A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Implementation of optically simulated luminescent dosimeter for quality control of gamma ray dose of an accelerator-based neutron source.

BACKGROUND: Neutron beams utilized for performing BNCT are composed of a mixture of neutrons and gamma rays. Although much of the dose delivered to the cancer cells comes from the high LET particles produced by the boron neutron capture reaction, the dose delivered to the healthy tissues from unwanted gamma rays cannot be ignored. With the increase in the number of accelerators for BNCT, a detector system that is capable of measuring gamma ray dose in a mixed neutron/gamma irradiation field is crucial. Currently, BeO TLDs encased in quartz glass are used to measure gamma ray dose in a BNCT irradiation field. However, this type of TLD is no longer commercially available. A replacement dosimetry system is required to perform the recommended ongoing quality assurance of gamma ray measurement for a clinical BNCT system. PURPOSE: The purpose of this study is to evaluate the characteristics of a BeO OSLD detector system under a mixed neutron and gamma ray irradiation field and to assess the suitability of the system for routine quality assurance measurements of an accelerator-based BNCT facility. METHODS: The myOSLD system by RadPro International GmbH was evaluated using the accelerator-based neutron source designed for clinical BNCT (NeuCure BNCT system). The readout constancy, linearity, dose rate effect, and fading effect of the OSLD were evaluated. Free-in-air and water phantom measurements were performed and compared with the TLD results and Monte Carlo simulation results. The PHITS Monte Carlo code was used for this study. RESULTS: The readout constancy was found to be stable over a month-long period and similar to the TLD results. The OSLD readout signal was found to be linear, with a high coefficient of determination (R2 ≥ 0.999) up to a proton charge of 3.6 C. There was no significant signal fading or dose rate dependency. The central axis depth dose and off-axis dose profile measurements agreed with both the TLD and Monte Carlo simulation results, within one standard deviation. CONCLUSION: The myOSLD system was characterized using an accelerator system designed for clinical BNCT. The experimental measurements confirmed the OSLD achieved similar, if not superior to, the currently utilized dosimetry system for routine QA of an accelerator-based BNCT system. The OSLD system would be a suitable replacement for the current TLD system for performing routine QA of gamma ray dose measurement in a BNCT irradiation field.

Narrative review of local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer.

The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.

Efficacy of Endoscopic Resection and Selective Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective chemoradiotherapy (CRT) based on findings from endoscopic resection (ER). METHODS: We performed a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed. RESULTS: Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%-94.7%) and 92.6% in all patients (90% confidence interval, 88.5%-95.2%). CONCLUSIONS: In a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.

Carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced non-small cell lung cancer: a multicenter Phase I/II study.

OBJECTIVES: We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30-40 mg/m2 two times daily) on Days 1-14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate. RESULTS: Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6-71.4%), and the median PFS was 16.8 months (95% CI 7.8-not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3-4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed. CONCLUSION: Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study.

OBJECTIVE: Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended SBRT boost dose for ICBT-ineligible cervical cancer patients. METHODS: Patients with untreated uterine cervical cancer (clinical stages IB1-IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole-pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in three fractions) were set; the treatment protocol began at 21 Gy (level 2). The 'rolling-six' design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as the occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. RESULTS: The median follow-up after registration was 17 (range, 8-32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); none of the patients exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. Although all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. CONCLUSIONS: The recommended dose of SBRT boost was 22.5 Gy in three fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.

A prospective multicentre feasibility study of stereotactic body radiotherapy in Japanese patients with spinal metastases.

OBJECTIVE: Stereotactic body radiotherapy has emerged as an attractive alternative to conventional radiotherapy for spinal metastases. However, it has limitations, including the need for advanced techniques and specific adverse effects. The present trial aimed to validate the feasibility and safety of stereotactic body radiotherapy in Japanese patients with spinal metastases. METHODS: Patients with one or two spinal metastases received stereotactic body radiotherapy of 24 Gy in two fractions. The primary endpoint was the proportion of severe adverse effects (≥ grade 3) in patients within 6 months after spine stereotactic body radiotherapy. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The treatment protocol was considered feasible and tolerable if the proportion of severe adverse effects was 10% or less. RESULTS: Overall, 20 spinal segments in 20 patients who registered between March 2014 and October 2015 were included. Minor and major deviations were observed in the planning of 2 and 0 cases, respectively. The treatment completion rate was 100%. The median follow-up after registration was 24.5 (range: 1-61) months. Although four patients experienced acute grade 2 adverse effects, no grade 3 or higher adverse effects were observed within 6 months after spine stereotactic body radiotherapy. Vertebral compression fractures were observed in two patients (14 and 16 months after stereotactic body radiotherapy). The local control and pain response rates at 6 months were 100 and 83%, respectively. CONCLUSION: This study demonstrated the feasibility and safety of spine stereotactic body radiotherapy in Japanese patients with spinal metastases.

Re-irradiation for painful bone metastases using stereotactic body radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) is expected to achieve safe and effective re-irradiation for painful bone metastases. This study aimed to clarify the efficacy of re-irradiation using SBRT for painful bone metastases. METHODS: Prospective database at our institution for the period between September 2013 and December 2017 were retrospectively reviewed for patients with: (1) painful bone metastases; (2) history of radiotherapy to the metastasis; and (3) SBRT performed as re-irradiation. Pain response, pain failure-free duration, analgesics medications, and adverse events were evaluated. Pain was evaluated using the Numerical Rating Pain Score, and pain response was evaluated based on International Consensus Pain Response Endpoints. Best response during follow-up was noted. Patients with complete or partial response were defined as showing pain response, and patients with pain progression were defined as showing pain failure. Adverse events were evaluated based on the RTOG/EORTC Late Radiation Morbidity Scoring Schema. RESULTS: Sixty-six patients selected from our database showed: median age, 65 years (range, 33-82 years); ECOG performance status, 0-1/2/3/4, 51/10/3/2; lesion histopathology, rectal/lung/renal/thyroid/other cancer, 13/11/9/5/28; median previous irradiated dose, 30 Gy (range, 8-70.4 Gy); median interval from latest irradiation, 21 months (range, 4-192 months); prescribed dose for SBRT, 24 Gy in 2 fractions/30 Gy in 5 fractions/35 Gy in 5 fractions, 51/13/2. Median follow-up after SBRT was 10 months (range, 1-37 months). Fifty-seven patients achieved pain response (86%). The 1-year pain failure-free rate was 55%. Median pain failure-free duration was 13 months (range, 1-24 months). Grade 4 adverse events were observed in six patients (vertebral compression fracture, n = 5; radiation myelopathy, n = 1). No other toxicities of Grade 3 or greater were encountered. CONCLUSIONS: Re-irradiation SBRT has potential to achieve good response and long-term pain control for painful bone metastases. Prospective analysis is necessary to confirm the safety and efficacy of SBRT as re-irradiation.

Clinical outcomes and prognostic factors of chemoradiotherapy for postoperative lymph node recurrence of esophageal cancer.

BACKGROUND: The therapeutic strategies and prognostic risk factors in patients with lymph node (LN) recurrence of esophageal cancer remain controversial. We assessed clinical outcomes and prognostic factors related to the use of chemoradiotherapy (CRT) for LN recurrence of esophageal squamous cell carcinoma (ESCC) after curative resection. METHODS: We retrospectively evaluated survival and prognostic factors in 57 patients with LN recurrence of ESCC after curative resection. Patients received CRT using 5-fluorouracil plus cisplatin (FP) or docetaxel. Radiotherapy was delivered at 2 Gy (total dose, 60-66 Gy; median, 60 Gy). RESULTS: The median follow-up duration was 24 (range, 3-116) months. The overall survival (OS) rates at 2, 3 and 5 years were 43.7%, 36.9% and 27.6%, respectively. In the univariate analysis of OS, treatment with FP, a single LN recurrence, and a single regional recurrence were associated with a significantly better prognosis (P = 0.04, P = 0.027 and P = 0.0001, respectively). In the multivariate analysis, the combination chemotherapy regimen [hazard ratio (HR), 2.50; 95% confidence interval (CI), 1.23-5.07] and the number of the regional LNs with recurrence (HR, 5.76; 95% CI, 1.22-27.12) were independent prognostic factors. CONCLUSION: Approximately 28% of ESCC patients with LN recurrence after curative resection could achieve long-term survival with CRT. Treatment with FP or patients with a single regional recurrence might improve the treatment outcome.

Palliative radiotherapy and chemoradiotherapy in stage IVA/B esophageal cancer patients with dysphagia.

BACKGROUND: Palliative therapeutic strategies in esophageal squamous cell carcinoma (ESCC) patients with dysphagia remain controversial. Only few studies have assessed therapeutic effect factors related to improvement in dysphagia score and nutrition-support-free survival (NSFS). OBJECTIVE: The present study assessed the efficacy and therapeutic effect factors related to the use of palliative radiotherapy (RT) and chemoradiotherapy (CRT) in ESCC patients with dysphagia. METHODS: We retrospectively evaluated 70 patients with stage IVA/B ESCC. Patients received RT of 30 Gy in 10 fractions or concurrent CRT using 5-fluorouracil plus cisplatin of 40 Gy in 20 fractions. The change in the dysphagia score from before to after treatment was assessed, and NSFS was evaluated. RESULTS: The median follow-up duration was 6 months (range 1-41 months). The overall rate of improvement in the dysphagia score was 60%. The median NSFS was 7.5 months. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions were associated with a significant improvement in the dysphagia score (p = 0.0036, p = 0.0069, and p = 0.03, respectively). NSFS was significantly longer with CRT than with RT (p = 0.048). CONCLUSION: Palliative RT and CRT are effective treatment options for ESCC patients with dysphagia. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions may improve dysphagia. CRT of 40 Gy in 20 fractions may improve NSFS.

[Definitive Radiotherapy for Esophageal Squamous Cell Carcinoma after Allogeneic Hematopoietic Stem Cell Transplantation with Conditioning of Total Body Irradiation].

A 24-year-old man with acute lymphoblasticleukemia underwent allogeneicperipheral blood stem cell transplantation (allo-PBSCT)from a human leukocyte antigen-matched sibling after myeloablative conditioning, with a regimen including total body irradiation(TBI)(12 Gy/6 fractions), 6 years ago. The patient developed extensive chronic graft-versus-host disease(cGVHD)of the skin, mouth, liver, and gut four months after allo-PBSCT. Treatment with cyclosporine and prednisolone was necessary to control the cGVHD. Six years after allo-PBSCT, the patient experienced odynophagia and was diagnosed with cervical esophageal squamous cell carcinoma(cT1bN1M0, cStage II B). Because we considered laryngeal preservation, risk of anastomotic leakage, and infection related to the operation, the patient was planned to receive chemoradio- therapy with 5-fluorouracil and cisplatin. Regarding irradiation, the patient received radiotherapy(50.4 Gy/28 fractions)for a primary tumor and lymph node without an elective nodal area. The patient achieved complete response and remained disease- free without any treatment-related complications for 3 years.

Involved-field chemoradiotherapy for postoperative solitary lymph node recurrence of esophageal cancer.

BACKGROUND: For patients with postoperative lymph node (LN) recurrent esophageal cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains controversial. We assessed the clinical outcomes and prognostic factors related to involved-field CRT for postoperative solitary LN recurrence of esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively evaluated 21 patients who had received curative resection, with LN recurrence of ESCC. Patients received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60 Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals, and prognostic factors. We defined elective nodal failure (ENF) as recurrence in a regional LN without involved-field failure. RESULTS: The median follow-up duration was 32 months (range, 4-106 months). Nine patients experienced failure-4 (19%) within involved-field and 5 (24%) with distant metastasis. No patients had ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was 78%. In the univariate analysis of OS, two factors, the maximal diameter of the metastatic LN < 25 mm and the absence of serum p53 antibodies (s-p53-Abs), were associated with a significantly better prognosis (p = 0.025 and p = 0.01, respectively). CONCLUSIONS: Involved-field CRT for postoperative solitary LN recurrence of ESCC did not cause ENF and was without severe toxicities. Two factors, a length of the metastatic LN < 25 mm and the absence of s-p53-Abs may improve the treatment outcome. Involved-field CRT is a treatment option worthy of consideration for postoperative solitary LN recurrence of ESCC.

A comparison of clinical outcomes between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) reduces the dose delivered to organs at risk. However, there have been few direct comparisons of IMRT with conventional three-dimensional conformal radiotherapy (3DCRT). The aim of this study was to evaluate the clinical benefit of IMRT in terms of toxicity and biochemical control. METHODS: The medical records of 203 consecutive patients with localized to non-metastatic (stage T1a-T3bN0M0) prostate cancer between 2007 and 2011 were retrospectively reviewed. The prescribed dose was 76 Gy delivered in 38 fractions in both the 3DCRT and IMRT treatment groups. The frequency of grade 2 or greater late gastrointestinal (GI) and genitourinary toxicity and biochemical control were estimated by the log-rank test and Cox proportional hazards model with and without adjustment by the propensity score for treatment choice. RESULTS: A total of 159 patients were included in the study (3DCRT: 70 patients, IMRT: 89 patients). The median follow-up period was 4.7 years. The estimated 5-year cumulative risk of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group (3.6 vs 13.2%, respectively, p = 0.022). After adjustment by propensity score, IMRT remained associated with a lower risk of late GI toxicity (hazard ratio 0.22; 95% confidence interval 0.058-0.85; p = 0.028). The 5-year biochemical failure-free rate was 93.2% in the 3DCRT group and 95.4% in the IMRT group (non-significant difference). CONCLUSIONS: The incidence of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group, while the biochemical control rates were no different between the two groups. These clinical data suggest the benefit of IMRT in the reduction of late GI toxicity.

Feasibility study of chemoradiotherapy followed by amrubicin and cisplatin for limited-disease small cell lung cancer.

To evaluate the feasibility of amrubicin plus cisplatin (AP) following chemoradiotherapy for limited-disease small-cell lung cancer, chemo-naïve patients aged 20-70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m2 on days 1-3, cisplatin 80 mg/m(2) on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions (EP-TRT), followed by three cycles of amrubicin 40 mg/m2 on days 1-3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. The EP-TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte-colony stimulating factor (G-CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [CI]) progression-free survival (PFS) was 41.9 (0-102) months, and the 5-year PFS rate (CI) was 41.9% (20.4-63.4%). The median overall survival (OS) has not been reached yet, and the 5-year OS rate (CI) was 57.8% (35.2-80.4%). In conclusion, EP-TRT followed by AP therapy was well-tolerated, although a large number of patients required G-CSF support.

Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604).

We carried out a phase I/II trial of chemoradiotherapy concurrent with S-1 and cisplatin to determine the maximum tolerated dose and recommended dose and to evaluate the efficacy and safety of this treatment in patients with esophageal carcinoma. Thoracic esophageal cancer patients with clinical stage II/III disease, excluding T4, were eligible. Chemotherapy consisted of S-1 at a dose of 60-80 mg/m(2) /day on days 1-14, and cisplatin at 75 mg/m(2) on day 1, repeated twice every 4 weeks. Single daily radiation of 50.4 Gy was given in 28 fractions concurrently starting on day 1. Patients achieving an objective response after chemoradiotherapy underwent two additional cycles of chemotherapy. Patient accrual was terminated early due to slow enrolment after 44 patients were accrued. In the phase I part, two of six patients experienced dose-limiting toxicities at each level of S-1 (S-1 60 or 80 mg/m(2) /day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m(2) /day. The complete response rate, the primary endpoint of phase II, was 59.5% (22/37; 90% confidence interval, 44.6-73.1%; weighted threshold, 57.2%; P = 0.46 by the exact binomial test) on central review. In the phase II part, 3-year progression-free survival was 48.4%, with a 3-year overall survival of 61.9%. Grade 3 or 4 toxicity in phase II included leukopenia (57.9%), neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Although this combination showed acceptable toxicity and favorable 3-year survival, the study did not meet its primary endpoint. This trial was registered at the UMIN Clinical Trials Registry as UMIN000000710.

Boron neutron capture therapy as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: A preliminary report.

OBJECTIVE: Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. PATIENTS AND METHODS: This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8-22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. RESULTS: The median hospital stay after BNCT was 2 days (1-6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. CONCLUSIONS: BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.

Application of stoichiometric CT number calibration method for dose calculation of tissue heterogeneous volumes in boron neutron capture therapy.

BACKGROUND: Monte Carlo simulation code is commonly used for the dose calculation of boron neutron capture therapy. In the past, dose calculation was performed assuming a homogeneous mass density and elemental composition inside the tissue, regardless of the patient's age or sex. Studies have shown that the mass density varies with patient to patient, particularly for those that have undergone surgery or radiotherapy. A method to convert computed tomography numbers into mass density and elemental weights of tissues has been developed and applied in the dose calculation process using Monte Carlo codes. A recent study has shown the variation in the computed tomography number between different scanners for low- and high-density materials. PURPOSE: The aim of this study is to investigate the effect of the elemental composition inside each calculation voxel on the dose calculation and the application of the stoichiometric CT number calibration method for boron neutron capture therapy planning. METHODS: Monte Carlo simulation package Particle and Heavy Ion Transport code System was used for the dose calculation. Firstly, a homogeneous cubic phantom with the material set to ICRU soft tissue (four component), muscle, fat, and brain was modelled and the NeuCure BNCT system accelerator-based neutron source was used. The central axis depth dose distribution was simulated and compared between the four materials. Secondly, a treatment plan of the brain and the head and neck region was simulated using a dummy patient dataset. Three models were generated; (1) a model where only the fundamental materials were considered (simple model), a model where each voxel was assigned a mass density and elemental weight using (2) the Nakao20 model, and (3) the Schneider00 model. The irradiation conditions were kept the same between the different models (irradiation time and irradiation field size) and the near maximum (D1%) and mean dose to the organs at risk were calculated and compared. RESULTS: A maximum percentage difference of approximately 5% was observed between the different materials for the homogeneous phantom. With the dummy patient plan, a large dose difference in the bone (greater than 12%) and region near the low-density material (mucosal membrane, 7%-11%) was found between the different models. CONCLUSIONS: A stoichiometric CT number calibration method using the newly developed Nakao20 model was applied to BNCT dose calculation. The results indicate the importance of calibrating the CT number to elemental composition for each individual CT scanner for the purpose of BNCT dose calculation along with the consideration of heterogeneity of the material composition inside the defined region of interest.