AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy.

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

Re-irradiation of a Classic Kaposi's Sarcoma Using Volumetric Modulated Arc Therapy.

A black male in his 60s diagnosed with classic Kaposi's sarcoma presented with multiple cutaneous nodules and edema of the right foot and lower leg. He was initially treated with alitretinoin 1% topical treatment. However, 16 months after treatment with the alitretinoin, the skin lesions progressed, and he subsequently underwent a course of radiation therapy to a total dose of 2000 centigrays (cGy) in five fractions to his right foot and lower extremities. Approximately 1.5 years after the radiation therapy was completed, multiple new lesions developed on the right foot and distal lower leg. He then underwent a course of re-irradiation to this area using volumetric modulated arc therapy (VMAT) to a total dose of 3300 cGy in 11 fractions. At a four-week follow-up visit, the skin lesions had completely resolved; however, the patient experienced mild edema and tenderness of the right foot and lower leg. Although long-term outcomes need to be followed, re-irradiation showed positive short-term outcomes for classic Kaposi's sarcoma.

Palliative Radiation Therapy in the Treatment of Desmoplastic Small Round Cell Tumors.

An early adolescent male presented with six months of nausea, vomiting, and constipation. A chest computed tomography (CT) scan revealed multiple pulmonary nodules of varying sizes and a 3.1 cm pleural-based mass-like density in the right lower pulmonary lobe suspicious for metastatic disease. A CT scan of the abdomen and pelvis revealed diffuse metastatic disease involving the lungs, liver, and peritoneum. An ultrasound (US)-guided core needle biopsy of the liver was performed, and the morphology and immunohistochemistry were consistent with a poorly differentiated carcinoma. Further workup was performed, and the patient was diagnosed with a desmoplastic small round cell tumor (DSRCT). The patient underwent eight cycles of chemotherapy, but his tumor metastasized to distant sites. He then underwent two courses of palliative radiation therapy to the pelvis. His cancer continued to progress, and he eventually succumbed to his disease. This case report evaluates the evidence, data, radiation dosages, and techniques for palliative radiation therapy for DSRCTs.

Adenocarcinoma involving the urinary bladder.

A man in his 70s previously diagnosed with an adenocarcinoma of the prostate, received external beam radiation therapy (EBRT) and brachytherapy 11 years ago. Ten years later, he developed urinary symptoms and a cystoscopy identified a bladder neck tumour. A transurethral resection of a bladder tumour was performed, and pathology revealed a high-grade adenocarcinoma consistent with a colorectal primary. A colonoscopy was unremarkable, and imaging studies showed tumour involving the bladder and prostate. Tumour markers and a CARIS genomic prevalence score also favoured a colorectal cancer primary.The patient refused surgery and underwent chemoradiation with a combination of EBRT and brachytherapy with concurrent capecitabine. Imaging studies obtained 6 months after reirradiation revealed an enlarged left-sided mesorectal lymph node concerning for disease recurrence. The lymph node was treated with Stereotactic Body Radiation Therapy and his post-treatment imaging revealed a response to treatment with no other evidence of disease.

Malignant Eccrine Spiradenoma of the Posterior Scalp: An Odd Presentation.

Malignant eccrine spiradenoma is a rare cutaneous adnexal neoplasm and is often a result of the malignant transformation of a benign eccrine spiradenoma. A woman without a history of skin cancer presented with a mass on her posterior scalp. An excisional biopsy was obtained, and histology was consistent with eccrine spiradenocarcinoma with the lesion extending to all margins of the excision specimen. Physical exam and imaging did not reveal lymph node involvement or distant spread of disease. It was recommended that the patient undergo wide local excision.

High grade leiomyosarcoma of the transverse colon with positive lymph node metastasis: to treat or not to treat with adjuvant radiation therapy?

Intra-abdominal leiomyosarcomas (LMSs) are aggressive malignant tumours arising from smooth muscle cells. These neoplasms are extremely rare and account for 10%-20% of primary soft tissue sarcomas and approximately 0.1% of all colorectal malignancies. Intra-abdominal LMS has a very poor prognosis with an estimated 5-year survival rate between 20% and 50% and the size of the tumour being the main determinant of prognosis. Treatment is further complicated by different anatomic variants with differing clinical behaviours impacting prognosis. Newer techniques in radiation treatment such as intensity-modulated, intraoperative electron and proton beam radiotherapies allow for cases with high probability of local recurrence or likelihood of residual microscopic disease after surgical resection to be treated with precise radiation doses to the targeted tumour volume. We present a case of high grade LMS of the distal transverse colon with positive lymph node metastasis treated by surgical excision followed by adjuvant radiotherapy and discuss the current role of radiotherapy.

Proton versus photon radiation therapy: A clinical review.

While proton radiation therapy offers substantially better dose distribution characteristics than photon radiation therapy in certain clinical applications, data demonstrating a quantifiable clinical advantage is still needed for many treatment sites. Unfortunately, the number of patients treated with proton radiation therapy is still comparatively small, in some part due to the lack of evidence of clear benefits over lower-cost photon-based treatments. This review is designed to present the comparative clinical outcomes between proton and photon therapies, and to provide an overview of the current state of knowledge regarding the effectiveness of proton radiation therapy.

Characterization of the Response of 9L and U-251N Orthotopic Brain Tumors to 3D Conformal Radiation Therapy.

In a study employing MRI-guided stereotactic radiotherapy (SRS) in two orthotopic rodent brain tumor models, the radiation dose yielding 50% survival (the TCD50) was sought. Syngeneic 9L cells, or human U-251N cells, were implanted stereotactically in 136 Fischer 344 rats or 98 RNU athymic rats, respectively. At approximately 7 days after implantation for 9L, and 18 days for U-251N, rats were imaged with contrast-enhanced MRI (CE-MRI) and then irradiated using a Small Animal Radiation Research Platform (SARRP) operating at 220 kV and 13 mA with an effective energy of ∼70 keV and dose rate of ∼2.5 Gy per min. Radiation doses were delivered as single fractions. Cone-beam CT images were acquired before irradiation, and tumor volumes were defined using co-registered CE-MRI images. Treatment planning using MuriPlan software defined four non-coplanar arcs with an identical isocenter, subsequently accomplished by the SARRP. Thus, the treatment workflow emulated that of current clinical practice. The study endpoint was animal survival to 200 days. The TCD50 inferred from Kaplan-Meier survival estimation was approximately 25 Gy for 9L tumors and below 20 Gy, but within the 95% confidence interval in U-251N tumors. Cox proportional-hazards modeling did not suggest an effect of sex, with the caveat of wide confidence intervals. Having identified the radiation dose at which approximately half of a group of animals was cured, the biological parameters that accompany radiation response can be examined.

Metastatic spread of serous ovarian carcinoma to the bilateral breasts: a rare presentation.

A woman presented with a mass in her right breast. She had previously been treated with carboplatin, paclitaxel and bevacizumab for serous ovarian carcinoma diagnosed 5 years previously and was currently on maintenance olaparib. A right breast mammogram demonstrated periareolar skin thickening and the physical examination revealed an erythematous, non-blanching cutaneous lesion. A punch biopsy revealed high-grade serous carcinoma of ovarian origin, positive for PAX-8, WT-1 and p53. Positron emission tomogram-CT scan showed diffusely increased fluorodeoxyglucose uptake in the right breast. She was treated with external beam radiation therapy to the right breast and regional lymphatics and received 5200 cGy in 20 fractions to the right breast and supraclavicular region with good response. Two weeks after completing radiation therapy, she presented with a new lesion inferior to her left areola, concerning for metastasis to the contralateral breast. Subsequent biopsy of the left breast identified metastatic serous ovarian carcinoma for which she received an additional 5200 cGy in 20 fractions to the breast.

Radiation induced mucoepidermoid carcinoma of the parotid gland following post-operative radiotherapy to the earlobe for keloid prophylaxis.

Radiation-induced malignancies (RIMs) are rare but well-documented late toxicities associated with exposure to radiation or radiotherapy. A keloid scar is a common benign proliferation of scar tissue which commonly develops at the site of an injury, such as on the earlobe after ear-piercing. While typically reserved for management of malignancies, radiotherapy is often utilized in the management of some benign conditions, including keloids. Given the benign nature of keloids, any theoretical late toxicity from radiotherapy, particularly a life-threatening toxicity such as a RIM, is particularly concerning. Here, we report a case of a 34-year-old male who presented with a radiation induced mucoepidermoid carcinoma of the parotid gland which developed in a previously irradiated field ten years after the patient received electron radiotherapy for a keloid of the earlobe. Using available literature, we estimate the risk of a RIM of the parotid gland from a typical course of radiotherapy to the earlobe as 0.007% per year.

Final Report from IBPRO: Impact of Multidisciplinary Collaboration on Research in Radiation Oncology.

An important hallmark of the field of radiation oncology has traditionally been multidisciplinary collaboration among its clinicians and scientists. Increased specialization, resulting from increased complexity, threatens to diminish this important characteristic. This article evaluates the success of a short-term educational environment developed specifically to enhance multidisciplinary collaboration. This NIH-funded educational course, named "Integration of Biology and Physics into Radiation Oncology (IBPRO)," was developed at Wayne State University, and designed to facilitate engagement among radiation oncologists, medical physicists and radiobiologists in activities that foster collaborative investigation. The question we address here is, "Did it work?" The 240 clinicians and researchers participating in IBPRO over the five years of the course were surveyed to quantify its effectiveness. In total, 95 respondents identified 45 institutional protocols, 52 research grant applications (19 of which have been funded thus far), 94 research manuscripts and 106 research presentations as being attributable to participation in IBPRO. The majority (66%) of respondents reported generating at least one of these research metrics attributable to participation in IBPRO, and these participants reported an average of nearly five such quantitative research metrics per respondent. This represents a remarkable contribution to radiation oncology research within a relatively short period through an intervention involving a relatively small number of radiation oncology professionals. Nearly two thirds of respondents reported ongoing collaborative working relationships generated by IBPRO. In addition, approximately 50% of respondents stated that specific information presented at IBPRO changed the way they practice, and 95% of respondents practicing in a clinical setting stated that, since participation in IBPRO, they have approached clinical dilemmas more collaboratively. Many collaborative working relationships generated by this course continue to actively drive research productivity. Additionally, one of the many enduring legacies of this course is the creation of a new debate series in a professional journal. IBPRO serves as a model for our ability to leverage collaborative learning in an educational intervention to foster multidisciplinary clinical and research collaboration. It has already had a profound impact on the profession of radiation oncology, and this impact can be anticipated to increase in the future.

Dosimetric evaluation of incorporating the revised V4.0 calibration protocol for breast intraoperative radiotherapy with the INTRABEAM system.

In breast-targeted intraoperative radiotherapy (TARGIT) clinical trials (TARGIT-B, TARGIT-E, TARGIT-US), a single fraction of radiation is delivered to the tumor bed during surgery with 1.5- to 5.0-cm diameter spherical applicators and an INTRABEAM x-ray source (XRS). This factory-calibrated XRS is characterized by two depth-dose curves (DDCs) named "TARGIT" and "V4.0." Presently, the TARGIT DDC is used to treat patients enrolled in clinical trials; however, the V4.0 DDC is shown to better represent the delivered dose. Therefore, we reevaluate the delivered prescriptions under the TARGIT protocols using the V4.0 DDC. A 20-Gy dose was prescribed to the surface of the spherical applicator, and the TARGIT DDC was used to calculate the treatment time. For a constant treatment time, the V4.0 DDC was used to recalculate the dosimetry to evaluate differences in dose rate, dose, and equivalent dose in 2-Gy fractions (EQD2) for an α/ß = 3.5 Gy (endpoint of locoregional relapse). At the surface of the tumor bed (i.e., spherical applicator surface), the calculations using the V4.0 DDC predicted increased values for dose rate (43-16%), dose (28.6-23.2 Gy), and EQD2 (95-31%) for the 1.5- to 5.0-cm diameter spherical applicator sizes, respectively. In general, dosimetric differences are greatest for the 1.5-cm diameter spherical applicator. The results from this study can be interpreted as a reevaluation of dosimetry or the dangers of underdosage, which can occur if the V4.0 DDC is inadvertently used for TARGIT clinical trial patients. Because the INTRABEAM system is used in TARGIT clinical trials, accurate knowledge about absorbed dose is essential for making meaningful comparisons between radiation treatment modalities, and reproducible treatment delivery is imperative. The results of this study shed light on these concerns.

Evaluation of the dosimetric impact of manufacturing variations for the INTRABEAM x-ray source.

INTRODUCTION: INTRABEAM x-ray sources (XRSs) have distinct output characteristics due to subtle variations between the ideal and manufactured products. The objective of this study is to intercompare 15 XRSs and to dosimetrically quantify the impact of manufacturing variations on the delivered dose. METHODS AND MATERIALS: The normality of the XRS datasets was evaluated with the Shapiro-Wilk test, the accuracy of the calibrated depth-dose curves (DDCs) was validated with ionization chamber measurements, and the shape of each DDC was evaluated using depth-dose ratios (DDRs). For 20 Gy prescribed to the spherical applicator surface, the dose was computed at 5-mm and 10-mm depths from the spherical applicator surface for all XRSs. RESULTS: At 5-, 10-, 20-, and 30-mm depths from the source, the coefficient of variation (CV) of the XRS output for 40 kVp was 4.4%, 2.8%, 2.0%, and 3.1% and for 50 kVp was 4.2%, 3.8%, 3.8%, and 3.4%, respectively. At a 20-mm depth from the source, the 40-kVp energy had a mean output in Gy/Minute = 0.36, standard deviation (SD) = 0.0072, minimum output = 0.34, and maximum output = 0.37 and a 50-kVp energy had a mean output = 0.56, SD = 0.021, minimum output = 0.52, and maximum output = 0.60. We noted the maximum DRR values of 2.8% and 2.5% for 40 kVp and 50 kVp, respectively. For all XRSs, the maximum dosimetric effect of these variations within a 10-mm depth of the applicator surface is ≤ 2.5%. The CV increased as depth increased and as applicator size decreased. CONCLUSION: The American Association of Physicist in Medicine Task Group-167 requires that the impurities in radionuclides used for brachytherapy produce ≤ 5.0% dosimetric variations. Because of differences in an XRS output and DDC, we have demonstrated the dosimetric variations within a 10-mm depth of the applicator surface to be ≤ 2.5%.