Conformal Technique Research Articles

Towards de novo design of transmembrane α-helical assemblies using structural modelling and molecular dynamics simulation.

Computational de novo protein design involves iterative processes consisting of amino acid sequence design, structural modelling and scoring, and design validation by synthesis and experimental characterisation. Recent advances in protein structure prediction and modelling methods have enabled the highly efficient and accurate design of water-soluble proteins. However, the design of membrane proteins remains a major challenge. To advance membrane protein design, considering the higher complexity of membrane protein folding, stability, and dynamic interactions between water, ions, lipids, and proteins is an important task. For introducing explicit solvents and membranes to these design methods, all-atom molecular dynamics (MD) simulations of designed proteins provide useful information that cannot be obtained experimentally. In this review, we first describe two major approaches to designing transmembrane α-helical assemblies, consensus and de novo design. We further illustrate recent MD studies of membrane protein folding related to protein design, as well as advanced treatments in molecular models and conformational sampling techniques in the simulations. Finally, we discuss the possibility to introduce MD simulations after the existing static modelling and screening of design decoys as an additional step for refinement of the design, which considers membrane protein folding dynamics and interactions with explicit membranes.

Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma.

External beam radiation therapy (EBRT) has increasingly been utilized in the treatment of hepatocellular carcinoma (HCC) due to technological advances with positive clinical outcomes. Innovations in EBRT include improved image guidance, motion management, treatment planning, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Moreover, proton beam therapy (PBT) and magnetic resonance image-guided radiation therapy (MRgRT) have expanded the capabilities of EBRT. PBT offers the advantage of minimizing low- and moderate-dose radiation to the surrounding normal tissue, thereby preserving uninvolved liver and allowing for dose escalation. MRgRT provides the advantage of improved soft tissue delineation compared to computerized tomography (CT) guidance. Additionally, MRgRT with online adaptive therapy is particularly useful for addressing motion not otherwise managed and reducing high-dose radiation to the normal tissue such as the stomach and bowel. PBT and online adaptive MRgRT are emerging technological advancements in EBRT that may provide a significant clinical benefit for patients with HCC.

Robust VMAT treatment planning for extremity soft tissue sarcomas.

Volumetric modulated arc therapy (VMAT) is a frequently employed and guideline-recommended radiotherapy (RT) modality for extremity soft tissue sarcomas (eSTS). Prior studies have demonstrated that significant tumor volume changes during treatment result in loss of target volume coverage with highly conformal techniques such as VMAT, but few solutions exist to these issues aside from adaptive replanning. Here, we describe a related but novel phenomenon in which relatively minor changes in surface volume contour (whether due to daily setup uncertainty, edema of peritumoral tissue, or progression or pseudo-progression of tumor volume itself) can result in unexpected subcutaneous hotspots. This phenomenon is of significant clinical concern given the known association between skin dose and major wound complications during preoperative RT for eSTS. By evaluating daily cone-beam CT (CBCT) images from thirteen eSTS patients treated with VMAT RT, we identify daily surface contour changes (range: 2 mm-15 mm, median: 8 mm) which are frequently below conventional adaptive replanning thresholds. When applied under experimental conditions, these external contour changes did not have major impacts on target volume coverage (range: 30.2%-91.2%, mean: 72.5%) but did result in unexpected hotspots of 125.8% on average (range: 110.0%-142.2%) in the subcutaneous tissues. To mitigate this issue, we develop a methodology for VMAT treatment planning using flash PTV and virtual bolus (VB) to produce robust treatment plans that are more resistant to target volume changes, surface contour changes, and setup uncertainties than conventional planning methods. With this methodology, robust plans were equivalent to standard plans at baseline, but, after incorporation of surface volume changes, both maintained target volume coverage (p < 0.001) and prevented development of subcutaneous hotspots (p < 0.001) better than standard plans. As such, this treatment planning methodology may facilitate development of robust VMAT treatment plans that minimize development of subcutaneous hotspots and preserve target volume coverage in the context of routine volumetric changes during preoperative RT.

Dosimetric Comparison of 3-dimensional Conformal Technique, Intensity-modulated, Volumetric Arc Modulation, and Helical Tomotherapy with Radixact in Patients with Breast Cancer

Dosimetric Comparison of 3-dimensional Conformal Technique, Intensity-modulated, Volumetric Arc Modulation, and Helical Tomotherapy with Radixact in Patients with Breast Cancer

Stereotactic body radiation therapy (SBRT) in patients with hepatocellular cancer-a narrative review and expert opinion.

Stereotactic body radiation therapy (SBRT) is a highly conformal technique of external beam radiotherapy precisely delivering high total (ablative) doses in a small number of fractions to clearly defined target volumes. Its development enabled efficient and safe radiation treatments in patients with localized hepatocellular cancer (HCC) unsuitable for other local treatment options. Moreover, it can be easily combined with several other therapy approaches. Thus, the aim of this narrative review is to outline the current role of SBRT in the multifocal treatment of HCC patients. We searched PubMed for articles dealing with SBRT alone, in combination with other local or systemic treatments or in comparison to other local treatments in patients with HCC. This included original articles, reviews and conceptional articles dealing with the technique of SBRT. All articles were analysed for suitability by two independent reviewers. This review summarizes the currently available evidence for SBRT as a definitive treatment for HCC as well as its role within combination approaches including bridging to transplantation. SBRT is an effective and safe definitive treatment option in patients with localized HCC unsuitable for surgery and/or other local therapies based on retrospective and prospective series. Its combination with other local treatments yields superior results compared to single modality treatment based on non-randomized data. A growing number of prospective trials confirmed at least similar if not superior rates of local control with low toxicities compared to well established other local treatments even in non-selected patients. SBRT is a promising tool in the treatment of HCC. It can be used either as definitive treatment, within combination approaches or as a bridging tool. Several phase III trials comparing SBRT with other local options are ongoing, which will further clarify its encouraging role.

Hypofractionated radiotherapy in postmastectomy locally advanced breast cancer: an interim report on acute toxicities and dosimetry.

There is a growing interest in the use of hypofractionation in the setting of post-mastectomy radiation therapy (PMRT). Here, we present an interim report on the acute toxicities and the dosimetry of a 15-day hypofractionated regimen. Patients aged 18-75 years who underwent mastectomy and had pathological stage IIB-IIIC or any clinical stage who had received neoadjuvant chemotherapy were treated with PMRT at a dose of 43.5 Gy in 15 fractions. Acute toxicities were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Between September 2020 and September 2021, 92 patients were enrolled in the study. Majority experienced grade 1 dermatitis during the course of treatment. Skin toxicities peaked two weeks after PMRT in which 57 patients (62%) had grade 2 dermatitis and 6 patients (7%) had grade 3 dermatitis. Most resolved one month after treatment, with all resolving at three months. Grade 2 fatigue occurred in 4 patients (4%). There were no grade 3 fatigue or pneumonitis of any grade. The average V95% for the chest wall, axilla, and supraclavicular fossa were 91.5%, 99.3%, and 97.5%, respectively. Average ipsilateral lung V17 was 43.6%, while the mean heart dose averaged at 3.46 Gy. This interim report showed that hypofractionated PMRT is associated with a low incidence of clinically significant acute toxicities. With the use of the 3-dimensional conformal radiotherapy technique and volume-based planning, adequate target volume coverage and acceptable heart doses were achieved, although with a slightly higher ipsilateral lung dose.

Epimutations and Their Effect on Chromatin Organization: Exciting Avenues for Cancer Treatment.

The three-dimensional architecture of genomes is complex. It is organized as fibers, loops, and domains that form high-order structures. By using different chromosome conformation techniques, the complex relationship between transcription and genome organization in the three-dimensional organization of genomes has been deciphered. Epigenetic changes, such as DNA methylation and histone modification, are the hallmark of cancers. Tumor initiation, progression, and metastasis are linked to these epigenetic modifications. Epigenetic inhibitors can reverse these altered modifications. A number of epigenetic inhibitors have been approved by FDA that target DNA methylation and histone modification. This review discusses the techniques involved in studying the three-dimensional organization of genomes, DNA methylation and histone modification, epigenetic deregulation in cancer, and epigenetic therapies targeting the tumor.

Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older

The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination. We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective." The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%. U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.

Cardiac Morbidity Following Chemoradiation in Stage III Non-small Cell Lung Cancer Patients: A Population-Based Cohort Study

AimsTo assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. Materials and methodsPatients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. ResultsIn total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4–22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. ConclusionThe risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy.

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.

Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in RBD may lower the affinity of previously developed antibodies. Therefore, rapid analysis of new variants and selection of a binding partner with high affinity is of great therapeutic importance. Here, we explore a computational approach based on molecular dynamics simulations and conformational clusterization techniques for the wild-type and omicron variants of RBD. Biochemical experiments support the hypothesis of the presence of several conformational states within the RBD assembly. The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen.

Definitive radiation therapy with dose escalation is beneficial for patients with squamous cell cancer of the esophagus.

We report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus(ESCC) who underwent definitive chemo-radiotherapy(dCRT) at our institute. Patients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT between January 2000 and March 2012 were retrospectively analyzed. Radiotherapy was delivered in two phases to a maximum dose of 63Gy in daily fractions of 1.8Gy using conventional or conformal techniques. OS and PFS were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroups performed using log-rank test. All data were analysed using SPSS Version 22. Three hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median KPS at presentation was 70. Two-third of patients were treated with conformal technique. Median dose of radiation delivered was 60Gy(range 30.6Gy-70Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1- and 3-yr OS were 80% and 62% respectively. Median PFS was 28 months; 1- and 3-yr PFS were 66% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis. Our study highlights that the delivery of higher RT doses (≥63Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.

An Area-Averaged Conformal Technique for the Electromagnetic Simulations of Debye Medium

A novel area-averaged dielectric conformal technique combined with the finite-difference time-domain (FDTD) method has been investigated in accuracy and efficiency for modeling curved dispersive medium objects in this article. The proposed method utilizes an effective average dielectric constant, which is derived by area averages of different dielectric regions in irregular cells cut by curved surfaces, to modify the magnetic field updating equations in auxiliary differential equation FDTD method. The accuracy and efficiency of the method are verified by comparing the radar cross section results produced by the method of moments and the FDTD method with very fine meshes, respectively. Numerical results show that good agreements can be achieved by using coarse mesh size (12 cells per wavelength). Further, the proposed method is devoted to analyzing the bio-electromagnetic effects of a dispersive human body in a vehicle platform to show its good ability in solving such complex problems.

Radiotherapy for Pediatric Malignancies: An Experience from a Tertiary Cancer Centre

Background: Incidences of pediatric malignancies are increasing. In management of various childhood malignancies like hematological, bone and soft tissue tumors radiotherapy plays a crucial role. RT treatment planning and delivery poses a challenge to clinicians. Hence with this study we wanted to know the radiotherapy practices in our institution. Materials and Methods: This was a retrospective study analyzing case records and RT charts of all pediatric malignancies who received radiation treatment for a period of 3 years from January 2018 to December 2021. Demographic details, RT details, toxicity details were carefully recorded. Results: Details of 73 pediatric malignancy cases who received RT were analyzed. Median age was 10 years and the majority were males (66%). Commonest malignancies which received RT treatment were ALL (30%), Brain tumors (26%) and bone and soft tissue tumors (22%). Radiotherapy was given as a part of radical intent treatment including neo adjuvant, definitive, adjuvant and prophylactic in 92% of patients. Conformal RT techniques in the form of 3DCRT and VMAT were used in majority (91%) cases. A significant proportion (27%) of cases required anesthesia for RT treatment delivery. 16% of patients had treatment break and common reasons for treatment break being infections (COVID, respiratory) and neutropenia. Grade 3 or more acute toxicities were observed in 14% of patients and hematological toxicity was the most frequent. Conclusion: Hematological and bone &amp; soft tissue tumors are the most common pediatric malignancies requiring RT as a part of multimodality treatment. For RT treatment delivery anesthesia services may be required in pediatric malignancies. Acute Grade 3 or more toxicities and treatment breaks are a concern and these pediatric cases require a properly coordinated supportive care during treatment.

Volumetric modulated arc therapy (VMAT) comparison to 3D-conformal technique in lung stereotactic ablative radiotherapy (SABR).

Stereotactic ablative radiotherapy (SABR) can be a curative option for non-small cell lung cancer (NSCLC) and oligometastatic lung disease. Volumetric modulated arc therapy (VMAT) has offered further advancements in terms of radiation dose shaping without compromising treatment times however there is potential for greater low-dose exposure to the lung. This study was to assess whether VMAT lung SABR would result in any increase to the dosimetry parameters compared with three-dimensional conformal radiotherapy (3D-CRT) that could confer increased risk of radiation pneumonitis. A total of 53 and 30 3D-CRT treatment plans of patients treated with 48 Gy in 4 fractions were compared. No statistically significant difference in planning target volumes between the VMAT 29.9 cc (range 12.4-58.5 cc) and 3D-CRT 31.2 cc (range 12.3-58.3 cc) P=0.79. The mean of total lung V5, ipsilateral lung V5 and contralateral lung V5 all showed a trend of being smaller in the VMAT treatment group- 14% versus 15.8%, 25.6% versus 30.4% and 1.6% versus 2.2%, respectively, but all were not statistically significant differences. Mean of the mean lung dose MLD, again showed a trend of being lower in the VMAT treatments but was also non-significant, 2.6 Gy versus 3.0 Gy, P=1.0. Mean V20 was the same in both cohorts, 3.3%. The dosimetry for 3D-CRT and VMAT plans were not significantly different including V5, and therefore we conclude that VMAT treatment is unlikely to be associated with an increased risk of radiation pneumonitis.

Multiple Facets of Modeling Electronic Absorption Spectra of Systems in Solution.

In this Perspective, we outline the essential physicochemical aspects that need to be considered when building a reliable approach to describe absorption properties of solvated systems. In particular, we focus on how to properly model the complexity of the solvation phenomenon, arising from dynamical aspects and specific, strong solute-solvent interactions. To this end, conformational and configurational sampling techniques, such as Molecular Dynamics, have to be coupled to accurate fully atomistic Quantum Mechanical/Molecular Mechanics (QM/MM) methodologies. By exploiting different illustrative applications, we show that an effective reproduction of experimental spectral signals can be achieved by delicately balancing exhaustive sampling, hydrogen bonding, mutual polarization, and nonelectrostatic effects.

RADT-26. PATTERNS OF RECURRENCE IN PATIENTS TREATED WITH RE-IRRADIATION FOR RECURRENT HIGH-GRADE GLIOMA

Abstract Purpose/Objective(s) Re-irradiation (ReRT) is often used to treat recurrent high grade glioma (HGG). There is limited literature regarding the patterns of recurrence following ReRT, which was investigated in the current study. Materials/METHODS Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated RT using conformal technique. Recurrence was documented as per decision in tumor board based on imaging with magnetic resonance imaging (MRI) or Flouroethyl-L-Tyrosine (FET) positron emission tomography (PET), which was registered with the planning CT. Failure patterns were classified as in-field, marginal, and out-field as decided by &amp;gt;50% recurrence volume within 95%, 20-95%, and outside 20% isodose lines, respectively. RESULTS Study population included 37 patients treated with median dose of 54 Gy (range 50.4-54 Gy). Before ReRT, 92% patients had undergone surgery (biopsy in 3, gross total resection in 9, subtotal resection in 22), 62% received concurrent chemo with ReRT, and 49% received maintenance chemotherapy. Median time to recurrence was 9 months (7-16 months, median 10 and 8 months respectively for in-field and marginal/out-field recurrence). In-field, marginal, and out-field recurrence were seen in 24 (65%), 10 (27%), and 3 (8%), respectively. Recurrence mapping was done using MRI, PET, or both in 27, 3, and 7, respectively. Of 24 patients with in-field recurrence, 8 and 16 had disease volume within gross tumor volume and clinical target volume, respectively. 2 patients had leptomeningeal dissemination (1 with majority of recurrence volume in-field and 1 with marginal failure in addition to metastatic disease). CONCLUSION Following ReRT for HGG, the majority of recurrence was in the high dose region, suggesting the use of conservative target volumes. Future studies are required for feasibility of dose-escalation to improve control rates, particularly in patients with long intervals from first course of RT.

RADT-42. EFFECTS OF RADIOTHERAPY FOR CNS NEOPLASMS IN PEOPLE WITH MULTIPLE SCLEROSIS

Abstract INTRODUCTION Patients with multiple sclerosis (MS) may be at higher risk of brain tumors (Khalil 2012, London 2020, etc.). However, MS patients have been reported to have adverse effects from radiotherapy, a mainstay of CNS treatment. In the last ten years, radiation techniques have improved. We submit a case report of an MS patient with demyelinating CNS lesions shortly after radiation therapy for an astrocytoma and review the literature. Case description: A 40-year-old woman with a history of MS treated with Siponimod underwent resection of a right frontotemporal grade 2 astrocytoma, IDH mutant. She received adjuvant proton radiotherapy (54 Gy(RBE) over 30 fractions) followed by temozolomide chemotherapy. She tolerated radiotherapy well and only experienced grade 1 dermatitis, fatigue, and hair loss within the field of treatment. 1-month post radiation MRI was stable. 4 months post radiation there was an asymptomatic new typical demyelinating lesion on FLAIR without T1 or contrast changes. This was outside the high dose radiation field (i.e. received ~30 Gy(RBE)). Her Siponimod had been held for concerns of interactions with radiation or chemotherapy. DISCUSSION Cases have been reported of people with MS experiencing adverse effects from radiotherapy. Murphy, et al., reported a 30-year-old woman with MS experiencing an attack of demyelination 2 months after radiotherapy (50 Gy over 25 fractions), and Borges, et al. presents a 28-year-old patient who experienced radiotherapy-induced inflammatory demyelination after receiving whole-ventricular irradiation (24 Gy over 15 fractions). Miller, et al., reported 6 patients without exacerbations of MS but had developed grade 4 neurotoxicity in a median of 1 year; most of those patients were treated with older radiation techniques, however. Radiotherapy effects in people with MS is a topic that should be revisited in the era of more conformal RT techniques, effective MS therapies, and cancer treatment including immunotherapy.

Moderne definitive Radiochemotherapie – State of the Art-Umsetzung und neue Konsolidierungsstrategien

BackgroundIn locally advanced non-small-cell lung cancer (NSCLC), the addition of chemotherapy to radiotherapy and consolidation with durvalumab leads to a significant increase in overall survival and represents the most profound innovation of the last decade.ObjectivesAnalysis of new possibilities for the state-of-the-art implementation of definitive radiochemotherapy concepts.Materials and methodsEvaluation of prospective and randomised studies regarding improvements in treatment outcomes.ResultsOverall survival benefit of consolidating checkpoint inhibitor therapy after combined radiochemotherapy with durvalumab is 43% (95% confidence interval 38–47%) versus 33% (27–40%) in the placebo group in an updated analysis of the PACIFIC trial for 5‑year survival; stratified hazard ratio for death is 0.72 (95% CI 0.59–0.89, p = 0.0025). In the dose escalation studies, increased pulmonary and oesophageal side effects were observed, so no immediate clinical benefit could be derived from the increase in local efficacy. Improved imaging before and during therapy and optimised possibilities of dose application, especially by using intensity-modulated radiotherapy (IMRT), allow selective sparing of healthy structures, which increases the ability to safely intensify radiotherapy also in connection with new immunomodulatory substance combinations.ConclusionThe integration of immunotherapy, the stringent use of fluorodeoxyglucose positron emission tomography (FDG-PET) in staging and radiation planning, the widespread use of highly conformal radiation techniques (IMRT; volumetric modulated arc therapy, VMAT) and the consistent application of image-guided radiotherapy have led to significant improvements in treatment outcomes.

Local control results in extremity soft tissue sarcomas

Aim: The aim of this study is to investigate local control results and effective predictive factors in local control of extremity soft tissue sarcomas, retrospectively. Material and Method: 51 patients underwent postoperative adjuvant radiotherapy (RT) in Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital between October 2008-January 2022. Patients who underwent post-operative adjuvant RT were treated with 60-68 Gy in 2 phases from 2 Gy /day using conformal radiotherapy technique. IMA chemotherapy protocol was applied to 31.4% of the patients after radiotherapy. Results: The median follow up time was 46 months range (1-135). Recurrence was detected in 5 of the patients and the mean time of recurrence was 11.6 months (min: 3-max: 27). 10 patients developed metastasis at follow-up, the mean time until metastasis was 27 months (min: 18- max: 46). The mean overall survival (OS) was 103 (min:4-max:139) months and the OS of 2, 5 and 10 years were 93%, 65% and 60%, respectively. Disease-free survival (DFS) was 97 (min:4-max:139) months; 2, 5 and 10 years of DFS were 77%, 65% and 60%, respectively. The OS in patients aged ≥65 years old was significantly lower than in patients &amp;lt;65 years old (p=0.02). Overall and disease-free survival was significantly lower in patients undergoing chemotherapy (p=0.037 for overall survival, p=0.013 for disease-free survival). The occurrence of recurrence, metastasis or death within 3 years after the operation was significantly higher than after 3 years (p&amp;lt;0.001). Local failure was significantly higher in grade 3 tumors (p=0.05). All patients who recurred had grade 3 tumors. Metastasis and excitus were significantly higher in the follow-up of patients who underwent chemotherapy at one point during their treatment (p=0.027 for metastasis, p=0.042). Conclusion: While favorable local control results are obtained with adjuvant high dose-conformal radiotherapy in extremity sarcomas, close follow up is important for distant metastasis and local recurrence, especially in the first 3 years.

Comparative Evaluation of Brachial Plexus Sparing for Comprehensive Reirradiation of High Risk Recurrent or New Primary Breast Cancer

<h3>Purpose/Objective(s)</h3> Recurrent or new primary breast cancer with an indication for comprehensive regional nodal irradiation (RNI) in the setting of prior radiotherapy (RT) to the supraclavicular area (SCV) and upper axilla presents a unique treatment challenge due to cumulative brachial plexus (BP) dose tolerance. Brachial plexopathy is a debilitating potential consequence of RT, and BP dose monitoring is needed for comprehensive reirradiation (reRT). We hypothesize that pencil beam scanning proton therapy (PBS-PT) and photon volumetric-modulated arc therapy (VMAT) are conformal techniques that allow BP relative dose-sparing, while maintaining target volume (TV) dose. A comparative evaluation was performed to assess each approach. <h3>Materials/Methods</h3> In this IRB-approved retrospective study, all patients with ipsilateral recurrent or new primary breast cancer previously treated with photon RT, then receiving PBS-PT reRT to TV with at least partial BP overlap, were identified. VMAT plans were developed by photon breast dosimetrists using matched individualized BP dose constraints (BP maximum 17.1-53.9 Gy) used in the PBS-PT course. BP and TV DVH parameters were assessed. Patient and tumor characteristics, treatment parameters, clinical outcomes, and toxicities were collected. The median follow-up from the start of reRT was 10.5 months. <h3>Results</h3> Ten consecutive patients were identified. Median patient age was 58 years (41-82), with median time between RT courses of 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (42.6-60.0), 50.4 Gy(RBE) (45.0-64.4), and 102.4 Gy(RBE) (95.0-120.0), respectively. PBS-PT and VMAT plans matched BP doses, with the median maximum and mean BP cumulative doses 86.6 Gy (RBE) and 60.7 Gy (RBE) for PBS-PT and 87.5 Gy and 60.2 Gy for VMAT, respectively. TV coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were generally lower for VMAT vs. IMPT plans: axilla level II were 84.8%, 91.8%, and 75.7% vs. 90.9% (p=0.17), 88.3% (p=0.04), and 84.5% (p<0.01); axilla level III were 89.8%, 75.1%, and 64.0% vs. 95.4% (p=0.39), 91.8% (p=0.12), and 86.5% (p=0.32); and SCV were 83.0%, 74.3%, and 67.2% vs. 90.9% (p=0.41), 82.1% (p=0.13), and 68.2% (p=0.76), respectively. One patient developed symptoms of brachial plexopathy with neuropathy in the ulnar nerve distribution without pain or weakness. This patient had the highest maximum cumulative BP dose of the entire cohort (106.1 Gy(RBE)). <h3>Conclusion</h3> VMAT and PBS-PT provide conformal RT plans that can provide BP dose sparing but some surrounding compromise of the adjacent TV at risk. In this cohort, PBS-PT improved BP sparing and TV coverage versus VMAT. Further study with uniform TV and prescription parameters will be useful for direct comparison of the two modalities as the approach to this clinical situation continues to be refined. Longer follow-up will be needed to characterize the implication of cumulative BP dose on risk of developing clinically-significant brachial plexopathy.