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.

Comparison of 3D Conformal Proton Therapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Photon Therapy for Retroperitoneal Sarcoma.

Background: External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). Intensity-modulated radiation therapy has been shown to improve target coverage and reduce doses to OAR. Objectives: To compare target coverage and dose to OAR with 3D conformal proton therapy (3D CPT), intensity-modulated proton therapy (IMPT), and intensity-modulated photon therapy (IMXT). Methods: We performed a comparative study of treatment plans with 3D CPT, IMPT, and IMXT for ten patients with retroperitoneal sarcomas. RT was delivered to 50.4 Gy to the clinical target volume (CTV), the structures considered at risk for microscopic disease. Results: CTVs ranged from 74 to 357 cc (mean 188 cc). Dose conformity was improved with IMPT, while 3D CPT provided better dose homogeneity. Mean dose to the liver, small bowel, and stomach was reduced with IMPT compared with 3D CPT or IMXT. Conclusions: IMPT, 3D CPT, and IMXT provide excellent target coverage for retroperitoneal sarcomas. OAR dose is lower with IMPT and 3D CPT, and IMPT achieves the closest conformity. These techniques offer the opportunity for further dose escalation to areas with positive margins.

Imaging primary lung cancers in mice to study radiation biology.

PURPOSE: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. METHODS AND MATERIALS: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. RESULTS: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. CONCLUSIONS: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

An effective preoperative three-dimensional radiotherapy target volume for extremity soft tissue sarcoma and the effect of margin width on local control.

PURPOSE: There is little information on the appropriate three-dimensional (3D) preoperative radiotherapy (XRT) volume for extremity soft-tissue sarcomas (STS). We retrospectively analyzed the pattern of local failure (LF) to help elucidate optimal field design. METHODS AND MATERIALS: We analyzed the 56 patients who underwent computed tomography-planned XRT for Stage I to III extremity STS between June 2000 and December 2006. Clinical target volume (CTV) included the T1 post-gadolinium-defined gross tumor volume with 1- to 1.5-cm radial and 3.5-cm longitudinal margins. Planning target volume expansion was 5 to 7 mm, and >or=95% of dose was delivered to the planning target volume. Preoperative XRT was 44 to 50.4 Gy (median, 50). Postoperative boost of 10 to 20 Gy was given to 12 patients (6 with positive and 6 with close margins). RESULTS: Follow-up ranged from 15 to 76 months (median, 41 months). The 5-year local control, freedom from distant metastasis, disease-free survival, and overall survival were 88.5%, 80.0%, 77.5% and 82.8%, respectively. Three patients (all with positive margin) experienced local failure (LF) as first relapse (2 isolated, 1 with distant failure), and 2 additional patients (all with margin<1 mm) had late LF after distant metastasis. The LFs were within the CTV in 3 patients and within and also extending beyond the CTV in 2 patients. CONCLUSIONS: These target volume definitions appear to be appropriate for most patients. No local recurrences were observed with surgical margins >or=1 mm, and it appears that these may be adequate for patients with extremity STS treated with preoperative radiotherapy.

Inter- and intramouse heterogeneity of radiation response for a growing paired organ.

An intensive search for predictive markers of individual radiation response of apparently normal tissues in cancer patients is in progress at the genetic and epigenetic levels. However, the relative impact of variability at these levels is not clear. Experimental results obtained in inbred rodents, which have significantly reduced genetic heterogeneity relative to a population of human patients, may help to clarify this issue. We investigated a paired-organ mouse system in a strain of inbred mice to evaluate the intermouse variability of normal tissue radiation response, singled out from measurement errors and stochastic effects. The legs of 5-day-old C3H mice were homogeneously gamma-irradiated with a range of single doses. The lengths of the right and left tibiae were measured in 30 kVp X-ray images taken at the time of irradiation and at 84 days postirradiation. The dose-effect curves were smooth and well defined, with bone growth retardation evident at approximately 14 Gy and higher, and were marginally gender-dependent. The intramouse (left compared to right) variability of the tibia length on day 89, which characterized stochastic effects, was not distinguishable from the measurement error for doses less than 16-18 Gy and slightly exceeded measurement errors only at the largest doses of 20-22 Gy. The corresponding intermouse variability was greater than the measurement error and stochastic effects at all doses used. Interestingly, the total variability, judged by the gamma(50) values of approximately 7 we obtained, was similar to that reported for severe late reactions in human normal tissue. If the variations of response determined by epigenetic events in human patients free of known factors associated with altered radiation sensitivity are comparable to those observed in this mouse model, our results imply a relatively low power of genetic approaches alone to predict individual side effects in radiotherapy.

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison.

PURPOSE: To compare intensity-modulated photon radiotherapy (IMRT) with three-dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT). METHODS AND MATERIALS: Ten patients were planned with both 3D-CPT (two parallel-opposed lateral fields) and IMRT (seven equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning. RESULTS: At least 98% of the planning target volume received the prescription dose. IMRT plans yielded better dose conformity to the target, whereas proton plans achieved higher dose homogeneity and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more than 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, whereas rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was reduced by up to 35% compared with the standard lateral configuration, whereas the bladder V70 increased by less than 10%. CONCLUSIONS: In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range lower than 50% of the target prescription was substantially lower with proton therapy.

Design of 4D treatment planning target volumes.

PURPOSE: When using non-patient-specific treatment planning margins, respiratory motion may lead to geometric miss of the target while unnecessarily irradiating normal tissue. Imaging different respiratory states of a patient allows patient-specific target design. We used four-dimensional computed tomography (4DCT) to characterize tumor motion and create treatment volumes in 10 patients with lung cancer. These were compared with standard treatment volumes. METHODS AND MATERIALS: Four-dimensional CT and free breathing helical CT data of 10 patients were acquired. Gross target volumes (GTV) were delineated on the helical scan as well as on each phase of the 4D data. Composite GTVs were defined on 4DCT. Planning target volumes (PTV) including clinical target volume, internal margin (IM), and setup margin were generated. 4DPTVs with different IMs and standard PTVs were compared by computing centroid positions, volumes, volumetric overlap, and bounding boxes. RESULTS: Four-dimensional PTVs and conventional PTVs differed in volume and centroid positions. Overlap between 4DPTVs generated from two extreme tumor positions only compared with 10 respiratory phases was 93.7%. Comparing PTVs with margins of 15 mm (IM 5 mm) on composite 4D target volumes to PTVs with 20 mm (IM 10 mm) on helical CT data resulted in a decrease in target volume sizes by 23% on average. CONCLUSION: With patient-specific characterization of tumor motion, it should be possible to decrease internal margins. Patient-specific treatment volumes can be generated using extreme tumor positions on 4DCT. To date, more than 150 patients have been treated using 4D target design.

Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques.

PURPOSE: To compare the dosimetry of proton and photon-electron three-dimensional, conformal, external beam accelerated partial breast irradiation (3D-CPBI). METHODS AND MATERIALS: Twenty-four patients with fully excised, Stage I breast cancer treated with adjuvant proton 3D-CPBI had treatment plans generated using the mixed-modality, photon-electron 3D-CPBI technique. To facilitate dosimetric comparisons, planning target volumes (PTVs; lumpectomy site plus 1.5-2.0 cm margin) and prescribed dose (32 Gy) were held constant. Plans were optimized for PTV coverage and normal tissue sparing. RESULTS: Proton and mixed-modality plans both provided acceptable PTV coverage with 95% of the PTV receiving 90% of the prescribed dose in all cases. Both techniques also provided excellent dose homogeneity with a dose maximum exceeding 110% of the prescribed dose in only one case. Proton 3D-CPBI reduced the volume of nontarget breast tissue receiving 50% of the prescribed dose by an average of 36%. Statistically significant reductions in the volume of total ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose were also observed. The use of protons resulted in small, but statistically significant, reductions in the radiation dose delivered to 5%, 10%, and 20% of ipsilateral and contralateral lung and heart. The nontarget breast tissue dosimetric advantages of proton 3D-CPBI were not dependent on tumor location, breast size, PTV size, or the ratio of PTV to breast volume. CONCLUSIONS: Compared to photon-electron 3D-CPBI, proton 3D-CPBI significantly reduces the volume of irradiated nontarget breast tissue. Both approaches to accelerated partial breast irradiation offer exceptional lung and heart sparing.

Dosimetric comparison of two different three-dimensional conformal external beam accelerated partial breast irradiation techniques.

PURPOSE: We compare the dosimetry of two techniques for three-dimensional, conformal, external beam, accelerated partial breast irradiation (3D-CPBI) in the supine position. METHODS AND MATERIALS: Sixteen patients with Stage I breast cancer had PBI treatment plans generated using the multiple, noncoplanar photon field technique and the three-field, mixed-modality technique. Planning target volumes (PTVs; lumpectomy site plus 1.5-2.0 cm margin) and total dose (32 Gy) were held constant to facilitate dosimetric comparisons. Plans were optimized for conformality and PTV coverage. RESULTS: Mixed-modality plans employed fewer fields than multiple, noncoplanar photon field plans (mean 3.2 vs. 4.1). Both techniques provided comparable PTV coverage and in all cases, 95% of the PTV received 90% of the prescribed dose. Volumes of ipsilateral breast receiving greater than 16 Gy were similar; however, the mean volume of ipsilateral breast receiving 8 Gy was significantly lower for mixed-modality plans (58% vs. 66%). No differences in the volumes of ipsilateral lung or heart receiving greater than 5 Gy were observed, however, the mixed-modality technique delivered 2.5 Gy to larger volumes of these organs. CONCLUSIONS: Both techniques for supine position, 3D-CPBI provides excellent normal tissue sparing with adequate PTV coverage. The multiple, noncoplanar photon field technique exposes smaller volumes of ipsilateral lung and heart to low dose radiation at the expense of increased plan complexity and larger irradiated breast volumes.

Clinical experience with a 3D surface patient setup system for alignment of partial-breast irradiation patients.

PURPOSE: To assess the utility of surface imaging on patient setup for accelerated partial-breast irradiation (APBI). METHODS AND MATERIAL: A photogrammetry system was used in parallel to APBI setup by laser and portal imaging. Surface data were acquired after laser and port-film setup for 9 patients. Surfaces were analyzed in comparison to a reference surface from the first treatment session by use of rigid transformations. The surface model after laser setup was used in a simulated photogrammetry setup procedure. In addition, breathing data were acquired by surface acquisition at a frame rate of 7 Hz. RESULTS: Mean 3D displacement was 7.3 mm (SD, 4.4 mm) and 7.6 mm (SD, 4.2 mm) for laser and port film, respectively. Simulated setup with the photogrammetry system yielded mean displacement of 1 mm (SD, 1.2 mm). Distance analysis resulted in mean distances of 3.7 mm (SD, 4.9 mm), 4.3 mm (SD, 5.6 mm), and 1.6 mm (SD, 2.4 mm) for laser, port film, and photogrammetry, respectively. Breathing motion at isocenter was smaller than 3.7 mm, with a mean of 1.9 mm (SD, 1.1 mm). CONCLUSIONS: Surface imaging for PBI setup appears promising. Alignment of the 3D breast surface achieved by stereo-photogrammetry shows greater breast topology congruence than when patients are set up by laser or portal imaging. A correlation of breast surface and CTV must be quantitatively established.

Initial dosimetric experience using simple three-dimensional conformal external-beam accelerated partial-breast irradiation.

PURPOSE: Several accelerated partial-breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. We present our initial experience using three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Sixty-one patients with tumors of 2 cm or less and negative axillary nodes were treated with 3D-CRT accelerated partial-breast irradiation (APBI) between August 2003 and March 2005. The prescribed radiation dose was 32 Gy in 4-Gy fractions given twice daily. Efforts were made to minimize the number of beams required to achieve adequate planning target volume (PTV) coverage. RESULTS: A combination of photons and electrons was used in 85% of patients. A three-field technique that consisted of opposed, conformal tangential photons and enface electrons was employed in 43 patients (70%). Nine patients (15%) were treated with a four-field arrangement, which consisted of three photon fields and enface electrons. Mean PTV volumes that received 100%, 95%, and 90% of the prescribed dose were 93% +/- 7%, 97% +/- 4%, and 98% +/- 2%, respectively. Dose inhomogeneity exceeded 10% in only 7 patients (11%). Mean doses to the ipsilateral lung and heart were 1.8 Gy and 0.8 Gy, respectively. CONCLUSIONS: Simple 3D-CRT techniques of APBI can achieve appropriate PTV coverage while offering significant normal-tissue sparing. Therefore, this noninvasive approach may increase the availability of APBI to patients with early-stage breast cancer.

A phantom evaluation of a stereo-vision surface imaging system for radiotherapy patient setup.

External beam irradiation requires precise positioning of the target relative to the treatment planning coordinate system. A three-dimensional (3D) surface imaging system for patient positioning has recently been installed in one of our linear accelerator (linac) rooms. The device utilizes close-range photogrammetry to generate a 3D model of the patient's surface. This geometric model can be made to look like a digital camera image if wrapped with a gray-level image (texture mapping) that shows surface coloration. The system is calibrated to the linac coordinate system and has been designed as a patient setup device. To reproduce patient position in fractionated radiotherapy, the daily patient surface model is registered to a previously recorded reference surface. Using surface registration, the system calculates the rigid-body transformation that minimizes the distance between the treatment and the reference surface models in a region-of-interest (ROI). This transformation is expressed as a set of new couch coordinates at which the patient position best matches with the reference data. If respiratory motion is a concern, the surface can be obtained with a gated acquisition at a specified phase of the respiratory cycle. To analyze the accuracy of the system, we performed several experiments with phantoms to assess stability, alignment accuracy, precision of the gating function, and surface topology. The reproducibility of surface measurements was tested for periods up to 57 h. Each recorded frame was registered to the reference surface to calculate the required couch adjustment. The system stability over this time period was better than 0.5 mm. To measure the accuracy of the system to detect and quantify patient shift relative to a reference image, we compared the shift detected by the surface imaging system with known couch transitions in a phantom study. The maximum standard deviation was 0.75 mm for the three translational degrees of freedom, and less than 0.1 degrees for each rotation. Surface model precision was tested against computed tomography (CT)-derived surface topology. The root-mean-square rms of the distance between the surfaces was 0.65 mm, excluding regions where beam hardening caused artifacts in the CT data. Measurements were made to test the gated acquisition mode. The time-dependent amplitude was measured with the surface imaging system and an established respiratory gating system based on infrared (IR)-marker detection. The measured motion trajectories from both systems were compared to the known trajectory of the stage. The standard deviations of the amplitude differences to the motor trajectory were 0.04 and 0.15 mm for the IR-marker system and the 3D surface imaging system, respectively. A limitation of the surface-imaging device is the frame rate of 6.5 Hz, because rapid changes of the motion trajectory cannot be detected. In conclusion, the system is accurate and sufficiently stable to be used in the clinic. The errors computed when comparing the surface model with CT geometry were submillimeter, and deviations in the alignment and gating-signal tests were of the same magnitude.

Internal target volume determined with expansion margins beyond composite gross tumor volume in three-dimensional conformal radiotherapy for lung cancer.

PURPOSE: Gross tumor volume (GTV) of lung cancer defined by fast helical CT scan represents an image of moving tumor captured at a point in active respiratory movement. However, the method for defining internal margins beyond GTV to account for its expected physiologic movement and all variations in size and shape during the administration of radiation has not been established. The goal of this study was to determine the internal margins with expansion margins beyond individual GTVs defined with (1) fast scan at shallow free breathing, (2) breath-hold scans at the end of tidal volume inspiration and expiration, and (3) 4-s slow scan to approximate the composite GTV of all scans. METHODS AND MATERIALS: A series of sequential CT scans were acquired with (1) a fast helical scan at shallow free breathing and (2) breath-hold scans at the end of tidal volume expiration and inspiration for the first 6 patients, and (3) a 4-s slow scan at quiet free breathing, which was added for the latter 7 patients. We fused breath-hold scans and the 4-s slow scan to the fast scan at shallow free breathing to generate the composite GTV. Margins necessary to encompass the composite GTV beyond individual GTVs defined by either fast scan at quiet free breathing, breath-hold scans, or the 4-s slow scan at quiet free breathing were defined as expansion or internal margins and termed the internal target volumes. The centroid of the tumor volume was also used as another reference for tumor movement. RESULTS: Thirteen patients with 14 tumors were enrolled into the study. Substantial tumor movement was noted by either the extent of internal margins beyond each GTV or the movement of the centroid. Internal margins varied significantly according to the method of CT scanning for determination of GTV. Even for tumors in the same lobe of the lung, a wide range of internal margins and significant variation in the centroid movement in all directions (x, y, and z) were observed. The GTV of a single fast helical scan at free breathing (n = 14) required the largest internal margin (mean, 3.5 mm; maximum, 18 mm; standard deviation [SD], 4.2 mm) to match the composite GTV, compared with those of the 4-s slow scan (mean 2.7 mm, maximum 14 mm, SD 3.5 mm) or combined breath-hold scans (mean 1.1 mm, maximum 9 mm, SD 1.9 mm). Internal margins (expansion margins) required to approximate the composite GTV in 95% of cases were 13 mm, 10 mm, and 5 mm for the GTVs of a single fast scan, 4-s slow scan, and breath-hold scans at the end of tidal volume inspiration and expiration, respectively. CONCLUSIONS: The internal margins required to account for the internal tumor motion in three-dimensional conformal radiotherapy are substantial. For the use of symmetric and population-based margins to account for internal tumor motion, GTV defined with breath-hold scans at the end of tidal volume inspiration and expiration has a narrower range of internal margins in all directions than that of either a single fast scan or 4-s slow scan.