External Beam Research Articles

Abstract 3057: Development of radiation-triggered phosphor platform for localized activation in combinatory cancer treatment

Abstract A defined spatial and temporal control of induction of toxicity in response to external ionizing radiation such as X-rays has unique clinical benefits over conventional systems such as passive drug delivery or its activation. Here, we have combined X-rays with well characterized nanoscintilators emitting light that activates paired photosensitizers in photodynamic therapy (PDT) that improves the prowess of PDT to deep seated tumor treatment. Yttrium oxide nanoparticle construct doped with Europium (YOE) and coated with a silica layer entrapping methylene blue (MB) as the photosensitizer was fabricated. The nanoconstruct (YSM, for YOE, silica, MB) was decorated with polyethylene glycol (PEG) to make it biocompatible and characterized extensively for physicochemically parameters. Transmission electron microscopy (TEM) revealed a resultant average nanoparticle diameter of 24.1 ± 5.7 nm, and dynamic light scattering (DLS) a hydrodynamic diameter of 135.3 ± 17.9 nm. This nanoconstruct was evaluated for its ability to generate singlet oxygen reactive oxygen species upon irradiation using singlet oxygen sensor green (SOSG) fluorescence assay. Further, demonstrated that this nanoconstruct was taken up by cancer cells in vitro and by tumors in vivo. The uptake of YSM particles by Panc02 murine pancreatic cancer cells was tested by inductively coupled plasma – mass spectrometry. This demonstrated robust uptake in cells after 24hr incubation. No noticeable cell death occurred with doses of 0 Gy and 4 Gy, cell viability decreased significantly after a dose of 8 Gy irradiation in cells cultured with YSM when compared to controls. Since 8 Gy is within the range of a clinically applicable dose used routinely in stereotactic radiotherapy regimens, these results verified the potential of YSM to be used as scintillator-photosensitizer complexes for x-ray activated photodynamic therapy. Finally the biodistribution of YSM nanoconstructs in vivo in C57BL6 mice harboring subcutaneous Panc02 tumors show YSM accumulation in tumors. A versatile, biocompatible Yttrium oxide scintillator-photosensitizer complex (YSM) that can generate x-ray induced cytotoxic reactive oxygen species is fabricated. This is capable of facilitating x-ray activated photodynamic therapy (XPDT (external beam) and/or iXPDT (internal x-ray source)). It shows promise in maximizing the efficacy of the combinatory treatment and enhanced improvement of the quality of life and overall survival of cancer patients. Citation Format: Rao V. Papineni, Sunil Krishnan, Ajayan Pulickel, Onur Sahin. Development of radiation-triggered phosphor platform for localized activation in combinatory cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3057.

Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low, and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabeled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

GSOR05 Presentation Time: 2:50 PM: FINITO (Freehand Interstitial Needles in Addition to Tandem and Ovoid) - A Novel Hybrid Brachytherapy Technique for Locally Advanced Cervical Cancer

Purpose: Women with locally advanced cervical cancer (LACC) most commonly present with disease that extends out laterally from the cervix to the parametrium/sidewall. Traditionally, external beam parametrial/sidewall boosts have been added to the standard pelvic treatment in addition to tandem-based brachytherapy. A hybrid approach, by adding an interstitial component to the intracavitary applicators, has the potential to target both central tumor and asymmetric lateral extension of disease. There is a variety of hybrid applicators currently available on the market, but they are expensive and confine the user to specific equipment and technology.

Nasal vestibule and columella cancer: a therapeutic and reconstructive conundrum.

Nasal vestibular cancers are rare entities among the head and neck cancers. The treatment options are varied. Although surgical treatment plays an important role, postablative defects are difficult to reconstruct. This review aims to discuss the current views in the management of these cancers and issues related to the reconstruction of the complex surgical defects. Nasal vestibular cancers are a distinct rare entity of head and neck cancers. These cancers are staged using the AJCC-TNM system for nonmelanoma cutaneous cancers of head and neck or the Wang classification. Early lesions are best treated by either surgery or radiation giving excellent cure rates. Advanced stages tumours need combined treatment with surgery and adjuvant radiation therapy. Primary radiation therapy can be offered by external beam or interstitial brachytherapy. Surgical treatment varies from endonasal resections, Mohs' chemosurgery to open excisions. Even though the Wang system of classification is used by majority of reports due its clinical utility, it has a drawback of not taking into account the tumour size as done by the AJCC system. Brachytherapy has been reported to be offering excellent cure rates with low morbidity in early tumours. Surgical treatment is also effective in early lesions, but its role is more established in advanced lesions. Reconstruction of the surgical defects is often a challenge, to preserve functional integrity and cosmesis. Various techniques, including skin grafts, local flaps, free flaps and prosthetics, form part of the reconstructive armamentarium.

Novel use of a vaginal cylinder purposed dually as obturator and localiser for stereotactic ablative radiotherapy delivery

AbstractBackground:Vaginal cancer is a rare malignancy that poses a challenge to treat and cure, as surgical excision requires life-changing procedures because of the proximity and involvement of rectum, bladder and anus. We report in this case study the successful delivery of stereotactic ablative radiotherapy (SABR) for a patient with vaginal cancer after previous radiotherapy.Methods:A 71-year-old white female who presented with dyspareunia and irritative urinary symptoms proven by biopsy was our candidate patient. Subsequent PET/CT revealed a hypermetabolic 3 cm lesion at the 12–1 o’clock position in the distal vagina involving the clitoris. The patient was initially treated with volumetric-modulated arc therapy (VMAT) with simultaneous integrated boost technique to the involved nodes, and later upon recurrence treated with SABR using 30 Gy in six fractions.Findings:To our knowledge, this is the first report of a vaginal cylinder used to physically distance organs at risk from the treatment target and also as a localising device with image guidance for the delivery of SABR using an external beam.

Effects of mainshock-aftershock sequences on fragility analysis of RC buildings with ageing

This paper presents the seismic vulnerability assessment of existing RC buildings designed according to previous non-seismic codes that are exposed to various levels of corrosion and mainshock-aftershock sequences. A refined finite element model of an existing four-storey reinforced concrete building is adopted. Twenty as-recorded natural ground motions are collected from international databases to perform incremental dynamic analyses for the inelastic response of the testbed building. The effects of corrosion are applied on external beams and columns to simulate a realistic exposure. The robust fragility assessment is conducted for a range of seismic intensity measures. Moreover, a new intensity measure, based on the modified acceleration spectrum intensity, is proposed. Such seismic parameter accounts for the elongation period experienced by structures during earthquake events and appears to be more reliable and accurate for corroded RC structures than the most adopted peak ground acceleration and spectral acceleration at the first natural period. The results of the comprehensive numerical simulations contribute to providing relevant indications on the non-linear response of existing corroded buildings under multiple excitations and, highlight that current seismic codes are no longer conservative for such detrimental phenomena.

Patient-reported quality of life with interstitial partial breast brachytherapy and external beam whole breast radiotherapy: a comparison using propensity-score matching.

PurposeThe aim of this study was to compare patient-reported quality of life (QOL) scores after accelerated partial breast irradiation (APBI) using interstitial brachytherapy vs. external beam whole breast radiotherapy (WBRT) for breast cancer.Material and methodsWomen with breast cancer treated with WBRT or APBI after breast conservation surgery were enrolled in this prospective study. Single cross-sectional QOL assessment was performed using EORTC QLQ-C30 and BR-23 questionnaires. Patients treated with APBI were propensity-score matched to similar cohort of patients treated with WBRT. QOL scores were analyzed for the entire unmatched cohort and compared between the two matched cohorts using Student’s two-tailed t-test. P-value of < 0.05 was considered statistically significant, and a 10-point difference between mean scores was considered clinically meaningful.ResultsA total of 64 APBI patients were matched with 99 WBRT patients out of the entire study cohort of 320 cases. QOL scores for functional scales of QLQ-C30 were similar between the two groups for both matched and unmatched cohorts, while symptom scores of QLQ-C30 did not show any clinically significant difference. Functional scales of BR-23 did not show any clinical or statistically significant difference. Among symptom scales of BR-23, scores were similar for APBI and WBRT groups except for a worse score of “upset by hair loss” sub-scale in the brachytherapy group of the matched cohort (51.9 vs. 22.7, p = 0.006).ConclusionsPatients undergoing APBI reported similar QOL compared to WBRT when matched for various factors.

The beams with composite reinforcement inclined sections’ finite element modeling operation results comparison with the results of the laboratory samples’ tests

The results of a numerical experiment are presented, within the framework of which finite element modeling of the reinforced concrete beams support sections with external composite reinforcement beams inclined sections operation was carried out, as well as their comparison with the results of an experiment carried out on real laboratory samples, similarly reinforced on the support areas by external composite U-shaped cross clamps. The strength of inclined sections of both real laboratory specimens and their design models was considered. Both numerical and real experiments were carried out at three values of the shear fracture span: 1.5h0; 2.0h0 and 2.5h0. The obtained results of the numerical experiment are compared with the results of laboratory tests on beams in order to analyze the accuracy of the calculation results and to find the optimal method for modeling and taking into account the external composite reinforcement clamps in the design models that would most accurately reflect their contribution to the operation of the inclined section of bent reinforced concrete elements. For the numerical experiment, the method of finite element modeling of samples was used. An assessment of the method used for computational modeling of the operation of inclined sections reinforced with external composite reinforcement is given.

Effect of Radiotherapy in Addition to Surgery in Early Stage Endometrial Cancer: A Population-Based Study.

Simple SummaryEndometrial cancer is a relatively common tumor among women above the age of 50. The treatment of endometrial cancer in an early stage (FIGO I) is still under dispute. The standard treatment of surgery also includes radiotherapy in certain risk groups. In our study, we assessed the value of radiotherapy (external beam or brachytherapy) on survival in a large population-based cohort of early endometrial cancer cases (FIGO I), with operative treatment respecting known risk factors. The data are based on the epidemiological cancer registries (Robert Koch Institute) from 2000–2017 and encompassed 12,718 cases. We found that radiotherapy is especially beneficial when the tumor infiltrates the muscular tissue (myometrium) of the uterus to a large extend. Radiotherapy was also advantageous in all histopathological grades (cell differentiation). Future studies need to compare different treatment options in an experimental prospective design.Background: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials. Methods: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded operative treatment (n = 12,718, 2000–2017). We computed hazard ratios (HR) from relative survival models in relation to the mortality of the general population with 95% confidence intervals (CI). Multivariate models were adjusted for age, stage (IA vs. IB), grading, and chemotherapy. Radiotherapy included external radiotherapy and brachytherapy. Results: Cases with a favorable risk profile (FIGO IA, G1/G2) had a slightly lower survival rate, relative to the general population (FIGO IA: 0.9, G1: 0.91). The proportion of FIGO IA cases was lower in the radiotherapy group (52.6%) vs. cases without radiotherapy (78.6%). Additional treatment with radiotherapy was beneficial in FIGO IB (HR = 0.74) and all histopathological grades, but not FIGO IA cases (HR = 0.93) cases. Compared to IA tumors, IB cases had a HR of 1.51 (95% CI: 1.34–1.7). Conclusions: Radiotherapy in addition to surgery is beneficial for patients in a FIGO IB stage. Further studies need to address the impact of new techniques and risk assessment.

Immunogenicity of Externally Activated Nanoparticles for Cancer Therapy.

Simple SummaryRecent advances in treating cancer via stimulating an anti-tumor immune system response have resulted in extraordinary results for lymphomas and leukemias; however these therapies have not performed well in solid tumors. External beam therapies, such as radiotherapy, hyperthermia, and photodynamic therapy, that are clinically used for solid tumors are now being explored in combination with nanoparticle systems to stimulate a long-term anti-tumor immune system response. In this review, we detail the novel nanoparticle complexes that are being researched to activate an anti-tumor immune response in combination with external beam therapy in both the preclinical and clinical settings.Nanoparticles activated by external beams, such as ionizing radiation, laser light, or magnetic fields, have attracted significant research interest as a possible modality for treating solid tumors. From producing hyperthermic conditions to generating reactive oxygen species, a wide range of externally activated mechanisms have been explored for producing cytotoxicity within tumors with high spatiotemporal control. To further improve tumoricidal effects, recent trends in the literature have focused on stimulating the immune system through externally activated treatment strategies that result in immunogenic cell death. By releasing inflammatory compounds known to initiate an immune response, treatment methods can take advantage of immune system pathways for a durable and robust systemic anti-tumor response. In this review, we discuss recent advancements in radiosensitizing and hyperthermic nanoparticles that have been tuned for promoting immunogenic cell death. Our review covers both preclinical and clinical results, as well as an overview of possible future work.

Custom Blocks Made of Metal Grit for External Electron Beam Therapy

A new way of producing custom blocks for external electron beam therapy is described. The blocks are made of steel or lead grit uniformly distributed in epoxy resin. The proposed technique is user-friendly, inexpensive, and based on non-toxic materials.

Combined Use of a Transmission Detector and an EPID-Based In Vivo Dose Monitoring System in External Beam Whole Breast Irradiation: A Study with an Anthropomorphic Female Phantom

We evaluate the combined usage of two systems, the Integral Quality Monitor (IQM) transmission detector and SoftDiso software, for in vivo dose monitoring by simultaneous detection of delivery and patient setup errors in whole breast irradiation. An Alderson RANDO phantom was adapted with silicon breast prostheses to mimic the female anatomy. Plans with simulated delivery errors were created from a reference left breast plan, and patient setup errors were simulated by moving the phantom. Deviations from reference values recorded by both monitoring systems were measured for all plans and phantom positions. A 2D global gamma analysis was performed in SoftDiso for all phantom displacements. Both IQM signals and SoftDiso R-values are sensitive to small MU variations. However, only IQM is sensitive to jaw position variations. Conversely, IQM is unable to detect patient positioning errors, and the R-value has good sensitivity to phantom displacements. A gamma comparison analysis allows one to determine alert thresholds to detect phantom shifts or relatively large rotations. The combined use of the IQM and SoftDiso allows for fast identification of both delivery and setup errors and substantially reduces the impact of error identification and correction on the treatment workflow.

Looking Beyond D90: A Novel Way of Correlating Brachytherapy Quality With Local Control in Cervix Cancer

The current formalism for reporting and adding the effects of BT and external beam (EB) RT doses are based on a single metric, D90 to HR-CTV and its EQD2. Previously published work however, has demonstrated that BED(D90) is unable to distinguish between plans that are optimized differently or created with different applicator systems. In comparison, EUBED and gBEUD, which both integrate voxel level BED, are better at discerning these important differences. We sought to measure local control in women being treated with radiotherapy for locally advanced cervix cancer and assess its correlation with EUBED and gBEUD over the whole volume of HR-CTV compared to the traditional, single point metrics D90. 163 women with FIGO 2018 IB3-IIIC2 cervical cancer from 3 institutions were included. All women received EBRT ± chemotherapy and 3-5 fractions of intracavitary brachytherapy. The median follow-up for all women was 59.5 months (range 0-87 months). At this time 6.1% have had local recurrences, 12.2% distant recurrences, 1.2% both local and distant. Data was extracted from TPS and dosimetric and radiobiological quantities computed. EUBED and gBEUD were calculated for each fraction. EUBED uses an extra parameter α (range 0.05-0.5Gy-1) with smaller values typically associated with radioresistant tumors. Similarly, gBEUD uses a parameter a which allows a variable emphasis on hot/cold spots (range –5,5). Distributions were compared using the 2-sample Kolmogorov-Smirnoff test at 5% significance. Distributions of all dosimetric quantities were compared among institutions, starting with CTV size and D90. D90 did not distinguish between patient populations with different outcomes. EUBED integrates biological effect over a volume in a manner very similar with gBEUD for negative a. Such exponents are typically used in relation with local control emphasizing ‘cold spots.’ Interestingly, a large ‘hot’ volume is present in all T&O and T&R applications and some practitioners even emphasize contiguity of 150% or 200% isodoses in their plans. gBEUD for positive values [3.5] proved to be the only metric that successfully predicted local recurrence. Based on these findings, gBEUD should be included routinely to the set of parameters used to evaluate implants. This is particularly important now, when based on increased use of MRI and of hybrid devices one has the ability to create dose distributions which are significant departures from the classical pear.Tabled 1Abstract 3063; TableInstitutionABCHR-CTV Volume (cm3)41.6±15.031.9±14.936.2±21.0D90 (%PD)101.5±11.7112.5±24.3117.2±10.5 Open table in a new tab

Who are the optimal candidates for partial breast irradiation?

At the 2017St. Gallen International Expert Consensus Conference on the Primary Therapy for Early Breast Cancer, the consensus panel recognized "partial breast irradiation as an option for women meeting the low-risk criteria put forward by the American Society for Radiation Oncology/European Society for Radiotherapy and Oncology (ASTRO/ESTRO) guideline," although acknowledging that there was less evidence for this approach. Partial breast irradiation is defined as irradiation localized to the surgical resection cavity only as opposed to the entire breast. Accelerated partial breast irradiation (APBI) involves intensive treatment in a short time period. The methods vary, and three available APBI options are brachytherapy, external beam and intra-operative irradiation. The long-term follow-up results from two large-scale, well-designed phase III randomized clinical trials have been released. However, further discussion of the optimal treatment candidates and delivery method is needed before the clinical application of APBI as a mainstream breast conservation treatment.

External beam Total-IBA using DataFurnace

The self-consistent Ion Beam Analysis (IBA) of cultural heritage samples using the external beam is technically demanding. We report on the calibration of an analysis of glass samples from the Rosslyn Chapel where the interest will ultimately be in the full characterisation of the weathered glass. Such an analysis requires a comprehensive Total-IBA approach using p-PIGE and He-PIXE to obtain ”bulk” and surface Na, with H-PIXE/EBS for multielemental depth profiling to 10 μm and He-PIXE/EBS for higher depth resolution near the surface; also with two PIXE detectors as usual for the high and low energy parts of the spectrum. A revised NDF v.10 code capable of a self-consistent handling of all these signals at state-of-the-art accuracy is described, together with the calibration protocols required for such an analysis. Other capabilities of the NDF code not previously discussed are also reviewed.

Beam Monitors for Tomorrow: The Challenges of Electron and Photon FLASH RT

The emergent FLASH RadioTherapy (RT) uses ultrahigh dose-rate irradiation (up to 107 Gy/s instantaneous dose-rate in each μs pulse) to deliver a single high dose of irradiation in a very short time (less than 200 milliseconds). Pre-clinical studies at ultrahigh dose-rates recently showed an increased ratio between tumoricidal effect and normal tissue toxicity (therapeutic index), compared to conventional RT at standard Gy/min dose-rates. If confirmed by biological in vivo validations, this could represent a breakthrough in cancer treatment. However, the reliability and the accuracy of experimental studies are nowadays limited by the lack of detectors able to measure online the beam fluence at FLASH dose-rates. The behaviour of standard beam monitors (gas-filled ionization chambers) is compromised by the volume recombination caused by the amount of charges created per unit volume and unit time, due to the large dose-rate. Moreover, due to the lack of proper monitoring devices and to the uncertainties of its future applications, very few facilities are able to deliver at present FLASH irradiations. In this contribution, we report about the physical and technological challenges of monitoring high and ultra-high dose-rates with electrons and photon beams, starting from the pre-clinical and clinical constraints for new devices. Based on the extensive experience in silicon detectors for monitoring applications in RT with external beams, the work then investigates silicon sensors as a possible option to tackle such extreme requirements and a rugged thin and large (e.g. 10×10 cm2) flat detector (silicon-based sensor + readout electronics) is therefore outlined. This study aims at presenting the FLASH-RT dosimetry problem and analysing the possibilities for a silicon sensor to be employed as sensing device for several FLASH scenarios, including some ideas on the readout part. However, more detailed simulations and studies are demanded to delineate more precisely the technical choices to be undertaken in order to tackle the clinical accuracy required on the beam fluence, typically a few %, during photon and electron high and ultra-high irradiations, the required minimal perturbation of the beam and the high level of radiation resistance.

Predicting adherence of dose–volume constraints for personalized partial-breast irradiation technique

PurposeMulticatheter interstitial brachytherapy (MIB) and external-beam (EB) radiotherapy are established partial-breast irradiation (PBI) techniques. Although EB-PBI is widely available, it requires extra irradiated margins for target uncertainties. We examined the impact of EB-PBI on dose–volume constraints as compared to MIB-PBI. Methods and MaterialsAmong 653 patients receiving MIB-PBI between October 2008 and April 2020, consequent 159 patients after September 2018 were examined. Clinical target volume (CTV) included the lumpectomy cavity plus 1.0 cm. Planning target volume (PTV) for EB-PBI was defined as CTV with 1.0-cm expansion. Because the ratio of PTV to breast volume (RPB) was related to cosmesis, <25% of RPB was defined as suitable for the ipsilateral breast constraints. Preoperative breast size was classified as very small (<350 cm3), small (350–699 cm3), and medium or large (≥700 cm3). According to each category, the dose–volume constraints of the organs at risk were compared between the two PBI techniques. ResultsPatients including 84 very small, 59 small, and 16 moderate to large breasts were examined. Although RPB was suitable in all patients receiving MIB-PBI, it was achieved in 74 patients (46.5%) receiving EB-PBI (p < 0.0001). The suitable RPB in patients with very small, small, and moderate to large breast was 32.1%, 55.9%, and 100%, respectively (p < 0.0001). Normal-tissue constraints for the other organs could be satisfied in patients with moderate to large breasts. ConclusionAlthough EB-PBI may be an appropriate option for patients with moderate to large breasts, MIB-PBI could still be a crucial technique, especially for patients with small breasts.

The five “W”s and “How” of Targeted Alpha Therapy: Why? Who? What? Where? When? and How?

Cancer is the second cause of death and morbidity in Europe. Unfortunately, currently available treatments cannot permanently cure most cancers, especially when metastatic. New therapy approaches are, therefore, urgently needed. Radionuclide therapy deposits cytotoxic radiation by means of energetic particles (alfa, beta, and auger) labeled to a carrier that specifically targets cancer cells. Targeted Alpha Therapy is very promising, because alpha particles deliver high energy (i.e., cytotoxic effect) in a small range, binding a target cell population without significant harm to healthy tissues. The high linear energy transfer typical of alpha particles determines irreversible double-strand DNA breaks with per-unit absorbed doses of acute biologic effects three-to-seven times greater than the damage produced by external beam with photons or beta radiation. As consequence, cells—not equipped to efficiently repair this type of damage—typically undergo death. Therefore, Targeted Alpha Therapy is such a new approach to treat tumors. This article aimed to provide an overview (five “W”s and “How”) on Targeted Alpha Therapy.

Fast and fully-automated multi-criterial treatment planning for adaptive HDR brachytherapy for locally advanced cervical cancer

PurposeTo develop and evaluate a fast, automated multi-criterial treatment planning approach for adaptive high-dose-rate (HDR) intracavitary + interstitial brachytherapy (BT) for locally advanced cervical cancer. Methods and materialsTwenty-two previously delivered single fraction MRI-based HDR treatment plans (SFclin) were used to guide training of our in-house system for multi-criterial autoplanning, aiming for an autoplan quality superior to the training plans, while respecting the clinically desired “pear-shaped” dose distribution. Next, the configured algorithm was used to automatically generate treatment plans for 63 other fractions (SFauto). The SFauto plans were compared to the corresponding SFclin plans in blind pairwise comparisons by an expert clinician. Then, the effect of adaptive autoplanning on total treatment (TT) plans (external beam + 3 BT fractions) was evaluated for 16 patients by simulating the clinically applied adaptive strategy to generate TTauto plans and compare them with the corresponding clinical treatments (TTclin). ResultsIn the blind comparisons, all SFauto plans were considered clinically acceptable. In 62/63 comparisons, SFauto plans were considered at least as good as, or better than the corresponding SFclin. The average optimization time for autoplanning was 20.5 ± 19.2 s (range 4.4–106.4 s) per plan. In 14 of 16 TTauto plans, the desired total dose of 90 Gy (EQD2) was obtained, compared to only 9 in the corresponding TTclin, while autoplanning also decreased bladder and rectum doses. ConclusionsFast, fully-automated multi-criterial treatment planning for adaptive HDR-BT for locally advanced cervical cancer is feasible. Autoplans were superior to corresponding clinical plans.

The Landmark Series: Adjuvant Radiation Therapy for Breast Cancer.

Radiation therapy represents a cornerstone of breast cancer treatment both for patients undergoing breast conservation and for those receiving mastectomy. Trials evaluating breast-conserving therapy have established the benefit of adjuvant radiation therapy in terms of both local control and breast cancer mortality, whereas trials evaluating post-mastectomy radiation therapy have demonstrated improved survival for appropriately selected patients. More recent trials have confirmed that axillary node dissection can be omitted for patients who have positive sentinel nodes with no impairment at locoregional recurrence and improved outcomes. Additionally, new studies have validated the finding that the addition of regional nodal irradiation to patients with limited nodal disease provides improved outcomes. With a growing focus on treatment de-intensification, studies evaluating partial-breast irradiation with brachytherapy and external beam have demonstrated outcomes comparable with those of whole-breast irradiation, whereas further study is needed regarding intraoperative radiation therapy. This study reviews these landmark studies to present a roadmap for how adjuvant radiation therapy is used to treat breast cancer patients at this time.