Polymer implants in advancing age of radiation medicine

Midfacial reconstruction after tumor resection surgery is commonly conducted by using autologous bone grafts or alloplastic implants. Titanium is the most frequently used osteosynthesis material in these cases but causes disturbing metallic artifacts in CT imaging. The purpose of this experimental study was to evaluate whether the use of midfacial polymer implants reduces metallic artifacts in CT imaging to improve image quality. Zygomatic titanium (n = 1) and polymer (n = 12) implants were successively implanted in a human skull specimen. Implants were analyzed for their effect on Hounsfield Unit values (streak artifacts) and virtual growth in CT images (blooming artifacts) as well as image quality. Multi-factorial ANOVA and Bonferroni's post hoc test were used. Titanium (173.7 HU; SD ± 5.1) and hydroxyapatite containing polymers (155.3 HU; SD ± 5.9) were associated with significantly more streak artifacts compared to all other polymer materials. There was no significant difference in blooming artifacts between materials. The metallic artifact reduction algorithm showed no significant difference. Image quality was slightly better for polymer implants compared to titanium. Personalized polymer implants for midfacial reconstruction significantly reduce metallic artifacts in CT imaging which improves image quality. Hence, postoperative radiation therapy planning and radiological tumor aftercare around the implants are facilitated.

Dose Summation Strategies for External Beam Radiation Therapy and Brachytherapy in Gynecologic Malignancy: A Review from the NRG Oncology and NCTN Medical Physics Subcommittees

Short-term morbidity and long-term functional outcome of patients with an ileal pouch-anal anastomosis (IPAA) exposed to pelvic external beam radiation therapy (EBRT) remains unknown. We report the largest series to date regarding the effects of pelvic EBRT on: (i) 30-day postoperative outcomes; and (ii) long-term functional outcome following IPAA. A retrospective chart review was conducted of patients who received EBRT before or after IPAA between 1980 and 2017 across three international inflammatory bowel disease referral centres. Nineteen patients were included. Indications for EBRT were rectal adenocarcinoma (n=13), prostate adenocarcinoma (n=4) or anal squamous cell carcinoma (ASCC) (n=2). EBRT was given prior to IPAA in 12 (63%) patients and after IPAA in seven (37%). In EBRT before IPAA, patients had a median of 5 (range: 4-8) daytime bowel movements, 1 (range: 0-5) night-time bowel movement, no daytime incontinence, and only one patient used pads at a median follow up of 25(range: 11-163) months; one patient underwent pouch excision 15months after IPAA. In EBRT after IPAA, patients reported a median of 8 (range: 5-10) daytime and 2 (range: 0-5) night-time bowel movements, 80% had either daytime or night-time incontinence and 80% used pads at a median follow up of 90(range: 25-315) months. Pelvic EBRT administered prior to IPAA is associated with acceptable long-term function outcome. However, when pelvic EBRT is given to an IPAA insitu, most patients experience poor long-term pouch function without pouch failure.

To outline the indications for and our experience with postoperative adjuvant external-beam radiotherapy (EBRT) in patients with eyelid or conjunctival cancers. Twenty consecutive patients with primary eyelid or conjunctival cancer treated with surgical resection followed by postoperative EBRT between January 2000 and September 2006 were included. The indications for postoperative EBRT, type and dose of EBRT, oculoplastic reconstructive procedures, timing of EBRT in relation to reconstructive procedures, and the ocular side effects of EBRT were recorded. Sixteen women and 4 men ranged in age from 44 to 86 years (median, 64 years). The oculoplastic procedures included local flaps or direct closure of eyelid defect (12), tarsoconjunctival flap (6), full-thickness skin grafts (6), amniotic membrane grafts (2), other conjunctival reconstruction (2), tarsoconjunctival graft (1), and lacrimal stenting (1). The total radiation dose ranged from 26 to 63 Gy (median, 60 Gy). The indications for postoperative EBRT included aggressive histology, recurrent tumor, microscopic perineural invasion, advanced-stage disease, and microscopically positive or "close" margins. EBRT started 5 to 12 weeks (median, 7 weeks) after reconstructive procedures. The follow-up time ranged from 7 to 50 months (mean, 24 months). Thirteen patients experienced dry eye syndrome; 3 keratinization of conjunctiva; and 1 each blepharitis, trichiasis, radiation retinopathy/optic neuropathy, and exposure keratopathy. Postoperative EBRT can be used as adjuvant therapy after surgical resection of eyelid or conjunctival cancers and may obviate more radical surgery such as orbital exenteration in some patients. The ocular side effects from EBRT were relatively minor in most patients.

PurposeThe aim of the study was to assess selected methods of image registration available in the RaySearch software and their impact on the accuracy of mapping of doses deposited in the bladder during brachytherapy (BRT) of cervical cancer in images used during external beam radiotherapy (EBRT).Material and methodsThe study was based on data from ten patients. Cone-beam computed tomography (CBCT) images (BRT) were aligned with CT images (EBRT) using four registration methods: Reg_1 (rigid), Reg_2a, Reg_2b (hybrid), and Reg_3 (biomechanical). Image mapping accuracy was evaluated based on bladder’s anatomy. Sørensen-Dice coefficient (DSC) values were analyzed for all the registrations. Discrepancies between triangular mesh points set on the basis of bladder contours were analyzed. Dose distributions from BRT were transformed according to registration results and mapped on CT images. Original BRT doses deposited in 2 cm3 volume of the bladder were compared to those transformed and associated with bladder’s volume determined on CT images.ResultsMean DSC values amounted to 0.36 (Reg_1), 0.87 and 0.88 (Reg_2a and Reg_2b), and 0.97 (Reg_3). Significant differences were found between DSC for the following comparisons: Reg_3/Reg_1 (p = 0.001), Reg_2a/Reg_1 (p = 0.011), and Reg_2b/Reg_1 (p = 0.014). The lowest discrepancies between triangular mesh points were for Reg_3 (p < 0.001, Reg_3 vs. Reg_1, and p = 0.039, Reg_3 vs. Reg_2b). Finally, the lowest discrepancies between the original and transformed doses were found for Reg_3. Nevertheless, only 5 out of 10 observations for Reg_3 yielded error of less than 5%.ConclusionsBiomechanical registration (Reg_3) enabled the most accurate alignment between CBCT and CT images. Satisfactory registration results of anatomical structures do not guarantee a correct mapping of primary BRT doses on the bladder delineated on CT images during EBRT. The results of dose transformation based on biomechanical registration had an error of less than 5% for only 50% of the observations.

Alpha-particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, αRPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of α-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by α-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or β-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(α/β), has recently been proposed by the ICRU. In concert with EQD2(α/β), we introduce a new, redefined RBE quantity, named RBE2(α/β), as the ratio of the two linear coefficients that characterize the α particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either α particles or a single fraction of low-LET (137)Cs γ rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(α/β) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(α/β) and EQD2(α/β) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, α particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(α/β) is independent of absorbed dose for α-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE. Moreover, it provides a much needed foundation for the ongoing development of an α-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop αRPT as a single modality as well as for combination therapies.

Alpha-particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, αRPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of α-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by α-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or β-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(α/β), has recently been proposed by the ICRU. In concert with EQD2(α/β), we introduce a new, redefined RBE quantity, named RBE2(α/β), as the ratio of the two linear coefficients that characterize the α particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either α particles or a single fraction of low-LET 137Cs γ rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(α/β) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(α/β) and EQD2(α/β) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, α particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(α/β) is independent of absorbed dose for α-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE. Moreover, it provides a much needed foundation for the ongoing development of an α-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop αRPT as a single modality as well as for combination therapies.

e15163 Background: Although there is interest in racial disparities in prostate cancer outcomes among persons of African descent living in the United States there is scant data available regarding disease presentation and treatment response among black men living in Africa. In this study we evaluate disease presentation and early clinical outcomes among Ghanaian men with prostate cancer treated with external beam radiotherapy (EBRT). Methods: A total of 379 men with prostate cancer were referred to the National Center for Radiotherapy and Nuclear Medicine, Ghana, from January 2003 to December 2009. Data were collected regarding patient- and tumor-related factors such as age, prostate specific antigen (PSA), Gleason score, clinical stage, and use of hormonal therapy. For patients who received EBRT, freedom from biochemical failure (FFbF) was evaluated using Kaplan-Meier analysis. Results: The median age at diagnosis was 65 years. Of 379 patients referred for treatment 69.6% of all patients had initial PSA &gt;20ng/ml, and the median iPSA was 39.0 ng/ml. A total of 128 men representing 33.8% of overall cohort were diagnosed with metastatic disease at time of referral. We identified 166 men treated with EBRT or brachytherapy +/- androgen depravation therapy (ADT), and an additional 139 men treated with ADT alone (including orchiectomy in 38 patients). The median EBRT dose was 70 Gy, in 2 Gy per fraction. Among all EBRT patients with at least 2 years of follow-up after treatment (n=52; median follow-up time: 38.9 months), 5-year actuarial FFbF was 65.1%: 67.0% for patients with PSA &lt; 30.0 ng/mL and 63.2% for PSA ≥ 30.0 ng/mL [log-rank, p=0.586]. Conclusions: This is the largest series reporting on outcomes for prostate cancer treatment in West Africa. That one-third of patients presented with metastatic disease suggests potential need for earlier detection of prostate cancer to permit curative-intent local therapy. Data from this study will aid in the strategic development of a prostate cancer research roadmap in Ghana, with a focus on improving therapeutic approach as well as fostering a prudent allocation of scarce resources.

Prospective Long-term Health-related Quality of Life Outcomes After Surgery, Radiotherapy, or Active Surveillance for Localized Prostate Cancer

Recently, polymeric controlled delivery of chemotherapy has been shown to improve survival of patients with malignant glioma. We tested the delivery of IUdR via polymers for radiosensitization of experimental intracranial human malignant glioma. To assess efficacy, we measured the in vitro release, the in vivo delivery of IUdR and the resultant radiosensitization of experimental human U251 glioblastoma xenografts. In vitro: To measure release, increasing (10%, 30%, 50%) proportions of IUdR in synthetic [(poly(bis(p-carboxyphenoxy)-propane) (PCPP):sebacic acid (SA) polymer discs were serially incubated in buffered saline and the supernatant fractions were assayed. In vivo: To compare local vs. systemic delivery, mice bearing flank xenografts had intratumoral or contralateral flank IUdR polymer (50% loading) treatments. Mice bearing intracranial (i.c.) xenografts had i.c. vs. flank IUdR polymer treatments. Four or 8 days after implantation of polymers, mice were sacrificed and the percentage tumor cells that were labeled with IUdR was measured using quantitative microscopic immunohistochemistry. For comparisons of radiosensitization, mice bearing i.c. xenografts had i.c. vs. flank IUdR polymers and cranial fractionated external beam irradiation (2 Gy BID x 4 days). In vitro: Increasing percentage loadings of IUdR resulted in higher percentages of release: 43.7 +/- 0.1, 70.0 +/- 0.2, and 90.2 +/- 0.2 (p < 0.001 ANOVA) for the 10, 30, and 50% loadings, respectively. In vivo: For the flank tumors, both the ipsilateral and contralateral IUdR polymers resulted in similarly high percentages labeling of the tumors vs. time. For the ipsilateral IUdR polymers, the percentages of tumor cellular labeling after 4 vs. 8 days were 45.8 +/- 7.0 vs. 40.6 +/- 3.9 (p = NS. For the contralateral polymer implants, the percentages tumor cellular labeling were 43.9 +/- 10.1 vs. 35.9 +/- 5.2 (p = NS) measured 4 vs. 8 days after implantation. For the i.c. tumors treated with extracranial IUdR polymers, the percentages of tumor cellular labeling were low: 13.9 +/- 8.8 and 11.2 +/- 5.7 measured 4 and 8 days after implantation. For the i.c. tumors having the i.c. IUdR polymers, however, the percentages labeling were comparatively much higher: 34.3 +/- 4.9 and 35.3 +/- 4.0 on days 4 and 8, respectively. For the i.c. tumors, examination of the percentage cellular labeling vs. distance from the implanted IUdR polymer showed labeling was highest closest to the polymer disc. Radiosensitization: For mice bearing i.c. tumors and receiving flank vs. intracranial IUdR polymer treatments, the survival after external beam irradiation was significantly higher for the intracranial treatments: 49 + 8.9 vs. 80 + 4.1 (p = 0.03) days, respectively. Implantable biodegradable polymers provide the local, controlled release of IUdR and result in the high, local delivery of IUdR to experimental intracranial human malignant glioma. The local delivery and labeling result in improved survival following radiotherapy. This technique holds promise for the local delivery of IUdR for radiosensitization of human brain tumors.

The needs of modern surgery triggered the intensive development of transplantology, medical materials science, and tissue engineering. These directions require the use of innovative materials, among which porous polymers occupy one of the leading positions. The use of natural and synthetic polymers makes it possible to adjust the structure and combination of properties of a material to its particular application. This review generalizes and systematizes the results of recent studies describing requirements imposed on the structure and properties of synthetic (or artificial) porous polymer materials and implants on their basis and the advantages and limitations of synthesis methods. The most extensively employed, promising initial materials are considered, and the possible areas of application of polymer implants based on these materials are highlighted.

Brachytherapy Issues and Priorities in the Context of the Coronavirus Disease 2019 (COVID-19) Outbreak

Radionuclide imaging of endocrine diseases has been in clinical application for many years. Over the past six decades, an increasing number of radionuclides and radiolabeled compounds are available for imaging the endocrine organs/tissues functions. Radionuclide imaging provides functional as well as morphological information on multiple endocrine organs especially thyroid, parathyroid, and adrenal glands. Endocrine nuclear medicine includes not only diagnosis but also internal radionuclide therapy. Recently, radiolabeled peptides have also been used for diagnostic and for therapeutic purposes.

Background:Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART® (Intra-operative Avidination for Radionuclide Therapy).Aim:The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of 90Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient’s quality of life, including the cosmetic results after the combined treatment with IART® and EBRT, were assessed.Methods:After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq 90Y-biotin spiked with 185 MBq 111In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART® boost. Local toxicity and quality of life were evaluated.Results:Thirty-five patients were evaluated. No side effects were observed after avidin administration and 90Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 ± 4.0 Gy) to the surgical bed. At the end of IART®, no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART®+EBRT was well accepted by the patients, without any changes to their quality of life.Conclusions:These preliminary results support the hypothesis that IART® may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients.

To ensure the book was read in its entirety, the text was divided into thirds and apportioned equally to each reviewer; all 3 reviewers were assigned 4 chapters in common to read as well.This summary review by 3 individuals, each of whom is internationally recognized for expertise in the broad field of general cardiology, is offered in the spirit of helping the ESC achieve its stated objective of providing a textbook that is successful in covering the knowledge that should be required of all general cardiologists.