the placement of the 106Ru plaque applicator, it was possible to guarantee that the prescribed dose will be delivered to the tumor even if the standard placement is not possible for the juxtapapillary tumor.