Combined clinical and research training in medical physics in a multi-institutional setting: 13-year experience of Harvard Medical Physics Residency Program.

PURPOSE: This manuscript describes the structure, management and outcomes of a multi-institutional clinical and research medical physics residency program (Harvard Medical Physics Residency Program, or HMPRP) to provide potentially useful information to the centers considering a multi-institutional approach for their training programs. METHODS: Data from the program documents and public records was used to describe HMPRP and obtain statistics about participating faculty, enrolled residents, and graduates. Challenges associated with forming and managing a multi-institutional program and developed solutions for effective coordination between several clinical centers are described. RESULTS: HMPRP was formed in 2009 and was accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) in 2011. It is a 3-year therapy program, with a dedicated year of research and the 2 years of clinical training at three academic hospitals. A CAMPEP-accredited Certificate Program is embedded in HMPRP to allow enrolled residents to complete a formal didactic training in medical physics if necessary. The clinical training covers the material required by CAMPEP. In addition, training in protons, CyberKnife, MR-linac, and at network locations is included. The clinical training and academic record of the residents is outstanding. All graduates have found employment within clinical medical physics, mostly at large academic centers and graduates had a 100% pass rate at the oral American Board of Radiology exams. On average, three manuscripts per resident are published during residency, and multiple abstracts are presented at conferences. CONCLUSIONS: A multi-institutional medical physics residency program can be successfully formed and managed. With a collaborative administrative structure, the program creates an environment for high-quality clinical training of the residents and high productivity in research. The main advantage of such program is access to a wide variety of resources. The main challenge is creating a structure for efficient management of multiple resources at different locations. This report may provide valuable information to centers considering starting a multi-institutional residency program.

Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.

BACKGROUND AND PURPOSE: The appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms. METHODS: Thirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses. RESULTS: Compared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation. CONCLUSION: IBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal-limbic-midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.

[CT Characteristics of Consolidation Type of Pulmonary Cryptococcosis in Immunocompetent Patients].

Objective To analyze the CT characteristics of consolidation type of pulmonary cryptococcosis in immunocompetent patients,and thus improve the diagnosis of this disease. Methods A total of 20 cases with consolidation-type pulmonary cryptococcosis confirmed by pathological examinations were studied.Each patient underwent breath-hold multislice spiral CT,and 10 patients underwent contrast enhanced CT.The data including lesion number,lesion distribution,lesion density,performance of enhanced CT scan,accompanying signs,and prognosis were analyzed. Results The occurrence rates of single and multiple lesions were 80.0%(n=16)and 20.0%(n=4),respectively.In all the 16 multiple-lesion patients,the occurrence rate of unilateral lobar distribution was 56.0%(n=9).The 76 measurable lesions mainly presented subpleural distribution(71.1%,n=54)and lower pulmonary distribution(75.0%,n=57).A total of 39 lesions were detected in the 10 patients received contrast enhanced CT,in which 31 lesions(79.5%)showed homogeneous enhancement,34 lesions(87.2%)showed moderate enhancement,and all the lesions manifested angiogram sign.Consolidation lesions were accompanied by many CT signs,of which air bronchogram sign had the occurrence rate of 63.2%(n=48),including types Ⅲ(n =37)and Ⅳ(n=11).Other signs included halo signs(43/76,56.6%),vacuoles or cavities(9/76,11.8%),pleural thickening(14/20,70.0%),and pleural effusion(2/20,10.0%).After treatment,the lesions of 7 patients were basically absorbed and eventually existed in the form of fibrosis. Conclusions The lesions in the immunocompetent patients with consolidation type of pulmonary cryptococcosis usually occur in the lower lobe and close to the pleura,mainly presenting unilateral distribution.The CT angiogram signs,proximal air bronchogram signs,and halo signs are the main features of this disease,which contribute to the diagnosis.

Frameless angiogram-based stereotactic radiosurgery for treatment of arteriovenous malformations.

PURPOSE: Stereotactic radiosurgery (SRS) is an effective alternative to microsurgical resection or embolization for definitive treatment of arteriovenous malformations (AVMs). Digital subtraction angiography (DSA) is the gold standard for pretreatment diagnosis and characterization of vascular anatomy, but requires rigid frame (skull) immobilization when used in combination with SRS. With the advent of advanced proton and image-guided photon delivery systems, SRS treatment is increasingly migrating to frameless platforms, which are incompatible with frame-based DSA. Without DSA as the primary image, target definition may be less than optimal, in some cases precluding the ability to treat with a frameless system. This article reports a novel solution. METHODS AND MATERIALS: Fiducial markers are implanted into the patient's skull before angiography. Angiography is performed according to the standard clinical protocol, but, in contrast to the previous practice, without the rigid frame. Separate images of a specially designed localizer box are subsequently obtained. A target volume projected on DSA can be transferred to the localizer system in three dimensions, and in turn be transferred to multiple CT slices using the implanted fiducials. Combined with other imaging modalities, this "virtual frame" approach yields a highly precise treatment plan that can be delivered by frameless SRS technologies. RESULTS: Phantom measurements for point and volume targets have been performed. The overall uncertainty of placing a point target to CT is 0.4 mm. For volume targets, deviation of the transformed contour from the target CT image is within 0.6 mm. The algorithm and software are robust. The method has been applied clinically, with reliable results. CONCLUSIONS: A novel and reproducible method for frameless SRS of AVMs has been developed that enables the use of DSA without the requirement for rigid immobilization. Multiple pairs of DSA can be used for better conformality. Further improvement, including using nonimplanted fiducials, is potentially feasible.

Use of a realistic breathing lung phantom to evaluate dose delivery errors.

PURPOSE: To compare the effect of respiration-induced motion on delivered dose (the interplay effect) for different treatment techniques under realistic clinical conditions. METHODS: A flexible resin tumor model was created using rapid prototyping techniques based on a computed tomography (CT) image of an actual tumor. Twenty micro-MOSFETs were inserted into the tumor model and the tumor model was inserted into an anthropomorphic breathing phantom. Phantom motion was programed using the motion trajectory of an actual patient. A four-dimensional CT image was obtained and several treatment plans were created using different treatment techniques and planning systems: Conformal (Eclipse), step-and-shoot intensity-modulated radiation therapy (IMRT) (Pinnacle), step-and-shoot IMRT (XiO), dynamic IMRT (Eclipse), complex dynamic IMRT (Eclipse), hybrid IMRT [60% conformal, 40% dynamic IMRT (Eclipse)], volume-modulated are therapy (VMAT) [single-arc (Eclipse)], VMAT [double-arc (Eclipse)], and complex VMAT (Eclipse). The complex plans were created by artificially pushing the optimizer to give complex multileaf collimator sequences. Each IMRT field was irradiated five times and each VMAT field was irradiated ten times, with each irradiation starting at a random point in the respiratory cycle. The effect of fractionation was calculated by randomly summing the measured doses. The maximum deviation for each measurement point per fraction and the probability that 95% of the model tumor had dose deviations less than 2% and 5% were calculated as a function of the number of fractions. Tumor control probabilities for each treatment plan were calculated and compared. RESULTS: After five fractions, measured dose deviations were less than 2% for more than 95% of measurement points within the tumor model for all plans, except the complex dynamic IMRT, step-and-shoot IMRT (XiO), complex VMAT, and single-arc VMAT plans. Reducing the dose rate of the complex IMRT plans from 600 to 200 MU/min reduced the dose deviations to less than 2%. Dose deviations were less than 5% after five fractions for all plans, except the complex single-arc VMAT plan. CONCLUSIONS: Rapid prototyping techniques can be used to create realistic tumor models. For most treatment techniques, the dose deviations averaged out after several fractions. Treatments with unusually complicated multileaf collimator sequences had larger dose deviations. For IMRT treatments, dose deviations can be reduced by reducing the dose rate. For VMAT treatments, using two arcs instead of one is effective for reducing dose deviations.

Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy.

PURPOSE: There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. PATIENTS AND METHODS: Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. RESULTS: There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% (four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher (ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fisher's exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). CONCLUSION: The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.

Application of a novel microdosimetry analysis and its radiobiological implication for high-LET radiation.

For short-range high-LET radiation therapy, the biological effects are strongly affected by the heterogeneity of the specific energy distribution delivered to tumor cells. Three-dimensional information at the cellular level is ideal for this type of study, but it is extremely difficult to obtain. In this paper, a novel microdosimetry analysis, which obtains the specific energy distribution directly from the morphological information in individual autoradiographic sections, is applied to in vivo human glioblastoma multiforme and normal brain tissue in boron neutron capture therapy. Specific energy distributions were obtained for both specimens, and they are consistent with a uniform boron microdistribution. We also used a biophysical model for cell survival analysis based on the specific energy and were able to bridge it with the model based on the corresponding macroscopic parameter (dose) using existing experimental data. The survival constant for the microscopic model was determined; cell survival curves were predicted for uniform and non-uniform source distributions, i.e., sources and cell nuclei bound together totally or only partially. The results indicate that the behavior of the survival curve can vary widely, which may have important clinical implications.

Organ deformation and dose coverage in robotic respiratory-tracking radiotherapy.

PURPOSE: Respiratory motion presents a significant challenge in stereotactic body radiosurgery. Respiratory tracking that follows the translational movement of the internal fiducials minimizes the uncertainties in dose delivery. However, the effect of deformation, defined as any changes in the body and organs relative to the center of fiducials, remains unanswered. This study investigated this problem and a possible solution. METHODS AND MATERIALS: Dose delivery using a robotic respiratory-tracking system was studied with clinical data. Each treatment plan was designed with the computed tomography scan in the end-expiration phase. The planned beams were applied to the computed tomography scan in end-inspiration following the shift of the fiducials. The dose coverage was compared with the initial plan, and the uncertainty due to the deformation was estimated. A necessary margin from the clinical target volume to the planning target volume was determined to account for this and other sources of uncertainty. RESULTS: We studied 12 lung and 5 upper abdomen lesions. Our results demonstrated that for lung patients with properly implanted fiducials a 3-mm margin is required to compensate for the deformation and a 5-mm margin is required to compensate for all uncertainties. Our results for the upper abdomen tumors were still preliminary but indicated a similar result, although a larger margin might be required. CONCLUSION: The effect of body deformation was studied. We found that adequate dose coverage for lung tumors can be ensured with proper fiducial placement and a 5-mm planning target volume margin. This approach is more practical and effective than a recent proposal to combine four-dimensional planning with respiratory tracking.

Cyberknife radiosurgery for basal skull plasmacytoma.

The Cyberknife delivers frameless image-guided stereotactic radiosurgery to intracranial and extracranial tumors. We report our use of Cyberknife radiosurgery on a medullary plasmacytoma in the clivus extending into the foramen magnum. No acute toxicity was seen during or within 24 hours of treatment, and the subject had a complete and durable radiographic response on MRI 12+ months after treatment. To our knowledge, this is a first case of successful Cyberknife radiosurgery of a medullary plasmacytoma.

A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease.

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10B carrier, L-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg(-1) over 1 h (10 subjects), 300 mg kg(-1) over 1.5 h (two subjects), or 350 mg kg(-1) over 1.5-2 h (10 subjects). The pharmacokinetic profile of 10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.

A three-field breast treatment technique with precise geometric matching using multileaf collimator-equipped linear accelerators.

PURPOSE: Many authors have studied the problems associated with the three-field breast treatment, yet the proposed solutions present their own difficulties. This study presents a technique that overcomes these difficulties, reduces scatter to the contralateral breast, and improves setup reproducibility. METHODS AND MATERIALS: Patients are set up with both arms raised superiorly on a breast board. A precise field-match is achieved by rotating the couch and collimator of the tangents, while the supraclavicular field is half-beam blocked using an independent jaw. The posterior borders of the tangents are conformally defined by multileaf collimation. Measurements were performed to verify the field matching and evaluate scatter doses. RESULT: A smooth dose transition was found at the match line at all depths. Corner blocks and lower wedges were not used, which reduced the scatter to the contralateral breast compared with our prior technique. CONCLUSION: The technique achieves a precise match while removing constraints on the tangents' length and decreasing scatter dose. Procedures for simulation, planning, and treatment have been devised, along with a new patient setup routine incorporating orthogonal setup films and tattoos. This technique has been successfully implemented in routine treatment since September 2001. A program calculating the setup parameters is available at our website.