Technological Advances In Radiotherapy Research Articles

Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Long-term disease-free survival following comprehensive involved site radiotherapy for oligometastases.

Despite recent advances in drug development, durable complete remissions with systemic therapy alone for metastatic cancers remain infrequent. With the development of advanced radiation technologies capable of selectively sparing normal tissues, patients with oligometastases are often amenable to comprehensive involved site radiotherapy with curative intent. This study reports the long-term outcomes and patterns of failure for patients treated with total metastatic ablation often in combination with systemic therapy. Consecutive adult patients with oligometastases from solid tumor malignancy treated by a single high volume radiation oncologist between 2014 and 2021 were retrospectively analyzed. Oligometastases were defined as 5 or fewer metastatic lesions where all sites of active disease are amenable to local treatment. Comprehensive involved site radiotherapy consisted of stereotactic radiotherapy to a median dose of 27 Gy in 3 fractions and intensity modulated radiation therapy to a median dose of 50 Gy in 15 fractions. This study analyzed overall survival, progression-free survival, patterns of failure and toxicity. A total of 130 patients with 209 treated distant metastases were treated with a median follow-up of 36 months. The 4-year overall survival, progression-free survival, local control and distant control was 41%, 23%, 86% and 29%. Patterns of failure include 23% alive and free of disease (NED), 52% distant failure only, 9% NED but death from comorbid illness, 7% both local and distant failure, 4% NED but lost to follow-up, 4% referred to hospice before restaging, 1% local only failure, 1% alive with second primary cancer. Late grade 3+ toxicities occurred in 4% of patients, most commonly radionecrosis. Involved site radiotherapy to all areas of known disease can safely achieve durable complete remissions in patients with oligometastases treated in the real world setting. Distant failures account for the majority of treatment failures and isolated local failures are exceedingly uncommon. Oligometastases represents a promising setting to investigate novel therapeutics targeting minimal residual disease.

Ethics-Guided Radiation Therapy (EGRT): A necessity in radiation oncology practice

Medical ethics principles have been the basis of medical practice since early human civilization. The well-accepted principles are autonomy, beneficence, non-maleficence, and justice. With the advancement of academia, industry, medicine, and technology, there is a need to empower ethics-guided radiation therapy (EGRT). A PubMed search was done on Oct. 22, 2023, using the words: (“Radiotherapy”[Mesh]) AND “Ethics, Clinical”[Mesh]) and the results were a total of 58. Among these, 17 titles seem to be in relation, but only a handful were of intimate relation to ethics and radiotherapy. An additional handful of non-PubMed references were found. EGRT, in my opinion, is a new acronym for an old concept that needs further elaboration and experts’ consensus in the modern radiation oncology literature. In parallel with the technological advances in radiotherapy, like intensity-modulated radiation therapy “IMRT” and image-guided radiation therapy “IGRT,” we are aiming to create an initiative to establish EGRT to be like a model that every radiation oncologist can follow in the daily radiotherapy practice. The coming work will be composed of an extensive literature review, international survey, and expert consensus, and it is intended to be a base for further efforts in this aspect.

Role of Radiotherapy in Metastatic Renal Cell Carcinomas: An Evolutionary Journey in a Misunderstood Histological Type

Renal cell carcinoma (RCC) has traditionally been considered one of the most radioresistant tumors based on in vitro and clinical studies that utilized a low biologically effective dose. However, recent studies have suggested that administering a higher radiation dose to RCC can lead to satisfactory local control and potentially long-lasting disease control. Thanks to significant advances in radiotherapy technology, it is now feasible to deliver higher radiation doses to tumors while preserving the organs at risk. Furthermore, over the past decade, a crucial role of radiotherapy has emerged in metastatic cancers, both for symptom palliation and for the elimination of tumor niches. This review discusses the current evidence and future perspectives concerning the role of radiotherapy in metastatic RCC.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity

PurposeDespite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation. In this study, we assessed the efficacy of atorvastatin in protecting against the late effects of radiation exposure on systolic function, cardiac conduction, and atrial natriuretic peptide (ANP) following a clinically relevant partial-heart radiation exposure. Materials and MethodsFemale, 12-week old, C57BL/6j mice received an image-guided 16 Gy X-ray field to the base of the heart using a small animal radiotherapy research platform (SARRP), with or without atorvastatin from 1 week prior to irradiation until the end of the experiment. The animals were followed for 50 weeks with longitudinal transthoracic echocardiography (TTE) and electrocardiography (ECG) every 10 weeks, and plasma ANP every 20 weeks. ResultsAt 30–50 weeks, mild left ventricular systolic function impairment observed in the RT control group was less apparent in animals receiving atorvastatin. ECG analysis demonstrated prolongation of components of cardiac conduction related to the heart base at 10 and 30 weeks in the RT control group but not in animals treated with atorvastatin. In contrast to systolic function, conduction disturbances resolved at later time-points with radiation alone. ANP reductions were lower in irradiated animals receiving atorvastatin at 30 and 50 weeks. ConclusionsAtorvastatin prevents left ventricular systolic dysfunction, and the perturbation of cardiac conduction following partial heart irradiation. If confirmed in clinical studies, these data would support the use of statin therapy for cardioprotection during thoracic radiotherapy.

Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): A Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Low or Intermediate Risk Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer diagnosed among men in the United States, and the majority of patients are diagnosed with localized disease. Men with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages and the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but current PBT is significantly more costly than intensity-modulated radiotherapy (IMRT). The PARTIQoL trial (NCT01617161) is the first multicenter phase 3 randomized trial comparing protons to photons in the treatment of localized prostate cancer. Patients with low or intermediate risk prostate cancer (Stage T1c-T2c, PSA < 20, Gleason score ≤ 7) are randomized to receive either PBT or IMRT, with targeted recruitment efforts for minority populations. A companion registry study has concurrently enrolled patients who declined randomization or whose insurance denied coverage for PBT. Patients are stratified by clinical site, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). Participants are followed longitudinally to assess patient-reported outcomes (PROs) of bowel, urinary, and erectile function for 60 months after completion of radiotherapy (with an option for additional follow up through 10 years). Participants may also participate in correlative studies, including serial CT imaging during treatment and analyses of biopsy tissue, blood and urine specimens. The primary objective is to compare PROs of bowel function using the EPIC score at 24 months following completion of radiation. Secondary objectives are to assess treatment-related differences in urinary and erectile functions, adverse events, efficacy endpoints (biochemical control, metastasis-free survival, disease-specific survival, and overall survival), health state utilities, perceptions of care, late effects, cost-effectiveness, association between radiotherapy dose distribution and PROs, and to identify biomarkers of radiation response and toxicity. The randomized trial has completed accrual, with 450 patients enrolled at 27 sites between June 2012 and November 2021. 20.3% of patients enrolled are non-white. Accrual on the companion registry is active, with 354 patients enrolled as of February 2023. Follow-up for the primary endpoint on the randomized trial will be reached in 2024. The PARTIQoL randomized clinical trial will rigorously assess the clinical benefits of PBT relative to IMRT and results will inform decision making by patients, providers, policymakers, and payers.

Efficacy and Safety of Multifraction Stereotactic Radiation Therapy with Volumetric Modulated Arc Therapy Technique for Multiple Brain Metastases

Multifraction stereotactic radiotherapy (MF-SRT) with volumetric modulated arc therapy (VMAT) is the standard treatment option for patients with multiple brain metastases. VMAT has superior physical accessibility and economic accessibility compared with advanced radiotherapy technologies such as Tomo or Proton radiotherapy. However, existing studies has mainly focused on comparing the dosimetric parameters between distinct radiotherapy techniques. Moreover, single fraction stereotactic radiosurgery is preferentially recommended for treatment of brain metastases with maximum diameter <2cm compared with MF-SRT. There is a lack of clinical results of its efficacy and subgroup analyses according to diameter. Thus, we first report the detailed analysis of clinical results of SRT using VMAT for brain metastases. This study is a retrospective analysis of SRT for multiple brain metastasis using VMAT. The clinical efficacy of VMAT was evaluated by local control (LC) in 6-months, 1-year, and 2-year. A total of 63 patients with 214 brain metastases were enrolled. The most common fractionation schemes were 40 Gy/8F and 48 Gy/12F. In all, LC rates at 6-month, 1-year, and 2-year were 95.5%, 90.6%, and 76.8%, respectively. Using univariate and multivariate analyses according to stratification factors including maximum diameter, GTV volume, dose per fraction, fractions, inner structure, and BED (α/β = 10), we found that no factors were associated with 6-month LC, 1-year LC, and 2-year LC. 1-year LC rates for maximum diameter ≥1 and <2, ≥2 and <3, and ≥3 cm were 89.2%, 90.7%, and 95.7%, respectively. The 1-year LC rates for tumors with GTV <3, ≥3 and <5, ≥5 and <10, and ≥10 cc were 87.0%, 91.7%, 94.7%, and 96.6%, respectively. Interestingly, 1year-LC in GTV ≥3 cc tends to higher than those in GTV <3 cc, but there was no significant difference (94.4% vs 87%, P = 0.162). Brain radionecrosis (RN) was the most significant toxicity occurring in 10 (4.7%) out of the 214 treated brain metastases. Among 6 patients with RN, 4 (66.7%) had been treated with tyrosine kinase inhibitors. The use of MF-SRT with VMAT for multiple brain metastases showed a comparable clinical efficacy to other techniques described in the literature. And the LC rate for maximum diameter <2cm treated with MF-SRT VMAT was comparable to single fraction stereotactic radiosurgery as previously reported. The treatment-related toxicity was acceptable.

SAPERO: a new tool for safety analyses in advanced radiotherapy

Improving safety standards in advanced radiotherapy technologies, where historical experience is not sufficient due to innovation aspects, raises the need to perform studies using new tools that follow a holistic view of the process chain. Such studies are useful to identify additional critical elements compared to safety analyses carried out by classic tools. In this field, SAPERO (La SicurezzA del PazientE: tecniche avanzate ed innovative per la valutazione del rischio di eventi indesiderati all'interno del percorso assistenziale nel settore RadioterapicO) is a new assessment tool that allows to use integrated of Hierarchical Task Analysis (HTA); Failure Mode Effects and Criticality Analysis (FMECA); Cognitive Task Analysis (CTA); Human Error Assessment Reduction Technique (HEART). The methodological approaches have been suitably modified to address their operating in the medical sector under study. Some improvements have concerned the application of the fuzzy theory in FMECA and the use of a linguistic approach in HEART. In this paper, SAPERO application on a case study related to treatment procedures in helical tomotherapy performed at the radiotherapy department of ARNAS Civico hospital, Italy, is described. The results have allowed to provide suggestions aimed to improve the examined process.

Progress in Development of Dose Verification System Software KylinRay-Dose4D

Advanced radiotherapy technology enables the dose to more accurately conform to the tumor target area of the patient, providing accurate treatment for the patient, but the gradient of the patient's radiation dose at the tumor edge is getting larger, which putting forward higher requirements for radiotherapy dose verification. The dose verification system software KylinRay-Dose4D can verify the patient's pre-treatment plan and the in vivo/on-line dose during the patient's treatment, providing important reference for the physicist to modify the radiotherapy plan and ensuring that the patient receives accurate treatment. This study introduces the overall design and key technologies of KylinRay-Dose4D, and tests the pre-treatment plan dose checking calculation and 2D/3D dose verification through clinical cases. The test results showed that the 2D/3D gamma pass rate (3 mm/3%) of KylinRay-Dose4D reconstructed dose compared with TPS plan dose and measured dose is larger than 95%, which indicating that the reconstructed dose of KylinRay-Dose4D meets the requirement of clinical application.

Children's Oncology Group's 2023 blueprint for research: Radiation oncology.

Radiation oncology is an integral part of the multidisciplinary team caring for children with cancer. The primary goal of our committee is to enable the delivery of the safest dose of radiation therapy (RT) with the maximal potential for cure, and to minimize toxicity in children by delivering lower doses to normal tissues using advanced technologies like intensity-modulated RT (IMRT) and proton therapy. We provide mentorship for y ators and are actively involved in educating the global radiation oncology community. We are leaders in the effort to discover novel radiosensitizers, radioprotectors, and advanced RT technologies that could help improve outcomes of children with cancer.

Assessing Equity of Access to Proton Beam Therapy: A Literature Review

Proton beam therapy (PBT) is one of the most advanced radiotherapy technologies, with growing evidence to support its use in specific clinical scenarios and exponential growth of demand and capacity worldwide over the past few decades. However, geographical inequalities persist in the distribution of PBT centres, which translate into variations in access and use of this technology. The aim of this work was to look at the factors that contribute to these inequalities, to help raise awareness among stakeholders, governments and policy makers. A literature search was conducted using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The same search strategy was run in Embase and Medline and identified 242 records, which were screened for manual review. Of these, 24 were deemed relevant and were included in this analysis. Most of the 24 publications included in this review originated from the USA (22/24) and involved paediatric patients, teenagers and young adults (61% for children and/or teenagers and young adults versus 39% for adults). The most reported indicator of disparity was socioeconomic status (16/24), followed by geographical location (13/24). All the studies evaluated in this review showed disparities in the access to PBT. As paediatric patients make up a significant proportion of the PBT-eligible patients, equity of access to PBT also raises ethical considerations. Therefore, further research is needed into the equity of access to PBT to reduce the care gap.

Quality of life and survival outcomes of patients with inoperable esophageal squamous cell carcinoma after definitive radiation therapy: A multicenter retrospective observational study in China from 2015 to 2016

ObjectivesTo investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. MethodsIn this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon–Mann–Whitney test. Overall survival (OS) was estimated using the Kaplan–Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. ResultsThe data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70–3.47]; P < 0.001) or three-dimensional radiotherapy (3DRT; HR, 1.45 [95% CI, 1.14–1.84]; P = 0.003) had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO. Of the 716 (23.4%) long-term survivors who completed the HRQL questionnaire, nearly 70% patients were still able to swallow normally or almost normally, and >80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. ConclusionsThis large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Can nocturnal sleep after radiation therapy enhance treatment efficiency?

The new technological advances in radiation therapy (e.g., proton therapy and FLASH radiotherapy) have indicated high therapeutic effects in all cancer types. Recently, several scientific projects have been conducted for factors that can influence treatment responses in radiation oncology. Nocturnal sleep has effective healing properties, which are involved in the regulation of physical and biochemical factors. It could significantly increase the level of hormones, radical scavengers, and cytokines such as glutathione, melatonin, and interleukin-12. Many papers have been published about the role of sleep deprivation in diseases, but there is no scientific publication regarding the link between nocturnal sleep and radiation therapy. In the current paper, the links between nocturnal sleep, the immune system, and radiation therapy were evaluated to provide clear and understandable explanations for the hypothesis that nocturnal sleep after radiation therapy could improve treatment efficiency.

Review of the Pathogenesis, Diagnosis, and Management of Osteoradionecrosis of the Femoral Head.

Osteoradionecrosis (ORN) of the femoral head is an important issue for orthopedists and radiologists in clinical practice. With the rapid development of technological advances in radiation therapy and the improvement in cancer survival rates, the incidence of ORN is rising, and there is an unmet need for basic and clinical research. The pathogenesis of ORN is complex, and includes vascular injury, mesenchymal stem cell injury, bone loss, reactive oxygen species, radiation-induced fibrosis, and cell senescence. The diagnosis of ORN is challenging and requires multiple considerations, including exposure to ionizing radiation, clinical manifestations, and findings on physical examination and imaging. Differential diagnosis is essential, as clinical symptoms of ORN of the femoral head can resemble many other hip conditions. Hyperbaric oxygen therapy, total hip arthroplasty, and Girdlestone resection arthroplasty are effective treatments, each with their own advantages and disadvantages. The literature on ORN of the femoral head is incomplete and there is no criterion standard or clear consensus on management. Clinicians should gain a better and more comprehensive understanding on this disease to facilitate its early and better prevention, diagnosis, and treatment. This article aims to review the pathogenesis, diagnosis, and management of osteoradionecrosis of the femoral head.

Abstract ED8-2: The role of advanced radiation technology in reducing toxicity

Abstract Over the past decade, breast cancer radiotherapy has increasingly focused on techniques to improve treatment precision and limit toxicity. Surface guided radiotherapy and respiratory gating has allowed for improved cardiac sparing and the elimination of permanent skin tattoos in women receiving breast radiation, while rapid developments in the technological delivery of radiation via both volumetric arc therapy and proton beam radiation have shown promise in further improving target coverage and normal tissue sparing for breast cancer patients. Cutting edge innovations, including MR-guided radiotherapy and FLASH technology are now being explored as means to further improve treatment precision and decrease toxicity. The purpose of this talk is to highlight and discuss these advances in radiotherapy, review the existing evidence to support their use in the treatment of breast cancer, and detail specific patient populations that are most likely to benefit. Discussion will also focus on ongoing and future research aimed at improving our understanding and utilization of these novel advances in care. Citation Format: Melissa Mitchell. The role of advanced radiation technology in reducing toxicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED8-2.

Treatment of extranodal NK/T-cell lymphoma: From past to future.

Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.

Radiotherapy of early‐stage breast cancer

AbstractBreast cancer is the most prevalent disease for women. With advances in breast cancer screening, most breast cancers are now diagnosed in the early stages. With knowledge of different subtypes and their behavior, breast cancer treatment has become more individualized. Radiation therapy as one of the mainstays of breast cancer treatment has also been evolving. This review attempts to provide a summary of the most influential clinical studies that have driven the technological advances in radiation therapy for early‐stage breast cancer.

Phytoradiotherapy to enhance cancer treatment outcomes with cannabidiol, bitter melon juice, and plant hemoglobin.

Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, much of the world lacks access to expensive, modern treatment options. The need for innovative, cost-effective solutions that can improve patient treatment outcomes is essential. Phytomedicines have been shown to induce apoptotic tumor cell death, diminish tumor progression, reduce cancer incidence, alleviate harmful hypoxic conditions, and more. While an ample amount of research is available that characterizes many phytomedicines as having anti-cancer properties that increase tumor cell killing/control and mitigate the harmful side effects of radiation damage, little work has been done to investigate the synergistic effect of phytoradiotherapy: combining radiation treatment with phytomedicines. In this study, a protocol for testing the radiosensitizing effects of phytomedicines was validated and used to investigate the well-known plant based medicine cannabidiol (CBD) and the lesser-known medicinal fruit Bitter Melon. Additionally, based on its high concentration of plant hemoglobin which has been shown to abate hypoxia, the African-indigenous Justicia plant was tested in pancreatic adenocarcinoma mouse models. The studies reveal that these phytomedicines can effectively enhance tumor cell killing, minimize tumor growth, and prolong mice survival. There is certainly the need for additional research in this regard, however, phytoradiotherapy: the use of phytomedicines to enhance radiation therapy treatment outcomes, continues to show potential as a promising, innovative way to improve cancer care.

Radiotherapeutic Strategies to Overcome Resistance of Breast Cancer Brain Metastases by Considering Immunogenic Aspects of Cancer Stem Cells.

Breast cancer is the most diagnosed cancer in women, and symptomatic brain metastases (BCBMs) occur in 15-20% of metastatic breast cancer cases. Despite technological advances in radiation therapy (RT), the prognosis of patients is limited. This has been attributed to radioresistant breast cancer stem cells (BCSCs), among other factors. The aim of this review article is to summarize the evidence of cancer-stem-cell-mediated radioresistance in brain metastases of breast cancer from radiobiologic and radiation oncologic perspectives to allow for the better interpretability of preclinical and clinical evidence and to facilitate its translation into new therapeutic strategies. To this end, the etiology of brain metastasis in breast cancer, its radiotherapeutic treatment options, resistance mechanisms in BCSCs, and effects of molecularly targeted therapies in combination with radiotherapy involving immune checkpoint inhibitors are described and classified. This is considered in the context of the central nervous system (CNS) as a particular metastatic niche involving the blood-brain barrier and the CNS immune system. The compilation of this existing knowledge serves to identify possible synergistic effects between systemic molecularly targeted therapies and ionizing radiation (IR) by considering both BCSCs' relevant resistance mechanisms and effects on normal tissue of the CNS.