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In this technical report, patient with total pharyngolaryngectomy and jejunum interposition experienced lymph node metastasis in the reconstructed mesenteric lymph nodes. Because this patient received 45 Gy of whole neck radiation therapy 24 years ago and small bowel's tolerance dose of the reconstructed jejunum was considered to be low, spacer gel injection was applied during image-guided interstitial brachytherapy to decrease doses to the reconstructed jejunum and previously irradiated carotid artery.

Background Contour delineation, a crucial process in radiation oncology, is time-consuming and inaccurate due to inter-observer variation has been a critical issue in this process. An atlas-based automatic segmentation was developed to improve the delineation efficiency and reduce inter-observer variation. Additionally, automated segmentation using artificial intelligence (AI) has recently become available. In this study, auto-segmentations by atlas- and AI-based models for Organs at Risk (OAR) in patients with prostate and head and neck cancer were performed and delineation accuracies were evaluated. Methods Twenty-one patients with prostate cancer and 30 patients with head and neck cancer were evaluated. MIM Maestro was used to apply the atlas-based segmentation. MIM Contour ProtégéAI was used to apply the AI-based segmentation. Three similarity indices, the Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean distance to agreement (MDA), were evaluated and compared with manual delineations. In addition, radiation oncologists visually evaluated the delineation accuracies. Results Among patients with prostate cancer, the AI-based model demonstrated higher accuracy than the atlas-based on DSC, HD, and MDA for the bladder and rectum. Upon visual evaluation, some errors were observed in the atlas-based delineations when the boundary between the small bowel or the seminal vesicle and the bladder was unclear. For patients with head and neck cancer, no significant differences were observed between the two models for almost all OARs, except small delineations such as the optic chiasm and optic nerve. The DSC tended to be lower when the HD and the MDA were smaller in small volume delineations. Conclusions In terms of efficiency, the processing time for head and neck cancers was much shorter than manual delineation. While quantitative evaluation with AI-based segmentation was significantly more accurate than atlas-based for prostate cancer, there was no significant difference for head and neck cancer. According to the results of visual evaluation, less necessity of manual correction in AI-based segmentation indicates that the segmentation efficiency of AI-based model is higher than that of atlas-based model. The effectiveness of the AI-based model can be expected to improve the segmentation efficiency and to significantly shorten the delineation time.

Background There is no standard treatment for patients with recurrent high-grade gliomas who progress after bevacizumab treatment. We evaluated the outcomes of re-irradiation combined with bevacizumab for patients refractory to bevacizumab. Methods Between January 2015 and September 2019, patients with progression after bevacizumab treatment were treated with re-irradiation combined with bevacizumab (25 Gy in five fractions). Results Fourteen patients [glioblastoma, isocitrate dehydrogenase (IDH) wild type (N = 6), glioblastoma, IDH mutant (N = 4), anaplastic astrocytoma, IDH wild type (N = 1), anaplastic astrocytoma, IDH mutant (N = 1), glioblastoma, not otherwise specified (N = 1) and radiologically diagnosed brainstem glioma (N = 1)] were included in this study. The median survival and progression-free survival times after re-irradiation combined with bevacizumab were 6.1 and 3.8 months, respectively. The 6-month survival and progression-free survival rates were 54.5 and 15.7%, respectively. Patients with a Karnofsky performance status of ≥70 tended to have longer median survival time (9.3 vs. 5.4 months, respectively; P = 0.058) and had a significantly longer median progression-free survival time (4.2 vs. 3.7 months, respectively; P = 0.046) than those with a Karnofsky performance status of Conclusions Re-irradiation combined with bevacizumab for patients with recurrent high-grade gliomas who progress after bevacizumab treatment was feasible. Re-irradiation combined with bevacizumab is a potential treatment option, especially for patients with a Karnofsky performance status of ≥70.

Purpose This study compared the applicator position relative to the tracheal wall and dosimetric parameters between conventional and novel applicators among patients receiving endobronchial brachytherapy (EBBT) for intratracheal tumors. Methods and Materials Data from 7 patients who received EBBT for intratracheal tumors were retrospectively analyzed; 4 and 3 patients were treated with conventional (2-wing) or novel (5-wing) applicators, respectively. Applicator centrality was evaluated using the distance between the center of the trachea and main bronchus (TMB) lumen and path of source (L). Dosimetric parameters, including plans normalized to D2cc of the TMB = 45 Gy (normalized plan), were compared between the applicators. Results The mean and maximum values of L in cases of the 2-wing applicator group were approximately 5.0 mm and 10.0 mm, respectively. In the novel applicator group, the corresponding values were approximately 3.0 and 6.0 mm, respectively. In the normalized plan of the 2-wing applicator group, the ranges of median V90% of clinical target volume (CTV) and D0.1cc of the TMB in all cases were 23.0–91.9% and 66.3–153.1 Gy, respectively. In the 5-wing applicator group, the corresponding values were 69.2–83.8% and 60.4–84.5 Gy, respectively. Conclusions In the 5-wing applicator group, the range was narrow in all dose–volume parameters except for D2cc of the TMB. Compared to the conventional applicator, the 5-wing applicator can give a stable dose to the CTV and can reduce the maximum dose of the TMB. This suggests that stable EBBT can be given to any patient using the 5-wing applicator.

Purpose In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder. Methods and materials 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm3 covering doses of the OARs for each treatment. Results A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial–caudal direction from the midpoint on the rectal side. There were correlations between 2-cm3 covering doses and the gel spacer parameters: the volume on the rectal (p = 0.02) and bladder (p = 0.04) sides; the craniocaudal length on the rectal side (p > 0.05). Conclusions A gel spacer volume of ∼10 cm3 provides sufficient OAR DR if its gravity point is on the midpoint between the cylinder applicator and OAR, and its craniocaudal length covers the active length of the cylinder applicator.

Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.

Purpose The validity of the risk classification according to Ang for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains to be studied in patients treated by methods other than chemoradiotherapy and in Japanese patients. In this study, the validity of Ang's risk classification was studied in Japanese patients treated using various methods, including surgery.Material and Method Between 2010 and 2018, 122 patients with HPV-related OPSCC stages III and IV according to the TNM classification 7th edition (TNM-7) were treated curatively at a single institution in Japan. The median age was 62.7 years. Sixty-seven patients (54.9%) were classified as stage I according to the TNM 8th edition (TNM-8). Over 50% of the patients underwent surgery with or without adjuvant therapy. The influence of multiple factors on survival was determined.Results Age, amount of smoking, secondary cancer, and N-stage according to the TNM-7 significantly influenced survival. Ang's risk classification was also predictive of prognosis, but if 30 pack-years (PYs) instead of 10 PYs is employed to dichotomize the amount of smoking, the new risk classification can significantly better predict prognosis. According to the new risk classification, favorable and unfavorable risk patients showed 5-year progression-free survival, disease-specific survival, and overall survival rates of 72.7% and 35.9%, 94.6% and 76.2%, and 92.6% and 62.7%, respectively.Conclusions Even in patients treated by methods other than chemoradiotherapy and in Japanese patients, the combination of the amount of smoking and neck node status is useful in prognosis prediction.

Our previous study by Murakami N, Mori T, Nakamura S, Yoshimoto S, Honma Y, Ueno T, Kobayashi K, Kashihara T, Takahashi K, Inaba K, Okuma K, Igaki H, Nakayama Y, Itami J. (J Radiat Res. 2019 Jul 30. pii: rrz053. doi: 10.1093/jrr/rrz053. [Epub ahead of print]) showed that strong expression of epithelial cell adhesion molecule (EpCAM) was associated with radiation resistance in head and neck squamous cell cancer patients (SCC). In this study, the prognostic impact of histopathologic features including EpCAM for nasopharyngeal cancer (NPC) patients was investigated. Since 2009, our institution has performed chemoradiation for locally advanced NPC patients with intensity modulated radiation therapy (IMRT). Tri-weekly adjuvant cisplatin (CDDP, 80 mg/m2) was administered concurrently with definitive radiation therapy 70 Gy in 35 fractions. One month after radiation therapy, adjuvant chemotherapy of three cycles of CDDP/5 fluorouracil (5-FU) was administered. Using a pretreatment biopsy specimen, EBV-encoded small RNA in situ hybridization (EBER-ISH), EpCAM, p16 and p53 were assessed by immunohistochemical analysis. Between May 2009 and September 2017, 51 NPC patients received definitive radiation therapy. Five, 13, 17 and 16 patients were staged as I, II, III and IV, respectively. The median follow-up period for alive patients was 31.1 months (12.4–109.7 months). Three-year overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were 87.1, 57.1 and 85.7%, respectively. EpCAM, p16 and p53 were not associated with PFS, OS nor LRC. Three-year PFS for patients with keratinizing and non-keratinizing SCC were 25 and 60.5%, respectively (P = 0.033, hazard ratio 4.851 (95% confidence interval 1.321–17.814)).Prognosis of NPC patients with keratinizing SCC was worse than non-keratinizing SCC patients, suggesting a biological difference between the two types of tumor.

With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach.

The purpose of this study was to predict the survival time of patients with malignant glioma after radiotherapy with high accuracy by considering additional clinical factors and optimize the prescription dose and treatment duration for individual patient by using a machine learning model. A total of 35 patients with malignant glioma were included in this study. The candidate features included 12 clinical features and 192 dose–volume histogram (DVH) features. The appropriate input features and parameters of the support vector machine (SVM) were selected using the genetic algorithm based on Akaike’s information criterion, i.e. clinical, DVH, and both clinical and DVH features. The prediction accuracy of the SVM models was evaluated through a leave-one-out cross-validation test with residual error, which was defined as the absolute difference between the actual and predicted survival times after radiotherapy. Moreover, the influences of various values of prescription dose and treatment duration on the predicted survival time were evaluated. The prediction accuracy was significantly improved with the combined use of clinical and DVH features compared with the separate use of both features (P

Purpose: The purpose of this study was to investigate the overlaps between gross target volume (GTV) and the celiac artery (CA) and superior mesenteric artery (SMA) lymph node regions and to examine the dose incidentally irradiated to the CA and SMA lymph node regions by involved-field radiation therapy (IFRT) for locally advanced pancreatic cancer (LAPC). Methods and Materials: Fifty-nine patients who had LAPC without distant metastasis were included. They received IFRT at 50.4 Gy in 28 fractions with 3-dimensional conformal radiation therapy. We calculated the percentages of overlap of GTV in the CA and SMA lymph node regions and examined what cases tend to have an overlap. We also investigated the dose metrics of CA and SMA lymph node regions by IFRT and the frequency of CA or SMA lymph node metastasis after IFRT. Results: The median GTV volume was 52.2 mL. Median overlap percentages in the CA and SMA lymph node regions were 39.2% and 28.6%, respectively. There was a significant correlation between GTV volume and SMA overlap percentage (P < .001). Although the SMA overlap percentage was higher in the pancreas head (P = .028), the CA overlap percentage was higher in the pancreas body or tail (P = .002). Median mean dose, D95, and minimum dose in the CA lymph node region were 50.1 Gy, 48.7 Gy, and 45.9 Gy, respectively, and those in the SMA lymph node region 49.9 Gy, 47.3 Gy, and 39.2 Gy, respectively. CA lymph node metastases after IFRT were detected in 4 patients (6.8%). Conclusions: An overlap between GTV and CA-SMA lymph node regions was detected in many patients, and the CA and SMA lymph node regions were irradiated incidentally even by IFRT. Prophylactic lymph node regions might not be necessary in radiation therapy planning of LAPC.

Treatment options for patients with recurrent rectal cancer in pelvis represent a significant challenge because the balance of efficiency and toxicity needs to be pursued. This case report illustrates a treatment effect of image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for locally relapsed rectal cancer after salvage surgery. A 61-year-old male who underwent laparoscopic high anterior resection (LAP-HAR) with D3 lymph node dissection as a primary treatment for rectal cancer (pT3N0M0, well-differentiated adenocarcinoma) had relapsed locally 8 months after initial surgery, for which he underwent salvage abdominal perineal resection (APR), followed by adjuvant 8 cycles of XELOX (capecitabine and oxaliplatin) chemotherapy. He developed pelvic recurrence 1 year after the second surgery. Image-guided HDR-ISBT was performed (30 Gy/5 fractions/3 days) followed by external beam radiation therapy with 39.6 Gy in 22 fractions. There were no severe complications related to salvage radiotherapy. CEA was decreased from 24.5 ng/ml to 0.7 ng/ml, 4 months after the salvage radiotherapy. Complete response was noted on follow-up MRIs done on 2, 5, 8, and 14 months after the treatment. Hence, HDR-ISBT appears to be effective for locally recurrent rectal cancer even after salvage surgery.

A reliable biomarker can contribute to appropriate treatment selection in the management of head and neck squamous cell carcinoma (HNSCC). Recently, epithelial cell adhesion molecule (EpCAM) was shown to have prognostic features in several malignancies. However, it remains to be elucidated whether EpCAM predicts prognosis of HNSCC after radiotherapy. Therefore, the prognostic potential of EpCAM in HNSCC patients treated by radiotherapy was investigated in this study. All HNSCCs patients examined between January 2013 and December 2015 were analyzed for the expression of EpCAM. One hundred HNSCC patients were identified who were treated by primary radiotherapy. Intense expression of EpCAM was found in 29 HNSCC patients. Two-year overall survival (OS) for patients with intense EpCAM expression was 62.2%, whereas it was 87.9% for those without (P = 0.011). In multivariate analysis, intense EpCAM expression was found to be an independent prognostic factors for OS (P = 0.036). Overall, EpCAM was found to be an independent prognostic factor for HNSCC.

Background For brain metastases from non-specific primary tumors, the most frequently used and validated clinical prognostic assessment tool is Karnofsky performance status (KPS). Given the lack of prognostic factors of brain metastases from colorectal cancer (CRC) other than KPS, this study aimed to identify new prognostic factors. Methods This retrospective cohort study was conducted at a tertiary care cancer center. Subjects were patients with brain metastases from CRC among all patients who received initial treatment for CRC at the National Cancer Center Hospital from 1997 to 2015 (n = 7147). Prognostic clinicopathological variables for overall survival (OS) were investigated. Results There were 68 consecutive patients with brain metastases from CRC, corresponding to 1.0% of all patients with CRC during the study period. Median survival time was 6.8 months. One-year and 3-year OS rates were 28.0 and 10.1%, respectively. Among the six covariates tested (age, KPS, presence of extracranial metastases, control of primary lesion, number of brain metastases, and history of chemotherapy), multivariate analysis revealed KPS (score ≥ 70), number of brain metastases (1–3), and no history of chemotherapy to be independent factors associated with better prognosis. Conclusions In addition to KPS, the number of brain lesions and history of chemotherapy were independent prognostic factors for OS in patients with brain metastases from CRC. An awareness of these factors may help gastrointestinal surgeons make appropriate choices in the treatment of these patients.

Background The purpose of this study was to assess compliance with treatment planning in a dummy-run for a multicenter clinical trial involving patients with high-risk postoperative uterine cervical cancer using intensity-modulated radiation therapy (IMRT) (JCOG1402 trial). Methods For the dummy-run, we prepared a computed tomography dataset comprising two anonymized cases of post-hysterectomy cervical cancer. These were sent to the 47 participating institutions to assess institutional plan quality such as delineations and dose distributions. Results Central review showed 3 and 4 deviations per treatment plan on average. The deviations related to the nodal and vaginal cuff clinical target volume (CTV) delineation, which accounted for approximately 50% of the total deviations. The CTV vaginal cuff showed considerable differences in delineation compared with the nodal CTV. For the Dice similarity coefficient, case 1 showed a mean ± 1σ of 0.81 ± 0.03 and 0.60 ± 0.09 for the nodal and the CTV vaginal cuff, respectively, while these were 0.81 ± 0.04 and 0.54 ± 0.14, respectively, for case two. Of the 47 institutions, 10 were required to resubmit their treatment plan because the delineations, planning target volume margin, and required dose distributions were not in accordance with the JCOG1402 protocol. Conclusions The dummy-run test in postoperative uterine cervical cancer demonstrated substantial deviations in the delineations, particularly for the CTV vaginal cuff. The analysis data could provide helpful information on delineation and planning, allowing standardization of IMRT planning for postoperative uterine cervical cancer. Trial registration Japanese Clinical Trial Registry #: UMIN000027017 at https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000030672;language=J Electronic supplementary material The online version of this article (10.1186/s13014-019-1340-y) contains supplementary material, which is available to authorized users.

The current study retrospectively analyzed the results of radiotherapy for clinically localized sebaceous carcinoma of the eyelid.We reviewed records of 83 patients with histologically confirmed sebaceous carcinoma who were treated radiotherapeutically between 1983 and 2015. Sixty-five patients (78%) were initially treated with radiotherapy of curative intent, while the remaining 18 patients underwent postoperative radiotherapy due to tumor recurrence or positive surgical margins. Thirty-seven patients belonged to T1–2, while 46 belonged to T3–4. All 83 patients were treated with radiotherapy with a median radiation dose of 60 Gy. The median follow-up period was 92.1 months (range, 2.8–310.3 months). At the time of analysis, 13 patients (15.1%) died, and 36 patients (43.3%) had local recurrence. The 7-year overall survival, freedom from neck lymph node recurrence, and local control (LC) rates for all patients were 83.5%, 75.5%, and 52.3%, respectively. Patients with a tumor size ≤10 mm had a higher 7-year LC rate than those with a tumor size >10 mm (58.8% vs 46.6%, P = 0.054). Neck lymph node recurrence was observed in 17 patients (20%) and significantly related to the tumor size. Late toxicity of an eyelid dysfunction of grade 3 was observed in 1 patient with T3 tumor. Radiotherapy for sebaceous carcinoma of the eyelid is a reasonable alternative to surgical resection for tumors

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose–volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18–1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours.

Objective: To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy (ADT) in high-risk prostate cancer in three radiotherapy dose groups. Methods: Between 1998 and 2013, patients with high-risk prostate cancer underwent three-dimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy, 72 Gy, or 78 Gy with ADT. Prostate-specific antigen (PSA) relapse was defined using the Phoenix definition. PSA relapse-free survival (PRFS) was evaluated in each radiotherapy dose group. Moreover, high-risk patients were divided into H-1 (patients with multiple high-risk factors) and H-2 (patients with a single high-risk factor) as risk subgroups. Results: Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study. The median duration of ADT was 10.1 months. Age, Gleason score, T stage, and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses. The 4-year PRFS rates in Group-66 Gy, Group-72 Gy and Group-78 Gy were 72.7%, 81.6% and 90.3%, respectively. PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS, while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose. Conclusion: Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS. PRFS for patients in the H-1 subgroup was poor, but dose escalation in those patients was beneficial, while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS. Keywords: Prostate cancer, External beam radiotherapy, Dose escalation, Biochemical control

BACKGROUND Sinonasal undifferentiated carcinoma (SNUC) is a rare aggressive tumor that is often unresectable. Optimal treatment for patients with unresectable, locally advanced SNUC (LA-SNUC) has not been established, and the patient outcome remains poor. We report two cases of unresectable LA-SNUC in which induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy with concurrent cisplatin (CCRT), a standard treatment option for locally advanced head and neck cancer, demonstrated promising outcomes. CASE SUMMARY A 39-year-old man presented with tearing and pain in the right eye. A biopsy of the tumor invading the sinonasal cavities, right orbit and cranial base confirmed the diagnosis of LA-SNUC. Induction TPF chemotherapy induced remarkable tumor shrinkage and rapidly improved the symptoms. He subsequently received CCRT and achieved complete remission of the disease. The other case is a 21-year-old man who presented with worsening vision. The unresectable tumor involving the nasal septum and cranial base was pathologically diagnosed as SNUC. TPF chemotherapy followed by CCRT yielded complete remission of the disease with preserved visual function. Both patients have been disease-free for 44 mo. CONCLUSION Induction TPF chemotherapy followed by CCRT may remarkably improve the outcomes in LA-SNUC patients.

[Purpose] The validity of the risk classification according to Ang for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains to be studied in patients treated by methods other than chemoradiotherapy and in Japanese patients. In this study, the validity of Ang's risk classification was studied in Japanese patients treated using various methods, including surgery. [Material and Method] Between 2010 and 2018, 122 patients with HPV-related OPSCC stages III and IV according to the TNM classification 7th edition (TNM-7) were treated curatively at a single institution in Japan. The median age was 62.7 years. Sixty-seven patients (54.9%) were classified as stage I according to the TNM 8th edition (TNM-8). Over 50% of the patients underwent surgery with or without adjuvant therapy. The influence of multiple factors on survival was determined. [Results] Age, amount of smoking, secondary cancer, and N-stage according to the TNM-7 significantly influenced survival. Ang's risk classification was also predictive of prognosis, but if 30 pack-years (PYs) instead of 10 PYs is employed to dichotomize the amount of smoking, the new risk classification can significantly better predict prognosis. According to the new risk classification, favorable and unfavorable risk patients showed 5-year progression-free survival, disease-specific survival, and overall survival rates of 72.7% and 35.9%, 94.6% and 76.2%, and 92.6% and 62.7%, respectively. [Conclusions] Even in patients treated by methods other than chemoradiotherapy and in Japanese patients, the combination of the amount of smoking and neck node status is useful in prognosis prediction.

Purpose To increase the superficial dose and reduce the brain dose for radiotherapy of scalp angiosarcoma, we propose a novel irradiation technique of tangential irradiation volumetric modulated arc therapy (TI-VMAT). Methods TI-VMAT and the conventional VMAT treatment plans for thirteen scalp angiosarcoma patients were created with a prescribed dose of 70 Gy. Each treatment was normalized to cover 95% of the planning target volume (PTV) with its prescribed dose. To realize TI-VMAT, an avoidance structure (AS) function was applied. AS was defined as a contour subtracted PTV by a certain space from the brain contour. TI-VMAT treatment plans for six different spaces between PTV and AS were developed and compared with the conventional VMAT treatment plan with respect to the following dosimetric parameters: homogeneity index (HI) and conformity index (CI) of the PTV, mean brain dose, and brain volume irradiated with 20% (V20% [cc]), 40% (V40% [cc]), 60% (V60% [cc]), 80% (V80% [cc]), and 100% (V100% [cc]) of the prescribed dose. Results HI and CI were comparable between TI-VMAT and the conventional VMAT, the mean brain dose for TI-VMAT with AS defined by a space of 2.0 cm and jaw tracking was 14.27 Gy, which was significantly lower than that for the conventional VMAT (21.20 Gy). In addition, dosimetric parameters such as V20% [cc] were significantly suppressed compared to those for high doses. Conclusion Our proposed irradiation technique TI-VMAT shows the potential to reduce radiation doses in the brain with maintaining higher dose coverage on the PTV.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes dendritic cell differentiation from precursors, and consequently, enhances the antigen presentation process and adaptive immune responses. With such functions, GM-CSF has been used as immunotherapy in combination with radiotherapy for cancer treatment to augment the survival and activity of immune cells. However, an immune-suppressive tumor microenvironment may cause anergy of T cells. It has also been reported that GM-CSF contributes to the development of myeloid-derived suppressor cells from the precursors. In this study, to analyze the combined effect of GM-CSF and released factors from cancer cells after gamma-ray irradiation on bone marrow cell differentiation and dynamics, we established an in vitro culture system using mouse bone marrow cells, GM-CSF, and conditioned medium from gamma ray irradiated mouse melanoma B16 cells at 24 Gy. We analyzed the gene expression changes of the bone marrow-derived cells on day 6. The results showed that GM-CSF dose-dependently enhanced the differentiation of macrophages from bone marrow cells, their antigen-presenting function and polarization to type I. The results implied the induced macrophages from the bone marrow may potentially contribute to tumor immune responses in a systemic manner when GM-CSF is boosted during photon-beam radiation therapy.

Objective The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. Methods From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) Results Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50–60 Gy, 60–70 Gy, 70–80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. Conclusions The low-risk patients achieved favorable local control with CTVHR D90

Mycosis fungoides (MF) is a common, low-grade non-Hodgkin’s lymphoma of skin-homing T lymphocytes that can be treated via skin-directed radiotherapy. Our institution has implemented total skin electron therapy (TSET) with a 4.3 m source-to-surface distance (SSD) and 6 MeV electron beams with a beam spoiler. A 35-year-old male undergoing TSET desired to avoid radiotherapy-induced hair loss and temporary infertility; therefore, leakage dose to scalp and testicles was reduced with a special radiation shield composed of stacked lead sheets. The shields for the scalp and scrotal were of 3 mm and 6 mm, respectively. To assess leakage doses, a radiophotoluminescence glass dosimeter (RPLD) was placed at every fraction. The difference dose between the measured and prescribed dose at the calibration point was 2%. The top of the head and scrotal surface exhibited 18 cGy and 10 cGy, respectively. Thus, the dose to the scrotal surface was not beyond the testicular tolerance dose of 20 cGy. Results of semen analysis two months postradiotherapy were normal. There was no hair loss during or after radiation therapy. Therefore, the RPLD is a useful in vivo dosimeter that provides technical information on radiation shielding to allow for completion of TSET without hair loss or temporary infertility.

Background and PurposeMost locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop “in-field.” Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients.Materials and MethodsWe analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups.ResultsIn the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS.ConclusionOur initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT.

Background: This study evaluated the outcomes of reirradiation combined with bevacizumab (Bev) for patients with recurrent high-grade gliomas that progressed after treatment with Bev.Methods: Between January 2015 and September 2019, 14 patients who experienced progression after Bev treatment were treated with reirradiation consisting of 25 Gy in five fractions combined with Bev (ReRT/Bev). The isocitrate dehydrogenase (IDH) 1/2 mutation status was analysed by pyrosequencing. Results: The diagnoses of 14 patients at the time of reirradiation included six cases of glioblastoma (GBM) with IDH-wildtype, four cases of GBM with IDH-mutant, one case of anaplastic astrocytoma (AA) with IDH-wildtype, one case of AA with IDH-mutant, and one case of GBM not otherwise specified (NOS), and one case of radiologically diagnosed brainstem glioma. The median overall survival (OS) and progression-free survival (PFS) times with ReRT/Bev were 6.1 months and 3.8 months, respectively. The 6-month OS and PFS rates were 54.5% and 15.7%, respectively. The median OS and PFS did not differ significantly between patients with IDH-wildtype (N=7) and IDH-mutant (N=5) (OS: 7.3 [wildtype] vs 6.0 [mutant] months, p = 0.64; PFS: 3.8 [wildtype] vs 3.7 [mutant] months, p = 0.56). The median OS and PFS did not differ significantly between patients with a diagnosis of GBM (N=6) and those with a diagnosis of non-GBM (N=7) (OS: 9.3 [GBM] vs 6.0 [non-GBM] months, p = 0.19; PFS: 4.0 [GBM] vs 3.8 [non-GBM] months, p = 0.31). Four patients (28.6%) achieved a complete or partial radiological response and three patients (21.4%) experienced improvement after ReRT/Bev. Tumor recurrences were observed in 12 patients, including 3 (21.4%) in-field recurrence; 5 (35.7%) marginal recurrence, 3 (21.4%) out-field recurrence, and 1 (7.1%) had in-field and out-field recurrence. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%), and gastrointestinal haemorrhage in one (7.1%) with ReRT/Bev. Conclusions: ReRT/Bev for patients with high-grade glioma who experienced progression after Bev was effective and involved acceptable toxicities.

Purpose Adjuvant durvalumab has become a standard treatment after chemoradiation therapy for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Accordingly, predicting radiation pneumonitis (RP) requiring steroidal treatment (steroid-RP) is of utmost importance because steroidal administration is reported to weaken the effectiveness of immunotherapy. However, grade 2 RP was used as an index of RP in previous studies, but it is an ambiguous definition because it includes not only steroid-RP but also a mild cough requiring only a cough medicine. Therefore, in this study, steroid-RP was used for evaluating RP, and the purpose of this study was to investigate predictive factors of steroid-RP, including original simple interstitial lung abnormality scores (ILASs). Methods and Materials A total of 145 patients with LA-NSCLC who received definitive radiation therapy (DRT) in our institution from January 2014 to May 2017 were identified. Original ILASs, performance status, age, respiratory function, Brinkman index, concurrent administration of chemotherapy, and dose–volume histogram metrics of the lung were analyzed to evaluate their association with steroid-RP. Additionally, 3 diagnostic radiologists evaluated the patients’ pre-DRT chest computed tomography images and determined the simple ILASs. ILASs were rated as follows: 0: none; 1: abnormality without honeycombing (ground-glass attenuation, fine reticular opacity, and microcysts); and 2: honeycombing. Results The median follow-up period was 729 days. Thirty-one patients (21.4%) experienced steroid-RP. In the univariate analysis, lung V5/V10/VS5, Brinkman index, and ILASs were significant predictive factors of steroid-RP. Additionally, multivariate analysis including Brinkman index ≥840, lung V5 ≥37%, and an ILAS ≥1 revealed that only an ILAS (P = .001) was an independent predictive factor of steroid-RP. Conclusions The original simple ILAS was an easy-to-use tool and a significant predictive factor of steroid-RP in DRT in patients with LA-NSCLC.

Background In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation. Case presentation We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation. Conclusions Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

Background/aim We established a data-driven method for extracting spatial patterns of dose distribution associated with radiation injuries, based on patients with prostate cancer who underwent iodine-125 (I-125) seed implantation. Patients and methods Seventy-five patients underwent I-125 seed implantation for prostate cancer. We modeled the severity of lower urinary tract symptoms (LUTS) to be estimated using a linear model, which is formulated as an inner product between the dose distribution D and voxel-wise radiosensitivity B inside the prostate. For the estimation, tensor regression based on a low-rank decomposition with generalized fused lasso penalty was applied. Results The spatial distribution of B was visually assessed. Positive parameters appeared dominantly in the region close to the urethra and the prostate base. Conclusion Our tensor regression-based model can predict intra-organ radiosensitivity in a data-driven manner, providing a compelling parameter distribution associated with the development of LUTS after I-125 seed implantation for prostate cancer.

[Purpose] Tobacco smoking has been reported to influence the prognosis of human papilloma virus (HPV)-related orophageyngeal squamous cell carcinoma (OPSCC). However, it remains to be studied whether tobacco smoking equally affects the patients treated by various modalities. [Material and Method] From 2010 through 2018, 241 patients with OPSCC were treated in a single institution, out of which 144 patients had HPV-related OPSCC. P16 immunohistochemical staining was used as a surrogate of HPV infection. Two patients was excluded because of inadequate radiation dose, and the remaining 142 patients were the subject of this study. Median age was 63.8 years and more than 80% were male. More than 70% were smokers or ex-smokers with a median pack year of 17.3. Eighty-seven patients (61.3%) were classified as stage I.[Results] For all 142 patients with HPV-related OPSCC, overall survival (OS) and disease-specific survival (DSS) were 87.0% and 93.4% in 3 years, respectively. There were no differences of OS and DSS according to the stages by 8th edition of tumor, node, and metastasis (TNM) classification and the primary sites. OS and DSS were different by the amount of tobacco smoking expressed in pack year (PY) > 30 and < 30. Also the presence of secondary cancer impacted OS. However, the influence of the amount of tobacco smoking was reduced in the patients treated by radiation therapy. [Conclusions] The impact of tobacco smoking upon the prognosis of HPV-related OPSCC seems to be dependent upon therapeutic modalities.