Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

A retrospective study of chemotherapeutic effect without wide-margin surgery or radiation therapy in dogs with oral malignant melanoma.

Background: Effective treatment for canine oral malignant melanoma (e.g., curative-intent surgery) may not be feasible or radiation therapy may be unavailable. However, chemotherapy is usually an option, and more information is needed regarding its use without adequate local treatments. Objective: Our objective was to investigate the efficacy of chemotherapy in canine oral malignant melanoma without adequate local control, using carboplatin with dose reduction in small-breed dogs and metronomic chemotherapy. Animals and procedure: Client-owned dogs with histopathologically diagnosed oral malignant melanoma were retrospectively enrolled from 2016 to 2022. The chemotherapy protocol in each case was determined by the attending clinician. Results: Thirteen dogs were included. The median progression-free interval of all 13 dogs was 42 d (14 to 953 d). The median overall survival time of dogs with chemotherapy as their only systemic treatment was 181 d (50 to 960 d; n = 11). The median dosage of carboplatin was 250 mg/m2. Response to treatment and clinical stage were significant prognostic factors. Conclusion and clinical relevance: As chemotherapy provided a median survival of 6 mo, it could be considered when adequate local control is infeasible. Earlier clinical stages or achievement of at least stable disease during chemotherapy may indicate better survival in dogs.

Une étude rétrospective de l'effet chimiothérapeutique sur le mélanome malin buccal canin dépourvu de chirurgie et de radiothérapie á large marge : le stade clinique et la réponse au traitement prédisent les résultats du patient. Mise en contexte: Des traitements efficaces pour le mélanome malin oral canin, tels que la chirurgie á visée curative, ne sont parfois pas réalisables ou la radiothérapie n'est pas disponible dans certaines régions. La chimiothérapie reste une option de traitement et davantage d'informations devraient être fournies pour les cas qui n'ont pas eu accés á un traitement local adéquat. Objectif: Cette étude visait á étudier l'efficacité de la chimiothérapie dans le mélanome malin oral canin sans contrôle local adéquat, en utilisant le carboplatine avec réduction de dose chez les chiens de petite race et la chimiothérapie métronomique. Animaux et procédure: Treize chiens appartenant á des clients atteints d'un mélanome malin oral diagnostiqué par histopathologie ont été rétrospectivement inscrits de 2016 á 2022. Le protocole de chimiothérapie a été déterminé par le clinicien traitant. Résultats: L'intervalle médian sans progression des treize chiens était de 42 jours (14­953 jours). La durée médiane de survie globale des chiens ayant reçu une chimiothérapie comme seul traitement systémique était de 181 jours (50­960 jours; n = 11). La dose médiane de carboplatine était de 250 mg/m2. La réponse au traitement et le stade clinique étaient des facteurs pronostiques importants. Conclusion et pertinence clinique: La chimiothérapie pouvait encore être envisagée lorsqu'un contrôle local adéquat était impossible. Des stades cliniques plus précoces ou des patients atteignant au moins une maladie stable pendant la chimiothérapie peuvent indiquer une meilleure survie.(Traduit par les auteurs).

[Clinical study of ear keloids with surgical excision and intraoperative low-energy X-ray irradiation therapy].

Objective:To explore the clinical efficacy of surgical excision combined with low-energy X-ray irradiation in the treatment of ear keloids. Methods:Clinical data of 32 cases of ear keloid lesions that received surgical treatment alone or surgery combined with radiotherapy from March 2019 to November 2022 in the Department of Otorhinolaryngology Head and Neck Surgery of the Tianjin First Central Hospital were retrospectively analyzed. Among them, 10 cases received radiotherapy and 22 cases did not receive radiotherapy. The radiotherapy group received irradiation with a large divided dose of 50 kV low-energy X-rays. The mode of fractionation radiotherapy was as follows: the first was 10 Gy of intraoperative radiation therapy and the second was 8 Gy on the 3rd postoperative day for a total of 18 Gy. The local efficacy and skin radiation reaction were observed at a follow-up of 8-52 months. Results:The median follow-up was 26 months, and as of the date of the last follow-up, 9 cases were cured and 1 case was ineffective in the radiotherapy group, with an effective rate of 90.0%, while 9 cases were cured and 13 cases were ineffective in the no-radiotherapy group, with an effective rate of 40.9%. The recurrence of ear keloids was not related to the side, site, or etiology of the patient's onset（P>0.05）. Recurrence was related to whether or not the patients received radiotherapy（χ²=4.885, P<0.05）, and the recurrence rate in the radiotherapy group（10.0%） was significantly lower than that in the non-radiotherapy group（59.1%）. Conclusion:Surgical excision combined with low-energy X-ray irradiation therapy is an effective method of treating keloids in the ear, especially with intraoperative radiation therapy can achieve more satisfactory results.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Effects of far-infrared radiation lamp therapy on recovery from a simulated soccer-match in elite female soccer players.

We investigated the effects of far-infrared radiation (FIR) lamp therapy on changes in muscle damage and performance parameters following six sets of 15-min Loughborough intermittent shuttle test (LIST), a simulated soccer match. Twenty-four elite female soccer players (20-24 y) were assigned into FIR or sham treatment group (n = 12/group). The participants received a 60-min FIR or sham treatment (30 min per muscle) over knee extensors (KE) and flexors (KF) at 2, 25, 49, 73, and 97 h post-LIST. Maximal voluntary isometric contraction (MVC) torque and muscle soreness of the KE and KF, plasma creatine kinase (CK) activity as muscle damage markers, and several performance parameters including countermovement jump (CMJ) and Yo-Yo intermittent recovery test level 1 (YYIR1) were measured before and 1, 24, 48, 72, 96, and 120 h post-LIST. Changes in the measures were compared between groups by a mixed-design two-way ANOVA. The running distance covered during LIST and changes in the measures at 1-h post-LIST (before the treatment) were similar (p = 0.118-0.371) between groups. Changes in muscle damage markers at 24-120 h post-LIST were smaller (p < 0.05, η2 = 0.208-0.467) for the FIR (e.g., MVC-KE torque decrease at 48-h post-LIST: -1 ± 2%, peak KE soreness: 16 ± 10 mm, peak CK: 172 ± 42 IU/L) than sham group (-11 ± 9%, 33 ± 7 mm, 466 ± 220 IU/L, respectively). Performance parameters recovered faster (p < 0.05, η2 = 0.142-0.308) to baseline for the FIR (e.g., decreases at 48-h post-LIST; CMJ: 0 ± 1%, YYIR1: 0 ± 1%) than sham group (-6 ± 2%, -9 ± 6%, respectively). These results suggest that the FIR lamp therapy was effective for enhancing recovery from a soccer match.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

Radiomic Application for Head and Neck Squamocellular Tumor: Systematic Review.

Abstract: Radiomics represents the convergence of artificial intelligence and radiological data analysis, primarily applied in the diagnosis and treatment of cancer. In the head and neck region, squamous cell carcinoma is the most prevalent type of tumor. Recent radiomics research has revealed that specific bio-imaging characteristics correlate with various molecular features of Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Human Papillomavirus (HPV). These tumors typically present a unique phenotype, often affecting younger patients, and show a favorable response to radiation therapy. This study provides a systematic review of the literature, summarizing the application of radiomics in the head and neck region. It offers a comprehensive analysis of radiomics-based studies on HNSCC, evaluating its potential for tumor evaluation, risk stratification, and outcome prediction in head and neck cancer treatment.

Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

A comparative study in left-sided breast cancer treated with moderate deep inspiratory breath hold versus free breathing.

BACKGROUND: The moderate deep inspiratory breath hold (mDIBH) is a modality famed for cardiac sparing. Prospective studies based on this are few from the eastern part of the world and India. We intend to compare the dosimetry between mDIBH and free-breathing (FB) plans. METHODS: Thirty-two locally advanced left breast cancer patients were taken up for the study. All patients received a dose of 50 Gy in 25 fractions to the chest wall/intact breast, followed by a 10-Gy boost to the lumpectomy cavity in the case of breast conservation surgery. All the patients were treated in mDIBH using active breath coordinator (ABC). The data from the two dose volume histograms were compared regarding plan quality and the doses received by the organs at risk. Paired t-test was used for data analysis. RESULTS: The dose received by the heart in terms of V5, V10, and V30 (4.55% vs 8.39%) and mean dose (4.73 Gy vs 6.74 Gy) were statistically significant in the ABC group than that in the FB group (all p-values < 0.001). Also, the dose received by the LADA in terms of V30 (19.32% vs 24.87%) and mean dose (32.99 Gy vs 46.65 Gy) were significantly less in the ABC group. The mean treatment time for the ABC group was 20 min, while that for the free-breathing group was 10 min. CONCLUSIONS: Incorporating ABC-mDIBH for left-sided breast cancer radiotherapy significantly reduces the doses received by the heart, LADA, and left and right lung, with no compromise in plan quality but with an increase in treatment time.

Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

Comparison of High-intensity Laser Therapy with Extracorporeal Shock Wave Therapy in the Treatment of Patients with Plantar Fasciitis: A Double-blind Randomized Clinical Trial.

Background: The most common cause of heel pain is plantar fasciitis (PF). Although conservative treatments relieve pain in more than 90% of patients, it may remain painful in some cases. This study aimed to compare High-intensity Laser Therapy (HILT) with Extracorporeal Shock Wave Therapy (ESWT) in patients with PF. Methods: In this double-blinded randomized clinical trial (conducted in Yazd, Iran, from May 2020 to March 2021), patients were classified into two groups, including the ESWT and HILT, using online randomization. Nine sessions, three times a week for 3 weeks, were the treatment period in both groups. Visual Analogue Score (VAS), Heel Tenderness Index (HTI), and the SF36 questionnaire were compared and analyzed statistically at the beginning and 9 months after treatment. Results: 38 patients (19 in each group) completed the study. Results showed that pain and patient satisfaction improved significantly 3 months after treatment. The VAS and HTI decreased 3 months after treatment in both groups, which was statistically significant (P<0.001). The SF36 score in both groups increased 3 months after treatment, and this increase was statistically significant (P<0.001). Although the two modalities were effective based on VAS, HTI, and SF36, a significant statistical difference was observed between them (P=0.03, P=0.006, P=0.002, respectively), and the HILT was more effective. Conclusion: ESWT and HILT decrease pain and increase patient satisfaction in PF. Besides, both methods are non-invasive and safe. However, there is a significant difference between them, and HILT is more effective. Trial registration number: IRCT20210913052465N1.

The effect of physical exercise during radiotherapy on physical performance in patients with head and neck cancer: a trial within cohorts study protocol, the vital study.

BACKGROUND: During the last decade, twelve studies have been published investigating physical exercise interventions (PEIs) in patients with head and neck cancer (HNC) during radiotherapy (RT), chemoradiation (CRT) or bioradiation (BRT). These studies showed that these PEIs are safe and feasible. However, only two of these studies were randomised clinical trials (RCTs) with a satisfying sample size. Thereby, there is no cost-effectiveness study related to a PEI during RT, CRT or BRT ((C/B)RT) for patients with HNC. Therefore, the aim of this study is to investigate and compare physical performance, muscle strength, fatigue, quality of life (QoL), body mass index (BMI), nutritional status, physical activity, treatment tolerability, and health care related costs in patients with HNC with and without a 10 week PEI during (C/B)RT. METHODS: This study, based on a trial within cohorts (TwiCs) design, will contain a prospective cohort of at least 112 patients. Fifty-six patients will randomly be invited for an experimental 10 week PEI. This PEI consists of both resistance and endurance exercises to optimize physical performance, muscle strength, fatigue, QoL, BMI, nutritional status, physical activity, and treatment tolerability of (C/B)RT. Measurements are at baseline, after 12 weeks, 6 months, and at 12 months. Statistical analyses will be performed for intention-to-treat and instrumental variable analysis. DISCUSSION: This study seeks to investigate physical, QoL, and economic implications of a PEI. With a substantial sample size, this study attempts to strengthen and expand knowledge in HNC care upon PEI during (C/B)RT. In conclusion, this study is dedicated to provide additional evidence for PEI in patients with HNC during (C/B)RT. TRIAL REGISTRATION: protocol was registered at clinicaltrials.gov with number NCT05988060 on 3 August 2023.

Androgen deprivation alone versus combined with pelvic radiation for adverse events and quality of life in clinically node-positive prostate cancer.

The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Induction of therapeutic immunity and cancer eradication through biofunctionalized liposome-like nanovesicles derived from irradiated-cancer cells.

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Multi-institutional evaluation of a Pareto navigation guided automated radiotherapy planning solution for prostate cancer.

BACKGROUND: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. METHODS: The implemented 'Pareto Guided Automated Planning' (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a 'Protocol Based Automatic Iterative Optimisation' planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions' clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. RESULTS: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. CONCLUSIONS: PGAP enabled intuitive adaptation of automated protocols to an institution's planning aims and yielded plans more congruent with the institution's clinical preference than the locally produced manual clinical plans.

Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer: A Meta-Analysis.

The role of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) has been questioned in the era of magnetic resonance imaging (MRI). The purpose of this study was to re-evaluate the efficacy of PCI in patients with LS-SCLC. Three electronic databases were searched, including PubMed, Embase, and the Cochrane Library from January 2012 to April 2022. All relevant publications were included based on the inclusion criteria, and survival data and brain metastasis (BM) rates were extracted and pooled. Ten studies were selected which involved 532 patients who received PCI and 613 patients who did not receive PCI. In pooled estimates, PCI significantly improved overall survival (OS) and progression-free survival (PFS) [hazard ratio (HR) = 0.71, 95% confidence interval (CI): 0.61-0.82, p <0.001; HR = 0.68, 95% CI: 0.48-0.97, p = 0.03, respectively]. Additionally, the use of PCI was associated with a significant reduction in the risk of brain metastasis (BM, risk ratio = 0.64, 95% CI: 0.46-0.90, p = 0.009). In subgroup analyses. The authors found that the PCI effects on OS were independent of region and the use of brain imaging after initial treatment. These findings demonstrate that PCI improves OS and PFS while decreasing the risk of BM in patients with LS-SCLC, implying that PCI remains necessary even in the MRI era. Key Words: Prophylactic cranial irradiation, Small cell lung cancer, Magnetic resonance imaging, Brain metastasis.

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.