Clinical outcomes using a 3D printed tandem-needle-template and the EMBRACE-II planning aims for image guided adaptive brachytherapy in locally advanced cervical cancer.

BACKGROUND: Extensive local disease or narrow vagina may compromise brachytherapy (BT) in patients with cervical cancer. This is the first study to analyze long-term outcomes of using 3D printed vaginal tandem-needle templates (3DP TNT) for transvaginal insertion of needles in parallel (P) or parallel and oblique (P&O) direction to the tandem. MATERIAL AND METHODS: All patients treated with BT using 3DP TNT from 2015-2020 were included. Decision to use a 3DP TNT and preplanning were made after 4-5 weeks of external beam radiotherapy, based on gynecological examination and MRI with a tandem-ring applicator in situ. The TNT was 3D-printed in house consisting of a circular template with P&O holes for guidance of plastic needles and a shaft fitting the uterine tandem. Thus, the radioactive source was never in direct contact with the 3DP TNT. The TNT was 3D printed in a standard or personalized configuration. Planning aims were based on the Embrace II protocol. RESULTS: 101 patients (median age of 63 years) were included: 49 with P needles only and 52 with P&O needles. Personalized TNT was used in 19 patients in the P&O group. Performance status (WHO) was > 0 in 48%. FIGO2018 stage III-IV was present in 77%. T-score at diagnosis and BT was 9.1 and 6.3 respectively, with a significantly higher T-score in the P&O compared to P group. The mean high-risk CTV D90 was 93 Gy with no significant difference between the two groups. Three-year local control rates were 85%, 95%, 75% for the overall, P- and P&O group respectively and 68%, 80% and 56% for cancer specific survival. Grade ≥3 treatment related complications were observed in 10 (10%) patients. CONCLUSIONS: 3DP TNT for BT in cervical cancer provides successful management of very extensive local disease and/or unfavorable anatomy with the possibility for treatment individualization.

3D dose reconstruction based on in vivo dosimetry for determining the dosimetric impact of geometric variations in high-dose-rate prostate brachytherapy.

INTRODUCTION: In vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. MATERIALS AND METHODS: Twenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. RESULTS: Of 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters. The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D90% was 5%. In one fraction, the bladder D2cm3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). CONCLUSION: IVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy.

Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes.

BACKGROUND: Evidence suggests that prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) are at risk for cognitive decline (CD), but the underlying mechanisms are less clear. In the present study, changes in cognitive performance and structural brain connectomes in PC patients undergoing ADT were assessed, and associations of cognitive changes with endocrine status and risk genotypes were explored. METHODS: Thirty-seven PC patients underwent cognitive assessment, structural MRI, and provided blood samples prior to ADT and after 6 months of treatment. Twenty-seven age- and education-matched healthy controls (HCs) underwent the same assessments. CD was determined using a standardized regression-based approach and defined as z-scores ≤ -1.64. Changes in brain connectomes were evaluated using graph theory. Associations of CD with testosterone levels and genotypes (APOE, COMT, BDNF) were explored. RESULTS: Compared with HCs, PC patients demonstrated reduced testosterone levels (p < 0.01) and higher rates of decline for 13 out of 15 cognitive outcomes, with three outcomes related to two cognitive domains, i.e., verbal memory and visuospatial learning and memory, reaching statistical significance (p ≤ 0.01-0.04). Testosterone level changes did not predict CD. COMT Met homozygote PC patients evidenced larger reductions in visuospatial memory compared with Val carriers (p = 0.02). No between-group differences were observed in brain connectomes across time, and no effects were found of APOE and BDNF. CONCLUSIONS: Our results indicate that PC patients undergoing ADT may evidence CD, and that COMT Met homozygotes may be at increased risk of CD. The results did not reveal changes in brain connectomes or testosterone levels as underlying mechanisms. More research evaluating the role of ADT-related disruption of the dynamics of the hypothalamic-pituitary-gonadal axis is needed.

Accuracy of an in vivo dosimetry-based source tracking method for afterloading brachytherapy - A phantom study.

PURPOSE: To report on the accuracy of an in vivo dosimetry (IVD)-based source tracking (ST) method for high dose rate (HDR) prostate brachytherapy (BT). METHODS: The ST was performed on a needle-by-needle basis. A least square fit of the expected to the measured dose rate was performed using the active dwell positions in the given needle. Two fitting parameters were used to determine the position of each needle relative to the IVD detector: radial (away or toward the detector) and longitudinal (along the axis of the treatment needle). The accuracy of the ST was assessed in a phantom where the geometries of five HDR prostate BT treatments previously treated at our clinic were reproduced. For each of the five treatment geometries, one irradiation was performed with the detector placed in the middle of the implant. Furthermore, four additional irradiations were performed for one of the geometries where the detector was retracted caudally in four steps of 10-15 mm and up to 12 mm inferior of the most inferior active dwell position, which represented the prostate apex. The time resolved dose measurements were retrieved at a rate of 20 Hz using a detector based on an Al2 O3 :C radioluminescence crystal, which was placed inside a standard BT needle. Individual calibrations of the detector were performed prior to each of the nine irradiations. RESULTS: Source tracking could be applied in all needles across all nine irradiations. For irradiations with the detector located in the middle region of the implant (a total of 89 needles), the mean ± standard deviation (SD, k = 1) accuracy was -0.01 mm ± 0.38 mm and 0.30 mm ± 0.38 mm in the radial and longitudinal directions, respectively. Caudal retraction of the detector did not lead to reduced accuracy as long as the detector was located superior to the most inferior active dwell positions in all needles. However, reduced accuracy was observed for detector positions inferior to the most inferior active dwell positions which corresponded to detector positions in and inferior to the prostate apex region. Detector positions in the prostate apex and 12 mm inferior to the prostate resulted in mean ± SD (k = 1) ST accuracy of 0.7 mm ± 1 mm and 2.8 mm ± 1.6 mm, respectively, in radial direction, and -1.7 mm ± 1 mm and -2.1 mm ± 1.1 mm, respectively, in longitudinal direction. The largest deviations for the configurations with those detector positions were 2.6 and 5.4 mm, respectively, in the radial direction and -3.5 and -3.8 mm, respectively, in the longitudinal direction. CONCLUSION: This phantom study demonstrates that ST based on IVD during prostate BT is adequately accurate for clinical use. The ST yields submillimeter accuracy on needle positions as long as the IVD detector is positioned superior to at least one active dwell position in all needles. Locations of the detector inferior to the prostate apex result in decreased ST accuracy while detector locations in the apex region and above are advantageous for clinical applications.

Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in patients with newly diagnosed prostate cancer referred to androgen-deprivation therapy.

BACKGROUND: Evidence suggests that patients with prostate cancer (PCPs) receiving androgen-deprivation therapy (ADT) are at risk for cognitive impairment. Research with other populations with cancer indicates that cognitive impairment may also occur before systemic treatment. The authors assessed cognitive impairment in untreated PCPs referred to ADT and explored associations with structural brain networks, endocrine status, and selected genotypes. METHODS: Forty untreated PCPs and 27 healthy controls (HCs) who completed a questionnaire package underwent neuropsychological testing, magnetic resonance imaging, and blood sampling. Cognitive impairment was defined as a z score ≤-2 on 1 neuropsychological test or ≤-1.5 on 2 neuropsychological tests. Structural brain networks were investigated using diffusion-weighted imaging and graph theory. Associations of cognitive performance with patient-reported outcome measures (PROMs), brain networks, testosterone levels, and genotypes (apolipoprotein ε [APOE], catechol-O-methyltransferase [COMT], and brain-derived neurotrophic factor [BDNF]) were explored. RESULTS: PCPs performed poorer than HCs on 7 of 15 neuropsychological tests and exhibited a higher frequency of cognitive impairment (57.5% vs 22.2%; P ≤ .01 to .03). All neuropsychological outcomes were associated with ≥1 PROM (P ≤ .01 to .04). Compared with the HC group, the PCP group exhibited altered global network organization as well as disrupted regional network characteristics in frontal and temporal regions (P < .01). PCPs had lower testosterone levels (P < .01) than HCs, which correlated with better visuospatial performance (r = -0.33; P = .04). No effects were found of APOE, COMT, or BDNF. CONCLUSIONS: The current results suggest that untreated PCPs may demonstrate cognitive impairment and that psychological and behavioral symptoms (PROMs), as well as impairment in structural brain networks, might be the underlying mechanisms.

Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI.

PURPOSE: To quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration. METHODS AND MATERIALS: Twenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTVprostate+3mm. The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy. RESULTS: Needle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTVprostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively. CONCLUSIONS: Substantial needle migration in high-dose-rate brachytherapy occurs frequently in 1-3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy.

Time-resolved in vivo dosimetry for source tracking in brachytherapy.

PURPOSE: The purpose of this article is to demonstrate that brachytherapy source tracking can be realized with in vivo dosimetry. This concept could enable real-time treatment monitoring. METHODS: In vivo dosimetry was incorporated in the clinical routine during high-dose-rate prostate brachytherapy at Aarhus University Hospital. The dosimetry was performed with a radioluminescent crystal positioned in a dedicated brachytherapy needle in the prostate. The dose rate was recorded every 50-100 ms during treatment and analyzed retrospectively. The measured total delivered dose and dose rates for each dwell position with dwell times >0.7 s were compared with expected values. Furthermore, the distance between the source and dosimeter, which was derived from the measured dose rates, was compared with expected values. The measured dose rate pattern in each needle was used to determine the most likely position of the needle relative to the dosimeter. RESULTS: In total, 305 needles and 3239 dwell positions were analyzed based on 20 treatments. The measured total doses differed from the expected values by -4.7 ± 8.4% (1SD) with range (-17% to 12%). It was possible to determine needle shifts for 304 out of 305 needles. The mean radial needle shift between imaging and treatment was 0.2 ± 1.1 mm (1SD), and the mean longitudinal shift was 0.3 ± 2.0 mm (1SD). CONCLUSION: Time-resolved in vivo dosimetry can be used to provide geometric information about the treatment progression of afterloading brachytherapy. This information may provide a clear indication of errors and uncertainties during a treatment and, therefore, enables real-time treatment monitoring.

Vertebral Myeloma Mimicking Prostatic Carcinoma Metastasis in 68Ga-PSMA PET/CT.

Ga-PSMA PET/CT was performed in a 75-year-old man with newly diagnosed prostate cancer because of an equivocal lesion in the spine both on Tc-bone-SPECT/CT and MRI. Because of increased PSMA activity on PET/CT, the bone lesion was interpreted as metastasis from prostate cancer. Later, the patient was diagnosed as having monoclonal gammopathy of unknown significance. A biopsy was performed, and histological examination revealed multiple myeloma with PSMA expression in the neovessels but no metastatic prostate cancer cells. The patient was downstaged, and the treatment was changed accordingly. This case illustrates the importance of biopsies from PSMA PET-positive lesions.

Dosimetric impact of contouring and needle reconstruction uncertainties in US-, CT- and MRI-based high-dose-rate prostate brachytherapy treatment planning.

BACKGROUND AND PURPOSE: The purpose was to evaluate the dosimetric impact of target contouring and needle reconstruction uncertainties in an US-, CT- and MRI-based HDR prostate BT treatment planning. MATERIAL AND METHODS: US, CT, and MR images were acquired post-needle insertion in 22 HDR-BT procedures for 11 consecutive patients. Dose plans were simulated for an US-, CT- and MRI-based HDR-BT treatment planning procedure. Planning uncertainties in US- and CT-based plans were evaluated using MRI-based planning as reference. Target (CTVProstate) was re-contoured on MRI. Dose results were expressed in total equivalent dose given in 2Gy fractionation dose for EBRT (46Gy) plus 2 HDR-BT fractions. RESULTS: Uncertainties in US- and CT-based planning caused the planned CTVProstate-D90% to decrease with a mean of 2.9±5.0Gy (p=0.03) and 2.9±2.9Gy (p=0.001), respectively. The intra-observer contouring variation on MRI resulted in a mean variation of 1.6±1.5Gy in CTVProstate-D90%. Reconstruction uncertainties on US resulted in a dose variation of±3Gy to the urethra, whereas data for CT were not available for this. CONCLUSIONS: Uncertainties related to contouring and reconstruction in US- and CT-based HDR-BT treatment plans resulted in a systematic overestimation of the prescribed target dose. Inter-modality uncertainties (US and CT versus MR) were larger than MR intra-observer uncertainties.

Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer.

PURPOSE: To evaluate introduction of MRI-based high-dose-rate brachytherapy (HDRBT), including procedure times, dose-volume parameters, and perioperative morbidity. METHODS AND MATERIALS: Study included 42 high-risk prostate cancer patients enrolled in a clinical protocol, offering external beam radiotherapy + two HDRBT 8.5 Gy boosts. Time was recorded for initiation of anesthesia (A), fixation of needle implant (B), end of MR imaging (C), plan approval (D), and end of HDRBT delivery (E). We defined time A-E as total procedure time, A-B as operating room time, B-C as MRI procedure time, C-D as treatment planning time, and D to E as treatment delivery time. Dose-volume parameters were retrieved from the dose planning system. Results from the first 21 patients were compared with the last 21 patients. RESULTS: Total procedure time, operating room time, MRI procedure time, and treatment planning time decreased significantly from average 7.6 to 5.3 hours (p < 0.01), 3.6 to 2.4 hours (p < 0.01), 1.6 to 0.8 hours (p < 0.01), and 2.0 to 1.3 hours (p < 0.01), respectively. HDRBT delivery time remained unchanged at 0.5 hours. Clinical target volume prostate+3mmD90 fulfilled planning aim in 92% of procedures and increased significantly from average 8.3 to 9.0 Gy (p < 0.01). Urethral D0.1 cm(3) and rectal D2 cm(3) fulfilled planning aim in 78% and 95% of procedures, respectively, and did not change significantly. Hematuria occurred in (95%), hematoma (80%), moderate to strong pain (35%), and urinary retention (5%) of procedures. CONCLUSIONS: After introduction of MRI-based HDRBT, procedure times were significantly reduced. D90 Clinical target volumeprostate+3mm fulfilled constraints in most patients and improved over time, but not at expense of an increased urethral or rectal dose.

The influence of a rectal ultrasound probe on the separation between prostate and rectum in high-dose-rate brachytherapy.

PURPOSE: The aim of this study was to compare the distance between prostate and rectum as well as rectal dose-volume histogram (DVH) parameters for high-dose-rate (HDR) prostate brachytherapy (BT) with and without a transrectal ultrasound (US) probe in place during delivery. METHODS AND MATERIALS: The study included 20 patients with high-risk prostate cancer treated consecutively with combined external beam radiotherapy (EBRT) and MRI-based HDR-BT. The MRI-based HDR-BT dose plan and prostate gland contour were transferred to the US images after rigid MRI/US coregistration, followed by delineation of the rectum on US images acquired with a transrectal US probe. The prostate-rectum separation was estimated at the apex, reference, and base plane on the US (with rectal probe) and MR images (without rectal probe). Rectal DVH parameters for EBRT + HDR-BT given in equivalent 2 Gy fractionation doses were estimated and compared for US-based and MRI-based HDR-BT dose planning. RESULTS: The median (and range) prostate-rectum separation increased on MR images (without rectal probe) as compared with on US images (with rectal probe) by 10 mm (-5, 18) at the base, 1 mm (-2, 3) at the reference and decreased at the apex by 2 mm (-5, 11). The rectal D5.0cm3, D2.0cm3, and D0.1cm3 decreased by a median of 4 Gy (-1, 10), 4 Gy (-2, 13), and 7 Gy (-4, 26), respectively. CONCLUSIONS: MRI-based HDR-BT without a rectal US probe in place as compared with US-based BT with the probe in place demonstrated a significant increase in the prostate-rectum separation, with a potential of reducing rectal dose.

Identifying hypoxia in human tumors: A correlation study between 18F-FMISO PET and the Eppendorf oxygen-sensitive electrode.

INTRODUCTION: Polarographic oxygen-sensitive electrodes have demonstrated prognostic significance of hypoxia. However, its routine application is limited. (18)F-FMISO PET scans are a noninvasive approach, able to measure spatial and temporal changes in hypoxia. The aim of this study was to examine the association between measures of hypoxia defined by functional imaging and Eppendorf pO(2) electrodes. MATERIALS AND METHODS: A total of 18 patients were included, nine squamous cell carcinoma of the head and neck and nine soft tissue tumors. The tumor volume was defined by CT, MRI, (18)FDG-PET or by clinical examination. The oxygenation status of the tumors was assessed using (18)F-FMISO PET imaging followed by Eppendorf pO(2) electrode measurements. Data were compared in a 'virtual voxel', resulting in individual histograms from each tumor. RESULTS: The percentages of pO(2) ≤ 5 mmHg ranged from 9 to 94% (median 43%) for all 18 tumors. For (18)F-FMISO PET the T/M ratio ranged from 0.70 to 2.38 (median 1.13). Analyzing the virtual voxel histograms tumors could be categorized in three groups: Well oxygenated tumors with no hypoxia and concordance between the (18)F-FMISO data and the Eppendorf measurements, hypoxic tumors likewise with concordance between the two assays and inconclusive tumors with no concordance between the assays. CONCLUSION: This study analyzed the relationship between (18)F-FMISO PET and Eppendorf pO(2) electrode measurements by use of a virtual voxel model. There was a spectrum of hypoxia among tumors that can be detected by both assays. However no correlation was observed, and in general tumors were more hypoxic based on Eppendorf pO(2) measurements as compared to (18)F-FMISO PET.

Prospective study of 18FDG-PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA-13 study.

BACKGROUND: The benefit of a complementary fluorodeoxyglucose-positron emission tomography (FDG-PET) scan to standard workup for carcinoma of unknown primary (CUP) and metastatic neck lesions was prospectively studied. METHODS: Sixty-seven patients underwent standardized diagnostic workup according to national guidelines including panendoscopies, multiple mucosal biopsies, and diagnostic CT/MRI scans. Median follow-up was 40 months (range, 2-65 months). RESULTS: In 60 eligible patients, FDG-PET indicated a primary tumor or metastatic disease in 30 patients (50%). Additional investigations confirmed a primary tumor in 18 patients: hypopharynx in 5, oropharynx in 5, nasopharynx in 2, lung in 1, axilla in 1, bone in 1, rectum in 1, as well as multiple metastatic lesions from CUP in 2 patients. In retrospect, MRI was able to detect 1 of the PET-detected primaries, leading to an overall detection rate of PET of 29% in CUP. A therapeutic change of treatment was made in 25% as a consequence of FDG-PET. PET before panendoscopy demonstrated fewer false-positive pathological foci. CONCLUSION: FDG-PET is a valuable tool in addition to conventional extensive workup in CUP and neck metastases. Consequently, FDG-PET is now recommended as an early diagnostic modality in the workup of these patients.

Individual radiation response of parotid glands investigated by dynamic 11C-methionine PET.

BACKGROUND AND PURPOSE: Previously, we showed that the net metabolic clearance of 11C-methionine of the parotid gland, K, calculated from dynamic 11C-methionine PET, can be used as a measure of parotid gland function. The aim of this study was to investigate by dynamic 11C-methionine PET the individual radiation dose response relationship of parotid glands in head and neck cancer patients. PATIENTS AND METHODS: Twelve head and neck cancer patients were examined by dynamic 11C-methionine PET after radiotherapy. Parametric images of K were generated, co-registered and compared voxel-by-voxel with the 3D radiation dose plan within the parotid gland to assess the individual radiation dose-function relationship. RESULTS: In each patient, voxel-values of K decreased with increasing radiation dose. Population based analysis showed a sigmoid dose response relationship of parotid gland, from which we estimated a threshold radiation dose of 16 Gy and a mean TD50 of 30 Gy. TD50 ranged from 7 to 50 Gy in the group of patients. CONCLUSIONS: Individual radiation dose response of parotid glands can be measured by dynamic 11C-methionine PET. The dose response analysis revealed a sigmoid relationship, a threshold radiation dose of 16 Gy, and a mean TD50 of 30 Gy.

FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma.

Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET-positive patients progressed and 2 died. Three of 61 FDG-PET-negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.

11C-methionine PET, a novel method for measuring regional salivary gland function after radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: Loss of salivary gland function is a distressing side-effect of radiotherapy (RT) for head and neck cancer. The aim of this study was to develop a positron emission tomography (PET) method for measuring regional salivary gland function in the major salivary glands irradiated during RT. PATIENTS AND METHODS: Eight head and neck cancer patients were included; two were examined before RT and six after parotid sparing RT. Patients were examined by dynamic 11C-methionine PET of the major salivary glands and parotid gland salivary flow measurements. PET data were analysed using a kinetic model of salivary gland 11C-methionine metabolism, in which salivary gland function was quantified by the net metabolic clearance of 11C-methionine, K. Functional voxel-wise images of K were calculated and matched with the CT-dose-plan for comparing regional salivary gland function with the regional radiation dose. RESULTS: Parotid gland K correlated positively with parotid gland salivary flow, indicating that K can be used as an index of salivary gland function. K of parotid and submandibular glands was reduced dependent on the median radiation dose. In one patient, receiving a heterogeneous radiation dose to the parotid glands, regional salivary gland function was inversely correlated to the regional radiation dose. CONCLUSIONS: Salivary gland function can be measured by dynamic 11C-methionine PET. The net metabolic clearance of 11C-methionine of salivary glands was reduced dependent on the radiation dose. Dynamic 11C-methionine PET offers a method for studying the individual response of the major salivary glands to irradiation.