Radiotherapy Regimens Research Articles

Radiation-induced effects on TGF-β and PDGF receptor signaling in cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) consist of heterogeneous connective tissue cells and are often constituting the most abundant cell type in the tumor stroma. Radiation effects on tumor stromal components like CAFs in the context of radiation treatment is not well-described. This study explores potential changes induced by ionizing radiation (IR) on platelet-derived growth factor (PDGF)/PDGFRs and transforming growth factor-beta (TGF-β)/TGFβRs signaling systems in CAFs. Experiments were carried out by employing primary cultures of human CAFs isolated from freshly resected non-small cell lung carcinoma tumor tissues. CAF cultures from nine donors were treated with one high (1 × 18 Gy) or three fractionated (3 × 6 Gy) radiation doses. Alterations in expression levels of TGFβRII and PDGFRα/β induced by IR were analyzed by western blots and flow cytometry. In the presence or absence of cognate ligands, receptor activation was studied in nonirradiated and irradiated CAFs. Radiation exposure did not exert changes in expression of PDGF or TGF-β receptors in CAFs. Additionally, IR alone was unable to trigger activation of either receptor. The radiation regimens tested did not affect PDGFRβ signaling in the presence of PDGF-BB. In contrast, signaling via pSmad2/3 and pSmad1/5/8 appeared to be down-regulated in irradiated CAFs after stimulation with TGF-β, as compared with controls. Our data demonstrate that IR by itself is insufficient to induce measurable changes in PDGF or TGF-β receptor expression levels or to induce receptor activation in CAFs. However, in the presence of their respective ligands, exposure to radiation at certain doses appear to interfere with TGF-β receptor signaling.

Evaluation of Different Regimens of Palliative Radiation Therapy for Symptomatic Bone Metastases: An Audit From a Tertiary Care Hospital in Jharkhand, India.

Background This study aimed to assess the efficacy of different radiation therapy regimens in treating patients with symptomatic bone metastases. Methodology A retrospective study was conducted by assigning patients with symptomatic bone metastases from different primary cancers into three groups, namely, Arms A, B, and C. The radiation dose delivered in each arm was as follows: 8 Gray (Gy) in a single fraction for Arm A, 20 Gy in five fractions at the rate of 4 Gy per fraction for Arm B, and 30 Gy in 10 fractions at the rate of 3 Gy per fraction for Arm C. Each arm consisted of 15 patients. A comparison was conducted across all three arms to evaluate pain relief based on the Visual Analog Scale (VAS), performance score improvement based on the Eastern Cooperative Oncology Group (ECOG), and analgesic requirement based on the World Health Organization (WHO) step ladder at one week, one month, and three months. Results The pain relief was measured using the VAS in three different arms, i.e., Arm A, B, and C. After one week, the pain relief was 66.67%, 60%, and 60%, respectively. After one month, it was 73.33% in all three arms. At three months, it was 80%, 86.67%, and 86.67%, respectively. The study also measured the improvement in the ECOG performance score. The improvement in all three arms was 60% after one week and 66.67% in Arm A and 73.33% in Arms B and C after one month. After three months, the improvement was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. The decrease in analgesic usage was also measured in all three arms. After one week, it was 60% in all three arms. After one month, it was 66.67%, 73.33%, and 73.33% in Arms A, B, and C, respectively. At three months, it was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. No significant statistical difference was found between the three arms. Conclusions The efficacy of a single 8 Gy arm was almost equivalent to that of other arms of multifractionated regimens in terms of improvement in pain and performance score and decreased use of analgesics for a short duration of follow-up. For high-volume cancer centers and patients with economic constraints, a single-fraction regime provides effective palliation for painful bone metastases.

Pulmonary, Hepatic, and Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Telomere Biology Disorders.

This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients. TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.

The Impact of Extensive Surgical Resection of Butterfly Glioblastomas on Outcomes in the Presence of TERT Mutation and EGFR Amplification: A Retrospective Cohort Study.

This study aimed to assess if extensive surgical resection enhances outcomes in wild-type Isocitrate Dehydrogenase (IDH) butterfly glioblastoma (B-GBM) patients, despite the presence of Telomerase Reverse Transcriptase (TERT) mutation and Epidermal Growth Factor Receptor (EGFR) amplification. The study, retrospectively conducted from 2014 to 2022, involved 723 GBM patients, 41 of whom met the criteria for IDH wild-type B-GBM. Exclusion criteria comprised prior diagnoses or treatments for low-grade glial tumors. Surgeons, employing two approaches-partial and extensive surgery-categorized patients based on age, sex, tumor location, corpus callosum involvement, and genetic characteristics. The interval between initial surgery and tumor recurrence/tumor-free period (TR/TFP) and overall survival (OS) were recorded and compared between the partial and extensive resection groups, analyzing the impact of resection width on TR/TFP and OS. Preoperative assessments utilized thin-section cranial computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI). Intraoperatively, tumor excision was guided by sodium fluorescein, and margins were delineated via neuronavigation. Genetic alterations (TERT mutations and EGFR amplifications) were correlated with surgical type, TR/TFP, and OS. Karnofsky Performance Scale (KPS) evaluations were performed pre- and post-operatively and at key intervals, comparing outcomes between surgical groups. Standard radiotherapy and chemotherapy regimens were administered to all patients. Extensive resection yielded significantly longer TR/TFP compared to partial resection, despite TERT gene mutation and EGFR amplification being linked to shorter TR/TFP and OS. Its impact on OS, however, was not significant. KPS scores indicated a superior quality of life after extensive resection, with sustained improvement upon recurrence. Extensive resection of B-GBM, even in the presence of adverse genetic alterations, may prolong TR/TFP, offering patients a period of improved comfort with minimal distress.

Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study.

Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting. Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival. Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8). All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.

Hypofractionated radiotherapy for glioblastoma: A large institutional retrospective assessment of 2 approaches.

Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT). A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses. Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12). This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.

Hypofractionated Radiotherapy in Gynecologic Malignancies-A Peek into the Upcoming Evidence.

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide.

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Radiobiological evaluation of hypo-fractionated breast cancer radiotherapy regimens in comparison with conventional approaches

Abstract Purpose: This study compares tumor control probability (TCP) and normal tissue complication probability (NTCP) across different hypo-fractionated (HypoRT) and conventional breast radiotherapy regimens using radiobiological models. Materials and methods: Computed tomography data from 30 patients with left breast-conserving surgery were used to evaluate three HypoRT regimens (39 Gy and 41·6 Gy in 13 fractions, and 40 Gy in 15 fractions) and a conventional regimen (50 Gy in 25 fractions). Dose-volume histograms (DVHs) were extracted for radiobiological calculations using Equivalent Uniform Dose (EUD) and Poisson models for TCP, and EUD and LKB (Lyman-Kutcher-Burman) models for NTCP. Results: Conventional treatment achieved significantly higher TCP (95%) than all HypoRT regimens (p &lt; 0·001), with no significant differences between HypoRT regimens (p &gt; 0·05. The 39 Gy/13 fraction regimen showed the lowest lung NTCP (p &lt; 0·05). HypoRT regimens had significantly lower NTCP for the lungs and heart compared to the conventional regimen (p &lt; 0·01). TCP and NTCP values from Poisson and LKB models were higher than those from the EUD model (p &lt; 0·01). Conclusion: HypoRT regimens reduced NTCP, with the lowest values in the regime of 39 Gy/13 fractions regimen, though the conventional regimen had higher TCP.

Association of COX-inhibitors with cancer patients' survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis.

We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

Immunological signatures from irradiated cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) are abundant and influential elements of the tumor microenvironment (TME), giving support to tumor development in multiple ways. Among other mechanisms, CAFs are important regulators of immunological processes occurring in tumors. However, CAF-mediated tumor immunomodulation in the context of radiotherapy remains poorly understood. In this study, we explore effects of radiation on CAF-derived immunoregulatory signals to the TME. Primary CAF cultures were established from freshly collected human NSCLC lung tumors. CAFs were exposed to single-high or fractionated radiation regimens (1x18Gy or 3x6Gy), and the expression of different immunoregulatory cell-associated and secreted signaling molecules was analyzed 48h and 6 days after initiation of treatment. Analyses included quantitative measurements of released damage-associated molecular patterns (DAMPs), interferon (IFN) type I responses, expression of immune regulatory receptors, and secretion of soluble cytokines, chemokines, and growth factors. CAFs are able to survive ablative radiation regimens, however they enter into a stage of premature cell senescence. Our data show that CAFs avoid apoptosis and do not contribute by release of DAMPs or IFN-I secretion to radiation-mediated tumor immunoregulation. Furthermore, the secretion of relevant immunoregulatory cytokines and growth factors including TGF-β, IL-6, IL-10, TNFα, IL-1β, VEGF, CXCL12, and CXCL10 remain comparable between non-irradiated and radiation-induced senescent CAFs. Importantly, radiation exposure modifies the cell surface expression of some key immunoregulatory receptors, including upregulation of CD73 and CD276. Our data suggest that CAFs do not participate in the release of danger signals or IFN-I secretion following radiotherapy. The immune phenotype of CAFs and radiation-induced senescent CAFs is similar, however, the observed elevation of some cell surface immunological receptors on irradiated CAFs could contribute to the establishment of an enhanced immunosuppressive TME after radiotherapy.

Effect of exercise interventions on hospital length of stay and admissions during cancer treatment: a systematic review and meta-analysis

ObjectiveTo assess the effect of participating in an exercise intervention compared with no exercise during cancer treatment on the duration and frequency of hospital admissions.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE,...

Analysis of the impact of radiotherapy and surgical treatment regimens based on the SEER database on the survival outcomes of rectal cancer patients over 70 years.

This study evaluates the impact of different combinations of treatment regimens, such as additional radiation, chemotherapy, and surgical treatments, on the survival of elderly rectal cancer patients ≥ 70 years of age to support physicians' clinical decision-making. Data from a sample of elderly rectal cancer patients aged ≥ 70 years diagnosed from 2005-2015 from the US surveillance, epidemiology, and end results (SEER) database were retrospectively analyzed. The best cut-off point was selected using the x-tile software for the three continuity indices: age, tumor size, and number of regional lymph nodes. All patients were categorized into either the neoadjuvant radiotherapy and surgery group (R_S group), the surgical treatment group (S group), or the surgery and adjuvant radiotherapy group (S_R group). The propensity score allocation was used to match each included study subject in a 1:1 ratio, and the restricted mean survival time method (RMST) was used to predict the mean survival of rectal cancer patients within 5 and 10 years. The prognostic risk factors for rectal cancer patients were determined using univariate and multivariate Cox regression analyses, and nomograms were constructed. A subgroup stratification analysis of patients with different treatment combination regimens was performed using the Kaplan-Meier method, and log-rank tests were used for between-group comparisons. The model's predictive accuracy was assessed by receiver operating characteristic (ROC) curves, correction curves, and a clinical decision curve analysis (DCA). A total of 7556 cases of sample data from 2005 to 2015 were included, which were categorized into 6639 patients (87.86%) in the S group, 408 patients (5.4%) in the R_S group, and 509 patients (6.74%) in the S_R group, according to the relevant order of radiotherapy and surgery. After propensity score matching (PSM), the primary clinical characteristics of the groups were balanced and comparable. The difference in the mean survival time before and after PSM was not statistically significant in both R_S and S groups (P value > 0.05), and the difference in the mean survival time after PSM was statistically substantial in S_R and S groups (P value < 0.05). In the multifactorial Cox analysis, the M1 stage and Nodes ≥ 9 were independent risk factors. An age between 70-75 was an independent protective factor for patients with rectal cancer in the R_S and S groups. The Marital_status, T4 stage, N2 stage, M1 stage, and Nodes ≥ 9 were independent risk factors for patients with rectal cancer in the S_R and S groups, and an age between 70-81 was an independent protective factor. The ROC curve area, the model C index, and the survival calibration curve suggested good agreement between the actual and predicted values of the model. The DCA for 3-year, 5-year, and 10-year survival periods indicated that the model had some potential for application. The results of the study showed no significant difference in the overall survival (OS) between elderly patients who received neoadjuvant radiotherapy and surgery and those who received surgery alone; elderly patients who received surgery and adjuvant radiotherapy had some survival benefits compared with those who received surgery alone, though the benefit of adjuvant radiotherapy was not significant. Therefore, radiotherapy for rectal cancer patients older than 70 years old should be based on individual differences in condition, and a precise treatment plan should be developed.

Unlocking the Potential of Ultra-High Dose Fractionated Radiation for Effective Treatment of Glioblastoma in Mice.

Background: Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on tumor responses and brain injury in immunocompetent mice which can better mimic the tumor-host interactions observed in patients. We also evaluated the role of the hypoxia-inducible factor-1 alpha under radiation as potential target for combating radiation-induced brain injury. Methods: Naïve and Hif-1α+/- heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×105 human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. Bioluminescence imaging, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. Results: Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, Hif-1α+/- mice exhibited more severe vascular damage after fractionated radiation of 3×20 Gy. Conclusion: Ultra-high dose fractionated 3×20 Gy radiation has the potential to fully eradicate GBM cells at the cost of only mild brain injury. The Hif-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies.

Genetic profiling in radiotherapy: a comprehensive review.

This comprehensive review explores the pivotal role of radiotherapy in cancer treatment, emphasizing the diverse applications of genetic profiling. The review highlights genetic markers for predicting radiation toxicity, enabling personalized treatment planning. It delves into the impact of genetic profiling on radiotherapy strategies across various cancer types, discussing research findings related to treatment response, prognosis, and therapeutic resistance. The integration of genetic profiling is shown to transform cancer treatment paradigms, offering insights into personalized radiotherapy regimens and guiding decisions in cases where standard protocols may fall short. Ultimately, the review underscores the potential of genetic profiling to enhance patient outcomes and advance precision medicine in oncology.

Выбор режима фракционирования при глиомах 4 степени злокачественности в зависимости от возраста пациентов

The aim of the work is to study the effect of two dose fractionation regimens on subsequent survival in patients with grade 4 gliomas, depending on age. In 140 patients with morphologically confirmed grade 4 glioma, fractionation with the prescribed dose of 2 and 3 Gy was alternately used using a pairwise modeling strategy. Of these, 111 patients (79.3%) died, 99 (70.7%) from glioma progression. In the group &lt;50 years old, the median overall survival as of December 2023 was 31.11 months (95% Cl: 21.0-41.2), ≥50 years – 18.99 months (95% Cl: 16.0-21.0; p=0.014). In the group ≥50 years old with the fractionation mode of 3 Gy, the median overall survival was 21.32 months (n=47; 95% Cl: 12.1-30.6), with the mode of 2 Gy – 16.29 months (n=47; 95% Cl: 12.3-20.3; p=0.037). With glioblastoma, there are no statistical differences between the two irradiation programs – the medians are 20.0 and 16.4 months, respectively (p=0.118). In the group &lt;50 years old with the fractionation mode of 3 Gy, the median overall survival was 32.49 months (n=23; 95% Cl: 7.1-57.9), with the mode of 2 Gy – 29.11 months (n=23; 95% Cl: 17.6-40.6; p=0.717). With glioblastoma, there are no statistical differences between the two radiotherapy programs – the median is 18.3 and 23.7 months, respectively (p=0.710). The data obtained indicate the expediency of using hypofractive radiotherapy regimens for grade 4 gliomas in patients over 50 years of age, radiation therapy should be carried out with a sufficiently high dose level, including in patients over 70 years of age with good functional condition. In young patients, approaches with increasing single doses do not lead to improved results. The fractionation regimen with a dose of 2 Gy should be considered optimal for radiation therapy.

Radiotherapy in Extramammary Paget’s disease: It’s worth it? A Case Report and Literature Review

Extramammary Paget’s disease (EMPD) is a rare and heterogeneous clinical picture usually recorded on apocrine gland-bearing epidermis areas in extramammary sites, showing a potential invasive evolution and poor prognosis. At diagnosis, it could appear as a primary tumor with secondary co-exhisting visceral malignancies like in anus, male or female genital system, which should be assessed. This rare epidermal carcinoma generally occurs in individuals older than 60 years mainly in Caucasian female and Asian male ethnicity. Although the pathophisiology has been well established, its management is still controversial and requires a multidisciplinary team approach. There are several therapeutic strategies. Among them, radiotherapy is accounted as an effective option in primary or in adjuvant timing but up to now no definitive role has been assessed. Data by case series, case reports and retrospective analyses have provided results on the positive benefit of HDR brachytherapy or external beam radiotherapy (EBRT) mainly in very old patients not suitable for extended surgery, which remains the main treatment care. Long course radiotherapy is a big concern in elderly patients due to logistics and care assistance deficiencies, which makes their access difficult to the radiation centres. Thus, hypofractionated radiotherapy regimens could be a good compromise problem solving to provide excellent local control within a short treatment time. Herein, we present a case of EMPD occurring in a 80 years old woman with vulvo-perineal extension successfully treated with hypofractionated external beam radiotherapy as primary treatment using a schedule 300cGy/fr/51 Gy in 17 treatment days.

Sex Differences in Presentation, Treatment, and Survival in Patients Receiving Palliative (Chemo)Radiotherapy for Non-Small Cell Lung Cancer.

The aim of this study was to analyze sex differences in a real-world cohort of patients who received palliative thoracic radiotherapy or chemoradiotherapy for non-small cell lung cancer. Retrospectively, baseline, treatment, toxicity, and survival data from a single institution were analyzed. The study included 181 patients (82 females, 99 males). Despite borderline significant differences in disease presentation (T and N stage), final assignment to stage II, III or IV was similar. The same was true for target volume size. Neither radiotherapy parameters nor systemic treatment approaches were significantly different. Toxicity profiles and survival were similar too. Less than 1 out of 3 patients experienced high-grade toxicity, largely esophagitis. Median survival was 8.1 (males) versus 7.8 months (females) and the corresponding 2-year survival rates were 16 and 15%, respectively (p=0.78). Relevant sex differences were not observed in this study of common radiotherapy regimes such as 10 fractions of 3 Gy or 15 fractions of 2.8 Gy, the latter often combined with carboplatin/vinorelbine chemotherapy.

Factors affecting the survival of patients with glioblastoma treated with standard and hypofractionated radiation regimens

Background. Glioblastoma has the worst prognosis and is the most common primary tumor of the central nervous system (CNS) among adults. Since it is multimodal treatment that increases survival chances of patients with glioblastoma, the analysis of factors that affect survival is a necessary precondition for developing more effective therapeutic approaches for this cohort. Such analysis makes it possible to determine the subgroups of patients which demonstrate the biggest therapeutic benefit from certain types of multimodal treatment, thus leading to implementation of personalized neuro-oncological treatment. Purpose. To analyze factors affecting cancer-specific survival (CSS) of patients with glioblastoma in stratification of the cohort according to the regimen of adjuvant radiation therapy into groups of standard and hypofractionated treatment regimens. Materials and methods. The single-center non-randomized study is based on the analysis of the results of the cohort of 159 patients with primarily diagnosed glioblastoma that were treated over the period from 2014 to 2020 at the State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine». According to the regimen of radiation therapy, the patients of the cohort (n=159) were stratified into two groups: standard regimen group – 49 (30.8%) patients (30 fractions, total radiation dose of 60.0 Gy) and hypofractionated regimen group – 110 (69.2%) patients (15 fractions, total radiation dose of 52.5 Gy). The survival of the patients was analyzed by the Kaplan–Meier method. The log-rank test was used for comparing Kaplan–Meier survival curves for different studied groups. For the purpose of studying impact of independent variables on the survival, we used regression analysis according to semiparametric proportional hazards model. Hazard ratio was calculated with 95% confidence intervals (CI). Results and discussion. The median CSS in the total cohort was 16.6 (95% CI 14.1–17.8 months) months in median follow-up time of 23.8 (95% CI 21.9–27.3) months. In standard regimen group, the median CSS was 15.7 (95% CI 14.1–17.8) months in median follow-up time of 24.4 (95% CI 23.1–25.3) months. In hypofractionated regimen group, the median CSS was 17.5 (95% CI 14.6–19.7) months in median follow-up time of 22.3 (95% CI 21.3 – 27.2) months. According to the logrank test (taking into consideration cautions about its use), no statistically significant difference in CSS of patients of both groups was determined р=0.07&gt;0.05. For analysis of the impact of clinical factors (age, sex, radicality of the surgical treatment, chemotherapeutic treatment, functional status according to the Karnofsky scale) on the CSS of both groups, they were considered as the ones that may have different base hazard. Statistically significant impact of all studied covariates on the CSS was registered (p70 points, ceteris paribus. For male patients, the hazard of death is 1.7 times higher (р=0.016267; HR 1.7; 95% CI 1.1–2.5) than for female patients, ceteris paribus. Absence of chemotherapy in adjuvant treatment increases hazard of death by 2.37 times (HR 2.37; 95% CI 1.6–3.2), ceteris paribus. The hazard of death decreases, ceteris paribus, by 82% in chemotherapy with temozolomide and by 47% when the patient is younger than 60 years old (HR 0.53; 95% CI 0.4–0.8). Conclusions. This analysis is a stage of the study of differentiated treatment effect in groups of standard and hypofractionated regimens of radiation therapy in patients with glioblastoma. These data can be used for an in-depth subgroup analysis and serve as the basis for development of personalized approaches in treatment of neuro-oncological patients.

Radiotherapy and blockade of immune checkpoints in treatment of cancer patients

Background. Immunotherapy, which aims to use immune defense mechanisms to fight cancer, is a new area of anticancer treatment. A major breakthrough in tumor immunotherapy was the discovery of immune checkpoint proteins, which act as powerful suppressors of the immune system. Humanized monoclonal antibodies, which target these proteins, have proven to be clinically effective in patients with different types of cancer. However, the majority of patients do not respond to checkpoint inhibitor therapy, which necessitates the use of combination strategies to overcome resistance to immunotherapy. In recent years, the combination of radiotherapy and immune checkpoint inhibitors has attracted considerable attention and has been widely studied in preclinical and clinical trials. Much attention is given to the optimization of combined treatment regimens. However, the optimal radiation dose, fractionation scheme, radiation volumes, and radiation sequence in checkpoint inhibitor treatment still remain unclear. Purpose – to analyze and summarize data from preclinical and clinical trials aimed at solving problems related to the choice of optimal doses, fractionation, radiation volume, and sequencing of checkpoint inhibitor immunotherapy and radiotherapy. Materials and methods. For data search, we used Cochrane library and databases (Pubmed, Scopus, Google Scholar). The results of the studies published over the period from 2008 to 2023 were analyzed. Results and discussion. The evidence of the rationality of combining radiotherapy and checkpoint inhibitors in the treatment of cancer patients is shown. The data on the effects of radiation dose and fractionation on antitumor immune responses were analyzed. The results of works that deal with the search for the optimal sequence of radiotherapy and immune checkpoint inhibitors and the selection of the irradiation volume necessary for the generation of an effective systemic antitumor immune response are considered. Conclusions. Combined treatment with radiation therapy and immune checkpoint inhibitors is a promising strategy for patients with metastatic tumors. Preclinical and clinical data indicate that different radiation regimens can cause different effects on antitumor immunity. Further studies of doses and fractionation regimens of radiation therapy, irradiation volume, and the optimal time for each component of combination therapy are needed to determine the conditions for maximizing the immune response. The obtained results will help optimize the combination treatment regimens and wider implementation of such treatment in clinical practice.