Publications by authors named "Naoya Murakami"

125 Publications

Why not de-intensification for uterine cervical cancer?

Gynecol Oncol 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

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) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTV D were compared.

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 CTV D 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 D and incidence of late adverse events decreased as CTV D decreased.

Conclusions: The low-risk patients achieved favorable local control with CTV D <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.021DOI Listing
July 2021

Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy.

Sci Rep 2021 May 19;11(1):10567. Epub 2021 May 19.

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3-153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.
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http://dx.doi.org/10.1038/s41598-021-90139-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134569PMC
May 2021

Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases ≥ 2 cm in Patients With Head and Neck Squamous Cell Carcinoma.

Front Oncol 2021 27;11:651409. Epub 2021 Apr 27.

Department of Radiation Therapy in National Cancer Center Hospital, Tokyo, Japan.

Background And Purpose: Most 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 Methods: We 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.

Results: In 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.

Conclusion: Our 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.
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http://dx.doi.org/10.3389/fonc.2021.651409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112241PMC
April 2021

Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target.

Sci Rep 2021 Apr 13;11(1):8090. Epub 2021 Apr 13.

Division of Research and Development for Boron Neutron Capture Therapy, National Cancer Center Exploratory Oncology Research & Clinical Trial Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.

An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient neutron flux for treatment although the neutron flux is reduced over the lifetime of its target. In this study, the reduction was examined in the five targets, and a model was then established to represent the neutron flux. In each target, a reduction in neutron flux was observed based on the integrated proton charge on the target, and its reduction reached 28% after the integrated proton charge of 2.52 × 10 mC was delivered to the target in the system. The calculated neutron flux acquired by the model was compared to the measured neutron flux based on an integrated proton charge, and the mean discrepancies were less than 0.1% in all the targets investigated. These discrepancies were comparable among the five targets examined. Thus, the reduction of the neutron flux can be represented by the model. Additionally, by adequately revising the model, it may be applicable to other BNCT systems employing a Li target, thus furthering research in this direction. Therefore, the established model will play an important role in the accelerator-based BNCT system with a solid-state Li target in controlling neutron delivery and understanding the neutron output characteristics.
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http://dx.doi.org/10.1038/s41598-021-87627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044165PMC
April 2021

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer.

J Radiat Res 2021 May;62(3):511-516

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.
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http://dx.doi.org/10.1093/jrr/rraa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127693PMC
May 2021

Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix.

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, and 14 adenosquamous carcinoma) were enrolled. Somatic hotspot mutations in 50 cancer-related genes were detected using the Ion AmpliSeq Cancer Hotspot Panel v2. Human papillomavirus (HPV)-positivity was examined by polymerase chain reaction (PCR)-based testing and in situ hybridization assays. Programmed cell death-ligand 1 (PD-L1) expression was examined using immunohistochemistry. Somatic mutation data for 320 cases of cervical cancer from the Project GENIE database were also analyzed. NECC showed similar (, 32%; , 24%) and distinct (, 20%; , 16%; , 12%; , 12%) alterations compared with other histological types. The GENIE cohort had similar profiles and mutations in 27.6% of NECC cases. Eleven (44%) cases had at least one actionable mutation linked to molecular targeted therapies and 14 (56%) cases showed more than one combined positive score for PD-L1 expression. HPV-positivity was observed in all NECC cases with a predominance of HPV-18. We report specific gene mutation profiles for NECC, which can provide a basis for the development of novel therapeutic strategies.
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http://dx.doi.org/10.3390/cancers13061215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001835PMC
March 2021

Usefulness of Simple Original Interstitial Lung Abnormality Scores for Predicting Radiation Pneumonitis Requiring Steroidal Treatment After Definitive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100606. Epub 2020 Oct 31.

Department of Radiotherapy in National Cancer Center Hospital, Tokyo, Japan.

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 ( = .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.
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http://dx.doi.org/10.1016/j.adro.2020.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897760PMC
October 2020

High-dose-rate interstitial brachytherapy with hypoxic radiosensitizer KORTUC II for unresectable pelvic sidewall recurrence of uterine cervical cancer: a case report.

J Contemp Brachytherapy 2020 Dec 16;12(6):606-611. Epub 2020 Dec 16.

Department of Radiation Oncology, Osaka Medical College, Japan.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D, D, and D of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.
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http://dx.doi.org/10.5114/jcb.2020.101695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787211PMC
December 2020

Tensor Regression-based Model to Investigate Heterogeneous Spatial Radiosensitivity After I-125 Seed Implantation for Prostate Cancer.

In Vivo 2021 Jan-Feb;35(1):489-497

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

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 and voxel-wise radiosensitivity 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 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.
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http://dx.doi.org/10.21873/invivo.12283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880750PMC
June 2021

Prognostic Value of Epithelial Cell Adhesion Molecules in T1-2N0M0 Glottic Cancer.

Laryngoscope 2021 07 28;131(7):1522-1527. Epub 2020 Dec 28.

Division of Radiation Oncology, Department of Radiology, Showa University School of Medicine, Tokyo, Japan.

Objective: This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated.

Methods: Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16.

Results: A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07).

Conclusions: From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM.

Level Of Evidence: 3 Laryngoscope, 131:1522-1527, 2021.
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http://dx.doi.org/10.1002/lary.29348DOI Listing
July 2021

A dosimetric and centeredness comparison of the conventional and novel endobronchial applicators: A preliminary study.

Brachytherapy 2021 Mar-Apr;20(2):467-477. Epub 2021 Jan 19.

Department of Radiation Oncology, National Cancer Center Hospital, Chuo City, Tokyo, Japan.

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 D 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 V of clinical target volume (CTV) and D 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 D 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.
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http://dx.doi.org/10.1016/j.brachy.2020.11.005DOI Listing
January 2021

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BMC Urol 2020 Dec 14;20(1):196. Epub 2020 Dec 14.

Department of Radiation Therapy, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan.

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.
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http://dx.doi.org/10.1186/s12894-020-00767-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737272PMC
December 2020

Image-guided interstitial brachytherapy boost for keratinizing squamous cell carcinoma of inferior wall of the nasopharynx.

BJR Case Rep 2020 Dec 21;6(4):20200005. Epub 2020 Aug 21.

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.

High-dose-rate interstitial brachytherapy (HDR-ISBT) is relatively rarely applied for the head and neck cancer because of its anatomical complexity and difficulty of applicator placement. However, its dose distribution is more confined even better than intensity-modulated radiation therapy (IMRT) and can deliver a higher dose while sparing surrounding normal tissues. In this case report, the effectiveness of HDR-ISBT as a boost following IMRT for keratinizing squamous cell carcinoma of nasopharynx was presented. A 76-year-old female who suffered from cT3N0M0 keratinizing squamous cell carcinoma of the nasopharynx was treated with definitive concurrent chemoradiation therapy involving IMRT. However, physical examination and laryngoscope fibre finding showed evident residual tumour at 60 Gy of IMRT, then, boost HDR-ISBT was proposed. After delivering 66 Gy of IMRT, CT image-guided HDR-ISBT 4 Gy in a single fraction was performed under local anaesthesia and sedation. MRI taken 5 months after HDR-ISBT showed remarkable shrinkage of the primary tumour. After HDR-ISBT, the remaining session of IMRT was delivered from the next day until 70 Gy in 35 fractions. It was demonstrated that boost HDR-ISBT combined with IMRT for keratinizing squamous cell carcinoma of the nasopharynx was performed safely and showed favourable efficacy.
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http://dx.doi.org/10.1259/bjrcr.20200005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709071PMC
December 2020

Transvaginal artificial ascites infusion as a spacer in gynecological brachytherapy: a novel technique.

J Contemp Brachytherapy 2020 Oct 30;12(5):487-491. Epub 2020 Oct 30.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

This is a first paper to report on artificial ascites infusion via vaginal wall for pelvic interstitial brachytherapy. Artificial ascites is commonly used for treating liver tumors, with radiofrequency ablation and percutaneous artificial ascites infusion through the abdominal wall for pelvic brachytherapy has been previously reported by our group. However, the trans-abdominal needle approach under ultrasound guidance is unreliable due to poor visualization resulting in fluid injection into the abdominal wall or mesenterium and the rate of successful artificial ascites infusion was low. Target tumor of the vaginal cuff brachytherapy is usually adjacent to the intestine, and transvaginal artificial ascites infusion under trans-rectal ultrasonography is considered as a rational and simpler method to create a space between target volume and organs at risk, such as intestines or sigmoid colon, by increased visualization of the needle compared to trans-abdominal approach. Here, we report a practical experience of transvaginal artificial ascites infusion.
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http://dx.doi.org/10.5114/jcb.2020.100382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701932PMC
October 2020

Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.

Oral Oncol 2021 02 26;113:105091. Epub 2020 Nov 26.

Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. Electronic address:

Objectives: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC).

Materials And Methods: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis.

Results: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023).

Conclusion: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105091DOI Listing
February 2021

In situ photoacoustic analysis of near-infrared absorption of rhodium-doped strontium titanate photocatalyst powder.

Chem Commun (Camb) 2020 Nov 29;56(91):14255-14258. Epub 2020 Oct 29.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Kitakyushu 808-0196, Japan.

Near-infrared absorption of strontium titanate (SrTiO) doped with rhodium (Rh) was investigated by photoacoustic (PA) Fourier transform infrared spectroscopy. In the absence of an electron acceptor and the presence of a hole scavenger, the largest absorption change in the Rh valence state from tetravalent to trivalent was observed in Rh-doped SrTiO prepared at 1473 K, which showed the highest activity for hydrogen evolution. PA measurements revealed the effective redox cycle mechanism between tetravalent and trivalent Rh ions in Rh-doped SrTiO.
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http://dx.doi.org/10.1039/d0cc06414aDOI Listing
November 2020

Simultaneous Measurements of Photoabsorption and Photoelectrochemical Performance for Thickness Optimization of a Semiconductor Photoelectrode.

ACS Comb Sci 2020 12 22;22(12):791-795. Epub 2020 Oct 22.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Kitakyushu 808-0196, Japan.

We established a system for simultaneous measurements of photoelectrochemical (PEC) reaction and photoabsorption in a semiconductor photoelectrode. This system uses a photoacoustic technique and photoelectrodes with a film-thickness gradient that was prepared by electrophoretic deposition of tungsten(VI) oxide particles while pulling up a substrate. The system enabled high-throughput determination of optimum film thickness, and the results showed that irradiation direction has a significant influence on PEC performance for a photoelectrode with a thick film. Furthermore, the mechanism of enhancement of PEC performance by postnecking treatment was discussed.
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http://dx.doi.org/10.1021/acscombsci.0c00113DOI Listing
December 2020

Configuration analysis of the injection position and shape of the gel spacer in gynecologic brachytherapy.

Brachytherapy 2021 Jan-Feb;20(1):95-103. Epub 2020 Oct 1.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

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-cm 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-cm 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); and ventrodorsad thickness on each OAR (p << 0.05) sides. There was no significant difference in the DR between a volume of ∼10 cm and that of a higher volume (p >> 0.05).

Conclusions: A gel spacer volume of ∼10 cm 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.
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http://dx.doi.org/10.1016/j.brachy.2020.08.021DOI Listing
October 2020

Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

Invest New Drugs 2021 Apr 17;39(2):564-570. Epub 2020 Sep 17.

Department of Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.
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http://dx.doi.org/10.1007/s10637-020-00999-yDOI Listing
April 2021

Clinical outcomes of definitive whole pelvic radiotherapy for clinical lymph node metastatic prostate cancer.

Cancer Med 2020 09 4;9(18):6629-6637. Epub 2020 Aug 4.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background: In this study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node-positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph nodes (LN).

Methods: We retrospectively analyzed the data from cN1 patients who were treated with definitive RT and androgen deprivation therapy (ADT) between June 2004 and February 2016. All patients received localized irradiation to the prostate region and whole pelvis irradiation. Some patients received intensity-modulated radiation therapy with RT dose escalation to metastatic LN. Univariate analyses using log-rank test were performed to find prognostic factors between patient subgroups.

Results: Fifty-one consecutive patients were identified. The median follow-up period for all patients was 88 (range 20-157) months. Primary Gleason pattern and LN RT dose were statistically significant prognostic factors for relapse-free survival (RFS) and distant metastasis-free survival (DMFS). Especially, RT dose escalation (60 Gy or more) to metastatic LN significantly improved RFS and DMFS compared with standard dose RT (4-year RFS 90.6% vs 82.1%, 7-year RFS 90.6% vs 58.0%, P = .015; 4-year DMFS 90.6% vs 82.1%, 7-year DMFS 90.6% vs 62.8%, P = .023). The following factors were all statistically significant for biochemical relapse-free survival (BRFS): T stage, LN RT dose, local RT dose, and ADT duration period. Any significantly different toxicity was not seen for each LN or local RT dose except for the incident rate of grade 2 or more acute urinary retention, which was significantly higher in the higher LN RT dose (60 Gy or more) group by the Chi-square test.

Conclusions: RT dose escalation to metastatic LN in cN1 patients improves BRFS, RFS, and DMFS at 4 and 7 years, without increasing severe adverse events.
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http://dx.doi.org/10.1002/cam4.2985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520291PMC
September 2020

Image-guided interstitial brachytherapy boost for nasopharyngeal carcinoma: technical aspects.

J Contemp Brachytherapy 2020 Jun 30;12(3):294-302. Epub 2020 Jun 30.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Nasopharyngeal cancer generally responds well to concurrent chemoradiotherapy (CCRT). However, there is a small group of patients who respond poorly to CCRT, and experience local residual tumor or local relapse. Although several attempts have been performed to such a group of patients including re-irradiation with external beam radiation therapy (EBRT) or salvage surgery, clinical results remain unsatisfactory. Intracavitary brachytherapy (ICBT) boost after CCRT with EBRT has been explored, however, its efficacy is limited to those with superficial residual tumors. For those residual tumors thickness with more than 5 mm, interstitial brachytherapy (ISBT) boost would be an appropriate modality of choice. Here, we describe technical aspects of the high-dose-rate interstitial brachytherapy (HDR-ISBT) boost for nasopharyngeal cancer (NPC) patients who responded poorly to the CCRT with EBRT.
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http://dx.doi.org/10.5114/jcb.2020.96874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366018PMC
June 2020

A case report of a patient with bulky uterine cervical neoplasm who achieved complete response with "intentional internal high-dose policy" high-dose-rate interstitial brachytherapy.

Medicine (Baltimore) 2020 Jul;99(27):e20860

Department of Radiation Therapy, National Cancer Center Hospital, Tokyo.

Rationale: Gynecological high-dose-rate (HDR) brachytherapy has progressed for years, but it remains difficult for bulky tumors to be controlled locally. Dose limitations to organs at risk (OARs) are invariably obstacles in increasing the prescription dose. Additionally, it is controversial that the excessive hyperdose sleeve, the volume receiving a dose equal to or greater than twice the reference dose, should be eliminated in gynecological HDR brachytherapy. On the other hand, the technique of simultaneous integrated protection was reported for large hepatocellular carcinoma treatment, and similarly, internal high-dose brachytherapy could be used for treating bulky cervical carcinoma.

Patient Concerns: A 54-year-old female had irregular genital bleeding and lost 13 kg in one year.

Diagnosis: She was diagnosed with T3bN1M0 cervical cancer in another hospital. The transverse diameter of the primary tumor was 10.5 cm.

Interventions: The whole pelvis and para-aortic lymph node were irradiated with a total of 50 Gy in 25 fractions, but the size of the tumor showed only a slight decrease to 8.9 cm. After external beam radiotherapy, first-time high-dose-rate interstitial brachytherapy (HDR-ISBT) was administered without "intentional internal high-dose (IIHD) policy," the technique of high-dose administration to only the inside of the tumor. Considering the rectum dose limitation, in the additional 2 times of brachytherapy, "IIHD policy" HDR-ISBT was applied. In the second and third HDR-ISBT, the percentage of the volume exposed to 200% of the prescribed dose for high-risk clinical target volume increased by 241% and 204% compared with the first HDR-ISBT, while the doses to OARs were not significantly higher than those of the first-time HDR-ISBT.

Outcomes: Complete response was obtained, and no recurrence findings and side effects caused by HDR-ISBT have been detected for 2 years and 9 months.

Lessons: To our knowledge, this is the first report of IIHD HDR-ISBT for bulky cervical cancer. This technique can be the solution for treating bulky cervical cancer.
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http://dx.doi.org/10.1097/MD.0000000000020860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337609PMC
July 2020

How Much Was the Elective Lymph Node Region Covered in Involved-Field Radiation Therapy for Locally Advanced Pancreatic Cancer? Evaluation of Overlap Between Gross Target Volume and Celiac Artery-Superior Mesenteric Artery Lymph Node Regions.

Adv Radiat Oncol 2020 May-Jun;5(3):377-387. Epub 2019 Sep 13.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

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 ( < .001). Although the SMA overlap percentage was higher in the pancreas head ( = .028), the CA overlap percentage was higher in the pancreas body or tail ( = .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.
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http://dx.doi.org/10.1016/j.adro.2019.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278027PMC
September 2019

Stereotactic body radiation therapy for early-stage non-small-cell lung cancer in octogenarians and older: an alternative treatment.

J Radiat Res 2020 Jul;61(4):586-593

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

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.
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http://dx.doi.org/10.1093/jrr/rraa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336556PMC
July 2020

Determination of the internal quantum efficiency for photoelectrochemical reaction in a semiconductor photoelectrode by photoacoustic detection.

Chem Commun (Camb) 2020 May;56(40):5417-5420

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Kitakyushu 808-0196, Japan.

We showed for the first time the validity of photothermal measurement for determination of internal quantum efficiency, which is one of the most fundamental parameters for energy conversion systems. The measurement method using photoacoustic detection in the present study can be applied to a wide variety of samples and measurement conditions.
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http://dx.doi.org/10.1039/d0cc01911aDOI Listing
May 2020

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

J Radiat Res 2020 May;61(3):506-510

Department of Radiology, Kyoto Prefectural University Graduate School of Medical Science, Kyoto, Japan.

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.
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http://dx.doi.org/10.1093/jrr/rraa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299259PMC
May 2020

Per-oral interstitial brachytherapy catheter insertion for boost in case of recurrent tonsillar carcinoma: dosimetry and clinical outcome.

BJR Case Rep 2020 Mar 12;6(1):20190059. Epub 2020 Feb 12.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

High-dose-rate interstitial brachytherapy (HDR-ISBT) is relatively rarely applied for the head and neck cancer. However, its dose distribution is more confined than intensity modulated radiation therapy (IMRT) and can deliver higher dose while sparing surrounding normal tissues. In this case report, the effectiveness of HDR-ISBT as a boost following IMRT for post-operative recurrent oropharyngeal cancer patient was indicated. A 73-year-old male who developed local recurrence after surgery for oropharyngeal squamous cell carcinoma. Salvage IMRT up to 70 Gy concurrent with weekly cetuximab was planned. However, CT taken at 60 Gy found a residual tumor, then, boost HDR-ISBT was proposed. 1 week after 60 Gy of IMRT, HDR-ISBT, 12 Gy in 2 fractions, was delivered under local anesthesia. MRI taken 2 months after HDR-ISBT showed no residual tumor. It was demonstrated that boost HDR-ISBT following IMRT for local recurrence of oropharyngeal cancer was performed safely and showed favorable efficacy.
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http://dx.doi.org/10.1259/bjrcr.20190059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068101PMC
March 2020

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

J Contemp Brachytherapy 2019 Dec 25;11(6):573-578. Epub 2019 Dec 25.

Department of Radiation Oncology, Johann Wolfgang Goethe University Frankfurt, Germany.

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 D (CTV) values of both patients were 6.3 Gy and 6.6 Gy and the D (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.
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http://dx.doi.org/10.5114/jcb.2019.91225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964338PMC
December 2019
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