Eye Plaque Brachytherapy for Choroidal Malignant Melanoma: A Case Report on the Use of Innovative Technology to Expand Access, Improve Practice, and Enhance Outcomes.

Our institute established an eye plaque interstitial brachytherapy (EPIBT) program in 2007 using the Collaborative Ocular Melanoma Study (COMS) eye plaque. In this case report, we demonstrated an eye plaque treatment planned and executed using Eye Physics Plaque (Los Alamitos, CA) for a 72-year-old male patient with an extra-large tumor with a maximum width of 18.6 mm and height of 13.7 mm. The use of a customized eye plaque, manufactured through three-dimensional (3D) printing, has empowered us to plan and administer treatment for this patient with uveal melanoma. Without this option, enucleation, an option declined by the patient, or proton beam therapy (PBT), which the patient was unwilling to pursue in another state, would have been the alternative course of action. We were able to use more than one activity of the I-125 seeds, which enabled us to shape and reduce the dose to normal surrounding structures at risk within the orbit and in the vicinity of the orbital cavity. Using the dose evaluation tools available with the modern treatment planning system, we reduced the prescription dose from 85 to 70 Gy, with D90 of 140 Gy, thereby providing effective treatment and limiting risk organ doses. In summary, we were able to dose-deescalate without compromising the chances of controlling retinal/scleral tumors. The patient is doing well from a recent follow-up visit 12 months after the eye plaque brachytherapy treatment. The tumor was 4.80 mm high, 1/3 of the original height, and vision is back to 20/60, demonstrating a successful treatment.

Real World and Public Health Perspectives of Intraoperative Radiotherapy in Early-Stage Breast Cancer: A Multidisciplinary Analysis Beyond the Statistical Facts.

Breast conservation therapy (BCT) (usually a lumpectomy plus radiotherapy (RT)) has become a standard alternative to radical mastectomy in early-stage breast cancers with equal, if not higher, survival rates. The established standard of the RT component of the BCT had been about six weeks of Monday through Friday external beam RT to the whole breast (WBRT). Recent clinical trials have shown that partial breast radiation therapy (PBRT) to the region surrounding the lumpectomy cavity with shorter courses can result in equal local control, survival, and slightly improved cosmetic outcomes. Intraoperative RT (IORT) wherein RT is administered at the time of operation for BCT to the lumpectomy cavity as a single-fraction RT is also considered PBRT. The advantage of IORT is that weeks of RT are avoided. However, the role of IORT as part of BCT has been controversial. The extreme views go from "I will not recommend to anyone" to "I can recommend to all early-stage favorable patients." These divergent views are due to difficulty in interpreting the clinical trial results. There are two modalities of delivering IORT, namely, the use of low-energy 50 kV beams or electron beams. There are several retrospective, prospective, and two randomized clinical trials comparing IORT versus WBRT. Yet, the opinions are divided. In this paper, we try to bring clarity and consensus from a highly broad-based multidisciplinary team approach. The multidisciplinary team included breast surgeons, radiation oncologists, medical physicists, biostatisticians, public health experts, nurse practitioners, and medical oncologists. We show that there is a need to more carefully interpret and differentiate the data based on electron versus low-dose X-ray modalities; the randomized study results have to be extremely carefully dissected from biostatistical points of view; the importance of the involvement of patients and families in the decision making in a very transparent and informed manner needs to be emphasized; and the compromise some women may be willing to accept between 2-4% potential increase in local recurrence (as interpreted by some of the investigators in IORT randomized studies) versus mastectomy. We conclude that, ultimately, the choice should be that of women with detailed facts of the pros and cons of all options being presented to them from the angle of patient/family-focused care. Although the guidelines of various professional societies can be helpful, they are only guidelines. The participation of women in IORT clinical trials is still needed, and as genome-based and omics-based fine-tuning of prognostic fingerprints evolve, the current guidelines need to be revisited. Finally, the use of IORT can help rural, socioeconomically, and infrastructure-deprived populations and geographic regions as the convenience of single-fraction RT and the possibility of breast preservation are likely to encourage more women to choose BCT than mastectomy. This option can also likely lead to more women choosing to get screened for breast cancer, thus enabling the diagnosis of breast cancer at an earlier stage and improving the survival outcomes.

Reliable Radiation Technique to Minimize Ovarian Dose During Radiation Prophylaxis of Heterotopic Ossification.

BACKGROUND/AIM: Scattered radiation during radiotherapy (RT) directed at the hip joint poses concerns about ovarian function in patients of reproductive age. Here, we report the impact of using a split-beam technique (SBT) and different photon energies on the total ovary dose during radiation prophylaxis of heterotopic ossification (HO). PATIENTS AND METHODS: This was a single-institution, retrospective study of 32-patients with traumatic acetabular fractures (TAF). All underwent surgery followed by CT-based-RT within 72 h in a single fraction of 700 cGy. Ipsilateral (IL) and contralateral (CL) ovaries (OV) were contoured separately and dose volume histograms (DVH) generated. Additional planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6-18 MV) to investigate the difference in ovary dose among these maneuvers. RESULTS: The median Mean-dose delivered to ILOV was 59 cGy and the median Max-dose was 177 cGy. CLOV median Mean-dose was 6 cGy and median Max-dose was 10 cGy. SBT at the medial edge of the field led to a 27% and 22% dose reduction in the median Mean and Max. doses, respectively, to ILOV; 9% and 5% reduction was seen in the median Mean and Max. doses, respectively, to CLOV. Higher photon energies (10-18 MV) led to an additional 28% and 16 % reduction in median Mean and Max. doses, respectively, to ILOV when compared to those from 6 MV. The CLOV median Mean dose was reduced by 18% and the Max. dose was reduced by 12%. CONCLUSION: A biologically significant radiation dose is delivered to the ovaries during HO radiation prophylaxis at the hip joints. Ipsilateral ovarian dose could be reduced by half and contralateral by one-quarter by using CT-based treatment planning with a medial SBT and photon energies above 6 MV. We suggest using no more than 10 MV to minimize neutron contamination. Those techniques should be the standard of care as it provides a reliable method for minimizing the radiation dose to the ovaries, consequently, maximizing female fertility preservation during HO radiation prophylaxis. All female patients in childbearing age should be fully informed about ovarian radiation exposure and possible temporary alteration in ova production and morphology.

Testicular Dose During Prophylaxis of Heterotopic Ossification with Radiation Therapy.

AIM: A single-institution, retrospective study was performed to investigate potential techniques to minimize radiation exposure to the testicles during heterotopic ossification (HO) prophylaxis. We report the impact of split-beam technique (SBT) and different photon energies on the total dose of radiation received by the testicles during prophylaxis of HO. MATERIALS AND METHODS: Between 2008 and 2010, we identified 64 patients with traumatic acetabular fractures who underwent surgery followed by radiation therapy (RT) without testicular shielding. Postoperative RT was delivered within 72 h in a single fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to patient refusal. All patients underwent 3-D RT planning in which the testicles were contoured as a region of interest and dose-volume histograms (DVH) were generated. Additional treatment planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV) to study the effects of these maneuvers on the delivered dose to the testicles. RESULTS: In reviewing the DVH, it was noted that the mean dose delivered to the testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430). When SBT was utilized, a significant reduction in the mean (44%) and maximum (47%) doses delivered to the testicles was noted. Further reductions in the mean (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV) beams. The radiation doses to the testicles from the CT simulation and the two portal images were estimated to be 4 and 1.5 cGy, respectively. CONCLUSION: Low-dose prophylactic RT to prevent HO around the hip causes a low, but likely biologically meaningful, radiation dose to be delivered to the testicles. This dose could be further reduced by using a medial SBT and photon energies above 6 MV. Testicular shielding should be offered to all male patients receiving such RT. In addition, all patients should be informed about the consequences of testicular radiation as part of their informed consent.

Dosimetric comparison of brachytherapy sources for high-dose-rate treatment of endometrial cancer: (192)Ir, (60)Co and an electronic brachytherapy source.

OBJECTIVE: To compare high-dose-rate (HDR) brachytherapy systems with (192)Ir, (60)Co and electronic brachytherapy source (EBS) for treatment of endometrial cancers. METHODS: Two additional plans were generated per patient fraction using a (60)Co source and Xoft-EBS on 10 selected patients, previously treated with a vaginal cylinder applicator using a (192)Ir source. Dose coverage of "PTV_CYLD", a 5-mm shell surrounding the cylinder, was evaluated. Doses to the following organs at risk (OARs) the rectum, bladder and sigmoid were evaluated in terms of V35% and V50%, the percentage volume receiving 35% and 50% of the prescription dose, respectively, and D2cm(3), the highest dose to a 2-cm(3) volume of an OAR. RESULTS: Xoft-EBS reduces doses to all OARs in the lower dose range, but it does not always provide better sparing of the rectum in higher dose range as does evaluation using D2cm3. V150% and V200% for PTV_CYLD was up to four times greater for Xoft-EBS plans than for plans generated with (192)Ir or (60)Co. Surface mucosal (vaginal cylinder surface) doses were also 23% higher for Xoft-EBS than for (192)Ir or (60)Co plans. CONCLUSION: Xoft-EBS is a suitable HDR source for vaginal applicator treatment with advantages of reducing radiation exposure to OARs in the lower dose range, while simultaneously increasing the vaginal mucosal dose. ADVANCES IN KNOWLEDGE: This work presents newer knowledge in dosimetric comparison between (192)Ir or (60)Co and Xoft-EBS sources for endometrial vaginal cylinder HDR planning.

Radiation safety consideration during intraoperative radiation therapy.

Using in-house-designed phantoms, the authors evaluated radiation exposure rates in the vicinity of a newly acquired intraoperative radiation therapy (IORT) system: Axxent Electronic Brachytherapy System. The authors also investigated the perimeter radiation levels during three different clinical intraoperative treatments (breast, floor of the mouth and bilateral neck cancer patients). Radiation surveys during treatment delivery indicated that IORT using the surface applicator and IORT using balloons inserted into patient body give rise to exposure rates of 200 mR h(-1), 30 cm from a treated area. To reduce the exposure levels, movable lead shields should be used as they reduce the exposure rates by >95%. The authors' measurements suggest that intraoperative treatment using the 50-kVp X-ray source can be administered in any regular operating room without the need for radiation shielding modification as long as the operators utilise lead aprons and/or stand behind lead shields.

Computerized tomography-based radiotherapy improves heterotopic ossification outcomes.

PURPOSE: To report the impact of computerized tomography (CT) based radiotherapy (RT) on heterotopic ossification (HO) outcomes. METHODS: This is a single institution, retrospective study of 532 patients who were treated for traumatic acetabular fractures (TAF). All patients underwent open-reduction internal-fixation (ORIF) of the TAF followed by RT for HO prophylaxis. Postoperative RT was delivered within 72h, in a single fraction of 7Gy. The patients were divided into 2 groups based on RT planning: CT (A) vs. clinical setup (B). RESULTS: At a median follow up of 8years the incidence of HO was 21.6%. Multivariate regression analysis revealed that group (A) vs. (B) had HO incidence of 6.6% vs. 24.6% (p<0.001), respectively. Furthermore, HO Brooker grade ≥3 was observed in 2.2% vs. 10.8% (p=0.007) in group (A) vs. (B), respectively. Thus, the odds of developing HO and Brooker grades ≥3 were 4.7 and 4.5 times higher, respectively, in patients who underwent clinical setup. CONCLUSION: Our data suggest that using CT based RT allowed more accurate delineation of the tissues and better clinical outcomes. Although CT-based RT is associated with additional cost the efficacy of CT-based RT reduces the risk of HO, thereby decreasing the need for additional surgical interventions.

The influence of pregnancy on heterotopic ossification post-displaced acetabular fractures surgical repair.

Pregnancy is associated with maternal bone mineral density loss and modulation of calcium metabolism. We hypothesized that pregnancy may decrease the risk of heterotopic ossification (HO) after trauma. This is a single-institution, University of Mississippi Medical Center, retrospective study investigating the effect of pregnancy on the incidence HO after surgical repair (SR) of displaced acetabular fractures. Between January 1998 and 2010, 257 non-pregnant women (Group A) and 16 pregnant women (Group B) were identified. All the non-pregnant women received radiation therapy (RT) ± indomethacin. None of the pregnant women in group B received any prophylaxis. After a median follow-up of 6.6 years the incidence of HO in all patients was 27% (75/273). In Group A, non-pregnant, women who received RT ± indomethacin, 29% developed HO; HO risk was 0.4. In Group B, 16 pregnant patients, only one developed HO (6%); HO risk was 0.06. Thus, the risk of HO appears to be nearly six-fold higher in non-pregnant women despite prophylactic RT ± indomethacin. Our data suggest that pregnancy may be associated with a reduced risk of HO after SR of displaced acetabular fractures. Further analysis with a larger pregnant patient sample is necessary to confirm this finding.

Angular and radial dependence of the energy response factor for LIF-TLD micro-rods in 125L permanent implant source.

EGSnrc Monte Carlo simulations were used to calculate the angular and radial dependence of the energy response factor for LiF-thermoluminescence dosemeters (TLDs) irradiated with a commercially available (125)I permanent brachytherapy source. The LiF-TLDs were modelled as cylindrical micro-rods of length 6 mm and with diameters of 1 mm and 5 mm. The results show that for a LiF-TLD micro-rod of 1 mm diameter, the energy response relative to (60)Co gamma rays is 1.406 +/- 0.3% for a polar angle of 90 degrees and radial distance of 1.0 cm. When the diameter of the micro-rod is increased from 1 to 5 mm, the energy response decreases to 1.32 +/- 0.3% at the same point. The variation with position of the energy response factor is not >5% in a 6 cm x 6 cm x 6 cm calculation grid for the 5 mm diameter micro-rod. The results show that there is a change in the photon spectrum with angle and radial distance, which causes the variation of the energy response.

Comparison of the energy-response factor of LiF and Al2O3 in radiotherapy beams.

A Monte Carlo study of the energy-response factor of aluminium oxide (Al2O3) and lithium fluoride (LiF) TLDs in kilovoltage and megavoltage photon beams relative to 60Co gamma rays has been performed using EGSnrc Monte Carlo simulations. The sensitive volume of the detector was simulated as a disc of diameter 2.85 mm and thickness 1 mm. The phantom material was water and the irradiation depth was 2.0 cm in kilovoltage photon beams and 5.0 cm for megavoltage photon beams. The results show that the energy-response of the Al2O3 and LiF-TLDs is constant within 3% for photon beam energies in the energy range of 60Co gamma rays to 25 MV X rays. However, both detectors show an enhanced response for kilovoltage photon beams, which in the case of 50 kV X rays is 3.2 times higher than that for 60Co gamma rays. The energy-response factor was 1.46 for LiF irradiated in 50 kV X rays. The Al2O3 detector has an energy-response that is 2.2 times higher than that of LiF in 50 kV X rays decreasing to 1.19 for 250 kV X rays. The results show that the addition of 0.1 or 1% of carbon by weight (as dopant) into the Al2O3 does not change the Monte Carlo determined energy-response factor by more than 1%.

Energy response of an aluminium oxide detector in kilovoltage and megavoltage photon beams: an EGSnrc Monte Carlo simulation study.

A Monte Carlo study of the energy response of an aluminium oxide (Al(2)O(3)) detector in kilovoltage and megavoltage photon beams relative to (60)Co gamma rays has been performed using EGSnrc Monte Carlo simulations. The sensitive volume of the Al(2)O(3) detector was simulated as a disc of diameter 2.85 mm and thickness 1 mm. The phantom material was water and the irradiation depth chosen was 2.0 cm in kilovoltage photon beams and 5.0 cm in megavoltage photon beams. The results show that the energy response of the Al(2)O(3) detector is constant within 3% for photon beam energies in the energy range of (60)Co gamma rays to 25 MV X rays. However, the Al(2)O(3) detector shows an enhanced energy response for kilovoltage photon beams, which in the case of 50 kV X rays is 3.2 times higher than that for (60)Co gamma rays. There is essentially no difference in the energy responses of LiF and Al(2)O(3) detectors irradiated in megavoltage photon beams when these Al(2)O(3) results are compared with literature data for LiF thermoluminescence detectors. However, the Al(2)O(3) detector has a much higher enhanced response compared with LiF detectors in kilovoltage X-ray beams, more than twice as much for the case of 50 kV X rays.

An evaluation of the AAPM-TG43 dosimetry protocol for I-125 brachytherapy seed.

The EGSnrc Monte Carlo system has been used to calculate the dose distributions from 125I radioactive seeds (model 6711). The results showed that the agreement between EGSnrc and the American Association of Physicists in Medicine Task Group Report 43 (AAPM-TG43) dosimetry protocol is generally within +/-15% for radial distances less than 1.0 cm in both the transverse axis and longitudinal axis of the source. For radial distances between 1.0 and 2.5 cm the agreement between Monte Carlo simulations and the AAPM-TG43 dosimetry protocol is within +/-20%. In the longitudinal axis of the source the difference between Monte Carlo simulations and the AAPM-TG43 dosimetry is up to 40% for radial distances greater than 2.5 cm. The agreement between the EGSnrc/Monte Carlo simulation and the AAPM-TG43 dosimetry protocol improved significantly when recently published data of the anisotropic function were implemented (Weaver 1998 Med. Phys. 25 2271-8). The difference between Monte Carlo simulations and the AAPM-TG43 dosimetry protocol is not more than +/-10% in the transverse axis of the source up to a radius of 2.5 cm. The EGSnrc Monte Carlo simulation and the AAPM-TG43 with the Weaver anisotropic data were also used to investigate the differences in the dose distribution caused by small differences in the construction of individual seeds (Sloboda and Menon 2000 Med. Phys. 27 1789-99). The results show that a change in length of the silver rod containing the 125I radioactive material of 0.14 mm does not affect the dose distribution significantly in the transverse and longitudinal axes but a change of 0.13 mm in the thickness of the welded end of the encapsulation affected the dose significantly in the longitudinal axis of the source.

Dose perturbation effects in prostate seed implant brachytherapy with I-125.

EGSnrc Monte Carlo simulation was used to investigate dose perturbation effects in prostate seed implant brachytherapy using 125I radioactive seeds used in implant brachytherapy. Dose perturbation effects resulting from the seed mutual attenuation in a prostate seed implant consisting of 27 seeds were investigated. The results showed that for 125I seeds implanted into the prostate at 1.00 cm, 0.75 cm and 0.50 cm apart (uniform spacing), the dose perturbation effects are up to 10%. The volume of the target occupied by the 10% dose difference between the full Monte Carlo simulation and the single seed superposition model decreases with increasing seed spacing. Despite the differences between the Monte Carlo simulation and the simple superposition, there was no significant change in the dose volume histogram for 1 cm and 0.75 cm seed spacing. However, there was a significant change in the dose volume histogram when the seed spacing was 0.5 cm. An analysis of the external volume index (EI), coverage index (CI) and homogeneity index (HI) also showed that there is no difference in these indexes for the 1.00 cm and 0.75 cm seed spacing between the simple superposition model and the full Monte Carlo simulation. Compared to the full Monte Carlo simulations, the simple superposition model overestimated EI, CI and HI by 7%, 5% and 4% respectively for the 0.50 cm seed spacing.

Response of LiF-TLD micro-rods around 125I radioactive seed.

The EGSnrc Monte Carlo system has been used to calculate the energy response of LiF-TLDs of different sizes around 125I permanent brachytherapy sources. The source model includes the effects of an encapsulation, self-absorption within the source and in the welded ends of the encapsulation. The LiF-TLD material has cylindrical geometry (micro-rod) with diameters ranging from 1 mm to 5 mm and a length of 6 mm. The energy response factor (relative to 60(Co gamma-rays) for a LiF-TLD calibrated in 60Co gamma-rays and then irradiated by an 125I permanent brachytherapy source varies between 1.32 +/- 0.2% (1 SD) and 1.406 +/- 0.2% (1 SD) for 5 mm and 1 mm diameter micro-rods, respectively. The energy response factor depends on the radius and the polar angle (r, theta) of the measurement point. For a LiF-TLD of diameter 1 mm calibrated at 1 cm on the transverse axis (r = 1.0 cm, theta = 90) of the 125I source in water, the energy response factor decreases by a maximum of 3.5% within the 6 cm x 6 cm x 6 cm calculation region. For the 5 mm diameter LiF-TLD, the energy response factor decreases by a maximum of 5% in the same region. An examination of the photon energy spectra showed that the photon spectrum does not change significantly in water within the 3D calculation region (6 cm x 6 cm x 6 cm). The mass energy absorption coefficient ratio of water to LiF-TLDs does not vary by more than 0.5% in this calculation grid. The results, however, show that there is a change in the photon spectrum with distance from the source and with polar angle for LiF-TLDs. This difference in the energy spectrum gives rise to a difference in the mass energy absorption coefficient ratio of water to LiF (calculated by taking into account the difference in photon fluence in water and LiF) and that calculated assuming that the photon spectrum in water and in the LiF-TLD is identical.

The clinical implementation of a method for calculating the output factor and per cent depth dose for an electron beam.

A modified sector-integration method has been developed that predicts electron beam output factor at any point on the beam central axis, for a given source to surface distance (SSD), as a function of the geometry of the irradiated field. The main concept of this method is that with the arbitrary field shape divided into small sectors, the individual contributions from each sector can be calculated based on the sector radius, using a dataset consisting of circular inserts of standard radii. A computer program was developed based on this algorithm. The program interfaces to a digital camera that is used to capture the shape of the electron insert. We compared the calculated and the measured output factors and per cent depth doses (PDDs) at different SSDs for various rectangular inserts and a typical irregularly shaped insert used in our clinic. To determine the geometric limitations of this algorithm, a series of rectangular inserts were designed with the long-to-short axis ratio between 1:1 and 7:1. The agreement between calculation and measurement for the electron output and PDD was generally within 2% (or 2 mm) for energies from 6 to 20 MeV.