Radiotherapy Protocols Research Articles

A Pilot Trial of Proton-Based Cardiac Sparing Accelerated Fractionated Radiation Therapy in Unresectable Non-small Cell Lung Cancer With Extended Durvalumab Therapy (PARTICLE-D)

Purpose: Concurrent chemoradiotherapy is the current non-surgical standard of care for locally advanced non-small cell lung cancer (NSCLC). However, this is a difficult regimen to tolerate especially for those who are elderly, have multiple comorbidities or poor performance status. Alternative treatment regimens are needed for this vulnerable population. We report initial results of concurrent durvalumab, an immune checkpoint inhibitor, and hypofractionated, dose-escalating, proton external beam radiotherapy (EBRT).Patients and Methods: This phase I, pilot dose-escalation trial enrolled seven patients with newly diagnosed stage IIIA-IIIC NSCLC who were unable or unwilling to undergo concurrent chemoradiotherapy. Patients previously treated with immunotherapy were excluded. Five patients in the initial phase of this 3+3 study design received a fixed dose of durvalumab each 28-day cycle plus hypofractionated proton EBRT 60 Gy in 20 fractions while two patients received the escalation dose of 69 Gy in 23 fractions. The primary objective assessed safety while secondary objectives assessed feasibility and adverse events.Results: All patients experienced treatment-related adverse events, primarily grades 1-2. Pneumonitis and anemia were the most common. Only one dose limiting toxicity occurred, in arm one, which was a grade 3 pneumonitis leading to grade 5 pneumonia. Additionally, two delayed-onset grade 5 tracheal necrosis events occurred > 13 months after treatment initiation.Conclusions: Concurrent durvalumab plus hypofractionated proton EBRT was well tolerated in the short term. However, three treatment-related deaths, including two delayed-onset grade 5 tracheal necroses negatively impacted overall safety. A dose de-escalation protocol of proton-based radiotherapy plus durvalumab is warranted.

Effect of a 3-second Off-label Exposure on the Depth of Cure of Eight Resin-based Composites.

This study evaluated the depth of cure (DoC) of eight resin-based composites (RBCs) photocured using one multipeak light-curing unit (LCU) on the standard output setting for the manufacturer's RBC recommended exposure time and at a higher irradiance for 3 seconds. Three conventional RBCs: Tetric EvoCeram (Evo), Tetric N-Ceram (Cer), Tetric Prime (Pri); and five bulk-fill: Tetric N-Ceram Bulk Fill (CerBF), Opus Bulk Fill APS (OpusBF), Opus Bulk Fill Flow APS (OpusF), Tetric PowerFill (PFill) and Tetric PowerFlow (PFlow) were examined. Only PFill and PFlow are formulated to be photocured in 3 seconds. The RBCs were packed into a metal mold and photocured using a Bluephase PowerCure LCU for the RBC manufacturer's recommended exposure time on the standard mode and using the 3-second high irradiance mode. After photocuring, the specimens were immersed in a solvent for 1 hour. The length of the remaining RBC was measured and divided by 2. Data were analyzed using two-way analysis of variance (ANOVA) followed by the Tukey post hoc multiple comparison test (α=0.05). There was no significant difference in the DoC values for PFill and PFlow when photocured using the 3-second high irradiance protocol compared to the lower irradiance standard mode protocol. All other RBCs had significantly lower DoC values (p<0.001) when photocured off-label using the 3-second high irradiance mode. Of the eight RBCs tested, only PFill and PFlow achieved the same DoC when the high irradiance 3-second curing method was used compared to when their longer lower irradiance protocol was used.

Dosimetric Study and Robustness Analysis of Base Note Intensive Locked Field Radiotherapy for Left Breast Cancer.

The locked vision plan can make the left breast cancer heart and lung organs dose. The aim of the present study was to compare the dosimetric differences between field-locked and field-split plans in intensity-modulated radiotherapy for left-sided breast cancer, to explore the effect of field-locking on the low-dose region, and to evaluate its robustness to the radiotherapy target, in order to provide a reference for the selection of clinical radiotherapy protocols. A total of 30 patients were selected after radical left breast cancer surgery, and 7-field locked-field and split-field plans were developed to compare the dose difference (∆D) between the target area and each organ at risk, and to introduce offsets of 3, 5 and 7 mm in six directions and recalculate the perturbed dose distributions, and to compare the ∆D between the original and the perturbed plans according to the robustness of the plans. The results revealed that the D98%, D95% and Dmean values of the planning target volume (PTV) of the two plans differed little and were not statistically different. The locked field plan provided better protection for the left lung, right lung, heart, right breast and left anterior descending coronary artery. For PTV∆D98%, PTV∆D95%, PTV∆Dmean, the ∆D was higher for the Locked Fields plan, and for LungL∆5, LungL∆20 and Heart∆mean, the ∆D was higher for the original plan. It was concluded that the field-locking plan could reduce the low-dose area of the affected lung and provide improved protection to the remaining critical organs, and the field-locking plan was more robust in protecting critical organs. Meanwhile, the field-locking plan showed higher sensitivity to positional deviation for target PTV.

Effect of radiotherapy, immediate dentin sealing and irrigation simulating single- or two-visits endodontic treatment on the bond strength to pulp chamber dentin: an in vitro study.

This study aimed to evaluate the influence of radiotherapy and different endodontic treatment protocols on the bond strength to pulp chamber dentin. Eighty mandibular molars were randomly divided into two groups (n = 40): non-irradiated and irradiated (60Gy). The pulp chambers were sectioned, and each group was subdivided (n = 8), according to the endodontic treatment protocol: no treatment (Control); Single-visit; Two-visits; Immediate dentin sealing (IDS) + single-visit; and IDS + two-visits. Each endodontic treatment visit was simulated through irrigation with 2.5% NaOCl, 17% EDTA and distilled water. IDS was performed by actively applying two coats of a universal adhesive to the lateral walls of the pulp chamber. After, the pulp chambers were restored with resin composite and four sticks were obtained for microtensile test. In addition, the dentin of the pulp chamber roof was assessed for surface roughness, chemical composition, and topography after each treatment protocol. Two-way ANOVA, Tukey's post hoc, Mann-Whitney, Kruskal-Wallis and Dunn's post hoc were performed (α = 5%). The treatment protocol affected bond strength (p < 0.05), while the irradiation did not (p > 0.05). The control group presented the highest values (p < 0.05). The single-visit group demonstrated better performance compared to the other groups (p < 0.05), which did not differ from each other (p > 0.05) The use of IDS changed the surface roughness (p < 0.05), chemical composition (p < 0.05) and topography of the dentin. In conclusion, the treatment protocol influenced dentin adhesion, while irradiation did not.

MDB-80. PREVIOUS MANAGEMENT OF MEDULLOBLASTOMA IN A MIDDLE-INCOME COUNTRY: IDENTIFYING AREAS FOR IMPROVEMENT

Abstract BACKGROUND Medulloblastoma stands as the most prevalent malignant brain tumor among the pediatric population. Diagnosis, staging, and treatment protocols are well-established in high-income countries. However, in low- to middle-income countries, management practices often deviate and frequently prove inadequate, potentially impacting final outcomes significantly. In Costa Rica, a middle-income country, a study was conducted to document the prevailing management approaches for patients at the Hospital Nacional de Niños. METHODS Data from 31 children under the age of 13, treated between 2009 and 2015, were retrospectively analyzed. All patients were included in the study. Demographic details, initial symptoms, staging procedures, surgical interventions, histologic subtypes, treatment modalities, and survival outcomes were scrutinized. Risk stratification relied on age, CSF analysis (when available), and the extent of resection as per the neurosurgeon’s assessment. Due to incomplete staging, all patients received high-risk chemo - radiotherapy protocol. RESULTS The study identified 31 patients. Median age of 6.1 years (range, 0 -12), 51.1% being male. The most prevalent symptoms included headache, vomiting, and ataxia, manifesting in 93% of cases. Histological subtype was unspecified in 45.2% of patients. High-risk status was assigned to 11 patients (35.5%), with 8 of them aged under 3 years, while 20 patients (64.5%) were categorized as low risk, yielding a 5-year overall survival (OS) of 27% and 80%, respectively. Complete resection achieved in 21 cases, resulting in a 5-year OS of 71.5%, compared to 25% for 4 patients with incomplete resection. The overall 5-year OS rate was 61.3%. CONCLUSIONS This study underscores suboptimal practices in the diagnosis, staging, and management of medulloblastoma at the time of assessment. While outcomes for patients classified as standard are acceptable, they received intensified chemo/radiotherapy, potentially leading to heightened long-term adverse effects. Importantly, identified deficiencies have since been addressed. The impact of these interventions will be evaluated in future studies.

RADT-01. TUMOR VOLUME INCREASE AND NEED FOR RADIOTHERAPY PLAN ADAPTATION IN PEDIATRIC HIGH-GRADE GLIOMA AND DIFFUSE MIDLINE GLIOMA DURING A SIX-WEEK COURSE OF RADIOTHERAPY

Abstract BACKGROUND Pediatric High-Grade Glioma/ diffuse midline glioma (pHGG/DMG) growth during a six-week course of radiotherapy may precipitate geographical miss of target volumes and early disease progression. In a patient cohort, we retrospectively evaluated the evolution of tumor volumes during radiotherapy, the clinical need for plan adaptation, and potential correlation with local disease progression. METHODS Twenty-four pHGG/DMG patients (12M/12F, ages 4-20 years) with gross tumor volume (GTV) after debulking (n=7) or biopsy (n=17) received 30 fractions of Volumetric Modulated Arc Therapy within an adaptive radiotherapy-protocol. The GTV was defined by combined T1+FLAIR MRI sequence abnormalities. A 1-cm margin was applied for Clinical Target Volume (CTV). MRI-based target volume re-evaluation was performed at fraction 10 and 20, defining GTV increase &amp;gt;1mL as growth. The clinical need for plan adaptation was based on tumor volume changes. GTV increase and need for plan adaptation were evaluated against local progression-free survival (LPFS). RESULTS Median time between baseline MRI and radiotherapy start was 10 days (range 3-29). From baseline, GTV growth was observed in 7/24 patients at fraction 10, and in an additional 7/24 patients at fraction 20 (cumulative 14/24), corresponding to a mean volume increase of 21%/3.7mL (range [-7%/-2.7mL] to [+185%/24.4mL]) and 40%/8.7mL (range [-18%/-8.1mL] to [+329%/115.1mL]) after 10 and 20 fractions, respectively. At fraction 10 and 20, respectively 6 and 6 plans needed adaptation in a total of 11 patients. Baseline tumor volumes between patients with/without plan adaptation were equivalent. Median LPFS was 8.3 months (95%CI 8.0-12.7). No significant difference in LPFS was observed between patients with versus without GTV increase or plan adaptation. CONCLUSIONS Between MRI at baseline and at fractions 10 and 20, this adaptive radiotherapy protocol using 1-cm CTV margins demonstrated pHGG/DMG tumor volume increase with a clinical need for plan adaptations in 11/24 patients.

Keratinocyte cancer of the lower limb in the frail elderly – acceptable results for 96 lesions treated with a shortened radiotherapy protocol

Keratinocyte cancer of the lower limb in the frail elderly – acceptable results for 96 lesions treated with a shortened radiotherapy protocol

Cerenkov free micro-dosimetry in small-field radiation therapy technique

Objective. Optical fiber-based scintillating dosimetry is a recent promising technique owing to the miniature size dosimeter and quality measurement in modern radiation therapy treatment. Despite several advantages, the major issue of using scintillating dosimeters is the Cerenkov effect and predominantly requires extra measurement corrections. Therefore, this work highlighted a novel micro-dosimetry technique to ensure Cerenkov-free measurement in radiation therapy treatment protocol by investigating several dosimetric characteristics. Approach. A micro-dosimetry technique was proposed with the performance evaluation of a novel infrared inorganic scintillator detector (IR-ISD). The detector essentially consists of a micro-scintillating head based on IR-emitting micro-clusters with a sensitive volume of 1.5 × 10−6 mm3. The proposed system was evaluated under the 6 MV LINAC beam used in patient treatment. Overall measurements were performed using IBATM water tank phantoms by following TRS-398 protocol for radiotherapy. Cerenkov measurements were performed for different small fields from 0.5 × 0.5 cm2 to 10 × 10 cm2 under LINAC. In addition, several dosimetric parameters such as percentage depth dose (PDD), high lateral resolution beam profiling, dose linearity, dose rate linearity, repeatability, reproducibility, and field output factor were investigated to realize the performance of the novel detector. Main results. This study highlighted a complete removal of the Cerenkov effect using a point-like miniature detector, especially for small field radiation therapy treatment. Measurements demonstrated that IR-ISD has acceptable behavior with dose rate variability (maximum standard deviation ∼0.18%) for the dose rate of 20–1000 cGy s−1. An entire linear response (R 2 = 1) was obtained for the dose delivered within the range of 4–1000 cGy, using a selected field size of 1 × 1 cm2. Perfect repeatability (max 0.06% variation from average) with day-to-day reproducibility (0.10% average variation) was observed. PDD profiles obtained in the water tank present almost identical behavior to the reference dosimeter with a build-up maximum depth dose at 1.5 cm. The small field of 0.5 × 0.5 cm2 profiles have been characterized with a high lateral resolution of 100 µm. Significance. Unlike recent plastic scintillation detector systems, the proposed micro-dosimetry system in this study requires no Cerenkov corrections and showed efficient performance for several dosimetric parameters. Therefore, it is expected that considering the detector correction factors, the IR-ISD system can be a suitable dose measurement tool, such as in small-field dose measurements, high and low gradient dose verification, and, by extension, in microbeam radiation and FLASH radiation therapy.

Application of Palliative Hemostatic Radiotherapy in Canine Unresectable Oral Melanoma: A Case Report

A 9-year-old castrated male Schnauzer dog, weighing 11.6 kg, presented with a persistent hemorrhagic oral mass. An oral examination revealed a right maxillary oral mass characterized by continuous bleeding, halitosis, and severe pain. A cytological examination led to a provisional diagnosis of malignant melanoma, and, despite the option of aggressive surgery, the owner declined. The blood analysis indicated severe hemorrhagic anemia (hematocrit, 18.2%) requiring a blood transfusion. The patient underwent volumetric modulated arc therapy (VMAT) as part of a palliative radiation protocol, receiving six fractions of 6 Gy weekly for hemostasis and clinical improvement. The hemorrhaging ceased after the second fraction, with a subsequent rise in the hematocrit levels and the resolution of the anemia. Additionally, the intake increased following the second fraction, and effective pain management was achieved in the fourth fraction. Following the last fraction, computed tomography revealed a 20% reduction in the tumor size. This case highlights the potential use of radiotherapy for hemostasis in cases of inoperable hemorrhagic oral melanoma and represents the first report on the application of hemostatic radiotherapy in dogs.

233P 3-year outcome of radical chemoradiotherapy for anal squamous cell carcinoma (ASCC) using intensity-modulated radiation therapy (IMRT) protocol at Southend Hospital

233P 3-year outcome of radical chemoradiotherapy for anal squamous cell carcinoma (ASCC) using intensity-modulated radiation therapy (IMRT) protocol at Southend Hospital

Neoadjuvant chemo-immunotherapy following concurrent immuno-chemoradiotherapy and immune-maintenance therapy as primary treatment for locally advanced cervical cancer: A prospective, single-arm, phase 2 trial.

5533 Background: Immunotherapy in combination with chemoradiotherapy has shown good efficacy in locally advanced cervical cancer (LACC). We report on the efficacy of neoadjuvant camrelizumab plus chemotherapy (TP) following concurrent immuno-chemoradiotherapy and maintenance immunotherapy for LACC. Methods: Eligible participants were adults with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2018 stage IIB-IVA disease), ECOG PS score 0-2, and adequate bone marrow and organ function. All pts received 2 cycles neoadjuvant camrelizumab (200 mg d1 q3w) plus TP (albumin-bound Paclitaxel 260mg/m2 d1 q3w; cisplatin 75 mg/m2 d1-3 q3w) treatment, following 5-week external beam radiotherapy (EBRT) protocol (45-50 Gy/25 fractions with concurrent triweekly camrelizumab and cisplatin) to the whole pelvis plus brachytherapy every 3 weeks for 2 cycles, and then maintenance therapy of camrelizumab (200mg q3w, up to one year). The primary endpoint was progression-free survival (PFS) at 2 years. PFS was evaluated when at least 13 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.05. Results: 67 pts provided informed consent and 12 were excluded for not meeting eligibility. 55 pts received the investigational agent and were evaluable for safety and efficacy analyses. The median age was 54 years [IQR 50 to 60]; 51 [92.7%] were squamous cell carcinoma, and 4 [7.3%] were adenocarcinoma; 9 [16.4%] were stage IIB, 2 [3.6%] were IIIA, 5 [9.1%] were IIIB, 30 [54.5%] were IIIC1r, 6 [10.9%] were IIIC2r, and 3 [5.5%] were IVA. As of data cutoff (Jan. 15, 2024), median follow-up was 9.5 (IQR 7.1 to 10.3) months. Of the 55 pts, 1 (1.8%) pt underwent hysterectomy after EBRT because of pelvic empyema, and was excluded from response evaluation. At three months after brachytherapy, the overall remission rate was 100% (53 [98.1%] complete remission and 1 [1.9%] partial remission). We identified 3 (5.5%) pts with treatment failure (2 [3.6] distant metastasis, and 1 [(1.8%] para-aortic lymph node relapse) during follow-up; 1-year PFS was 90.6% (85.4%-95.8%). The most common clinically significant grade 3-4 adverse events (AEs) were decreased neutrophils (18.2%), thrombocytopenia (9.1%) and anemia (27.3%). Serious AEs occurred in 7 (12.7%), most commonly due to infectious complications. There were no treatment-related deaths. Conclusions: The interim data support Camrelizumab plus TP neoadjuvant chemo-immunotherapy following immuno-chemoradiotherapy and Camrelizumab maintenance therapy as an active go-forward regimen in LACC. No new safety signals were observed, and most AEs were mild to moderate. Clinical trial information: ChiCTR2200061097.

A phase II study of radiotherapy combined with docetaxel, cisplatin, and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer.

4029 Background: Recently, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery for patients with esophageal cancer have resulted in favorable prognosis, but extended radical esophagectomy with two-field or three-field (neck, mediastinum, and abdomen) lymph node dissection remains a standard treatment. However, there is recurrence in 30-50% of patients who have undergone an operation and there is loco-regional recurrence in 40-55% of patients with postoperative recurrence. The efficacy and safety of chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer have been reported, and the survival outcome has been improved; however, the median progression-free survival period according to past reports was 10 to 14 months, which was not enough. Recently, RT with docetaxel (DOC), cisplatin (CDDP) and 5-FU has shown better results than conventional standard treatment (CDDP+5-FU +radiotherapy) for primary esophageal cancer. The purpose of the phase II study was to evaluate the superior of definitive radiotherapy with DOC, CDDP and 5-FU to the standard treatment in patients with loco-regional recurrent esophageal cancer after curative resection. Methods: Between 2015 and 2023, this open-label, single-arm, phase II study of radiotherapy (60 Gy/30 fractions/6 weeks without prophylactic region) combined with chemotherapy consisting of 3 cycles of DOC (35 mg/m2), CDDP (40 mg/m2) and 5-FU (400 mg/m2/24 h for 5 days) for patients with postoperative loco-regional recurrent esophageal cancer was conducted at a single institution. The primary endpoint was progression-free survival rate. This trial was considered positive if median progression-free survival period was 24.0 months or more, which meaning superiority over conventional standard treatment. The secondary endpoints were overall survival rate and adverse events. This trial was registered with UMIN Clinical Trials Registry (UMIN000019269) and Japan Registry of Clinical Trials (jRCTs021200009). Results: A total of 29 patients were enrolled in this study. The regimen was completed in all the patients. The median observation period for survivors was 60 months (IQR, 30.0-75.5 months). The 5-year progression-free survival rate was 56.2% (95% CI = 37.4-75.0%) with a median progression-free survival period of 62.0 months (95% CI = 35.2-64.7 months). Only 2 patients showed grade 4 hematologic adverse events during chemoradiotherapy, and they had to be performed reduced chemotherapy; however, they also completed 3 cycles of concurrent chemotherapy. Grade 2 or higher late toxicity was not observed in any patients. Conclusions: The present protocol of radiotherapy combined with DOC, CDDP and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. It might be better than conventional treatment. Clinical trial information: UMIN000019269.

Differences between long- and short-wavelength light–induced retinal damage and the role of PARP-1 in retinal injury induced by blue light

Photobiomodulation (PBM) therapy uses light of different wavelengths to treat various retinal degeneration diseases, but the potential damage to the retina caused by long-term light irradiation is still unclear. This study were designed to detect the difference between long- and short-wavelength light (650-nm red light and 450-nm blue light, 2.55 mW/cm2, reference intensity in PBM)–induced injury. In addition, a comparative study was conducted to investigate the differences in retinal light damage induced by different irradiation protocols (short periods of repeated irradiation and a long period of constant irradiation). Furthermore, the protective role of PARP-1 inhibition on the molecular mechanism of blue light-induced injury was confirmed by a gene knockdown technique or a specific inhibitor through in vitro and in vivo experiments. The results showed that the susceptibility to retinal damage caused by irradiation with long- and short-wavelength light is different. Shorter wavelength lights, such as blue light, induce more severe retinal damage, while the retina exhibits better resistance to longer wavelength lights, such as red light. In addition, repeated irradiation for short periods induces less retinal damage than constant exposure over a long period. PARP-1 plays a critical role in the molecular mechanism of blue light-induced damage in photoreceptors and retina, and inhibiting PARP-1 can significantly protect the retina against blue light damage. This study lays an experimental foundation for assessing the safety of phototherapy products and for developing target drugs to protect the retina from light damage.

Upscaling irradiation protocols of Aedes albopictus pupae within an SIT program in Reunion Island.

The implementation of the sterile insect technique against Aedes albopictus relies on many parameters, in particular on the success of the sterilization of males to be released into the target area in overflooding numbers to mate with wild females. Achieving consistent sterility levels requires efficient and standardized irradiation protocols. Here, we assessed the effects of exposure environment, density of pupae, irradiation dose, quantity of water and location in the canister on the induced sterility of male pupae. We found that the irradiation of 2000 pupae in 130ml of water and with a dose of 40Gy was the best combination of factors to reliably sterilize male pupae with the specific irradiator used in our control program, allowing the sterilization of 14000 pupae per exposure cycle. The location in the canister had no effect on induced sterility. The results reported here allowed the standardization and optimization of irradiation protocols for a Sterile Insect Techniqueprogram to control Ae. albopictus on Reunion Island, which required the production of more than 300,000 sterile males per week.

Meta-Analysis of 5-Fraction Preoperative Radiotherapy for Soft Tissue Sarcoma.

Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.

Radiotherapy for Canine Apocrine Gland Anal Sac Adenocarcinoma: Survival Outcomes and Side Effects of a Palliative Treatment Protocol of 20 Gy in Five Consecutive Fractions.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198-569) and 628 days (95% CI 579-676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282-391 days), and 402 days (95% CI 286-517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.

A survey of the radiation safety practices of veterinary practitioners during portable equine radiography in Ireland.

Veterinary practitioners and other personnel involved in the examination are exposed to ionizing radiation while performing portable radiographs on horses. An online survey was distributed to all Veterinary Council of Ireland-registered practices where the self-reported practice profile is at least 20% equine work. The survey contained questions relating to radiation safety training, protocols, personal dosimetry and lead protection usage, repeat exposures, sedation, and personnel roles during the examination. The aim of the survey was to document the current radiation safety practices of equine veterinary practitioners during portable radiography. The results showed that although adherence to guidance set out by the Environmental Protection Agency (EPA) is reasonably good, compliance rates can be improved. Personal dosemeter usage and repeat rate reduction could particularly benefit from further improvement. This is of the utmost importance in ensuring that occupational radiation exposure to veterinary practitioners is kept to an absolute minimum during their daily practice.

Quad Shot Palliation, A Considerable Option for Non-Osseous Recurrent or Metastatic Malignancies in Elderly or Frail Patients.

Background: Palliative radiation therapy (RT) is increasingly recognized as a crucial component of care for patients with advanced, incurable malignancies. In Pakistan, where patients often present at advanced stages due to socio-economic barriers and limited healthcare access, efficient and effective treatment protocols are essential. Objective: This study aimed to evaluate the efficacy of the Quad Shot hypo-fractionated RT protocol for pain palliation in elderly and frail patients with recurrent or metastatic non-osseous malignancies. Methods: A quasi-experimental study was conducted at the Oncology Department of Ganga Ram Hospital, Lahore. Forty-two elderly patients with histologically confirmed inoperable malignancies and a WHO Performance Status of 2 to 3 were enrolled. Patients with prior RT or a second cancer were excluded. RT was delivered using a Cobalt-60 beam, with a total dose of 14 Gy divided into four fractions over two consecutive days. Pain severity was assessed using a 10-point scale before and four weeks after treatment. Statistical analysis was performed using the Wilcoxon Sign Rank Test on SPSS version 25.0. Results: The study population comprised 52% males and 48% females, with the majority of primary tumors located in the head and neck (64%). Post-treatment, the mean pain score significantly decreased from 8.04 ± 1.22 to 4.32 ± 0.89 (p &lt; 0.05). Conclusion: The Quad Shot hypo-fractionated RT protocol effectively reduces pain in elderly and frail patients with advanced malignancies, suggesting its suitability as a quick and effective palliative care option in resource-limited settings.

Fractionated irradiation induces radioresistant oral carcinoma cells with enhanced malignant phenotypes

ObjectiveThe fact that certain oral carcinoma patients experience radiotherapy failure implies that a more radioresistant and aggressive phenotype of surviving cancer cells potentially occurs during treatment. Our study aimed to establish radioresistant oral cancer cells through a fractionated irradiation protocol that mimics clinically relevant radiotherapy dosing strategies and to investigate all-round alterations in the malignant phenotype. MethodsRadioresistant oral carcinoma cells were generated by exposing Cal27 and Detroit 562 cells to 60 Gy radiation in 10 dose-escalating fractions and verified by cell immunofluorescence. Specific markers related to the epithelial–mesenchymal transition (EMT) process and the cancer stem cell (CSC) phenotype were assessed by Western blotting. Cell invasion and migration were evaluated using Matrigel-coated transwell and wound healing assays, respectively. Nontargeted metabolomics was used to mechanistically delineate the potential metabolic patterns linked to EMT and CSCs; the CSC phenotype was also examined by sphere formation assays and cell immunofluorescence. ResultsRadioresistant oral carcinoma cell lines were successfully established and validated. These cells exhibited enhanced EMT and increase in both cell invasion and migration. These radioresistant cells further demonstrated a high metabolic profile, notably marked by lipid metabolism reprogramming and functional enrichment of ATP-binding cassette (ABC) transporters. Consistently, enhanced CSC phenotype in radioresistant cells was confirmed by elevated expression of stemness markers and increased sphere-forming capacity. ConclusionRadioresistant oral carcinoma cells subjected to fractionated radiation exhibit an augmented malignant phenotype. The metabolic characteristics linked to enhanced EMT and CSC phenotypes provide potential targets for improving radiotherapy in oral carcinoma.

Management of the axilla in breast cancer patients: critical review, regional modified Delphi consensus and implementation in the Tuscan breast network.

Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity. In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice. (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy. This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.