Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

Brainstem NTCP and Dose Constraints for Carbon Ion RT-Application and Translation From Japanese to European RBE-Weighted Dose.

BACKGROUND AND PURPOSE: The Italian National Center of Oncological Hadrontherapy (CNAO) has applied dose constraints for carbon ion RT (CIRT) as defined by Japan's National Institute of Radiological Sciences (NIRS). However, these institutions use different models to predict the relative biological effectiveness (RBE). CNAO applies the Local Effect Model I (LEM I), which in most clinical situations predicts higher RBE than NIRS's Microdosimetric Kinetic Model (MKM). Equal constraints therefore become more restrictive at CNAO. Tolerance doses for the brainstem have not been validated for LEM I-weighted dose (D LEM I). However, brainstem constraints and a Normal Tissue Complication Probability (NTCP) model were recently reported for MKM-weighted dose (D MKM), showing that a constraint relaxation to D MKM|0.7 cm3 <30 Gy (RBE) and D MKM|0.1 cm3 <40 Gy (RBE) was feasible. The aim of this work was to evaluate the brainstem NTCP associated with CNAO's current clinical practice and to propose new brainstem constraints for LEM I-optimized CIRT at CNAO. MATERIAL AND METHODS: We reproduced the absorbed dose of 30 representative patient treatment plans from CNAO. Subsequently, we calculated both D LEM I and D MKM, and the relationship between D MKM and D LEM I for various brainstem dose metrics was analyzed. Furthermore, the NTCP model developed for D MKM was applied to estimate the NTCPs of the delivered plans. RESULTS: The translation of CNAO treatment plans to D MKM confirmed that the former CNAO constraints were conservative compared with D MKM constraints. Estimated NTCPs were 0% for all but one case, in which the NTCP was 2%. The relationship D MKM/D LEM I could be described by a quadratic regression model which revealed that the validated D MKM constraints corresponded to D LEM I|0.7 cm3 <41 Gy (RBE) (95% CI, 38-44 Gy (RBE)) and D LEM I|0.1 cm3 <49 Gy (RBE) (95% CI, 46-52 Gy (RBE)). CONCLUSION: Our study demonstrates that RBE-weighted dose translation is of crucial importance in order to exchange experience and thus harmonize CIRT treatments globally. To mitigate uncertainties involved, we propose to use the lower bound of the 95% CI of the translation estimates, i.e., D LEM I|0.7 cm3 <38 Gy (RBE) and D LEM I|0.1 cm3 <46 Gy (RBE) as brainstem dose constraints for 16 fraction CIRT treatments optimized with LEM I.

RBE-weighted dose in carbon ion therapy for ACC patients: Impact of the RBE model translation on treatment outcomes.

PURPOSE/OBJECTIVE: The purpose of this study is to assess the impact of the conversion scheme for relative biological effectiveness (RBE)-weighted dose (DRBE), implemented at our center, on treatment outcomes of adenoid cystic carcinoma (ACC) patients. MATERIAL/METHODS: Treatment plans of 78 ACC patients, optimized with the Local Effect Model (LEM), were recalculated with the modified Microdosimetric Kinetic Model (mMKM). DRBE to 95%, 50% and 2% (DV%) of the clinical target volume (CTV), were selected as relevant parameters to compare LEM and mMKM DRBE. The pattern of failure of ACC treatments was analyzed in relation to uncertainties involved in the DRBE translation methodology. RESULTS: mMKM recalculations of LEM plans, optimized to a prescription dose of 68.8 Gy(RBE), showed a D50% 8% higher, on average, than the expected value (60.8 Gy(RBE)), closer to the most frequently used mMKM prescription DRBE (64 Gy(RBE)). D95% and D2% deviations, with respect to the optimization goals in the two RBE systems, increased of 0.5% and 14.2%, respectively, due to the steeper mMKM RBE variation along the beam path. Local recurrences were mainly (63%) reported in areas where CTV coverage was not satisfactory in the original LEM plan and the mMKM analysis showed that OARs constraints were too conservative. CONCLUSION: No case of local recurrence could be explained by inadequate mMKM target coverage that was not already present in the LEM plan. New constraints have been defined for optic pathways and brainstem to improve target coverage with no expected increase in tissue complications.

Optic nerve constraints for carbon ion RT at CNAO - Reporting and relating outcome to European and Japanese RBE.

BACKGROUND AND PURPOSE: Until now, carbon ion RT (CIRT) dose constraints for the optic nerve (ON) have only been validated and reported in the NIRS RBE-weighted dose (DNIRS). The aim of this work is to improve CNAO's RBE-weighted dose (DLEM) constraints by analyzing institutional toxicity data and by relating it to DNIRS. MATERIAL AND METHODS: A total of 65 ONs from 38 patients treated with CIRT to the head and neck region in the period 2013-14 were analyzed. The absorbed dose (DAbs) of the treatment plans was reproduced and subsequently both DLEM and DNIRS were applied, thus relating CNAO clinical toxicity to DNIRS. RESULTS: Median FU was 47 (26-67) months. Visual acuity was preserved for the 56 ONs in which the old constraints were respected. Three ONs developed visual decline at DLEM|1% ≥71 Gy(RBE)/DLEM|20% ≥68 Gy(RBE), corresponding to DNIRS|1% ≥68 Gy(RBE)/DNIRS|20% ≥62 Gy(RBE). Dose recalculation revealed that NIRS constraints of DNIRS|1% ≤40 Gy(RBE)/DNIRS|20% ≤28 Gy(RBE) corresponded to DLEM|1% ≤50 Gy(RBE)/DLEM|20% ≤40 Gy(RBE). Reoptimization of treatment plans with these new DLEM constraints showed that the dose distribution still complied with NIRS constraints when evaluated in DNIRS. However, due to uncertainties in the method, and to comply with the EQD2-based constraints used at GSI/HIT, a more moderate constraint relaxation to DLEM|1% ≤45 Gy(RBE)/DLEM|20% ≤37 Gy(RBE) has been implemented in CNAO clinical routine since October 2018. CONCLUSION: New DLEM constraints for the ON were derived by analyzing CNAO toxicity data and by linking our results to the experience of NIRS and GSI/HIT. This work demonstrates the value of recalculating and reporting results in both DLEM and DNIRS.

Physicists' views on hadrontherapy: a survey of members of the Italian Association of Medical Physics (AIFM).

BACKGROUND: This study was based on a survey to investigate perceptions of hadrontherapy of the members of the Italian Association of Medical Physics (AIFM). The survey was digitally submitted to the 991 members between the end of January and the beginning of April 2016. METHODS: A 19-item questionnaire was designed focusing on advantages and disadvantages of hadrontherapy, current status and possible future improvements, and need and opportunities for future investments in Italy and abroad. Information about professional qualifications, main fields of clinical involvement and specific competencies of the respondents was also collected. RESULTS: The survey was completed by 121 AIFM members (response rate 12.2%). In the answers collected, it was shown that medical physicists expressed interest in hadrontherapy mainly for reasons of personal interest rather than for professional needs (90% ± 2.5% vs. 52% ± 4.3% of the respondents, respectively), with a good knowledge of the related basic aspects as well as of the pros and cons of its application. However, poor knowledge of the current status of hadrontherapy was observed among the medical physicists not directly involved at a professional level, who were less than 3% of the physicists working in radiotherapy. CONCLUSIONS: In light of these results, the implementation of new training and education initiatives should be devised to promote a deeper and global knowledge of hadrontherapy-related issues, not only from a theoretical point of view but also in practical terms. Moreover, a close collaboration between highly specialized medical physicists employed in hadrontherapy centers and others in oncology hospitals should be -encouraged.

Prognostic factors of adenoid cystic carcinoma of the head and neck in carbon-ion radiotherapy: The impact of histological subtypes.

PURPOSE: The aim of this study was to evaluate the effect of histological subtypes of head and neck adenoid cystic carcinoma (ACC) on the results of carbon-ion radiotherapy (CIRT). MATERIAL AND METHODS: Of the 113 patients with ACC who were treated with CIRT between December 2006 and July 2013, 100 patients with identified histological subtypes were enrolled in this study. CIRT at a total dose of 57.6 or 64.0Gy (RBE) was administered in 16 fractions. Histological grading was defined as the presence or absence of a solid growth pattern. RESULTS: Median follow-up was 60 months. 5-Year local control (LC), overall survival (OS) and distant metastasis free survival (DMFS) of all patients were 68.6%, 74.8% and 65.7%, respectively. On multivariate analysis, the prescribed dose (p=0.001) and gross tumor volume (p=0.002) were significant independent risk factors for LC. No significant difference for local control of solid/non-solid growth patterns was found (p=0.093). Solid growth pattern was an independent risk factor for both OS (p=0.033) and DMFS (p=0.024). CONCLUSIONS: CIRT appears able to locally control solid growth pattern ACC in the head and neck. Improved intervention is needed to extend DMFS and OS.

Phase II multi-institutional clinical trial on a new mixed beam RT scheme of IMRT on pelvis combined with a carbon ion boost for high-risk prostate cancer patients.

PURPOSE: Definition of the optimal treatment schedule for high-risk prostate cancer is under debate. A combination of photon intensity modulated radiotherapy (IMRT) on pelvis with a carbon ion boost might be the optimal treatment scheme to escalate the dose on prostate and deliver curative dose with respect to normal tissue and quality of dose distributions. In fact, carbon ion beams offer the advantage to deliver hypofractionated radiotherapy (RT) using a significantly smaller number of fractions compared to conventional RT without increasing risks of late effects. METHODS: This study is a prospective phase II clinical trial exploring safety and feasibility of a mixed beam scheme of carbon ion prostate boost followed by photon IMRT on pelvis. The study is designed to enroll 65 patients with localized high-risk prostate cancer at 3 different oncologic hospitals: Istituto Europeo di Oncologia, Fondazione IRCCS Istituto Nazionale dei Tumori, and Centro Nazionale di Adroterapia Oncologica. The primary endpoint is the evaluation of safety and feasibility with acute toxicity scored up to 1 month after the end of RT. Secondary endpoints are treatment early (3 months after the end of RT) and long-term tolerability, quality of life, and efficacy. RESULTS: The study is not yet recruiting; in silico studies are ongoing and we expect to start recruitment by 2017. CONCLUSIONS: The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.

Definitive carbon-ion radiotherapy for locally advanced parotid gland carcinomas.

BACKGROUND: The purpose of this study was to present our evaluation of the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for locally advanced parotid gland carcinomas. METHODS: Clinicopathological features and outcomes were evaluated in 46 patients receiving C-ion RT for parotid gland carcinomas. RESULTS: Sixteen patients had adenoid cystic carcinoma; 8 had adenocarcinoma, 8 had mucoepidermoid carcinoma, and 14 had other carcinomas. T2, T3, T4a, and T4b diseases were diagnosed in 3, 18, 8, and 17 patients, respectively. C-ion RT was provided to 25 patients as the primary treatment, to 20 patients for local recurrences after surgery, and to 1 patient for residual tumor after surgery. During follow-up (median duration, 62 months), 5-year local control and overall survival (OS) rates were 74.5% and 70.1%, respectively. Of the 30 patients without facial nerve palsy before C-ion RT, 25 showed no radiation-induced facial nerve palsy. CONCLUSION: C-ion RT is effective and has acceptable toxicity levels for locally advanced parotid gland carcinomas. © 2016 Wiley Periodicals, Inc. Head Neck 39: 724-729, 2017.

Long-term outcomes after carbon-ion radiotherapy for oral mucosal malignant melanoma.

Oral mucosal malignant melanoma (OMM) is extremely rare and has a poor prognosis. Owing to its rarity, it has not yet been possible to establish an optimal treatment modality. The objective of this study was to evaluate the long-term efficacy of carbon-ion radiotherapy (C-ion RT) for OMM. Between 1997 and 2013, 19 patients with OMM were treated with C-ion RT alone. Patient ages ranged from 44 to 84 years (median, 69 years). Nine men and 10 women were included. OMMs were restaged in accordance with the seventh edition of the tumour/node/metastasis (TNM) Staging System of the International Union Against Cancer. Before treatment, 14 patients had T3 disease and 5 had T4a disease. Three patients were classified as having N1 disease. All patients were classified as having M0. The hard palate was the most frequently involved oral subsite. All patients were treated with 57.6 Gy (relative biological effectiveness) in 16 fractions. The median follow-up period was 61 months (range, 8-190 months). The 5-year local control, overall survival and progression-free survival rates were 89.5%, 57.4% and 51.6%, respectively. For local control and overall survival, T classification was found to be a significant prognostic factor. Grade 2 and 3 osteoradionecrosis was observed in three and four patients, respectively. The presence of teeth within the planning target volume was a significant risk factor for developing osteoradionecrosis. C-ion RT was an effective treatment option with acceptable toxicity for OMM.

Radiation-induced Parotid Gland Atrophy in Patients with Head and Neck Cancer After Carbon-ion Radiotherapy.

BACKGROUND/AIM: This study aimed to clarify the relationship between dosimetric factors and parotid gland (PG) atrophy after carbon ion radiotherapy (C-ion RT). PATIENTS AND METHODS: Fifty-four patients with head and neck tumours were enrolled and 93 irradiated PGs were analyzed. Thirty and 24 patients were treated with total doses [relative biological effectiveness (RBE)] of 57.6 Gy and 64.0 Gy, respectively, in 16 fractions. PG volumes were measured using computed tomographic images obtained before C-ion RT and every 3-6 months thereafter. RESULTS: The median follow-up period was 46.4 months (range=24.0-123.0 months). Univariate analysis showed that PG volumes receiving more than 5, 10, 15, and 20 Gy RBE (V5, V10, V15 and V20, respectively), mean dose, and maximum dose were significantly associated with PG atrophy. Multivariate analysis indicated that only V5 was significantly associated with atrophy. CONCLUSION: Increasing V5 was a significant risk factor for PG atrophy after C-ion RT.

Dose prescription in carbon ion radiotherapy: How to compare two different RBE-weighted dose calculation systems.

BACKGROUND AND PURPOSE: In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values. MATERIAL AND METHODS: Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE. RESULTS: The MC+LEM_I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans. CONCLUSIONS: Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose.

Single-energy metal artefact reduction with CT for carbon-ion radiation therapy treatment planning.

OBJECTIVE: One approach to improving image quality of CT is to use metal artefact reduction image processing, such as single-energy metal artefact reduction (SEMAR). To quantify the impact of image correction on the quality of carbon-ion dose distribution, treatment planning using SEMAR was evaluated. METHODS: Using a head phantom into which metal screws could be inserted, we acquired standard planning CT images. We calculated dose distributions using phantom images with and without metal added, and with and without SEMAR. Hounsfield unit (HU) and dose distribution variation of these images with and without SEMAR were measured using metal-free image subtraction. We similarly analysed the image data sets of two patients with head and neck cancer who had dental implants. RESULTS: HU difference between metal-containing images and metal-free images without and with SEMAR were -79.5 ± 97.2 HU and -1.4 ± 19.5 HU on severe artefact area, respectively. The range of dose distribution difference from the prescribed dose between uncorrected and SEMAR-corrected images varied from -19.5% to -3.4% within planning target volume (PTV). PTV-D95 (%) for uncorrected and SEMAR-corrected image data were 82.4% and 95.4%, respectively. For data in patients with metal dental work, PTV-D95 (%) for uncorrected and SEMAR-corrected data were 92.2% and 92.5% (Patient 1), and 90.9% and 95.7% (Patient 2), respectively. CONCLUSION: SEMAR algorithm shows promise in improving CT image quality and in ensuring an accurate representation of dose distribution. ADVANCES IN KNOWLEDGE: SEMAR may improve treatment accuracy without the need for dental implant extraction in patients with head and neck cancer.

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base.

BACKGROUND: Most cases of adenoid cystic carcinoma (ACC) of the tongue base are radioresistant, and are diagnosed in the advanced stage. Therefore, we evaluated the safety and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced ACC of the tongue base. METHODS: Eighteen patients with ACC of the tongue base were treated with C-ion RT between May 2002 and April 2014. Seventeen patients had T4a disease and 1 patient had T2 disease before C-ion RT. RESULTS: The median follow-up period was 57 months (range, 10-132 months). The 5-year local control rate was 92%. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72% and 44%, respectively. Regarding late reactions, 2 patients developed grade 3 mandible osteoradionecrosis, and 1 had grade 3 hemorrhage of the tongue base. CONCLUSION: C-ion RT was effective with acceptable toxicities for locally advanced ACC of the tongue base. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2122-E2126, 2016.

Carbon ion radiotherapy for locally advanced squamous cell carcinoma of the external auditory canal and middle ear.

BACKGROUND: The prognosis of advanced squamous cell carcinoma (SCC) of the external auditory canal and middle ear remains poor. Carbon ion radiotherapy (C-ion RT) has shown promise for locally advanced head and neck cancer. Therefore, we evaluated the safety and efficacy of C-ion RT for locally advanced SCC of the external auditory canal and middle ear. METHODS: The cases of 13 patients with advanced (T3 and T4) SCC of the external auditory canal and middle ear who received C-ion RT as the primary treatment were reviewed. RESULTS: The median follow-up for all patients and the 7 surviving patients was 12 and 32 months, respectively. The 1-year and 3-year local control and overall survival (OS) rates were 72% and 54% and 70% and 40%, respectively. Severe temporal bone necrosis was observed in 2 patients. CONCLUSION: C-ion RT is effective and generally safe for locally advanced SCC of the external auditory canal and middle ear.

Feasibility of carbon ion radiotherapy for locally advanced sinonasal adenocarcinoma.

BACKGROUND AND PURPOSE: To evaluate the safety and efficacy of carbon ion radiotherapy (CIRT) for locally advanced sinonasal adenocarcinoma. MATERIAL AND METHODS: Twenty-two patients with sinonasal adenocarcinoma were treated with CIRT. CIRT was the primary treatment for 16 patients. Four patients received CIRT for local recurrence after surgery and two for residual tumour after surgery or chemotherapy. At the start of CIRT, 1 patient had T-classification (T) 2 disease, 2 had T3 disease, 5 had T4a disease, and 14 had T4b disease. Fourteen patients were treated with 57.6 Gy equivalent (GyE)/16 fractions, and 8, with 64.0 GyE/16 fractions. RESULTS: The median follow-up period was 43 months for all patients. The 3-year local control and loco-regional control rates for all patients were 76.9% (95% confidence interval [CI]=56.7-97.1%) and 61.3% (95% CI=38.5-84.1%), respectively. The 3-year overall survival and disease-specific survival rates were 59.1% (95% CI=38.6-79.6%) and 65.6% (95% CI=44.9-86.3%), respectively. Acute reactions of grade 3 of the skin and mucosa were observed in 2 and 4 patients, respectively. Late reactions included lateral visual loss (5 patients), mucosal ulceration (1 patient), and brain necrosis with clinical symptoms (1 patient). In the 5 patients who developed visual loss, the optic nerve was close to the tumour. CONCLUSIONS: CIRT was effective and generally safe for locally advanced sinonasal adenocarcinoma.

Carbon ion beam radiotherapy for sinonasal malignant tumors invading skull base.

Objective. To evaluate the treatment outcome and prognostic factors in patients with sinonasal malignant tumors invading skull base. Study Design and Setting. A retrospective clinical study at the Yamagata University School of Medicine. Subjects and Methods. Three patients with sinonasal malignant tumors invading skull base were presented in present study. All patients were treated with carbon ion beam radiotherapy. The prescribed dose to the center of the clinical target volume was 64.0 GyE/16 fractions over 4 weeks at 4.0 GyE/fraction per day. Results. All patients completed carbon ion beam radiotherapy without an interval. The mean observation period was 39.6 months (range: 11-54 months). There were no local or regional recurrences in all cases; however, one patient had a metastasis in distant organs. Regarding the complications, visual loss was observed in one eye of one patient whose optic nerve was entirely involved by the tumor and field of carbon ion beam radiotherapy. Radiation induced brain injury was observed in two patients; however, these patients do not complain about neurological abnormality and had no treatment for radiation induced brain necrosis. Conclusions. Carbon ion beam radiotherapy for sinonasal malignant tumors invading the skull base showed therapeutic effectiveness.

Effects of the dose-volume relationship on and risk factors for maxillary osteoradionecrosis after carbon ion radiotherapy.

BACKGROUND: Osteoradionecrosis (ORN) is a critical complication after carbon ion (C-ion) or photon radiotherapy (RT) for head and neck tumors. However, the risk factors for ORN after C-ion RT remain unclear. Therefore, the present study aimed to investigate the effects of the dose-volume relationship on and risk factors for ORN development after C-ion RT. We, however, focused on the maxillary bone because most tumors treated with C-ion RT were primarily located in the sinonasal cavity. METHODS: The patients enrolled in this study received more than 10% of the prescribed total dose of 57.6 Gy equivalent (GyE) in 16 fractions to their maxilla. All patients were followed up for more than 2 years after C-ion RT. Those with tumor invasion to the maxilla before C-ion RT or local recurrence after the treatment were excluded from the study to accurately evaluate the effects of irradiation on the bone. Sixty-three patients were finally selected. The severity of ORN was assessed according to the Common Terminology Criteria for Adverse Events version 4.0. The correlation between clinical and dosimetric parameters and ORN incidence was retrospectively analyzed. RESULTS: The median follow-up period was 79 months. Of the 63 enrolled patients, 26 developed ORN of grade ≥1. Multivariate analysis revealed that the maxilla volume receiving more than 50 GyE (V50) and the presence of teeth within the planning target volume were significant risk factors for ORN. Dose-volume histogram analysis revealed that V10 to V50 parameters were significantly higher in patients with ORN than in those without ORN. CONCLUSIONS: V50 and the presence of teeth within the planning target volume were independent risk factors for the development of ORN after C-ion RT using a 16-fraction protocol.

Risk factors for brain injury after carbon ion radiotherapy for skull base tumors.

BACKGROUND AND PURPOSE: This study aimed to determine the risk factors for radiation-induced brain injury (RIBI) after carbon ion radiotherapy (CIRT) for treating skull base tumors. MATERIALS AND METHODS: Between April 1997 and January 2009, CIRT at a total dose of 48.0-60.8Gy equivalent (GyE) was administered in 16 fractions to 47 patients with skull base tumors. Of these patients, 39 who were followed up with magnetic resonance imaging (MRI) for more than 24months were analyzed. RIBI was assessed according to the MRI findings based on the Late Effects of Normal Tissue-Subjective, Objective, Management, Analytic criteria; clinical symptoms were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer tables. The correlations of clinical and dosimetric parameters with incidence of ⩾grade 2 RIBI were retrospectively analyzed. RESULTS: The median follow-up period was 67months. The 5-year actuarial likelihoods of ⩾grade 2 RIBI and ⩾grade 2 clinical symptoms were 24.5% and 7.0%, respectively. Multivariate analysis demonstrated that the brain volume receiving more than 50GyE (V50) was a significant risk factor for the development of ⩾grade 2 RIBI (p=0.004). CONCLUSION: V50 was a significant risk factor for ⩾grade 2 RIBI after CIRT using a 16-fraction regimen.

Accuracy of methionine-PET in predicting the efficacy of heavy-particle therapy on primary adenoid cystic carcinomas of the head and neck.

BACKGROUND: We evaluated whether or not PET or PET/CT using L-methyl-[11C]-methionine (MET) can allow for the early prediction of local recurrence and metastasis, as well as the prognosis (disease-specific survival), in patients with adenoid cystic carcinoma of the head and neck treated by carbon ion beam radiotherapy. METHODS: This was a retrospective cohort study of sixty-seven patients who underwent a MET-PET or PET/CT study prior to and one month after the completion of carbon ion radiotherapy (CIRT). The minimum follow-up period for survivors was 12 months. The MET accumulation of the tumor was evaluated using the semiquantitative tumor to normal tissue ratio (TNR). A univariate analysis was conducted using the log-rank method, and the Cox model was used in a multivariate survival regression analysis. RESULTS: The average TNR prior to and following treatment was 4.8 (±1.5) and 3.0 (±1.3), respectively, showing a significant decrease following treatment. In the univariate analysis, a high TNR prior to treatment (TNRpre) was a significant factor for predicting the occurrence of metastasis and the disease-specific survival. A high TNR following treatment (TNRpost) was a significant factor for predicting the development of local recurrence. The residual ratio of TNR changes (TNRratio) seemed to be less useful than the TNRpre. In the multivariate analysis, the TNRpost and tumor size were the factors found to significantly influence the risk of local recurrence. The TNRpre, TNRratio and tumor size were all significant factors influencing the occurrence of metastasis. Regarding the disease-specific survival, the TNRpre and age were the only factors with a significant influence on the outcome. CONCLUSIONS: The TNRpre was a factor that was significantly related to the occurrence of metastasis and the disease-specific survival after CIRT for adenoid cystic carcinoma of the head and neck. The TNRpost was a factor that was significantly related to the development of local recurrence. Thus, MET-PET or PET/CT can be useful for predicting or determining the therapeutic efficacy of CIRT.