First Results of the Primary Outcome of a Phase II Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Breast Cancer Patients.

INTRODUCTION: A radiation (RT) boost to the tumor bed is an important component of breast-conserving therapy (BCT) in early breast cancer (BC). This prospective phase II study assessed the feasibility of delivering the RT boost pre-operatively. We hypothesize wound complication rates to be comparable to post-operative RT and the target boost volume to be smaller than standard post-operative RT. METHODS: This prospective phase II trial accrued 55 patients with clinically node negative BC eligible for BCT. Patients were treated with pre-operative RT boost of 1332 cGy in 4 fractions, followed by lumpectomy and post-operative adjuvant whole breast RT to 3663 cGy in 11 fractions. The primary outcome was to demonstrate the incidence of grade 3 or more wound complications was not inferior to lumpectomy with standard postoperative whole breast RT and boost (6- 20%). We also compared the pre-op boost volume to a mock boost volume that would have been done post-operatively. RESULTS: Fifty-five women were enrolled between June 2021 and October 2022. Median age was 64 years-old, (range 40-77). Forty-three patients had invasive cancers and 5 had DCIS. Median clinical tumor size was 13 mm, (range 5-26). Grade 3 wound dehiscence requiring surgical revision occurred in one patient (2%). There were no other grade 3 adverse events. Three patients (6%) had grade 2 infections requiring antibiotics. The target boost volume was significantly lower that the mock post-operative volume (11cc vs. 56 cc; p <.001) Cosmetic outcome at 1st follow up was very good or excellent in 87% of patients and none had poor cosmetic outcome. CONCLUSION: The use of a pre-operative RT boost followed by whole breast RT as administered here resulted in an acceptable primary outcome with a similar rate of post-operative wound complications and smaller boost volume compared to standard postoperative RT. This approach is currently under consideration for cooperative group Phase III trial.

A new positive output DC-DC buck-boost converter based on modified boost and ZETA converters.

A new DC-DC buck-boost converter with a wide conversion ratio is presented in this paper. The proposed buck-boost converter consists of a combination of modified boost converter and ZETA converter, which has the advantages of both converters such as continuous input/output current and positive polarity of the output voltage. The combination of these two converters achieves semi-quadratic voltage gain and makes the proposed converter suitable for industrial and renewable energy applications. With a voltage gain higher than that of the ZETA converter and modified boost converter, the proposed converter also reduces input current stress due to its continuity. Two operating states are available for this converter in continuous conduction mode. This converter has two switches that operate simultaneously and can be easily controlled. The converter's output voltage ripple and output capacitor current stress are reduced as a result of continuous output current. Computational analysis and the introduced structure efficiency considering the influence of parasitic elements are presented in this paper. The small signal modelling and closed-loop control, as well as simulation and experimental results are also presented. This converter has also been compared with other similar and recently presented topologies. Finally, a 40-60 W, 20-76 V for boost mode and 10 V for buck mode prototype was implemented to verify the accuracy of the computational analysis.

The modulation of temporal predictability on attentional boost effect.

INTRODUCTION: The attentional boost effect, characterized by better memory for background scenes coinciding with a detection target than a nontarget, is believed to stem from a temporary increase in attentional capacity at the time of an acute behavior-related event occurring. Sisk and Jiang's study found that the attentional boost effect also occurs when the target's appearance was predictable. Unfortunately, the duration of the predictive interval in Sisk and Jiang's study was fixed. Since different predictive intervals had different weakening degrees to the acuteness of the target, this fixed duration hindered further investigation into the impact of different levels of predictability on the attentional boost effect. METHOD: Using the encoding-recognition paradigm and the remembering/knowing paradigm, and setting target stimuli with different predictive interval in target detection tasks, the current study aimed to explore the influence of varying the duration of the predictive interval on the attentional boost effect. RESULTS: The attentional boost effect was observed only in the short and medium predictive duration conditions, but not in the long predictive duration condition. Moreover, as the duration of the predictive interval increased, participants' memory performance on target-paired words gradually declined, while their memory performance on distractor-paired and baseline-paired words gradually improved. CONCLUSIONS: Predictability may alter the task demands, allowing participants to more effectively allocate attentional resources to the two tasks at hand.

Oncoplastic breast surgery - a pictorial classification system for surgeons and radiation oncologists (OPSURGE).

INTRODUCTION: Changes to the tumour bed following oncoplastic breast surgery complicate the administration of adjuvant radiotherapy. Consensus guidelines have called for improved interdisciplinary communication to aid adjuvant boost radiotherapy. We propose a framework of tumour bed classification following oncoplastic surgery to enhance understanding and communication between the multidisciplinary breast cancer team and facilitate effective and more precise delivery of adjuvant boost radiotherapy. METHODS: A classification system was devised by grouping oncoplastic procedures based on skin incision, tissue mobilization, tumour bed distortion, seroma formation and flap reconstruction. The system is supplemented by a colour-coded pictorial guide to tumour bed rearrangement with common oncoplastic procedures. RESULTS: A 5-tier framework was developed. Representative images were produced to describe tumour bed alterations. CONCLUSION: The proposed framework (OPSURGE) improves the identification of the primary tumour bed after initial breast-conserving surgery, which is imperative to both the surgeon in planning re-excision and the radiation oncologist in planning boost radiotherapy.

Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial.

BACKGROUND: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

A novel advanced hybrid fuzzy MPPT controllers for renewable energy systems.

At present, the availability of nonrenewable sources and their usage for electric vehicle technology is reducing gradually because of their disadvantages are more environmental pollution, direct effect on human health, less reliability, and taking more time to start functioning. So, in this article, the proton exchange membrane fuel cell (PEMFC) is considered for the automotive application because of its advantages quick startup, more power density, more safety to handle, high efficiency, and capability of operating at very low operational temperature conditions. However, the drawback of PEMFC is very difficult to identify the accurate MPP position of the fuel system. Here, the improved variable step genetic algorithm is added with the adaptive neuro-fuzzy inference system for tracking the operational point of the proposed system with high efficiency. These hybrid MPPT controller features are easy to understand, more accurate, have a better dynamic response, and have low design complexity. The evaluated proposed MPPT controller operational efficiency, and settling time of the converter voltage at different fuel stack temperature conditions are 98.7402%, and 0.01607 s respectively. Finally, the boost converter is used in this work to enhance the voltage supply capability of the entire system. The proposed system is investigated by applying the MATLAB tool.

Physical and clinical results of a radiation bra in patients treated with total skin electron beam therapy.

Total skin electron beam therapy (TSEBT) in female patients with large or pendulous breasts is usually associated with shaded inframammary folds. In this analysis, 18 patients with cutaneous malignancy and pendulous breasts were irradiated with a radiation bra and five patients received TSEBT without bra. All patients had moderate or severe sagging of the breasts. The median inframammary dose in the radiation bra group was 89% of the prescription dose versus 4% in the group without bra. The usage of the radiation bra enables an adequate radiation dose for the inframammary folds during TSEBT with no additional local irradiation.

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

Performance comparison between PID and Fuzzy logic controllers for the hardware implementation of traditional high voltage DC-DC boost converter.

This research introduces a hardware implementation of DC-DC boost converter designed to elevate the DC voltage generated by renewable sources while effectively regulating it against line and load fluctuations for inverter application. The main objective is to boost the DC link voltage to the level of Vmax in the output AC voltage obtained from inverter circuits. This enables the inverters for transformer-less power conversion from DC to AC to reduce magnetic losses, size and weight of the inverter circuits used in the utility application. The proposed converter's topology and switching sequences play a crucial role in enhancing overall performance. Utilizing a Zero Current Switching (ZCS) technique, the converter efficiently recovers stored energy from the magnetics. The proposed converter attained the output voltage of 350 V at its current of 1A from the input voltage of 20 V at its current of 19 A. The ZCS technique and the topology of the converter enhances the efficiency to 92 %. The study employs traditional Proportional-Integral (PI) and Proportional-Integral-Derivative (PID) controllers for effective voltage regulation, analysing time domain specifications. Additionally, a Fuzzy logic controller is introduced as an alternative to PID controllers to compare their performance metrics, evaluating the optimization of the converter's transient and steady-state behaviours. The proposed converter is designed, simulated and their performance metrics are analysed using MATLAB for both with and without controllers. The step-time characteristics of the proposed converter with load resistance of RL = 500 Ω and an input voltage of Vi = 20 V has been determined and analysed. The PID system attained a rise time of 88.781 ms, an overshoot value of 9.341 %, and a steady-state error of 0.00043. The fuzzy system achieved a low-rise time of 10.624 ms, a low overshoot of 0.55 %, and a steady-state error of 0.0584. The hardware prototype of the proposed converter is implemented with a FPGA based PID and Fuzzy logic controllers for providing better voltage regulation and to improve the performance metrics of the converter. The simulation and experimental findings are contrasted, examined, and confirmed to ensure improved consistency in performance measures.

Transformer-less high gain DC-DC converter design and analysis for fuel cell vehicles.

High-power converters with significant gains represent established configurations that hold appeal for applications in the industrial and commercial sectors, such as fuel cell electric vehicles (FCEV), energy backup systems, and automotive headlamps. Existing literature predominantly features topologies employing a single-duty ratio. However, this singular approach may not be dependable for operations with high-duty cycles, necessitating the incorporation of additional components to enhance voltage gain. To address this, the current study introduces the concept of time-sharing within the context of a high-gain non-isolated DC-DC converter. This innovative approach achieves substantially higher output voltage gains, approximately 13.33 times that of the input voltage. The analysis of the proposed converter is approached from various perspectives. Finally, it is examined within the MATLAB/Simulink environment, where the theoretical analysis is validated, and an efficiency of 97.4% is achieved.

Heterologous Prime-Boost Immunization Strategies Using Varicella-Zoster Virus gE mRNA Vaccine and Adjuvanted Protein Subunit Vaccine Triggered Superior Cell Immune Response in Middle-Aged Mice.

Purpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response. Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared. Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation. Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.

Immunogenicity and protective efficacy of the HC009 mRNA vaccine against SARS-CoV-2.

With the rapid global spread of COVID-19 and the continuous emergence of variants, there is an urgent need to develop safe and effective vaccines. Here, we developed a novel mRNA vaccine, HC009, based on new formulation by the QTsome delivery platform. Immunogenicity results showed that the prime-boost immunization strategy with HC009 was able to induce robust and durable humoral immunity, as well as Th1-biased cellular responses in rodents or non-human primates (NHPs). After further challenge with live SARS-CoV-2 virus, HC009 provided adequate protection against virus infection in hACE2 transgenic mice. Therefore, HC009 could provide significant immune protection against SARS-CoV-2.

Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates.

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.

Sequential Immunization with Vaccines Based on SARS-CoV-2 Virus-like Particles Induces Broadly Neutralizing Antibodies.

Although many people have been vaccinated against COVID-19, infections with SARS-CoV-2 seem hard to avoid. There is a need to develop more effective vaccines and immunization strategies against emerging variants of infectious diseases. To understand whether different immunization strategies using variants sequence-based virus-like particles (VLPs) vaccines could offer superior immunity against future SARS-CoV-2 variants, our team constructed VLPs for the original Wuhan-Hu-1 strain (prototype), Delta (δ) variant, and Omicron (ο) variant of SARS-CoV-2, using baculovirus-insect expression system. Then we used these VLPs to assess the immune responses induced by homologous prime-boost, heterologous prime-boost, and sequential immunizations strategies in a mouse model. Our results showed that the pro+δ+ο sequential strategies elicited better neutralizing antibody responses. These sequential strategies also take advantage of inducing CD4+ T and CD8+ T lymphocytes proliferation and tendency to cytokine of Th1. Currently, our data suggest that sequential immunization with VLPs of encoding spike protein derived from SARS-CoV-2 variants of concern may be a potential vaccine strategy against emerging diseases, such as "Disease X".

[Short- and medium-term tolerance of hypofractionated prostate radiotherapy with simultaneous integrated boost]. / Tolérance à court et moyen terme d'une radiothérapie prostatique hypofractionnée selon la technique du boost intégré.

PURPOSE: This retrospective study was conducted to ensure that irradiation of the pelvic lymph node areas associated with simultaneous hypofractionated boost to the prostate according to the protocol implemented at the university hospital of Tours (France) does not result in excess urinary and digestive toxicity in the short and medium term. MATERIALS AND METHODS: The study population included patients with localized unfavourable intermediate or high-risk prostate cancer. The dose delivered was 65Gy in 25 fractions of 2.6Gy to the prostate and seminal vesicles, and 50Gy in 25 fractions of 2Gy to the pelvic lymph nodes. Acute toxicity events (between the start of radiotherapy and the first follow-up consultation) and medium-term toxicity events (after the first follow-up consultation) were assessed using the CTCAE version 5.0 classification. RESULTS: Sixty-three patients were treated according to the protocol between January 1st, 2020, and October 31st, 2022. The majority of them had high-risk prostate cancer (79%). The median follow-up was 15 months. Very few patients reported grade 3-4 toxicity acutely (6% urinary and 0% digestive toxicity) or in the medium term (7% urinary and 0% and digestive toxicity). CONCLUSION: Radiotherapy of pelvic lymph node areas with simultaneous hypofractionated boost to the prostate is feasible, with low rates of severe acute and medium-term toxicity.

A novel development of wide voltage supply DC-DC converter for fuel stack application with PSO-ANFIS MPPT controller.

The present power production companies are working on renewable energy systems because their features are more reliable for the local energy consumers, high continuity in the energy production, and less cost is required for maitainence. In this article, the proton exchange membrane fuel stack (PEMFS) renewable energy is utilized to supply energy to the automotive systems. Here, the PEMFS is selected because of its merits are high energy density, quick system response concerning the source operational temperature, and more suitable for electric vehicle application. However, the PEMFS supplied voltage is completely nonlinear which is solved by utilizing the modified particle swarm optimization with adaptive neuro-fuzzy inference system (MPSO with ANFIS) controller. This hybridization-based maximum power point tracking controller provides more accuracy, high power point identifying speed, best dynamic response at different fuel stack functioning temperature conditions, and easy maitainence. Here, the fuel stack generated current is very high which is optimized by introducing the new DC-DC converter. The advantages of this DC-DC converter are more voltage transformation ratio, low-level voltage stress appearing across the switches, and wide voltage gain. The overall system is investigated by utilizing the MATLAB/Simulink tool.

Predicting Learning: Understanding the Role of Executive Functions in Children's Belief Revision Using Bayesian Models.

Recent studies suggest that learners who are asked to predict the outcome of an event learn more than learners who are asked to evaluate it retrospectively or not at all. One possible explanation for this "prediction boost" is that it helps learners engage metacognitive reasoning skills that may not be spontaneously leveraged, especially for individuals with still-developing executive functions. In this paper, we combined multiple analytic approaches to investigate the potential role of executive functions in elementary school-aged children's science learning. We performed an experiment that investigates children's science learning during a water displacement task where a "prediction boost" had previously been observed-children either made an explicit prediction or evaluated an event post hoc (i.e., postdiction). We then considered the relation of executive function measures and learning, which were collected following the main experiment. Via mixed effects regression models, we found that stronger executive function skills (i.e., stronger inhibition and switching scores) were associated with higher accuracy in Postdiction but not in the Prediction Condition. Using a theory-based Bayesian model, we simulated children's individual performance on the learning task (capturing "belief flexibility"), and compared this "flexibility" to the other measures to understand the relationship between belief revision, executive function, and prediction. Children in the Prediction Condition showed near-ceiling "belief flexibility" scores, which were significantly higher than among children in the Postdiction Condition. We also found a significant correlation between children's executive function measures to our "belief flexibility" parameter, but only for children in the Postdiction Condition. These results indicate that when children provided responses post hoc, they may have required stronger executive function capacities to navigate the learning task. Additionally, these results suggest that the "prediction boost" in children's science learning could be explained by increased metacognitive flexibility in the belief revision process.

Deep phosphotyrosine characterisation of primary murine T cells using broad spectrum optimisation of selective triggering.

Sequencing the tyrosine phosphoproteome using MS-based proteomics is challenging due to the low abundance of tyrosine phosphorylation in cells, a challenge compounded in scarce samples like primary cells or clinical samples. The broad-spectrum optimisation of selective triggering (BOOST) method was recently developed to increase phosphotyrosine sequencing in low protein input samples by leveraging tandem mass tags (TMT), phosphotyrosine enrichment, and a phosphotyrosine-loaded carrier channel. Here, we demonstrate the viability of BOOST in T cell receptor (TCR)-stimulated primary murine T cells by benchmarking the accuracy and precision of the BOOST method and discerning significant alterations in the phosphoproteome associated with receptor stimulation. Using 1 mg of protein input (about 20 million cells) and BOOST, we identify and precisely quantify more than 2000 unique pY sites compared to about 300 unique pY sites in non-BOOST control samples. We show that although replicate variation increases when using the BOOST method, BOOST does not jeopardise quantitative precision or the ability to determine statistical significance for peptides measured in triplicate. Many pY previously uncharacterised sites on important T cell signalling proteins are quantified using BOOST, and we identify new TCR responsive pY sites observable only with BOOST. Finally, we determine that the phase-spectrum deconvolution method on Orbitrap instruments can impair pY quantitation in BOOST experiments.

In Silico Study of Simultaneous Integrated Boost Carbon-Ion Radiotherapy for Locally Advanced Pancreatic Cancer.

BACKGROUND/AIM: Carbon-ion radiotherapy (CiRT) has been used for the treatment of locally advanced pancreatic cancer (LAPC) with uniform dose plan. The aim of the present study is to investigate the effectiveness of a simultaneous integrated boost (SIB) technique with scanned CiRT against LAPC. MATERIALS AND METHODS: Data of 21 patients with LAPC were used to compare two treatment planning approaches: a conventional uniform dose approach and a SIB approach. A relative biological effectiveness (RBE)-weighted dose (DRBE) of 55.2 Gy (RBE) in 12 fractions was prescribed to the planning target volume (PTV) in the conventional approach. In the SIB approach, DRBE of 67.2 Gy (RBE) and 43.2 Gy (RBE) in 12 fractions were prescribed to a high-risk PTV (HR-PTV) and low-risk PTV (LR-PTV), respectively. The DRBE and dose-averaged linear energy transfer (LETd) of targets and gastrointestinal tracts as organs at risk (OARs) were evaluated. RESULTS: The HR-PTV D90% and LR-PTV D90% were 64.4±0.6 and 42.5±0.1 Gy (RBE) in SIB approach compared to the PTV D90% of 54.1±0.4 Gy (RBE) in the conventional approach. All SIB plans achieved the D2cc lower than 46 Gy (RBE) and V30 lower than 4 cm3 within OARs. The SIB approach increased the minimum LETd within the GTV to 44 keV/µm or higher for 20 out of 21 patients as compared to 16 out of 21 patients in the conventional approach. CONCLUSION: The SIB approach effectively increased the RBE-weighted dose and LETd within the HR-PTV and GTV by accumulating the high-LET stopping carbon-ions into the HR-PTV in addition to the decreased RBE-weighted dose to OARs.

Sequential Moderate Hypofractionated Boost in Breast Cancer Patients: A Monoinstitutional Analysis of Late Side Effects.

BACKGROUND/AIM: In breast cancer (BC) patients who have received breast-conserving surgery, moderate hypofractionation is standard of care for whole-breast irradiation (HF-WBI). On the other hand, the fractionation schedule for the boost is less well defined. A previous prospective study of our group aimed at evaluating acute and late cutaneous and subcutaneous side effects related to a sequential hypofractionated boost (HB) in patients who had received HF-WBI. The present study aimed at evaluating late side effects at a longer follow-up. PATIENTS AND METHODS: From 2014 to 2015, 219 BC patients received moderate HF-WBI (42.4 Gy in 16 fractions) at the Radiation Oncology Section of the University of Perugia. Patients with negative prognostic factors received a HB (2.65 Gy for 4 or 5 fractions). Late side effects were assessed using the Common Terminology Criteria for Adverse Events v5.0. Univariate and multivariate analyses estimated predictive factors for late toxicity. RESULTS: Median follow-up was 8.6 years (range=6.7-9.6). One hundred and sixty-five patients were evaluable in the present analysis; HB was administered to 47.3% of them. Late cutaneous and subcutaneous side effects occurred in 26/165 patients (15.8%); and all were G1. In univariate analysis ≥10 excised lymph nodes and HB administration emerged as risk factors for late side effects (p=0.003 and p=0.041, respectively). In multivariate analysis only ≥10 excised lymph nodes were confirmed as a risk factor for side effects (OR=3.431; 95%CI=1.209-9.737). CONCLUSION: HB after HF-WBI was safe and well-tolerated, even at a long-term follow-up; consequently, it can be used in routine practice.