Breakthrough of Hypoxia Limitation by Tumor-Targeting Photothermal Therapy-Enhanced Radiation Therapy.

Purpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.

Clinical application of a GPU-accelerated monte carlo dose verification for cyberknife M6 with Iris collimator.

PURPOSE: To apply an independent GPU-accelerated Monte Carlo (MC) dose verification for CyberKnife M6 with Iris collimator and evaluate the dose calculation accuracy of RayTracing (TPS-RT) algorithm and Monte Carlo (TPS-MC) algorithm in the Precision treatment planning system (TPS). METHODS: GPU-accelerated MC algorithm (ArcherQA-CK) was integrated into a commercial dose verification system, ArcherQA, to implement the patient-specific quality assurance in the CyberKnife M6 system. 30 clinical cases (10 cases in head, and 10 cases in chest, and 10 cases in abdomen) were collected in this study. For each case, three different dose calculation methods (TPS-MC, TPS-RT and ArcherQA-CK) were implemented based on the same treatment plan and compared with each other. For evaluation, the 3D global gamma analysis and dose parameters of the target volume and organs at risk (OARs) were analyzed comparatively. RESULTS: For gamma pass rates at the criterion of 2%/2 mm, the results were over 98.0% for TPS-MC vs.TPS-RT, TPS-MC vs. ArcherQA-CK and TPS-RT vs. ArcherQA-CK in head cases, 84.9% for TPS-MC vs.TPS-RT, 98.0% for TPS-MC vs. ArcherQA-CK and 83.3% for TPS-RT vs. ArcherQA-CK in chest cases, 98.2% for TPS-MC vs.TPS-RT, 99.4% for TPS-MC vs. ArcherQA-CK and 94.5% for TPS-RT vs. ArcherQA-CK in abdomen cases. For dose parameters of planning target volume (PTV) in chest cases, the deviations of TPS-RT vs. TPS-MC and ArcherQA-CK vs. TPS-MC had significant difference (P < 0.01), and the deviations of TPS-RT vs. TPS-MC and TPS-RT vs. ArcherQA-CK were similar (P > 0.05). ArcherQA-CK had less calculation time compared with TPS-MC (1.66 min vs. 65.11 min). CONCLUSIONS: Our proposed MC dose engine (ArcherQA-CK) has a high degree of consistency with the Precision TPS-MC algorithm, which can quickly identify the calculation errors of TPS-RT algorithm for some chest cases. ArcherQA-CK can provide accurate patient-specific quality assurance in clinical practice.

Peptide Conjugated Boron Neutron Capture Therapy for Enhanced Tumor Targeting.

A cutting-edge non-invasive cancer treatment method called boron neutron capture therapy (BNCT) allows for the removal of cancerous tumor cells with the least possible damage to healthy tissue. It involves the exposure of cancer cells with low-energy thermal neutrons, boron-10 (10B) cellular uptake causes cancer cell death by producing alpha particles and recoiling lithium-7 (7 Li) nuclei. Despite positive outcomes from clinical trials conducted all around the world, these substances have relatively limited tumor selectivity or low boron content per molecule. The development of new boron delivery agents with more selectivity and enhanced boron loading would advance this technique and promote its use in clinics as a primary cancer treatment. As peptide-binding cell surface receptors are typically overexpressed on cancer cells, they can be seen as interesting targets for targeted tumor therapy. The attachment of meta-carboranes to peptide conjugates that target tumor cells specifically by their overexpressed receptors may be a method to get around these problems. A state-of-the-art overview of current developments in the application of BNCT for cancer targeted therapy via peptide conjugation is the goal of this review.

Progression in low-intensity ultrasound-induced tumor radiosensitization.

BACKGROUND: Radiotherapy (RT) is a widely utilized tumor treatment approach, while a significant obstacle in this treatment modality is the radioresistance exhibited by tumor cells. To enhance the effectiveness of RT, scientists have explored radiosensitization approaches, including the use of radiosensitizers and physical stimuli. Nevertheless, several approaches have exhibited disappointing results including adverse effects and limited efficacy. A safer and more effective method of radiosensitization involves low-intensity ultrasound (LIUS), which selectively targets tumor tissue and enhances the efficacy of radiation therapy. METHODS: This review summarized the tumor radioresistance reasons and explored LIUS potential radiosensitization mechanisms. Moreover, it covered diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound-targeted intravascular microbubble destruction, ultrasound-mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presented the limitations and prospects of employing LIUS-RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications. RESULTS AND CONCLUSION: LIUS employs cost-effective equipment to foster tumor radiosensitization, curtail radiation exposure, and elevate the quality of life for patients. This efficacy is attributed to LIUS's ability to utilize thermal, cavitation, and mechanical effects to overcome tumor cell resistance to RT. Multiple experimental analyses have underscored the effectiveness of LIUS in inducing tumor radiosensitization using diverse strategies. While initial studies have shown promising results, conducting more comprehensive clinical trials is crucial to confirm its safety and effectiveness in real-world situations.

Gold nanoparticle-enhanced radiotherapy: Dependence of the macroscopic dose enhancement on the microscopic localization of the nanoparticles within the tumor vasculature.

In gold nanoparticle-enhanced radiotherapy, intravenously administered nanoparticles tend to accumulate in the tumor tissue by means of the so-called permeability and retention effect and upon irradiation with x-rays, the nanoparticles release a secondary electron field that increases the absorbed dose that would otherwise be obtained from the interaction of the x-rays with tissue alone. The concentration of the nanoparticles in the tumor, number of nanoparticles per unit of mass, which determines the total absorbed dose imparted, can be measured via magnetic resonance or computed tomography images, usually with a resolution of several millimeters. Using a tumor vasculature model with a resolution of 500 nm, we show that for a given concentration of nanoparticles, the dose enhancement that occurs upon irradiation with x-rays greatly depends on whether the nanoparticles are confined to the tumor vasculature or have already extravasated into the surrounding tumor tissue. We show that, compared to the reference irradiation with no nanoparticles present in the tumor model, irradiation with the nanoparticles confined to the tumor vasculature, either in the bloodstream or attached to the inner blood vessel walls, results in a two to three-fold increase in the absorbed dose to the whole tumor model, with respect to an irradiation when the nanoparticles have already extravasated into the tumor tissue. Therefore, it is not enough to measure the concentration of the nanoparticles in a tumor, but the location of the nanoparticles within each volume element of a tumor, be it inside the vasculature or the tumor tissue, needs to be determined as well if an accurate estimation of the resultant absorbed dose distribution, a key element in the success of a radiotherapy treatment, is to be made.

Biomarker-driven molecular imaging probes in radiotherapy.

Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

Experimental study on the safety of photobiologic regulation therapy in the treatment of some non-epidermal tumors.

This study investigates the impact of Photobiomodulation (PBM) at different wavelengths on non-superficial cancer cells. Utilizing three laser protocols (650 nm, 810 nm, and 915 nm), the research explores cytotoxic effects, ROS generation, and cell migration. Results reveal varied responses across cell lines, with 810 nm PBM inducing significant ROS levels and inhibiting PAN-1 cell migration. The study suggests potential therapeutic applications for PBM in non-superficial cancers, emphasizing the need for further exploration in clinical settings.

Prospective monitoring of patients undergoing radiotherapy during COVID-19.

OBJECTIVE: The objective of this study was to evaluate the quality of life of consecutive patients undergoing radiotherapy during the coronavirus disease 2019 pandemic at a private hospital in Southern Brazil from September 2020 to September 2021. METHODS: This study was approved by the Research Ethics Board under project number 112 on April 17, 2020, and it was a prospective descriptive cohort study conducted in a Brazilian radiotherapy department from September 2020 to September 2021. It involved the weekly administration of the European Organisation for Research and Treatment of Cancer Questionnaire Core 30 questionnaires via telephone to consecutively assess patients with pathology-proven cancer diagnoses. These questionnaires captured both demographic data and patients' concerns related to the pandemic, providing a comprehensive overview of their quality of life during radiotherapy treatment. RESULTS: In this study, 141 patients were analyzed, predominantly female (69.5%) with an average age of 61 years. Breast and prostate were the most treated sites, accounting for 51 and 19% of cases, respectively. The majority of treatments lasted between 3 and 5 weeks (73.77%). A small fraction (4.26%) tested positive for coronavirus disease 2019. The findings also highlighted a relatively high quality of life, with mean global scores of 77.95 and emotional functioning scores of 87.53, indicating maintained well-being during treatment. CONCLUSIONS: Oncological patients continuing radiotherapy at our center during the pandemic experienced a low coronavirus disease 2019 infection rate and maintained a high quality of life with minimal emotional distress throughout their treatment period.

Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.

Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.

Natural Guardians: Natural Compounds as Radioprotectors in Cancer Therapy.

Cancer remains a significant global health challenge, with millions of deaths attributed to it annually. Radiotherapy, a cornerstone in cancer treatment, aims to destroy cancer cells while minimizing harm to healthy tissues. However, the harmful effects of irradiation on normal cells present a formidable obstacle. To mitigate these effects, researchers have explored using radioprotectors and mitigators, including natural compounds derived from secondary plant metabolites. This review outlines the diverse classes of natural compounds, elucidating their roles as protectants of healthy cells. Furthermore, the review highlights the potential of these compounds as radioprotective agents capable of enhancing the body's resilience to radiation therapy. By integrating natural radioprotectors into cancer treatment regimens, clinicians may improve therapeutic outcomes while minimizing the adverse effects on healthy tissues. Ongoing research in this area holds promise for developing complementary strategies to optimize radiotherapy efficacy and enhance patient quality of life.

Systemic therapy and radiotherapy related complications and subsequent hospitalisation rates: a systematic review.

BACKGROUND: Hospitalisation  resulting from complications of systemic therapy and radiotherapy places a substantial burden on the patient, society, and healthcare system. To formulate preventive strategies and enhance patient care, it is crucial to understand the connection between complications and the need for subsequent hospitalisation. This review aimed to assess the existing literature on complications related to systemic and radiotherapy treatments for cancer, and their impact on hospitalisation rates. METHODS: Data was obtained via electronic searches of the PubMed, Scopus, Embase and Google Scholar online databases to select relevant peer-reviewed papers for studies published between January 1, 2000, and August 30, 2023. We searched for a combination of keywords in electronic databases and used a standard form to extract data from each article. The initial specific interest was to categorise the articles based on the aspects explored, especially complications due to systemic and radiotherapy and their impact on hospitalisation. The second interest was to examine the methodological quality of studies to accommodate the inherent heterogeneity. The study protocol was registered with PROSPERO (CRD42023462532). FINDINGS: Of 3289 potential articles 25 were selected for inclusion with ~ 34 million patients. Among the selected articles 21 were cohort studies, three were randomised control trials (RCTs) and one study was cross-sectional design. Out of the 25 studies, 6 studies reported ≥ 10 complications, while 7 studies reported complications ranging from 6 to 10. Three studies reported on a single complication, 5 studies reported at least two complications but fewer than six, and 3 studies reported higher numbers of complications (≥ 15) compared with other selected studies. Among the reported complications, neutropenia, cardiac complications, vomiting, fever, and kidney/renal injury were the top-most. The severity of post-therapy complications varied depending on the type of therapy. Studies indicated that patients treated with combination therapy had a higher number of post-therapy complications across the selected studies. Twenty studies (80%) reported the overall rate of hospitalisation among patients. Seven studies revealed a hospitalisation rate of over 50% among cancer patients who had at least one complication. Furthermore, two studies reported a high hospitalisation rate (> 90%) attributed to therapy-repeated complications. CONCLUSION: The burden of post-therapy complications is emerging across treatment modalities. Combination therapy is particularly associated with a higher number of post-therapy complications. Ongoing research and treatment strategies are imperative for mitigating the complications of cancer therapies and treatment procedures. Concurrently, healthcare reforms and enhancement are essential to address the elevated hospitalisation rates resulting from treatment-related complications in cancer patients.

Antibody targeting of anaerobic bacteria warms cold tumors and improves the abscopal effect of radiotherapy.

BACKGROUND: The combination of immune checkpoint inhibitors with radiotherapy can enhance the immunomodulation by RT and reduce the growth of distant unirradiated tumors (abscopal effect); however, the results are still not very satisfactory. Therefore, new treatment options are needed to enhance this effect. Our previous study showed that the combination of Bifidobacterium (Bi) and its specific monoclonal antibody (mAb) could target and alleviate hypoxia at the tumor site and act as a radiosensitizer. In this study, we explored the anti-tumor efficacy of quadruple therapy (Bi + mAb and RT + αPD-1). The current study also aimed to probe into the complex immune mechanisms underlying this phenomenon. METHODS: Constructed 4T1 breast and CT26 colon cancer tumor models. A comprehensive picture of the impact of constructed quadruple therapy was provided by tumor volume measurements, survival analysis, PET/CT imaging, immune cell infiltration analysis and cytokine expression levels. RESULTS: The abscopal effect was further amplified in the "cold" tumor model and prolonged survival in tumor-bearing mice. Bi can colonized in primary and secondary tumors and direct the mAb to reach the tumor site, activate complement, enhance the ADCC effect and initiate the innate immune response. Then combined with αPD-1 and radiotherapy to stimulate adaptive immune response and synergize with cytokines to expand the immune efficacy and generate effective anti-tumor immune response. CONCLUSIONS: Bi was used as an artificially implanted anaerobic target to cause a transient "infection" at the tumor, causing the tumor to become locally inflamed and "hot", and at the same time, mAb was used to target Bi to enhance the local immune effect of the tumor, and then combined with radiotherapy and αPD-1 to amplify the abscopal effect in multiple dimensions. Therefore, the present study provided a new idea for the multipotent immune-activating function of antibody-targeted anaerobic bacteria for the RT treatment of extensively metastasized cancer patients.

Literature review: potential non-thermal molecular effects of external radiofrequency electromagnetic fields on cancer.

INTRODUCTION: There is an ongoing scientific discussion, that anti-cancer effects induced by radiofrequency (RF)-hyperthermia might not be solely attributable to subsequent temperature elevations at the tumor site but also to non-temperature-induced effects. The exact molecular mechanisms behind said potential non-thermal RF effects remain largely elusive, however, limiting their therapeutical targetability. OBJECTIVE: Therefore, we aim to provide an overview of the current literature on potential non-temperature-induced molecular effects within cancer cells in response to RF-electromagnetic fields (RF-EMF). MATERIAL AND METHODS: This literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (PubMed) and Scopus (Elsevier) was conducted on March 23rd, 2024. Essential criteria herein included the continuous wave RF-EMF nature (3 kHz - 300 GHz) of the source, the securing of temperature-controlled circumstances within the trials, and the preclinical nature of the trials. RESULTS: Analysis of the data processed in this review suggests that RF-EMF radiation of various frequencies seems to be able to induce significant non-temperature-induced anti-cancer effects. These effects span from mitotic arrest and growth inhibition to cancer cell death in the form of autophagy and apoptosis and appear to be mostly exclusive to cancer cells. Several cellular mechanisms were identified through which RF-EMF radiation potentially imposes its anti-cancer effects. Among those, by reviewing the included publications, we identified RF-EMF-induced ion channel activation, altered gene expression, altered membrane potentials, membrane oscillations, and blebbing, as well as changes in cytoskeletal structure and cell morphology. CONCLUSION: The existent literature points toward a yet untapped therapeutic potential of RF-EMF treatment, which might aid in damaging cancer cells through bio-electrical and electro-mechanical molecular mechanisms while minimizing adverse effects on healthy tissue cells. Further research is imperative to definitively confirm non-thermal EMF effects as well as to determine optimal cancer-type-specific RF-EMF frequencies, field intensities, and exposure intervals.

Role of external radiation in benign tumors: A clinical outcome and safety audit of 7 years from a tertiary care center in India.

PURPOSE: Radiotherapy (RT) is a well-established modality for treating malignancies, but its role in treatment of benign lesions has not been well explored. Herein, we present a retrospective analysis of a 7-year data regarding the benefit and the safety profile of RT for treating benign tumors in our institute. MATERIALS AND METHODS: Data of 23 patients who received RT for benign tumors from January 2015 to April 2022 were retrieved, and a retrospective analysis was conducted. All the pertinent demographic data, treatment and follow-up data were retrieved. The most common presentations were nasopharyngeal angiofibroma, vertebral hemangioma, paraganglioma, and others. The most common sites of occurrence were head and neck (43%) and paravertebral region (22%). Volumetric modulated arc therapy was the most commonly employed RT technique (39%), followed by three-dimensional conformal RT (34%) and two-dimensional conventional radiotherapy (26%). The median RT dose delivered was 36 Gy (range: 20-54 Gy). RESULTS: The median follow-up duration was 53 months (range: 3-120 months). Nine (39%) patients had progressive disease with a median time to progression of 8 months (range: 1-30 months). The median disease-free survival (DFS) was 70 months, while the 1-, 3-, and 5-year DFS rates were 97%, 88%, and 62%, respectively. Four patients (17%) died, all due to disease progression. The 1-, 3-, and 5-year overall survival rates was 97%, 85%, and 50%, respectively. The rate of radiation-induced cancer (RIC) was 0% as none of the patients had developed RIC secondary to radiation. CONCLUSION: RT is a safe and an effective option to manage benign tumors either in an adjuvant setting or in inoperable patients requiring definitive treatment, as well as in a setting to alleviate symptoms, providing excellent survival benefits. However, further prospective studies with much higher sample size are required to establish the absolute benefit and to estimate the risk of RIC, which will further direct for a better utilization of RT in treating benign tumors.

A prospective study on the effect of tumor shrinkage on exit fluence gamma pass rate in high precision radiotherapy and influence of phantom setup error in patient-specific quality assurance.

PURPOSE: Objective parameters for decision on adaptive radiotherapy depend on patient, tumor and treatment related factors. Present study reports geometric uncertainties occurring during high precision radiotherapy, beam fluence analysis and serial exit dose measurement as a patient-specific tool for adaptive radiotherapy. MATERIALS AND METHODS: Serial exit dose fluence of 24 patients (at baseline and mid-treatment) undergoing IMRT/VMAT treatment were measured. Baseline and midtreatment exit dose evaluation was done using gafchromic films in predefined region of interest. Difference of volume of GTV at baseline (from simulation CT scan) and midtreatment CBCT scan was calculated (ΔGTV). RESULTS: Population based systematic errors (mm) were 4.15, 2.26, 0.88 and random errors (mm) were 2.56, 3.69, and 2.03 in mediolateral (ML), craniocaudal (CC) and anteroposterior (AP) directions respectively. Gamma pass rate reduced with incremental shift. For a 5 mm shift, maximum deviation was found in anteroposterior axis (22.16 ± 7.50) and lowest in mediolateral axis (12.85 ± 4.95). On serial measurement of exit dose fluence, tumor shrinkage significantly influenced gamma pass rate. The mean gamma pass rate was significantly different between groups with 50% shrinkage of tumor volume (86.36 vs 96.24, P = 0.008, on multivariate analysis P = 0.026). CONCLUSION: Rapid fall of gamma pass rate was observed for set up error of ≥3 mm. Serial measurement of exit dose fluence by radiochromic film is a feasible method of exit dose comparison in IMRT/VMAT, where EPID dosimetry is not available with linear accelerator configuration. Our study suggests that there is a significant difference between gamma pass rates of baseline and mid treatment exit dose fluence with greater than 50% tumor shrinkage.

Theranostic digital twins: Concept, framework and roadmap towards personalized radiopharmaceutical therapies.

Radiopharmaceutical therapy (RPT) is a rapidly developing field of nuclear medicine, with several RPTs already well established in the treatment of several different types of cancers. However, the current approaches to RPTs often follow a somewhat inflexible "one size fits all" paradigm, where patients are administered the same amount of radioactivity per cycle regardless of their individual characteristics and features. This approach fails to consider inter-patient variations in radiopharmacokinetics, radiation biology, and immunological factors, which can significantly impact treatment outcomes. To address this limitation, we propose the development of theranostic digital twins (TDTs) to personalize RPTs based on actual patient data. Our proposed roadmap outlines the steps needed to create and refine TDTs that can optimize radiation dose to tumors while minimizing toxicity to organs at risk. The TDT models incorporate physiologically-based radiopharmacokinetic (PBRPK) models, which are additionally linked to a radiobiological optimizer and an immunological modulator, taking into account factors that influence RPT response. By using TDT models, we envisage the ability to perform virtual clinical trials, selecting therapies towards improved treatment outcomes while minimizing risks associated with secondary effects. This framework could empower practitioners to ultimately develop tailored RPT solutions for subgroups and individual patients, thus improving the precision, accuracy, and efficacy of treatments while minimizing risks to patients. By incorporating TDT models into RPTs, we can pave the way for a new era of precision medicine in cancer treatment.

Bystander Effects in Spatially Fractionated Radiation Therapy: From Molecule To Organism To Clinical Implications.

The standard of care for radiation therapy is numerous, low-dose fractions that are distributed homogeneously throughout the tumor. An alternative strategy under scrutiny is to apply spatially fractionated radiotherapy (high and low doses throughout the tumor) in one or several fractions, either alone or followed by conventional radiation fractionation . Spatial fractionation allows for significant sparing of normal tissue, and the regions of tumor or normal tissue that received sublethal doses can give rise to beneficial bystander effects in both cases. Bystander effects are broadly defined as biological responses that are significantly greater than would be anticipated based on the radiation dose received. Typically these effects are initiated by diffusion of reactive oxygen species and secretion of various cytokines. As demonstrated in the literature, spatial fractionation related bystander effects can occur locally from cell to cell and in what are known as "cohort effects," which tend to take the form of restructuring of the vasculature, enhanced immune infiltration, and development of immunological memory. Other bystander effects can take place at distant sites in what are known as "abscopal effects." While these events are rare, they are mediated by the immune system and can result in the eradication of secondary and metastatic disease. Currently, due to the complexity and variability of these bystander effects, they are not thoroughly understood, but as knowledge improves they may present significant opportunities for improved clinical outcomes.

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

BACKGROUND: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. METHODS: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. RESULTS: The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). CONCLUSIONS: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Which Modality of SFRT Should be Considered First for Bulky Tumor Radiation Therapy, GRID or LATTICE?

Spatially fractionated radiation therapy (SFRT), also known as the GRID and LATTICE radiotherapy (GRT, LRT), the concept of treating tumors by delivering a spatially modulated dose with highly non-uniform dose distributions, is a treatment modality of growing interest in radiation oncology, physics, and radiation biology. Clinical experience in SFRT has suggested that GRID and LATTICE therapy can achieve a high response and low toxicity in the treatment of refractory and bulky tumors. Limited initially to GRID therapy using block collimators, advanced, and versatile multi-leaf collimators, volumetric modulated arc technologies and particle therapy have since increased the capabilities and individualization of SFRT and expanded the clinical investigation of SFRT to various dosing regimens, multiple malignancies, tumor types and sites. As a 3D modulation approach outgrown from traditional 2D GRID, LATTICE therapy aims to reconfigure the traditional SFRT as spatial modulation of the radiation is confined solely to the tumor volume. The distinctively different beam geometries used in LATTICE therapy have led to appreciable variations in dose-volume distributions, compared to GRID therapy. The clinical relevance of the variations in dose-volume distribution between LATTICE and traditional GRID therapies is a crucial factor in determining their adoption in clinical practice. In this Point-Counterpoint contribution, the authors debate the pros and cons of GRID and LATTICE therapy. Both modalities have been used in clinics and their applicability and optimal use have been discussed in this article.