Motion modeling from 4D MR images of liver simulating phantom.

BACKGROUND AND PURPOSE: A novel method of retrospective liver modeling was developed based on four-dimensional magnetic resonance (4D-MR) images. The 4D-MR images will be utilized in generation of the subject-specific deformable liver model to be used in radiotherapy planning (RTP). The purpose of this study was to test and validate the developed 4D-magnetic resonance imaging (MRI) method with extensive phantom tests. We also aimed to build a motion model with image registration methods from liver simulating phantom images. MATERIALS AND METHODS: A deformable phantom was constructed by combining deformable tissue-equivalent material and a programmable 4D CIRS-platform. The phantom was imaged in 1.5 T MRI scanner with T2-weighted 4D SSFSE and T1-weighted Ax dual-echo Dixon SPGR sequences, and in computed tomography (CT). In addition, geometric distortion of the 4D sequence was measured with a GRADE phantom. The motion model was developed; the phases of the 4D-MRI were used as surrogate data, and displacement vector fields (DVF's) were used as a motion measurement. The motion model and the developed 4D-MRI method were evaluated and validated with extensive tests. RESULT: The 4D-MRI method enabled an accuracy of 2 mm using our deformable phantom compared to the 4D-CT. Results showed a mean accuracy of <2 mm between coordinates and DVF's measured from the 4D images. Three-dimensional geometric accuracy results with the GRADE phantom were: 0.9-mm mean and 2.5 mm maximum distortion within a 100 mm distance, and 2.2 mm mean, 5.2 mm maximum distortion within a 150 mm distance from the isocenter. CONCLUSIONS: The 4D-MRI method was validated with phantom tests as a necessary step before patient studies. The subject-specific motion model was generated and will be utilized in the generation of the deformable liver model of patients to be used in RTP.

Retrospective four-dimensional magnetic resonance imaging of liver: Method development.

Purpose of our research was to develop a four-dimensional (4D) magnetic resonance imaging (MRI) method of liver. Requirements of the method were to create a clinical procedure with acceptable imaging time and sufficient temporal and spatial accuracy. The method should produce useful planning image sets for stereotactic body radiation therapy delivery both during breath-hold and in free breathing. The purpose of the method was to improve the localization of liver metastasis. The method was validated with phantom tests. Imaging parameters were optimized to create a 4D dataset compressed to one respiratory cycle of the whole liver with clinically reasonable level of image contrast and artifacts. Five healthy volunteers were imaged with T2-weighted SSFSE research sequence. The respiratory surrogate signal was observed by the linear navigator interleaved with the anatomical liver images. The navigator was set on head-feet - direction on the superior surface of the liver to detect the edge of diaphragm. The navigator signal and 2D liver image data were retrospectively processed with a self-developed MATLAB algorithm. A deformable phantom for 4D imaging tests was constructed by combining deformable tissue-equivalent material and a commercial programmable motor unit of the 4D phantom with a clinically relevant range of deformation patterns. 4D Computed Tomography images were used as reference to validate the MRI protocol. The best compromise of reasonable accuracy and imaging time was found with 2D T2-weighted SSFSE imaging sequence using parameters: TR = 500-550 ms, images/slices = 20, slice thickness = 3 mm. Then, image processing with number of respiratory phases = 8 constructed accurate 4D images of liver. We have developed the 4D-MRI method visualizing liver motions three-dimensionally in one representative respiratory cycle. From phantom tests it was found that the spatial agreement to 4D-CT is within 2 mm that is considered sufficient for clinical applications.

MRI-only based radiation therapy of prostate cancer: workflow and early clinical experience.

BACKGROUND: Magnetic resonance imaging (MRI) is the most comprehensive imaging modality for radiation therapy (RT) target delineation of most soft tissue tumors including prostate cancer. We have earlier presented step by step the MRI-only based workflow for RT planning and image guidance for localized prostate cancer. In this study we present early clinical experiences of MRI-only based planning. MATERIAL AND METHODS: We have analyzed the technical planning workflow of the first 200 patients having received MRI-only planned radiation therapy for localized prostate cancer in Helsinki University Hospital Cancer center. Early prostate specific antigen (PSA) results were analyzed from n = 125 MRI-only patients (n = 25 RT only, n = 100 hormone treatment + RT) and were compared with the corresponding computed tomography (CT) planned patient group. RESULTS: Technically the MRI-only planning procedure was suitable for 92% of the patients, only 8% of the patients required supplemental CT imaging. Early PSA response in the MRI-only planned group showed similar treatment results compared with the CT planned group and with an equal toxicity level. CONCLUSION: Based on this retrospective study, MRI-only planning procedure is an effective and safe way to perform RT for localized prostate cancer. It is suitable for the majority of the patients.

Converting from CT- to MRI-only-based target definition in radiotherapy of localized prostate cancer: A comparison between two modalities.

PURPOSE: To investigate the conversion of prostate cancer radiotherapy (RT) target definition from CT-based planning into an MRI-only-based planning procedure. MATERIALS AND METHODS: Using the CT- and MRI-only-based RT planning protocols, 30 prostate cancer patients were imaged in the RT fixation position. Two physicians delineated the prostate in both CT and T2-weighted MRI images. The CT and MRI images were coregistered based on gold seeds and anatomic borders of the prostate. The uncertainty of the coregistration, as well as differences in target volumes and uncertainty of contour delineation were investigated. Conversion of margins and dose constraints from CT- to MRI-only-based treatment planning was assessed. RESULTS: On average, the uncertainty of image coregistration was 0.4 ± 0.5 mm (one standard deviation, SD), 0.9 ± 0.8 mm and 0.9 ± 0.9 mm in the lateral, anterior-posterior and base-apex direction, respectively. The average ratio of the prostate volume between CT and MRI was 1.20 ± 0.15 (one SD). Compared to the CT-based contours, the MRI-based contours were on average 2-7 mm smaller in the apex, 0-1 mm smaller in the rectal direction and 1-4 mm smaller elsewhere. CONCLUSION: When converting from a CT-based planning procedure to an MRI-based one, the overall planning target volumes (PTV) are prominently reduced only in the apex. The prostate margins and dose constraints can be retained by this conversion.

Feasibility of MRI-based reference images for image-guided radiotherapy of the pelvis with either cone-beam computed tomography or planar localization images.

PURPOSE: This study introduces methods to conduct image-guided radiotherapy (IGRT) of the pelvis with either cone-beam computed tomography (CBCT) or planar localization images by relying solely on magnetic resonance imaging (MRI)-based reference images. MATERIAL AND METHODS: Feasibility of MRI-based reference images for IGRT was evaluated against kV CBCT (50 scans, 5 prostate cancer patients) and kV & MV planar (5 & 5 image pairs and patients) localization images by comparing the achieved patient position corrections to those obtained by standard CT-based reference images. T1/T2*-weighted in-phase MRI, Hounsfield unit conversion-based heterogeneous pseudo-CT, and bulk pseudo-CT images were applied for reference against localization CBCTs, and patient position corrections were obtained by automatic image registration. IGRT with planar localization images was performed manually by 10 observers using reference digitally reconstructed radiographs (DRRs) reconstructed from the pseudo-CTs and standard CTs. Quality of pseudo-DRRs against CT-DRRs was evaluated with image similarity metrics. RESULTS: The SDs of differences between CBCT-to-MRI and CBCT-to-CT automatic gray-value registrations were ≤1.0 mm & ≤0.8° and ≤2.5 mm & ≤3.6° with 10 cm diameter cubic VOI and prostate-shaped VOI, respectively. The corresponding values for reference heterogeneous pseudo-CT were ≤1.0 mm & ≤0.7° and ≤2.2 mm & ≤3.3°, respectively. Heterogeneous pseudo-CT was the only type of MRI-based reference image working reliably with automatic bone registration (SDs were ≤0.9 mm & ≤0.7°). The differences include possible residual errors from planning CT to MRI registration. The image similarity metrics were significantly (p≤0.01) better in agreement between heterogeneous pseudo-DRRs and CT-DRRs than between bulk pseudo-DRRs and CT-DRRs. The SDs of differences in manual registrations (3D) with planar kV and MV localization images were ≤1.0 mm and ≤1.7 mm, respectively, between heterogeneous pseudo-DRRs and CT-DRRs, and ≤1.4 mm and ≤2.1 mm between bulk pseudo-DRRs and CT-DRRs. CONCLUSION: This study demonstrated that it is feasible to conduct IGRT of the pelvis with MRI-based reference images.

Toward a more patient-specific model of post-radiotherapy saliva secretion for head and neck cancer patients.

BACKGROUND: Reduction of saliva secretion is a common side effect following radiotherapy (RT) for cancer of the head and neck region. The aim of this study is to predict the post-RT salivary function for individual patients prior to treatment and to recognise possible differences in individual radiosensitivity. MATERIAL AND METHODS: A predictive model for post-RT salivary function was validated for 64 head and neck cancer patients. The input parameters for the model were salivary excretion fraction (sEF) measured by 99mTc-pertechnetate scintigraphy, total stimulated salivary flow and mean absorbed dose for the major salivary glands. SEF values after RT relative to the baseline before RT (rEF) were compared among the patients using the distance ΔrEF between single gland rEF and the corresponding expected value at the dose response curve. RESULTS: A significant correlation (R = 0.86, p = 0.018) was found between the modelled and the measured values of stimulated salivary flow six months after RT. The average prediction error for the saliva flow rate was 6 ml/15 min. A linear relationship between ΔrEF for the left and the right parotid glands was observed both six (R = 0.53) and 12 (R = 0.79) months after RT. The average of absolute values of ΔrEF was 0.20 for parotid glands and 0.22 for submandibular glands. CONCLUSIONS: The salivary flow model was validated for 64 patients. The results imply, that one explanation for the discrepancies between the predicted and the measured salivary flow rate values and the common variations found in ΔrEF for the parotid glands may be differences in patients' individual response to radiation. However, quantitative extraction of individual radiosensitivity would require further studies in order to take it into account in predictive models.

Influence of MRI-based bone outline definition errors on external radiotherapy dose calculation accuracy in heterogeneous pseudo-CT images of prostate cancer patients.

BACKGROUND: This work evaluates influences of susceptibility-induced bone outline shift and perturbations, and bone segmentation errors on external radiotherapy dose calculation accuracy in magnetic resonance imaging (MRI)-based pseudo-computed tomography (CT) images of the male pelvis. MATERIAL AND METHODS: T1/T2*-weighted fast gradient echo, T1-weighted spin echo and T2-weighted fast spin echo images were used in bone detection investigation. Bone edge location and bone diameter in MRI were evaluated by comparing those in the images with actual physical measurements of fresh deer bones positioned in a gelatine phantom. Dose calculation accuracy in pseudo-CT images was investigated for 15 prostate cancer patients. Bone outlines in T1/T2*-weighted images were contoured and additional segmentation errors were simulated by expanding and contracting the bone contours with 1 mm spacing. Heterogeneous pseudo-CT images were constructed by adopting a technique transforming the MRI intensity values into Hounsfield units with separate conversion models within and outside of bone segment. RESULTS: Bone edges and diameter in the phantom were illustrated correctly within a 1 mm-pixel size in MRI. Each 1 mm-sized systematic error in bone segment resulted in roughly 0.4% change to the prostate dose level in the pseudo-CT images. The prostate average (range) dose levels in pseudo-CT images with additional systematic bone segmentation errors of -2 mm, 0 mm and 2 mm were 0.5% (-0.5-1.4%), -0.2% (-1.0-0.7%), and -0.9% (-1.8-0.0%) compared to those in CT images, respectively, in volumetric modulated arc therapy treatment plans calculated by Monte Carlo algorithm. CONCLUSIONS: Susceptibility-induced bone outline shift and perturbations do not result in substantial uncertainty for MRI-based dose calculation. Dose consistency of 2% can be achieved reliably for the prostate if heterogeneous pseudo-CT images are constructed with ≤± 2 mm systematic error in bone segment.

Cone beam CT doses in radiotherapy patient positioning in Finland-prostate treatments.

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.

Commissioning of MRI-only based treatment planning procedure for external beam radiotherapy of prostate.

In radiotherapy, target tissues are defined best on MR images due to their superior soft tissue contrast. Computed tomography imaging is geometrically accurate and it is needed for dose calculation and generation of reference images for treatment localization. Co-registration errors between MR and computed tomography images can be eliminated using magnetic resonance imaging-only based treatment planning. Use of ionizing radiation can be avoided which is especially important in adaptive treatments requiring several re-scans. We commissioned magnetic resonance imaging-only based procedure for external radiotherapy, treatment planning of the prostate cancer. Geometrical issues relevant in radiotherapy, were investigated including quality assurance testing of the scanner, evaluation of the displacement of skin contour and radiosensitive rectum wall, and detection of intraprostatic fiducial gold seed markers used for treatment localization. Quantitative analysis was carried out for 30 randomly chosen patients. Systematic geometrical errors were within 2.2 mm. The gold seed markers were correctly identified for 29 out of the 30 patients. Positions of the seed midpoints were consistent within 1.3 mm in magnetic resonance imaging and computed tomography. Positional error of rectal anterior wall due to susceptibility effect was minimal. Geometrical accuracy of the investigated equipment and procedure was sufficient for magnetic resonance imaging-only based radiotherapy, treatment planning of the prostate cancer including treatment virtual simulation.

Synthetic computed tomography based dose calculation in prostate cancer patients with hip prostheses for magnetic resonance imaging-only radiotherapy.

Background and purpose: Metallic hip prostheses cause substantial artefacts in both computed tomography (CT) and magnetic resonance (MR) images used in radiotherapy treatment planning (RTP) for prostate cancer patients. The aim of this study was to evaluate the dose calculation accuracy of a synthetic CT (sCT) generation workflow and the improvement in implant visibility using metal artefact reduction sequences. Materials and methods: The study included 23 patients with prostate cancer who had hip prostheses, of which 10 patients had bilateral hip implants. An in-house protocol was applied to create sCT images for dose calculation comparison. The study compared prostheses volumes and resulting avoidance sectors against planning target volume (PTV) dose uniformity and organs at risk (OAR) sparing. Results: Median PTV dose difference between sCT and CT-based dose calculation among all patients was 0.1 % (-0.4 to 0.4%) (median(range)). Bladder and rectum differences (V50Gy) were 0.2 % (-0.3 to 1.1%) and 0.1 % (-0.9 to 0.5%). The median 3D local gamma pass rate for partial arc cases using a Dixon MR sequence was Γ20%2mm/2% = 99.9%. For the bilateral full arc cases, using a metal artefact reconstruction sequence, the pass rate was Γ20%2mm/2% = 99.0%. Conclusions: An in-house protocol for generating sCT images for dose calculation provided clinically feasible dose calculation accuracy for prostate cancer patients with hip implants. PTV median dose difference for uni- and bilateral patients with avoidance sectors remained <0.4%. The Outphase images enhanced implant visibility resulting in smaller avoidance sectors, better OAR sparing, and improved PTV uniformity.

Palliative intensity modulated radiotherapy of bone metastases based on diagnostic instead of planning computed tomography scans.

Background and purpose: Radiotherapy (RT) treatment planning is as a standard based on a computed tomography (CT) scan obtained at the planning stage (pCT), while most of the decisions whether to treat by RT are based on diagnostic CT scans (dCT). Bone metastases (BM) are the most common palliative RT target. The objective of this study was to investigate if a palliative RT treatment plan of BMs could be made based on a dCT with sufficient accuracy and safety, without sacrificing any treatment quality. Materials and methods: A retrospective study with 60 BMs of 8 anatomical sites was performed. RT planning was performed using intensity-modulated radiation therapy/volumetric modulated arc therapy techniques in dCT and transferred to pCT. The dose of clinical target volumes (CTVs), D(CTVV95%, V50%), were compared between plans for dCT and pCT. Patient setup was investigated in cone-beam CT scans. Results: The differences of D(CTVV95%, V50%) between dCT and pCT plans were the lowest in the pelvis (1.0%, 1.1%), lumbar spine (0.6%, 0.7%) and thoracic spine (0.7%, 2.1%), while the differences were higher in cervical spine (3.7%, 1.9%), long bones (2.3%, 0.8%), and costae (1.6%, 1.4%). The patient set-up was acceptable for 100% of the pelvic and lumbar, for 92% of thoracic spine cases, and for <80% of cases in other sites. Conclusion: This study showed the feasibility of using dCT images in palliative RT planning of BMs in thoracic, lumbar spine and pelvic sites, indicating the potential suitability of this strategy for clinical use.

Chemoradiation for oesophageal cancer: the choice of treatment modality.

BACKGROUND: Locally advanced oesophageal cancer can be treated with definitive chemoradiation (dCRT) or with neoadjuvant chemoradiation followed by surgery (nCRT + S), but treatment modality choice is not always clear. The aim of this study was to investigate the factors associated with the choice of treatment modality in locally advanced oesophageal cancer. METHODS: This was a retrospective cohort study of 149 patients treated with dCRT(n = 85) or nCRT + S (n = 64) for oesophageal cancer in Helsinki University Hospital in 2008-2018. Logistic regression was used to analyse factors associated with choice of treatment modality and to compare dosimetric factors with postoperative complications. Multivariate analyses identified factors associated with survival. RESULTS: Surgery was performed after chemoradiation as planned on 64/91 patients (70%). 28/64 had pathological complete response (44%). Probability of nCRT + S was higher in stages I-III versus IV (OR 3.62, 95% CI 1.53-8.53; P = .003), ECOG 0-1 versus 2 (OR 6.99, 95% CI 1.81-26.96; P = .005) or in the middle/lower vs upper oesophageal tumours (OR 5.61, 95% CI 1.83-17.16, P = .003). Probability for surgery was lower, if patient had lost > 10% of body weight (OR 0.46, 95% CI 0.21-0.98, P = 0.043). Patients in the nCRT + S group had significantly better median overall survival (mOS) and local control than the dCRT group (60 vs. 10 months, P < .001 and 53 vs. 6 months, P < 0.0001, respectively). 10/85 (12%) patients died within three months after dCRT. In multivariate analysis, nCRT + S was associated with improved mOS (HR 0.28, 95% CI 0.17-0.44, P < .001). Current smokers had worse mOS (HR 2.02, 95% CI 1.04-3.92, P = .037) compared to never-smokers. No significant dosimetric factor associated with postoperative complications was found. CONCLUSION: The overall clinical status of the patients and the stage of the cancer guide the choice of treatment modalities, leading to overtreatment. Patients with better prognoses were more likely operated after chemoradiation, although there is no evidence of OS benefit in previous randomized trials. On the other hand, the prognosis was poor for patients with poor general health and advanced cancers, despite the chemoradiation. Thus, there are signs of overtreatment. MDT practice should be recommended to optimise the choice of treatment modalities. Smoking status is an independent factor associated with survival.

From Nuclear Reactor-Based to Proton Accelerator-Based Therapy: The Finnish Boron Neutron Capture Therapy Experience.

The authors review the results of 249 patients treated with boron neutron capture therapy (BNCT) at the Helsinki University Hospital, Helsinki, Finland, from May 1999 to January 2012 with neutrons obtained from a nuclear reactor source (FiR 1) and using l-boronophenylalanine-fructose (l-BPA-F) as the boron delivery agent. They also describe a new hospital BNCT facility that hosts a proton accelerator-based neutron source for BNCT. Most of the patients treated with nuclear reactor-derived neutrons had either inoperable, locally recurrent head and neck cancer or malignant glioma. In general, l-BPA-F-mediated BNCT was relatively well tolerated with adverse events usually similar to those of conventional radiotherapy. Twenty-eight (96.6%) out of the evaluable 29 patients with head and neck cancer and treated within a clinical trial either responded to BNCT or had tumor growth stabilization for at least 5 months, suggesting efficacy of BNCT in the treatment of this patient population. The new accelerator-based BNCT facility houses a nuBeam neutron source that consists of an electrostatic Cockcroft-Walton-type proton accelerator and a lithium target that converts the proton beam to neutrons. The proton beam energy is 2.6 MeV operating with a current of 30 mA. Treatment planning is based on Monte Carlo simulation and the RayStation treatment planning system. Patient positioning is performed with a 6-axis robotic image-guided system, and in-room imaging is done with a rail-mounted computed tomography scanner. Under normal circumstances, the personnel can enter the treatment room almost immediately after shutting down the proton beam, which improves the unit capacity. ClinicalTrials.gov ID: NCT00114790.

Determination of acceptance criteria for geometric accuracy of magnetic resonance imaging scanners used in radiotherapy planning.

BACKGROUND AND PURPOSE: Magnetic resonance imaging is increasingly used in radiotherapy planning; yet, the performance of the utilized scanners is rarely regulated by any authority. The aim of this study was to determine the geometric accuracy of several magnetic resonance imaging scanners used for radiotherapy planning, and to establish acceptance criteria for such scanners. MATERIALS AND METHODS: The geometric accuracy of five different scanners was measured with three sequences using a commercial large-field-of-view phantom. The distortion magnitudes were determined in spherical volumes around the scanner isocenter and in cylindrical volumes along scanner z-axis. The repeatability of the measurements was determined on a single scanner with two quality assurance sequences with three single-setup and seven repeated-setup measurements. RESULTS: For all scanners and sequences except one, the mean and median distortion magnitude was <1 mm and <2 mm in spherical volumes with diameters of 400 mm and 500 mm, respectively. For all sequences maximum distortion was <2 mm in spherical volume with diameter of 300 mm. The mean standard deviation of marker-by-marker distortion magnitudes over repeated acquisitions was ≤0.6 mm with both tested sequences. CONCLUSIONS: All tested scanners were geometrically accurate for their current use in radiotherapy planning. The acceptance criteria of geometric accuracy for regulatory inspections of a supervising authority could be set according to these results.

Acquisition-weighted MRSI for detection and quantification of BNCT 10B-carrier L-p-boronophenylalanine-fructose complex, a phantom study.

Proton magnetic resonance spectroscopy (1H MRS) is a potential method to detect and quantify a boron neutron capture therapy 10B-carrier compound, L-p-boronophenylalanine (BPA), in the brain. However, optimal positioning of MRS voxel to capture tissue with maximal BPA concentration can be challenging. Three dimensional proton magnetic resonance spectroscopic imaging (3D 1H MRSI) provides spectral data covering a large spatial volume, which is a major advantage in detecting and quantifying BPA. BPA detection limit in phantom conditions was determined at 1.5 T using a 3D 1H MRSI protocol with clinically acceptable nominal spatial resolution and duration. Quantification tests for aqueous phantom were performed using both single voxel MRS and 3D MRSI. In 3D MRSI, BPA detection limit was approximately 1.0 mM and BPA quantification accuracy was better than +/-5%. The results suggest that MRSI would be a feasible method for in vivo BPA evaluation in clinical conditions.

Boron neutron capture therapy for locally recurrent head and neck squamous cell carcinoma: An analysis of dose response and survival.

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma (HNSCC) that recurs locally is a therapeutic challenge. We investigated the efficacy of boron neutron capture therapy (BNCT) in the treatment of such patients and the factors associated with treatment response and survival. METHODS AND MATERIALS: Seventy-nine patients with inoperable, locally recurred HNSCC were treated with l-boronophenylalanine-mediated BNCT in Espoo, Finland, between February, 2003 and January, 2012. Prior treatments consisted of surgery and conventionally fractionated radiotherapy to a median cumulative dose of 66 Gy (interquartile range [IQR], 59-70 Gy) administered with or without concomitant chemotherapy. Tumor response was assessed using the RECISTv.1.0 criteria. RESULTS: Forty patients received BNCT once (on 1 day), and 39 twice. The median time between the 2 treatments was 6 weeks. Forty-seven (68%; 95% confidence interval [CI], 57-79%) of the 69 evaluable patients responded; 25 (36%) had a complete response, 22 (32%) a partial response, 17 (25%) a stable disease lasting for a median of 4.2 months, and 5 (7%) progressed. The patients treated with BNCT twice responded more often than those treated once. The median follow-up time after BNCT was 7.8 years. The 2-year locoregional progression-free survival rate was 38% and the overall survival rate 21%. A high minimum tumor dose and a small volume were independently associated with long survival in a multivariable analysis. CONCLUSIONS: Most patients responded to BNCT. A high minimum tumor dose from BNCT was predictive for response and survival.

Boron neutron capture therapy in the treatment of locally recurred head and neck cancer.

PURPOSE: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. METHODS AND MATERIALS: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. RESULTS: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). CONCLUSIONS: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy.

Radiation sensitive polymer gels are among the most promising three-dimensional dose verification tools developed to date. Polymer gel dosimeter known by the acronym MAGIC has been tested for evaluation of its use in boron neutron capture (BNCT) dosimetry. We irradiated a large (diameter 10 cm, length 20 cm) cylindrical gel phantom in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. Gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator to compare dose response in the two different types of beams. Irradiated gel phantoms were imaged using MRI to determine their relaxation rate R2 maps. The measured and normalized dose distribution in the epithermal neutron beam was compared to the dose distribution calculated by computer simulation. The results support the feasibility MAGIC gel in BNCT dosimetry.

Diffusion-weighted magnetic resonance imaging for evaluation of salivary gland function in head and neck cancer patients treated with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSES: Permanent xerostomia as a result of radiation-induced salivary gland damage remains a common side effect of radiotherapy (RT) of the head and neck. The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing the post-RT salivary gland function in patients with head and neck cancer (HNC). MATERIALS AND METHODS: In this prospective study, 20 HNC patients scheduled for bilateral neck chemoradiotherapy (CRT) with weekly cisplatin went through diffusion-weighted magnetic resonance imaging (DW-MRI) and salivary gland scintigraphy (SGS) prior to and at a mean of six months after completing the treatment. The changes in apparent diffusion coefficient (ADC) before and after treatment were compared with ejection fraction (EF) measured with SGS and the radiation dose absorbed by the salivary glands. RESULTS: As a result of gustatory stimulation with ascorbic acid, the ADC showed a biphasic response with an initial increase and subsequent decrease. This pattern was seen both before and after RT. Post-RT ADC increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between pre- and post-RT ADCs at rest and EF measured with SGS was found. CONCLUSIONS: DW-MRI seems a promising tool for detection of physiological and functional changes in major salivary glands after RT.