Hypofractionation Research Articles

Evaluation of dose and anatomy variability for nasopharyngeal carcinoma radiotherapy with a new fully integrated CT-linac

The goal of this study was to investigate the variability of target volume and parotid gland dose distribution for nasopharyngeal carcinoma (NPC), and to explore the shifting patterns of parotid gland centroid and neck radius during radiotherapy. Twenty patients with NPC were enrolled. The target volume dose difference between planning dose and recalculated dose on weekly CT was analyzed. The recalculated doses on every weekly CT were cumulated to assess the difference between delivered dose and planning dose. The relationship of parotid gland centroid deviation with dose was studied, and the shrinking distances of neck radius were calculated for cervical vertebra 1, 2, 3 levels (C1, C2, C3). The ratio of GTVs and CTVs doses on weekly CTs to the doses on planning CT was all above 0.98; the dose of PTVs on weekly CT tended to decrease compared with planning. RMD was defined as the ratio of the mean dose of the left and right parotid glands (L-PG, R-PG) to the planning mean dose. The fitted relationships of RMD and the deviation of centroid (D) for L-PG and R-PG were: RMD=0.37*D+0.98 (R2 = 0.62, p < 0.001) and RMD = 0.33*D+0.97 (R2 = 0.72, p < 0.001), respectively. The order of neck radius shrinking distance at different levels was C1>C2=C3. In this study, we quantitatively analyzed the dosimetric variabilities of target volumes, and established linear models of parotid gland dose and its centroid deviation, which provides fractional and full-course dose evaluation during radiotherapy for NPC.

PO0421: Hypo Fractionated External Beam Irradiation with Single Fraction HDR Boost in the Treatment of Intermediate / High Risk Prostate Cancer

PO0421: Hypo Fractionated External Beam Irradiation with Single Fraction HDR Boost in the Treatment of Intermediate / High Risk Prostate Cancer

Evaluation of antimicrobial activity of plant extracts and column fractions of hexane extract against Mycobacterium kansaii

The aim of this study is to assess the antibacterial efficacy of aerial parts of the Ageratum conyzoides plant extracts and column fractions against Mycobacterium kansaii. The antimicrobial experiments were performed using five doses (0.1 µg/ml, 1 µg/ml, 10 µg/ml, 100 µg/ml, 1000 µg/ml) of plant extracts and column fractions. The results showed notable inhibitory effects on Mycobacterium kansaii. The results indicated that the extract of A. conyzoides exhibited action against all the tested bacterial isolates, with the level of activity varying depending on the concentration. The hexane extract exhibited antibacterial activity, with mean zones of inhibition measuring 97.88±9.46 and 27.1±3.33, while the ethanol extract showed a mean zone of inhibition of 100.6±3.42 and 36.77±1.74 against M.kansaii, respectively. Nevertheless, the hexane extract's three column fractions exhibited average inhibition zones of 98.60±1.0 and 23.11±4.35, 90.02±10.22 and 21.94±6.77, 99.32±3.04 and 17.23±5.26 for the third, fourth, and fifth (last sample) respectively. The findings of this study provide evidence for the conventional utilization of the Ageratum plant and emphasize the necessity for further comprehensive research to explore potential alternatives to current antibacterial medications.

Improved heterogeneity handling in the collapsed cone dose engine for brachytherapy.

Model-based dose calculation algorithms (MBDCA), such as the Advanced Collapsed cone Engine (ACE) in Oncentra Brachy® can be used to overcome the limitations of the TG-43 formalism. ACE is a point kernel superposition algorithm that calculates the total dose separated into primary, first-scatter, and multiple-scatter dose. Albeit ACE yields accurate results under most circumstances, several studies have reported underestimations of the dose to cortical bone. These underestimations are likely caused by approximations in the handling of multiple-scatter dose for non-water media. Such would result in noticeable deviations where the multiple-scatter is a considerable fraction of the total dose, that is, at greater distances from the source. To improve and test the accuracy of the multiple-scatter dose component in the ACE algorithm to remedy its inaccuracy for non-water geometries. A careful analysis of the transport and absorption of the multiple-scatter energy fluence revealed an inconsistency in the scaling of energy absorption ratios for non-water media of the multiple-scatter kernel. We implemented an updated algorithm version, ACEcorr, and tested it for three different geometries. All had a single 192Ir-source at the center of a cubic water phantom with a box-shaped heterogeneity of either cortical bone or air, positioned at different distances from the source. Dose distributions for the three cases were calculated with ACE and ACEcorr and compared to Monte Carlo simulations, using the percentage dose difference ratio as figure-of-merit. All dose calculation methods scored separately the dose deposited by primary, first-scattered, and multiple-scattered photons. The accuracy of the updated algorithm ACEcorr was superior to ACE. In the cortical bone heterogeneity, the mean percentage dose difference ratio for the total dose improved from to (in the worst case) by our update. Less impact was seen in the air heterogeneity, where both ACE and ACEcorr deviated less than 2% from the Monte Carlo results. The algorithm update mainly concerns the multiple-scattered dose component, but an accompanying data processing update also had a small effect ( 0.5% difference) on the primary and first-scattered dose. The calculation times were not affected. The updates to ACE improved the accuracy of multiple-scatter dose calculation for non-water media, without increasing calculation times.

A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy

This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL). Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy3 equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy3 equivalent dose in 2Gy fractions). Escalation followed a standard 3 + 3 design with a 6-patient expansion at the maximally tolerated hypofractionated DS. Dose-limiting toxicity was defined as Common Terminology Criteria for Adverse Events v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or G4 gastrointestinal (GI) or genitourinary toxicities thereafter. QOL was assessed longitudinally through 24 months with the Expanded Prostate Cancer Index Composite short form. Between January 2018 and December 2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No dose-limiting toxicities were observed on any DS, and thus, expansion occurred at DS3. The cumulative incidence of G3 GI and genitourinary toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was the most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The biochemical progression-free survival was 91% at both 24 and 60 months. The maximally tolerated hypofractionated DS for hypofractionated, risk volume-adapted PORT was determined to be DS3 (36.4 Gy to the prostate bed and 47.1 Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.

Optimization and characterization of a dose-controllable orodispersible dexamethasone film for personalized medicine

Decadron® tablets are commercially available in 0.5 and 4 mg formulations, often requiring the use of multiple tablets or fractional doses when the required dosage is unavailable. This practice can lead to inaccuracies and handling difficulties associated with tablet splitting and crushing tablets into powder. This study aimed to develop an orodispersible dexamethasone film that would allow precise dose control and overcome these challenges. The film formulation was optimized by dissolving varying amounts of hypromellose, glycerol, and dexamethasone in ethanolic solutions. These solutions were cast and dried at different thicknesses. Statistical optimization using the design of experiments was used to determine the ideal film composition. The optimized films met pharmaceutical standards, with a mass variation ≦ 2 %, thickness variation ≦ 2.5 %, and disintegration time ≦ 20 s. The uniform distribution of dexamethasone within the film enabled easy content control based on the film area. Dissolution testing indicated that the dissolution behavior of the film formulation behaved similarly to commercial tablets for up to 90 min. In conclusion, the developed orodispersible film offers precise dexamethasone dose control and addresses the limitations of tablet splitting, positioning it as a promising candidate for personalized medicine applications.

Use of Population-Based Compartmental Modeling and Retinol Isotope Dilution to Study Vitamin A Kinetics and Total Body Stores Among Ghanaian Women of Reproductive Age

BackgroundLimited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID). ObjectivesObjectives were to apply population-based (“super-subject”) modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals. MethodsWomen (n=89) ingested a dose of [2H6]retinyl acetate and blood samples (3/woman) were collected from 6 h–91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FDp) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS. The latter were used in the RID equation TBS (μmol) = FaS x 1/SAp (where SAp is plasma retinol specific activity) to predict TBS at various times. ResultsModel-predicted TBS was 973 μmol (n=87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [e.g., 252–3848 μmol on d 14 (n=86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37. ConclusionsSuper-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion. Trial is registered (NCT04632771) at https://clinicaltrials.gov.

Fractional Doses of Pneumococcal Conjugate Vaccine - A Noninferiority Trial.

Pneumococcal conjugate vaccines are an expensive component of the routine immunization schedule. Fractional-dose regimens may be one option to increase the sustainability of the vaccine program. We assessed whether the immunogenicity of fractional doses of the 10-valentand 13-valent pneumococcal conjugate vaccines (PCV10 [GSK] and PCV13 [Pfizer], respectively) would be noninferior to that of the full doses and analyzed the prevalence of vaccine-serotype carriage. We randomly assigned healthy infants in Kenya to one of seven equal-sized trial groups. Participants in groups A through F were assigned to receive either a fractional or full dose of PCV10 or PCV13, administered as two primary doses plus one booster dose. In group A, participants received a full dose of PCV13; group B, a 40% dose of PCV13; group C, a 20% dose of PCV13; group D, a full dose of PCV10; group E, a 40% dose of PCV10; and group F, a 20% dose of PCV10. Participants in the seventh group (group G) received a full dose of PCV10 as three primary doses without a booster. Immunogenicity was assessed 4 weeks after the primary series of doses and 4 weeks after the booster dose. Noninferiority could be declared 4 weeks after the primary series if the difference in the percentage of participants with a threshold response was not more than 10% and 4 weeks after administration of the booster if the ratio of the geometric mean concentration (GMC) of IgG was more than 0.5. A vaccine dose was prespecified as noninferior if it met the noninferiority criterion for at least 8 of the 10 vaccine types in the PCV10 groups or at least 10 of the 13 vaccine types in the PCV13 groups. Carriage was assessed when participants were 9 months and 18 months of age. In the per-protocol analysis, 40% of a full dose of PCV13 met the noninferiority criterion for 12 of 13 serotypes after the primary series and for 13 of 13 serotypes after the booster. The immunogenicity of the 20% dose of PCV13 and of the 40% and 20% doses of PCV10 was not noninferior to that of the full doses. Vaccine serotype-type carriage prevalence was similar across the PCV13 groups at 9 months and 18 months of age. In a three-dose schedule (two primary doses and a booster), 40% doses of PCV13 were noninferior to full doses for all included serotypes. Lower doses of PCV13 and PCV10 did not meet the criteria for noninferiority. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03489018; Pan African Clinical Trial Registry number, PACTR202104717648755.).

Anti-inflammatory Effect of n-Hexane Fraction of Kentut leaves (Paederia scandens L.) on Male White Rats (Rattus novergicus)

The anti-inflammatory effect of fart plant leaf extract (Paederia scandens L.) on white rats (Rattus norvegicus) has been carried out. This research shows that the effective dose of the n-hexane fraction of P. scandens leaf extract provides the best anti-inflammatory effect on white rats' feet soles. The study used an artificial edema formation method and periodically measured the volume of white mice's legs using a plethysmometer. The doses used for the extract are 100mg/200g BW, 150mg/200g BW, and 200mg/200g BW. The research data was observed visually. The effective dose of P. scandens leaf extract, which has the best anti-inflammatory effect, is 150mg/200g BW.

Definitive particle therapy using protons or carbon ions for dedifferentiated liposarcoma

BackgroundParticle therapy is effective for the treatment of soft tissue sarcomas. However, the clinical outcomes of definitive particle therapy, particularly for dedifferentiated liposarcoma (DDLS), remain unknown. PurposeTo analyze the treatment outcomes of proton and carbon ion particle therapies for DDLS. MethodsWe retrospectively included patients with DDLS who were treated with particle therapy between 2008 and 2022. The local control (LC), progression-free survival (PFS), and overall survival (OS) rates were evaluated. ResultsFifty-seven patients were included in this analysis. The median patient age was 68 years (range, 36–91 years). The most common tumor site was the retroperitoneum (n = 37), with a median gross tumor volume (GTV) of 181 cm3. Twenty-nine patients received proton therapy, and 28 patients received carbon ion therapy. The most common fractionation dose was 70.4 Gy (relative biological effectiveness) in 32 fractions (72.7 Gy equivalent dose in 2 Gy fractions [EQD2]). The median follow-up time was 33 months (range, 1–128 months). The 3-year LC, PFS, and OS rates were 73.1 %, 44.6 %, and 70.6 %, respectively. Patients who received a higher prescribed dose (≥72.7 Gy EQD2) showed significantly better LC (p = 0.04) than did those who received a lower prescribed dose. Moreover, those with a larger GTV (≥181 cm3) had significantly worse OS (p = 0.04) than did those with a smaller GTV. Late adverse events occurred in five (9 %) patients. ConclusionsParticle therapy using protons or carbon ions for the treatment of DDLS is safe and provides good OS and LC. However, further studies with longer follow-up periods and larger cohorts are warranted.

Fractionation dose optimization facilities the implementation of transmission proton FLASH-RT

Objective.The beam switching time and fractional dose influence the FLASH effect. A single-beam-per-fraction (SBPF) scheme using uniform fractional dose (UFD) has been proposed for FLASH- radiotherapy (FLASH-RT) to eliminate the beam switching time. Based on SBPF schemes, a fractionation dose optimization algorithm is proposed to optimize non-UFD plans to maximize the fractionation effect and dose-dependent FLASH effect.Approach.The UFD plan, containing five 236 MeV transmission proton beams, was optimized for 11 patients with peripheral lung cancer, with each beam delivering a uniform dose of 11 Gy to the target. Meanwhile, the non-UFD plan was optimized using fractionation dose optimization. To compare the two plans, the equivalent dose to 2 Gy (EQD2) for the target and normal tissues was calculated with anα/βratio of 10 and 3, respectively. Both UFD and non-UFD plans ensured that the target received an EQD2 of 96.3 Gy. To investigate the overall improvement in normal tissue sparing with the non-UFD plan, the FLASH-enhanced EQD2 was calculated.Main results.The fractional doses in non-UFD plans ranged between 5.0 Gy and 24.2 Gy. No significant differences were found in EQD22%and EQD298%of targets between UFD and non-UFD plans. However, theD95%of the target in non-UFD plans was significantly reduced by 15.1%. The sparing effect in non-UFD plans was significantly improved. The FLASH-enhanced EQD2meanin normal tissue and ipsilateral lung was significantly reduced by 3.5% and 10.4%, respectively, in non-UFD plans. The overall improvement is attributed to both the FLASH and fractionation effects.Significance.The fractionation dose optimization can address the limitation of multiple-beam FLASH-RT and utilize the relationship between fractional dose and FLASH effect. Consequently, the non-UFD scheme results in further improvements in normal tissue sparing compared to the UFD scheme, attributed to enhanced fractionation and FLASH effects.

Five-Year Prostate-Specific Membrane Antigen Positron Emission Tomography-Based Outcomes of Spot-Scanning Proton Radiation Therapy for Localized Prostate Cancer: A Single Institution Experience

PURPOSE: We report 5-year oncologic outcomes of a prospective series of patients with prostate cancer treated with spot-scanning proton therapy (SSPT).METHODS AND MATERIALS: A prospective registry identified patients with prostate cancer treated with SSPT between January 2016 and December 2018. Five-year overall survival (OS), local control (LC), biochemical failure (BF), regional and distant failures, and adverse events (AEs) were assessed. Biochemical failure was defined as rise in PSA ≥ 2.0 ng/mL above nadir PSA. Baseline-adjusted toxicities were assigned using CTCAE v5.0.RESULTS: With a median follow up of 4.4 years, 284 prostate cancer patients were treated with SSPT. Median total radiation dose was 79.2 Gy over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for conventional fractionation (CF), hypofractionation (HF), and stereotactic body radiation therapy (SBRT), respectively. Biochemical failure rate for all patients was 6.7%. Five-year LC rates for CF, HF, and SBRT were 100%, 100%, and 97.3%, respectively (p = 0.07). Regional recurrences occurred in 12 (4.2%) patients: 8 treated with CF, 2 with HF, and 2 with SBRT (p = 0.62). Distant failures occurred in 12 patients (4.2%): 5 treated with CF, 7 with HF, and none with SBRT (p = 0.05). Five-year OS for patients treated with CF, HF, and SBRT SSPT were 88.1%, 86.1%, and 97.2%, respectively (p = 0.1). Acute and chronic grade 2+ GI AEs occurred in 8 (2.8%) and 51 (18.0%) patients, respectively. Acute and chronic grade 3+ GI AEs occurred in 3 (1.1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ GU-related AEs were observed in 71 (25%) and 63 (22.2%) patients, respectively. Acute and chronic grade 3+ GU toxicity were observed in 3 (1.1%) and 6 (2.1%) patients, respectively.CONCLUSIONS: SSPT provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates.

Impact of kV-cone beam computed tomography dose on DNA repair mechanisms: A pilot study

PurposeIn head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs.In this study, we asked whether the imaging low dose added to a following fraction dose (2Gy) may affect the biological response in terms of DNA repair. Material and methodsUsing an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM. ResultsThe median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity. ConclusionThe preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT.

Neutralizing Nanobodies against Venoms from Naja haje Species Captured in North Africa.

Snakebite envenoming (SBE) remains a severely neglected public health issue, particularly affecting tropical and subtropical regions, with Africa experiencing an estimated 435,000 to 580,000 snakebites annually, leading to high morbidity and mortality rates, especially across Africa and Asia. Recognized as a Neglected Tropical Disease, SBE management is further complicated by the inadequate efficacy of current antivenom treatments. Of particular concern are cobras (Naja sp.), whose neurotoxins can induce rapid fatal respiratory paralysis. In this study, we investigate the potential of nanobodies as a promising next-generation of immunotherapeutics against cobra venoms. Through a dual strategy of the characterization of venom toxic fractions from cobras captured for the first time in Algeria and Tunisia biotopes, coupled with in vitro assays to evaluate their interactions with acetylcholine receptors, and subsequent immunization of dromedaries to produce specific nanobodies, we identified two lethal fractions, F5 and F6, from each venom, and selected five nanobodies with significant binding and neutralizing of 3DL50 (0.74 mg/kg). The combination of these nanobodies demonstrated a synergistic effect, reaching 100% neutralizing efficacy of 2DL50 lethal venom fraction (0.88 mg/kg) doses in mice. Additionally, our findings highlighted the complex mechanism of cobra venom action through the lethal synergism among its major toxins.

Microdosimetry for BNCT: First measurements at different site sizes

Microdosimetric techniques are a valuable tool for beam quality monitoring in BNCT, due to their capability to distinguish different contributions to the total dose and provide physics-based quantities related to biological effectiveness of this composite radiation field. To this aim, measurements are generally performed with gas detectors simulating a tissue-equivalent site size between 0.5 and 2 μm. This work presents instead measurements for site sizes up to 10 μm, performed in the thermal neutron field produced by the accelerator-based MUNES source available at INFN-LNL. An avalanche-confinement TEPC with boron doping in the cathode walls was used. Photon and neutron dose fractions were discriminated in the measured dose-weighted distributions based on their different lineal energy range. In the neutron component two separate peaks could be distinguished for site sizes of 5 μm and greater, the origin of which was tentatively related to contributions due to protons and alpha particles. These results allow to assess the impact of increasing site diameter on the measured relative dose contributions and provide valuable reference data for biological modelling and for comparison with solid-state microdosimeters.

Ultra-fast Digital DPC Yielding High Spatio-temporal Resolution for Low-Dose Phase Characterization.

In the scanning transmission electron microscope, both phase imaging of beam-sensitive materials and characterization of a material's functional properties using in situ experiments are becoming more widely available. As the practicable scan speed of 4D-STEM detectors improves, so too does the temporal resolution achievable for both differential phase contrast (DPC) and ptychography. However, the read-out burden of pixelated detectors, and the size of the gigabyte to terabyte sized data sets, remain a challenge for both temporal resolution and their practical adoption. In this work, we combine ultra-fast scan coils and detector signal digitization to show that a high-fidelity DPC phase reconstruction can be achieved from an annular segmented detector. Unlike conventional analog data phase reconstructions from digitized DPC-segment images yield reliable data, even at the fastest scan speeds. Finally, dose fractionation by fast scanning and multi-framing allows for postprocess binning of frame streams to balance signal-to-noise ratio and temporal resolution for low-dose phase imaging for in situ experiments.

Randomised controlled trials on radiation dose fractionation in breast cancer: systematic review and meta-analysis with emphasis on side effects and cosmesis

ObjectiveTo provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival...

Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study

BackgroundAdvanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.MethodsWe use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.ResultsIn vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response.ConclusionsThere is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

Investigation of the linear accelerator low dose rate mode for pulsed low-dose-rate radiotherapy delivery

Purpose. Pulsed volumetric modulated arc therapy (VMAT) was proposed as an advanced treatment that combines the biological benefits of pulsed low dose rate (PLDR) and the dosimetric benefits of the intensity-modulated beams. In our conventional pulsed VMAT technique, a daily fractional dose of 200 cGy is delivered in 10 arcs with 3 min intervals between the arcs. In this study, we are testing the feasibility of pulsed VMAT that omits the need to split into ten arcs and excludes any beam-off gaps. Methods. The study was conducted using computed tomographic images of 24 patients previously treated at our institution with the conventional PLDR technique. Our newly installed Elekta machine has a low dose rate option on the order of 25 MU min−1. PLDR requires an effective dose rate of 6.7 cGy min−1 with attention being paid to the maximum dose received within any point within the target not to exceed 13 cGy min−1. The quality of treatment plans was judged based on dose-volume histograms, isodose distribution, dose conformality to the target, and target dose homogeneity. The dose delivery accuracy was assessed by measurements using the MatriXX Evolution 2D array system. Results. All cases were normalized to cover 95% of the target volume with 100% of the prescription dose. The average conformity index was 1.03 ± 0.08 while the average homogeneity index was 1.05 ± 0.02. The maximum reported dose rate at any point within the target was 10.44 cGy min−1. The mean dose rate for all pulsed VMAT plans was 6.88 ± 0.1 cGy min−1. All cases passed our gamma analysis with an average passing rate of 99.00% ± 0.48%. Conclusion. The study showed the applicability of planning pulsed VMAT using Eclipse and its successful delivery on our Elekta linac. Pulsed VMAT using the machine’s low dose rate mode is more efficient than our previous pulsed VMAT delivery.

Functional outcomes following external beam radiation therapy for patients with prior holmium laser enucleation of the prostate.

Holmium laser enucleation of the prostate (HoLEP) is an increasingly popular size-independent technique of treating male voiding dysfunction due to benign prostatic hypertrophy. Some patients after HoLEP may develop clinically significant prostate cancer and opt for definitive treatment with external beam radiation therapy (EBRT). Little is known about the safety of EBRT after HoLEP and how it may functionally impact voiding after HoLEP has altered the anatomy of the prostate. Our study aimed to assess patient-reported voiding outcomes following EBRT after HoLEP with a focus on incontinence related patient outcomes. This study was conducted with approval from our hospital's institutional review board. Patients that underwent HoLEP followed by EBRT were identified and data were collected in a retrospective nature from a single surgeon HoLEP cohort over the past 4years (2019-2023). Patient demographics, disease and radiation therapy characteristics, radiation therapy, and baseline voiding symptoms were recorded. Current functional voiding outcomes were also collected via phone-call or portal communication in a cross-sectional manner with questions pertaining to type of incontinence, IPSS quality of life score, and administration of the Michigan incontinence symptom index (M-ISI). Adverse events encountered during follow-up were recorded. 24 patients were identified who received RT for prostate cancer after HoLEP with an average age of 73.6 (± 5.3). One third of patients reported no incontinence whatsoever after radiation and of those who experienced incontinence, the majority felt that it was not worsened after radiation. Median IPSS QoL score following radiation was 1 (range 0-6), median M-ISI Severity Score was 4 out of a maximum of 32, and median M-ISI bother score was 0 out of a maximum of 8. One patient developed a bladder neck contracture (BNC) approximately 1year following his radiation therapy (approximately 18months after HoLEP) causing bothersome incontinence and LUTS. In our cohort most patients who received RT after HoLEP reported a high urinary-symptom related quality of life and a low rate of urinary incontinence. One patient who received SBRT suffered a BNC which is a known adverse event with RT but given our small sample size it remains unclear if the risk is higher in patients receiving RT after HoLEP. Larger studies should focus on examining the rate of bladder neck contracture in patients receiving RT after HoLEP, particularly focusing on whether the degree of dose fractionation may impact their development.