The aim of our study is to retrospectively report the radiobiological aspects for intensity-modulated proton therapy (IMPT) against intensity-modulated radiation therapy (IMRT) for patients with head and neck cancer treated at our institution. A secondary goal is to reinforce current model-based approaches to head and neck cancer patient selection for IMPT.

Eighteen patients were evaluated with prescription doses ranging from 50 to 70 Gy delivered in 2 Gy per fraction. The dose volume histograms (DVH) were used to calculate equivalent uniform dose (EUD), tumour control probability (TCP) and normal tissue complication probability (NTCP) for biophysical comparison using mechanistic mathematical dose response models. Absolute values of TCP and NTCP were then compared between IMPT and IMRT.

The dose models demonstrate a minimal radiobiological advantage for IMPT compared to IMRT in treating head and neck cancers. Absolute values of TCP were slightly higher, while absolute values of NTCP were slightly lower for IMPT versus IMRT.

Further studies are needed to determine if the radiobiological advantage indeed translates to a therapeutic advantage for patients.

This investigation quantifies the dose enhancement effect and dose distribution modifications due to the presence of high-z nanospheres in a proton beam.

Various proton pencil beams of therapeutic energies (60–226 MeV) and spatial distribution of 2·7 mm spot size diameter were simulated onto a water phantom utilising the TOPAS Monte Carlo toolkit version 3.6.1. The simulation modelled either water or nanospheres of high-z materials (gold, silver or platinum) at the location of the Bragg Peak (BP) to compare the differences of the resulting dose distributions.

The introduction of the nanospheres increases the maximum dose, narrows the BP and shifts the BP location upstream compared to the water phantom with no nanospheres.

This work shows that the local dose can be enhanced with the use of high-z nanoparticles in proton therapy, thereby increasing patient safety and decreasing side effects with the same amount of delivered radiation.

Intensity-modulated radiation therapy (IMRT) has revolutionised the way head and neck cancers can be treated. It allows for a more conformal treatment plan when compared to 3D conformal radiation therapy. In paediatric patients, however, IMRT continues to deliver higher doses than desirable. Proton beam therapy on the other hand has the potential to further spare organs-at-risk.

A 16-year-old boy with a left-sided paraganglioma of the left base of skull manifested by headaches, neck pain and tongue cramping was simulated, planned and treated with proton therapy with significant contralateral organ-at-risk sparing.

For this patient, dosimetric plan comparison between photon and proton plans clearly showed better sparing of contralateral organs-at-risk with protons. The contralateral parotid gland received a mean dose of 386·3 cGy with photons, whereas it received 1·3 cGy (CGE) in the proton plan.

The dosimetric advantage of proton beam over photon beam therapy has successfully been demonstrated in this case study for a paediatric patient with a head and neck tumour. Sparing of contralateral structures is especially important in paediatric patients who are at a greater risk of secondary malignancies due to possible long life expectancy.

This study aims to look at the trends in our head and neck cancer patient population over the past 5 years with an emphasis on the past 2 years to evaluate how the coronavirus disease 2019 (COVID-19) pandemic has impacted our disparities and availability of care for patients, especially those living in rural areas. An additional aim is to identify existing disparities at our institution in the treatment of head and neck patients and determine solutions to improve patient care.

A retrospective chart review was performed to identify patients who were consulted and subsequently treated with at least one fraction of radiation therapy at our institution with palliative or curative intent. Patient demographic information was collected including hometown, distance from the cancer centre based on zip-codes and insurance information and type of appointment (in-person or telehealth). Rural–urban continuum codes were used to determine rurality.

A total of 490 head and neck cancer patients (n = 490) were treated from 2017 to 2021. When broken down by year, there were no significant trends in patient population regarding travel distance or rurality. Roughly 20–30% of our patients live in rural areas and about 30% have a commute > 50 miles for radiation treatment. A majority of our patients rely on public insurance (68%) with a small percentage of those uninsured (4%). Telehealth visits were rare prior to 2019 and rose to 5 and 2 visits in 2020 and 2021, respectively.

Head and neck cancer patients, despite rurality or distance from a cancer centre, may present with alarmingly enough symptoms despite limitations and difficulties with seeking medical attention even during the COVID-19 pandemic in 2020. However, providers must be aware of these potential disparities that exist in the rural population and seek to address these.

The dosimetric and clinical advantages offered by implementation of pencil beam scanning (PBS) proton therapy for moving thoracic tumours is hindered by interplay effect. The purpose of this study is to evaluate the impact of large proton beam spot size along with adaptive aperture (AA) and various motion mitigation techniques on the interplay effect for a range of motion amplitudes in a three-dimensional (3D) respiratory motion phantom.

Point doses using ionisation chamber (IC) and planner dose distributions with radiochromic film were compared against the corresponding treatment planning system (TPS) information. A 3D respiratory motion phantom was scanned either for static or 4D computed tomographic (CT) technique for 6-, 10- and 14-mm motion amplitudes in SI direction. For free breathing (FB) treatment, a tumour was contoured on maximum intensity projection scan and an average scan was used for treatment planning. Each FB treatment was delivered with one, three and five volumetric repaintings (VRs). Three phases (CT40–60%) were extracted from the 4D-CT scans of each motion amplitude for the respiratory-gated treatment and were used for the treatment planning and delivery. All treatment plans were made using AA and robustly optimised with 5-mm set-up and 3·5% density uncertainty. A total of 26 treatment plans were delivered to IC and film using static, dynamic and respiratory-gated treatments combinations. A percent dose difference between IC and TPS for the point dose and gamma indices for film–TPS planner dose comparison was used.

The dose profile of film and TPS for the static phantom matched well, and percent dose difference between IC and TPS was 0·4%. The percent dose difference for all the gated treatments were below 3·0% except 14-mm motion amplitude-gated treatment. The gamma passing rate was more than 95% for film–TPS comparison for all gated treatment for the investigated gamma acceptance criteria. For FB treatments, the percent dose difference for 6-, 10- and 14-mm motion amplitude was 1·4%, −2·7% and −4·1%, respectively. As the number of VR increased, the percent difference between measured and calculated values decreased. The gamma passing rate met the required tolerance for different acceptance criteria except for the 14-mm motion amplitude FB treatment.

The PBS technique for the FB thoracic treatments up to 10-mm motion amplitude can be implemented with an acceptable accuracy using large proton beam spot size, AA and robust optimisation. The impact of the interplay effect can be reduced with VR and respiratory-gated treatment and extend the treatable tumour motion amplitude.

Vaginal cancer is a rare malignancy that poses a challenge to treat and cure, as surgical excision requires life-changing procedures because of the proximity and involvement of rectum, bladder and anus. We report in this case study the successful delivery of stereotactic ablative radiotherapy (SABR) for a patient with vaginal cancer after previous radiotherapy.

A 71-year-old white female who presented with dyspareunia and irritative urinary symptoms proven by biopsy was our candidate patient. Subsequent PET/CT revealed a hypermetabolic 3 cm lesion at the 12–1 o’clock position in the distal vagina involving the clitoris. The patient was initially treated with volumetric-modulated arc therapy (VMAT) with simultaneous integrated boost technique to the involved nodes, and later upon recurrence treated with SABR using 30 Gy in six fractions.

To our knowledge, this is the first report of a vaginal cylinder used to physically distance organs at risk from the treatment target and also as a localising device with image guidance for the delivery of SABR using an external beam.

To identify treatment outcome, dose uniformity, treatment time, toxicity among 3D conformal therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) for non-small-cell lung cancer (NSCLC) based on literature review.

A literature search was conducted using PubMed/MEDLINE, BMC—part of Springer Nature, Google Scholar and iMEDPub Ltd with the following keywords for filtering: 3D-CRT, IMRT, VMAT, lung cancer, local control and radiobiology. A total of 14 publications were finally selected for the comparison of 3D-CRT, IMRT and VMAT to determine which technique is superior or inferior among these three.

Compared to 3D-CRT, IMRT delivers more precise treatment, has better conformal dose coverage to planning target volume (PTV) that covers gross tumour with microscopic extension, respiratory tumour motion and setup margin. 3D-CRT has large number of limitations: low overall survival (OS), large toxicity, secondary malignancies.

It is difficult to choose the best technique for treating NSCLC due to patient conditions and technique availability. A high-precision treatment may improve tumour control probability (TCP) and patient’s quality of life. VMAT, whether superior or not, needs more clinical trials to treat NSCLC and requires longer dose optimisation time with the greatest benefit of rapid treatment delivery, improved patient comfort, reduced intrafraction motion and increased patient throughput compared to IMRT and 3D-CRT.

The objective of this study has been to identify monitor unit (MU) and treatment time variations, volume coverage dissimilarity among 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans for head and neck cancer (HNC) based on literature review.

A number of HNC cases were studied with the investigation of conformity and homogeneity index.

When high-dose modulation was required around small organs at risk (OARs), a clinically acceptable IMRT plan was achieved as VMAT usually required longer dose optimisation time. The greatest benefit of VMAT has been rapid treatment delivery allowing improved patient comfort, reduced intra-fraction motion and increased patient throughput. In some papers, 3D-CRT was shown not to meet well the requirements on parotid glands. One paper showed that cerebellum dose was lower for 3D-CRT than IMRT. However, it was found in other papers that OAR sparing with 3D-CRT was reasonable but in complex cases not enough.

IMRT usually consists of several treatment fields with different directions, hundreds of beam lets with modulated intensity, an advantage over 3D-CRT, whereas VMAT has advantage over IMRT due to rotating beam utilisation. VMAT has lower total MU and treatment times than IMRT and 3D-CRT, while maintaining similar dosimetric endpoints.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy typically involving the skin. The majority of MCC involves the head/neck region and the extremities. Despite the aggressive nature of the disease, there have been several case studies that report spontaneous regression. We report a unique case of spontaneous regression of an MCC in a peculiar region in the anterior mediastinum with no cutaneous involvement.

A 50-year-old man who presented with a mobile low anterior neck mass, proven by biopsy, to be MCC. Subsequent PET/CT confirmed an FDG (Flurodeoxyglucose)-avid upper mediastinal mass. The mass gradually regressed over the course of 1 month subsequent to biopsy and was no longer palpable on exam or visible on subsequent CT scans. The patient was treated with intensity modulated radiation therapy with a total dose of 6,160 cGy in 28 fractions to the site of previously visible primary disease. At-risk nodal basins were also treated. On subsequent follow-up, the patient continued to have no clinical or radiographic signs of disease.

Spontaneous regression of an MCC is rare but has been reported mostly in the head/neck region following biopsy. It is unknown why spontaneous regression occurs. There is a possibility that biopsy may stimulate T-lymphocytes resulting in spontaneous regression.

This is the first case to our knowledge of spontaneous regression of an MCC in the anterior mediastinum with no cutaneous involvement. Most MCC are seen clinically due to skin changes with a majority of cases occurring in the head/neck region.

This study dosimetrically compared volumetric-modulated arc therapy (VMAT) to intensity-modulated arc therapy (IMRT) for patients with liver carcinoma.

Ten patients with liver carcinoma previously treated with IMRT or VMAT were retrospectively selected for this study. Each patient received a total dose of 54 Gy in 1·8 Gy fractions. Dosimetric evaluations for each patient were performed using the dose–volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OAR). All dosimetric parameters were statistically analysed using mean values, standard deviations and p-values for determining the significance. The conformality index (CI) and homogeneity index (HI) were calculated and compared. For efficiency evaluation, monitor units (MUs) and beam on times (BOT) were recorded.

Compared to IMRT, VMAT plans showed significant differences in the heterogeneity with p < 0·01 and insignificant differences in both conformality and normal tissue sparing. VMAT required marginally fewer mean MU and shorter BOT when compared to IMRT with insignificant differences.

For radiation therapy treatment of liver carcinoma, IMRT and VMAT can achieve similar PTV coverage and normal tissue sparing. Treatment time is only marginally shorter with VMAT versus IMRT with insignificant differences.

Inflammatory bowel disease (IBD) [i.e., Crohn’s disease (CD) and ulcerative colitis (UC)] has been considered a relative contraindication for radiation therapy (RT) to the abdomen or pelvis, potentially preventing patients with a diagnosis of IBD from receiving definitive therapy for their malignancy.

Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) conventions, a PubMed/MEDLINE literature search was conducted using the keywords RT, brachytherapy, inflammatory bowel disease, Crohn’s disease, ulcerative colitis and toxicity.

A total of 1,206 publications were screened with an addition of 8 studies identified through hand searching. Nineteen studies met the inclusion criteria for quantitative analysis. The total population across all studies was 497 patients, 50·5% having UC, 37% having CD and an additional 12·5% having unspecified IBD. Primary gastrointestinal malignancy (55%) followed by prostate cancer (40%) composed the bulk of the population. Acute and late grade 3 or greater gastrointestinal specific toxicity ranged from 0–23% to 0–13% respectively for those patients with IBD treated with RT to the abdomen or pelvis. In the literature reviewed, RT does not appear to increase fistula or stricture formation or IBD flares; however, one study did note RT to be a statistically significant risk factor for subsequent IBD flare on multivariate analysis.

A review of reported acute and late toxicities suggests that patients with IBD should still be considered for definitive radiotherapy. Patient characteristics including IBD distribution relative to the irradiated field, inflammatory activity at the time of radiation, overall disease severity and disease phenotype in the case of CD (fistulising versus stricturing versus inflammatory only) should be considered on an individual basis when evaluating potential patients. When possible, advanced techniques with strict organ at risk dose constraints should be employed to limit toxicity in this patient population.

Microcomputers play an increasingly important role in the delivery of radiation therapy. Exposure to neutron irradiation can produce undesirable effects in modern microcomputers. The objective of this study is to measure acute and cumulative effects of neutron exposure of Intel-based microcomputers in photon and proton therapy treatment environments.

Multiple computers were irradiated with neutrons produced from MEVION S250 passive scattering proton therapy and from Varian 21EX Linear Accelerator photon therapy systems. The energy of the proton beam was 232 MeV and the photon beam energies were 6 and 18 MV. Rates of fatal errors in computer processing unit (CPU) cores were measured.

Varying rates of fatal system errors due to upsets in the CPU cores were observed. Post-exposure routine stress testing revealed no permanent hardware defects in the random access memory (RAM) or hard disk drive (HDD) of any tested systems. Microchip manufacturers fit increasingly high numbers of transistors in the same volume and the susceptibility to radiation thus increases.

This work explores if the process size of a microchip is the dominant factor and also looked at the short- and long-term effects of neutron irradiation on modern microprocessors in a clinical environment. Additionally, methods of effective shielding are proposed.

Supine orientation is the standard treatment position for radiation therapy for head and neck cancer. Some patients, however, cannot tolerate this due to pooling of secretions and airway concerns, and theoretically, treatment would be better tolerated in a prone position. Here, we described the first prone treatment setup and delivery for a patient with head and neck cancer.

A 68-year-old male patient with inoperable locally advanced, T4aN0M0, squamous cell carcinoma of the maxillary sinus was simulated, planned, and treated in prone position due to sinus congestion.

Prone position was well tolerated by the patient, who then did not require daily anaesthesia for airway secretion management. The prone dosimetry demonstrated good target coverage and normal tissue sparing. His treatment setup was found to be reproducible throughout the course of therapy.

We successfully demonstrated the feasibility of prone treatment position for patients with head and neck cancer who are unable to tolerate supine position due to unmanageable secretions. Consideration should be given to prone treatment when designing both radiation therapy protocols and individual treatment plans.

This technical note describes a quantitative assessment of the production of radioactive materials during a year-long clinical operation of a Mevion S250i Hyperscan proton therapy system. The production of accumulated radioactive materials plays an important role in determining radiation safety in and around the proton therapy facilities.

We have conducted a weekly room survey, every week for a year, during normal clinical operation.

We estimated the accumulated activity from secondary neutron activation on aluminium structures at 3 m away from isocentre in the beamline to be less than 300 μCi.

As the number of proton therapy facilities has steadily increased, the need for the tool to provide precise dose simulation for complicated clinical and research scenarios also increase. In this study, the treatment head of Mevion HYPERSCAN pencil beam scanning (PBS) proton therapy system including energy modulation system (EMS) and Adaptive Aperture™ (AA) was modelled using TOPAS (TOolkit for PArticle Simulation) Monte Carlo (MC) code and was validated during commissioning process.

The proton beam characteristics including integral depth doses (IDDs) of pristine Bragg peak and in-air beam spot sizes were simulated and compared with measured beam data. The lateral profiles, with and without AA, were also verified against calculation from treatment planning system (TPS).

All beam characteristics for IDDs and in-air spot size agreed well within 1 mm and 10% separately. The full width at half maximum and penumbra of lateral dose profile also agree well within 2 mm.

The TOPAS MC simulation of the MEVION HYPERSCAN PBS proton therapy system has been modelled and validated; it could be a viable tool for research and verification of the proton treatment in the future.

The purpose of this study is to investigate the feasibility of proton arc therapy (PAT) using the double-scattering MEVION-S250 proton system. The treatment planning and dose delivery parameters from PAT were compared with conventional treatment planning techniques.

PAT was simulated with multiple conformal and fixed-aperture beams (5–15) using the MEVION-S250-double-scattering proton system. Conformal apertures were simulated with the Eclipse-treatment-planning system: (a) using a static single aperture that provides the best average conformal circular or rectangular apertures to cover the tumour from different angular views (SPAT), and (b) dynamic conformal apertures of the tumour shape at each irradiation angle that can be obtained from a multi-leaf-collimator system (DPAT).

The DPAT and SPAT plans provided superior dose coverage and sparing of normal tissues in comparison with conventional plans (CPT). The entrance normal tissue and skin doses (<40%) were lowered significantly by delivering dose from different directions over a wider angular view compared to conventional plans that have large entrance dose from only two fields. While the mean and minimum doses from PAT and CPT were comparable, the maximum doses from arc plans were lower than the maximum doses in conventional plans. The SPAT and DPAT plans had comparable dose parameters for regularly shaped targets. The heterogeneity index (HI) was superior in PAT plans which improved with increasing number of beams in arc plans for the different treatment sites. The conformality index (CI) depends on the treatment site and complexity of the shape of the planning target volume where for brain, pancreatic and lung tumours, PAT plans conformality was comparable and sometimes superior to CPT; and HI and CI were generally better in DPAT compared to SPAT.

PAT plans have superior dose coverage and sparing of normal tissues compared to CPT plans using the MEVION double-scattering system as shown in this simulation study. Ideally, conformal proton arcs require beam shaping and dose delivery with the gantry moving; however, the MEVION double-scattering system lacks a multi-leaf collimator system and cannot deliver dose during gantry rotation. The single aperture conformal proton therapy technique is more time and cost effective compared with conventional techniques that are used currently with the MEVION proton therapy system because of the elimination of the need for patient-specific compensators. In present study, PAT was simulated with the MEVION double-scattering proton therapy system; however, it can be performed also with other proton therapy systems.

Accurate localisation of target position is crucial when using techniques with sharp dose fall off such as volumetric modulated arc therapy (VMAT). Gold seed fiducial markers have been used for target localisation in image-guided radiation therapy for various tumors including intact prostate cancers. However, their role for target localisation in post-prostatectomy radiotherapy is unclear. This study was undertaken to determine the feasibility and effectiveness of gold seed fiducial markers in patients undergoing prostate bed VMAT.

The institutional radiation oncology database was used to analyse the treatment data of 18 post-prostatectomy patients with implanted gold seed fiducial markers. The shifts of the fiducial markers were reviewed, tabulated and statistically analysed.

Three hundred and eighty-six orthogonal pair images for 18 patients were reviewed. Specifically, the average gold seed fiducial shifts were 0·34 cm in the superior–inferior (S/I) axis (0·31 SD), 0·31 cm (0·29 SD) in the anterior–posterior (A/P) axis and 0·28 cm (0·25 SD) in the lateral axis (R/L). As a result, the 95% probability of fiducial marker displacement was 0·96 cm in the S/I, 0·89 cm in the A/P and 0·78 cm in the R/L axes. The most frequent shifts occurred in the inferior, left and posterior directions. The percentage of shifts more than 0·5 cm were 19·74, 21·56 and 12·47% for the S/I, A/P and R/L axes, respectively.

In the absence of fiducial markers, non-uniform planning target volume (PTV) margins of 1 cm for S/I, 9 mm for A/P and 8 mm for the lateral direction are necessary for target localisation in post-prostatectomy radiotherapy. By improving prostate bed localisation, gold seed fiducial markers can decrease PTV margins, reduce normal tissue radiation exposure and allow for dose-escalated and/or hypofractionated radiotherapy to be considered in appropriate clinical scenarios.

The purpose of this study is to investigate quantitatively the correlation of displacement vector fields (DVFs) from different deformable image registration (DIR) algorithms to register images from helical computed tomography (HCT), axial computed tomography (ACT) and cone beam computed tomography (CBCT) with motion parameters.

CT images obtained from scanning of the mobile phantom were registered with the stationary CT images using four DIR algorithms from the DIRART software: Demons, Fast-Demons, Horn–Schunck and Lucas–Kanade. HCT, ACT and CBCT imaging techniques were used to image a mobile phantom, which included three targets with different sizes (small, medium and large) that were manufactured from a water-equivalent material and embedded in low-density foam to simulate lung lesions. The phantom was moved with controlled cyclic motion patterns where a range of motion amplitudes (0–20 mm) and frequencies (0·125–0·5 Hz) were used.

The DVF obtained from different algorithms correlated well with motion amplitudes applied on the mobile phantom for CBCT and HCT, where the maximal DVF increased linearly with the motion amplitudes of the mobile phantom. In ACT, the DVF correlated less with motion amplitudes where motion-induced strong image artefacts and the DIR algorithms were not able to deform the ACT image of the mobile targets to the stationary targets. Three DIR algorithms produce comparable values and patterns of the DVF for certain CT imaging modality. However, DVF from Fast-Demons deviated strongly from other algorithms at large motion amplitudes.

The local DVFs provide direct quantitative values for the actual internal tumour shifts that can be used to determine margins for the internal target volume that consider tumour motion during treatment planning. Furthermore, the DVF distributions can be used to extract motion parameters such as motion amplitude that can be extracted from the maximal or minimal DVF calculated by the different DIR algorithms and used in the management of the patient motion.

Volumetric modulated arc therapy (VMAT), an extension of intensity modulated radiation therapy (IMRT), employs modifications in gantry rotation speed, machine dose rate and multi-leaf collimator motion to deliver a three-dimensional dose distribution. This study compared VMAT to IMRT for patients with anal carcinoma.

Sixteen patients previously treated with IMRT were retrospectively selected. Each patient received a total dose of 57·6–63·0 Gy in 1·8 Gy fractions. A single- or double-isocenter multi-arc VMAT treatment plan was generated using Eclipse RapidArc system with the same computed tomography image sets and optimisation constraints used for IMRT. Dose–volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OARs), and monitor units (MUs) and beam on times (BOTs) were used for comparison.

IMRT and VMAT plans showed insignificant differences in PTV homogeneity and conformity and sparing hips and bowel. VMAT required fewer mean MU and shorter BOT per plan (1,597 MU, 2·66 min) compared to IMRT (2,571 MU, 4·29 min) with p < 0·0001.

Fewer MU and shorter BOT for VMAT may decrease the damage from secondary radiation and treatment delivery uncertainty due to intra-fraction tumour motion, leading to higher machine throughput and improving patient comfort, with less treatment time.

In this article, our goal is to compare the TMR10 and convolution dose calculation algorithm in GammaPlan used in stereotactic radiosurgery (SRS) treatments with Gamma Knife and to assess if the algorithms produce clinically significant differences.

Treatment plans were analysed from ten patients who have undergone Gamma Knife SRS treatments. Patient plans were retrospectively recalculated using Lesksell GammaPlan 10 treatment software utilising the TMR10 and convolution dose calculation algorithms in order to create a paired dataset for comparison. Evaluation was based on the dose volume histogram (parameters of minimum, mean, maximum and integral doses.

The ratios of average integral doses calculated by the convolution dose calculation algorithm to the average integral doses calculated by the TMR10 algorithm are 0·997 for the target (p=0·028), 1·048 (p=0·48) for the skull and 1·005 (p=0·68) for the brainstem.

Although doses calculated with the convolution algorithm resulted in slightly higher mean integral doses for the brainstem and skull critical structures when compared to that of TMR10 doses, these results were not statistically or clinically significant. Thus we continue to use the TMR10 algorithm at our clinic.