BACKGROUND:The HIT network was established in 2000 to create a population-based structure aiming to improve survival rates and reduce late effects for children with central nervous system (CNS) tumors by conducting comprehensive clinical trials. METHODS:The HIT network currently consists of 10 coordinating trial centers mandated by the German Society for Pediatric Oncology and Hematology (GPOH) to conduct clinical trials and research projects, and to provide counseling to local centers for individual patients. The network is complemented by 11 reference centers (neuropathology, tumor biology, neuroradiology, pediatric neurosurgery, cerebrospinal fluid [CSF], assessments, radiotherapy, genetics), biostatistical support, and currently 72 local treatment sites. RESULTS:Numbers of children and adolescents with newly diagnosed CNS tumors registered to trials and registries increased from approximately 500 to more than 600 per year, corresponding to >95% of affected HIT-eligible children and adolescents in Germany. Clinical counseling and upfront reference assessments ensure homogeneous clinical standards and avoid inadequate treatment of individual patients. Since 2007, the established reference services have been partially re-funded by German health insurances. DISCUSSION:The HIT network provides a unique structure for population-based state-of-the-art diagnostic assessments, treatment recommendations and counseling. It increases the "a priori" accuracy of stratification parameters, and the timely inclusion into clinical trials and tumor-specific registries. Favorable outcomes are achieved within the trials and registry landscape, for example, through consistent reference assessments, reducing the gap to real world data. Resulting data facilitate representative, unbiased high-quality research projects across all CNS tumor entities. Interdisciplinary cooperation and competitive scientific output are enhanced.
BACKGROUND: Systematic assessment of patient-reported outcomes (PROs) is essential for identifying supportive care needs in oncology. In contrast to paper-based assessments, digital tools offer key advantages such as real-time data availability, improved data quality, and workflow integration. However, digitalization also entails conceptual and technical challenges, including integration into existing clinical systems, data privacy, IT-security, usability, and data quality. DIGITALIZATION CONCEPT: This short report outlines the development and implementation of a modular digitalization strategy for PRO assessment at the University Cancer Center Regensburg. Based on the ONCO-ROUTES screening tool, the digital concept integrates common standards and applies features such as skip logic, metadata tracking, and optional response settings to balance data quality with patient autonomy. PRO data are temporarily stored and retrieved automatically by the tumor documentation system at regular intervals. Patient representatives of the advisory board were involved in the conception from the initial development stages, including focus groups. Particular emphasis was placed on usability and the respective technical setup including necessary communication interfaces. PRO results can be directly integrated into oncological patient records and hospital databases in a structured format and considered in the context of treatment. CONCLUSION: The concept and technical solution proved feasible for clinical implementation, enabling structured, patient-centered PRO collection in routine oncology care. Its modular design allows for adaptation to other clinical settings and supports broader efforts to digitally integrate PROs into everyday clinical routine.
BACKGROUND AND OBJECTIVE:Multidisciplinary tumor boards (MTBs) are the gold standard for oncological treatment planning, but their implementation is resource intensive. Large language models (LLMs) such as ChatGPT-4 and Claude 3.5 Sonnet have emerged as scalable tools for clinical decision support. As their comparative performance in urological oncology remains largely untested in prospective trials, this study aimed to prospectively evaluate them against real MTBs. METHODS:In this prospective, multicenter, noninferiority study (DRKS00034797), we evaluated whether therapeutic recommendations by ChatGPT-4 and Claude 3.5 Sonnet were noninferior to those of MTBs across 110 representative case scenarios involving locally advanced or metastatic genitourinary cancer. Standardized prompts elicited recommendations from both LLMs, which were rated independently by two blinded uro-oncologists using the validated modified System Causability Scale (mSCS). The predefined noninferiority margin was 0.15 mSCS points. KEY FINDINGS AND LIMITATIONS:The mean mSCS score of the MTBs was 0.849 (standard deviation [SD] = 0.157), setting the noninferiority margin at 0.699. Claude 3.5 Sonnet scored 0.731 (SD = 0.178; 95% confidence interval [CI]: 0.697-0.765), narrowly missing noninferiority. ChatGPT-4 scored 0.660 (SD = 0.193; 95% CI: 0.623-0.696), clearly below the margin. A subgroup analysis revealed better LLM performance in locally advanced versus metastatic cases (p < 0.05). Limitations include the use of synthetic cases and inherent LLM output variability. CONCLUSIONS AND CLINICAL IMPLICATIONS:Neither LLM matched the MTB standards. These findings highlight the current limitations of public LLMs, or of their use in our study, in supporting complex oncological decisions. This underscores the need for further validation and contextual refinement before integration into multidisciplinary care.
Background:. In very advanced tongue cancer, definite radiochemotherapy (RCHT) is often preferred over total or near total glossectomy due to organ preservation and functionality, particularly swallowing. Methods:. This retrospective study compares the functionality and survival of 10 patients with very advanced tongue cancer who received (sub)total glossectomy with prior or adjuvant RCHT and reconstruction by a musculocutaneous anterolateral thigh flap. All 10 patients had comparable tongue carcinomas treated by definite RCHT. Airway protection and swallow efficiency were evaluated by fiberoptic endoscopic evaluation of swallowing and graded using the Rosenbek Penetration and Aspiration Scale (PAS) and the Yale Pharyngeal Residue Severity Rating Scale (YPRS). Results:. Of 10 surgical patients, 7 were completely oralized after a mean of 17 days. For surgical patients, PAS scores swallowing saliva (mean 1.6 versus 2.9, P = 0.04) as well as vallecula (mean 4.0 versus 2.9, P = 0.05) and piriform sinus (mean 3.5 versus 2.5, P = 0.05) YPRS scores for saliva were significantly lower compared with definite RCHT. Irrespective of treatment, age older than 65 years (YPRS sinus piriformis H2O 3.4 versus 2.5, P = 0.47), body mass index less than 20 kg/m2 (PAS Jelly 4.7 versus 2.2, P = 0.015, YPRS sinus piriformis 4.0 versus 2.7, P = 0.028), and Karnovsky index less than 80 (PAS saliva 2.8 versus 1.6, P = 0.049) were associated with worse swallowing. Speech was intelligible in 80% of patients of both groups. Overall survival did not differ between the surgical group and definite RCHT. Conclusions:. Patients after (sub)total glossectomy with RCHT and adequate reconstruction with a musculocutaneous anterolateral thigh flap show equal or even better swallowing compared with patients after definite RCHT for advanced tongue cancer.
Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological “cold” breast cancers by neoadjuvant irradiation into their “hot” variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced “in-situ vaccination”, especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype –specific manner. According to the “bench to bedside” principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.
The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM-based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This preparatory study establishes a robust methodological foundation for the forthcoming CONCORDIA trial, including the validation of the System Causability Scale (SCS) and its modified version (mSCS), as well as the selection of LLMs for urological cancer treatment recommendations based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen’s K > 0.74), and internal consistency (all Cronbach’s Alpha > 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p < 0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.
Spinal meningiomas (SM) are lesions with a mostly favorable oncological and surgical prognosis and a low incidence of tumor recurrence. SM account for approximately 1.2-12.7% of all meningiomas and 25% of all spinal cord tumors. Typically, SM are located in the intradural extramedullary space. SM grow slowly and spread laterally into the subarachnoid space, stretching and sometimes incorporating the surrounding arachnoid but rarely the pia. Standard treatment is surgery with the primary aims of achieving complete tumor resection as well as improving and recovering neurologic function. Radiotherapy may be considered in case of tumor recurrence, for challenging surgical cases, and for patients with higher-grade lesions (World Health Organization grade 2 or 3); however, radiotherapy is mostly used as an adjuvant therapy for SM. New molecular and genetic profiling increases the understanding of SM and may uncover additional treatment options.
The programmed cell death 1 ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD‐L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD‐L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD‐L1 in various cellular compartments of six well‐characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD‐L1 in its well‐known glycosylated/deglycosylated state at 40–55 kDa. In addition, we detected previously unknown PD‐L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD‐L1 variant expression is cell‐cycle‐dependent. Immunofluorescence staining of PD‐L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD‐L1 trafficking remain less understood; however, proximity ligation assays showed a cell‐cycle‐dependent interaction of the cytoskeletal protein vimentin with PD‐L1, whereas vimentin could serve as a potential shuttle for nuclear PD‐L1 transportation. Mass spectrometry after PD‐L1 co‐immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD‐L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD‐L1 and multiple tumor cell‐intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition.
Objective: Numerous studies analyzed lymphovascular invasion (LVI) in various malignant diseases, however, little is known about the role of lymphatic invasion (LI) as well as vascular invasion (VI) in oral squamous cell carcinoma (OSCC). The aim of this study is to illuminate the role of LI and VI in a population-based cohort study. Methods: We retrospectively analyzed 745 primarily resected OSCC patients in Eastern Bavaria for histopathologically verified LI and VI. Overall survival (OS) and recurrence-free survival (RFS) were calculated, whereas analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.4 years. Results: LI was found in 115 patients (15.4%), VI was diagnosed in 23 cases (3.1%). LI correlated significantly with distinct anatomical sites (p = 0.004), increasing pT-classification (p < 0.001), lymph node involvement (p < 0.001), higher grading (p < 0.001), advanced UICC-stages (p < 0.001) and adjuvant therapies (p < 0.001). Similar results were found for VI. Survival analysis resulted in a significantly decreased five-year OS and RFS in patients with diagnosed LI (OS: 41.1%, RFS: 38.3%) in contrast to LI-negative cases (OS: 66.8%, RFS: 59.7.7%, p < 0.001). Analogous outcomes were seen for patients with VI. Additionally, LI was identified as a predictive parameter, indicating individual patients' response to adjuvant therapies. Conclusion: This population-based cohort study underlines the unfavorable aspect of LI and VI on outcome in OSCC. Including LI and VI in existing staging systems could help to stratify patients' risk for adverse outcome and consecutively determine adjuvant treatment in malignant disease.
Abstract Background: Craniopharyngioma is an embryonic tumor of low-grade malignancy. Children and adolescents with this diagnosis are analyzed concerning quality of life (QoL) and (progression-free) survival within the project KRANIOPHARYNGEOM 2007. Methods: The prospective, multi-center project consists of a randomized, unblinded substudy with adaptive design and an observational study. The randomized substudy for incompletely resected patients compares direct postsurgical radiation with radiation at progression. Endpoint is self-assessment of QoL measured by PEDQOL. In explorative analyses, the influence of additional factors was analyzed using linear mixed models. Results: In the interim analysis of the randomized substudy according to the intention-to-treat approach only marginal differences concerning QoL between the two treatment groups were observed (n=24). The explorative analyses (n=131) show that ant-/ and posterior preoperative hypothalamic involvement and postoperative hypothalamic lesions are associated with decreased QoL. After complete resection, the QoL is lower than with incomplete resection. Radiation, which is often performed due to progression after incomplete resection, is associated with reduced quality of life. Conclusion: In order to achieve best QoL for children and adolescents with craniopharyngioma, hypothalamus-sparing therapeutic approaches are recommended. Based on the current data, it is not possible to recommend the optimal time for radiotherapy after incomplete resection with regard to QoL.
Purpose Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. Methods and materials The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. Results We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. Conclusion Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.
es ist uns eine Freude, Ihnen auch in dieser Ausgabe der Monatsschrift Kinderheilkunde Einblicke in aktuelle Themen der Kinderonkologie zu geben, die im Rahmen unserer Jahrestagung am 22./23.11.2019 in Frankfurt präsentiert und diskutiert werden. Bei dieser Herbsttagung werden wir am Freitagvormittag zunächst Empfehlungen zu Impfungen und Supportivtherapien betrachten. Im weiteren Tagesverlauf werden wir uns mit aktuellen Aspekten der Knochentumorstudien sowie der Gentherapie und KMT bei Hämoglobinopathien beschäftigen. Zum Abschluss des ersten Tages wird es ein Update zur GPOH Phase I/II Netzwerkstruktur geben. Am zweiten Tag beschäftigen wir uns mit den neuen Daten und Konzepten auf dem Gebiet der Leukämien inklusive Rezidive sowie Hirntumoren. Zum Abschluss gibt es noch einen interessanten Einblick in die aktuellen Immuntherapiestudien sowie zu CAR-T-Zellen. Auszüge über Neuerungen in den Therapieoptimierungsstudien finden Sie in dieser Ausgabe. Ich wünsche Ihnen viel Spaß beim Lesen dieser spannenden Abstracts!
BACKGROUND:Craniopharyngioma is a tumor of low histological malignancy resulting from an anomaly of embryonic development. Affected children and adolescents are being studied with respect to their quality of life, progression-free survival, and overall survival in the framework of the ongoing KRANIOPHARYNGEOM 2007 project.METHODS:This prospective, multicenter project consists of a randomized trial with an adaptive design combined with a purely observational study. The randomized, unblinded trial includes patients whose tumors have been incompletely resected and is intended to compare the outcomes of immediate postoperative radiotherapy versus radiotherapy on progression. Its primary endpoint is quality of life as assessed subjectively by the patients them- selves with the "Pediatric Quality of Life" questionnaire (PEDQOL). In exploratory analyses, linear mixed models were used to study the effect of further factors on quality of life.RESULTS:An interim intention-to-treat analysis of the randomized trial revealed only minor differences between the treatment arms with respect to quality of life (n = 24). The exploratory analyses (n = 131) showed that preoperative involvement of, or operative damage to, the anterior and posterior regions of the hypothalamus was associated with a lower quality of life. Complete resection was followed by a lower quality of life than incomplete resection. Radiotherapy, a common treatment for tumors that progress after incomplete resection, was also associated with a lower quality of life.CONCLUSION:Hypothalamus-sparing treatment approaches are recommended to optimize the quality of life of children and adolescents with cranio- pharyngioma. The available evidence does not support any recommendation as to when radiotherapy should be performed after incomplete resection so that the best quality of life can be achieved.
BACKGROUND:To overcome the compromised wound healing in radiation induced chronic wounds platelet-rich plasma (PRP), as therapeutic agent, is current subject of studies. PRP is associated with pro-angiogenic effects. Nevertheless, effects of platelet-rich plasma in cutaneous wound healing processes are poorly understood so far.METHODS:In this study, the migration of endothelial cells, fibroblasts and keratinocytes in conjunction with platelet-rich plasma treatment is investigated in the context of radiation effects. Additionally, cell proliferation and viability after external radiation was analyzed regarding treatment by platelet-rich plasma.RESULTS:All cell cultures showed a trend towards decreasing proliferation and viability after irradiation irrespective of PRP. Upon PRP treatment, irradiated fibroblasts as well as endothelial cells showed an enhanced proliferation whereas proliferation and viability of keratinocytes was reduced after PRP treatment. Scratch assays support the positive effect of PRP on fibroblast and endothelial cell migration, whereas a negative effect on keratinocytes was observed after PRP treatment.CONCLUSIONS:The present study documents both deleterious effects of external radiation as well as the protective effect of PRP. In summary, increased viability, proliferation and migration are indeed a consequence of the pro-proliferative effect exerted by PRP. Therefore, treatment with PRP products might be useful in the management of chronic radiogenic wounds.
One of the major challenges in radiation therapy is the interference with tissue repair processes due to hypoxic characteristics and pH dysregulation. In this study, we present dual imaging of pH and oxygenation in vitro based on luminescent biocompatible sensor foils that allow studying the effects of irradiation on different cell types in culture. Different sensitivities of fibroblast and oral squamous carcinoma cells were observed by complementing oxygen and pH differences with proliferation assays. This study highlights especially the distinct role of oxygen after irradiation and the difference in proliferation processes of irradiated normal dermal cells in contrast to irradiated tumor cells.
Background Epicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri. Material and methods The analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated. Results A significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain. Conclusion Radiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.
Abstract Pediatric patients suffering from ependymoma are usually treated with cranial or craniospinal three‐dimensional (3D) conformal radiotherapy (3DCRT). Intensity‐modulated techniques spare dose to the surrounding tissue, but the risk for second malignancies may be increased due to the increase in low‐dose volume. The aim of this study is to investigate if the flattening filter free (FFF) mode allows reducing the risk for second malignancies compared to the mode with flattening filter (FF) for intensity‐modulated techniques and to 3DCRT. A reduction of the risk would be advantageous for treating pediatric ependymoma. 3DCRT was compared to intensity‐modulated radiation therapy (IMRT) and volumetric‐modulated arc therapy (VMAT) with and without flattening filter. Dose–volume histograms (DVHs) were compared to evaluate the plan quality and used to calculate the excess absolute risk (EAR) to develop second cancer in the brain. Dose verification was performed with a two‐dimensional (2D) ionization chamber array and the out‐of‐field dose was measured with an ionization chamber to determine the EAR in peripheral organs. Delivery times were measured. Both VMAT and IMRT achieved similar plan quality in terms of dose sparing in the OAR and higher PTV coverage as compared to 3DCRT. Peripheral dose in low‐dose region, which is proportional to the EAR in organs located in this region, for example, gonads, bladder, or bowel, could be significantly reduced using FFF. The lowest peripheral EAR and lowest delivery times were hereby achieved with VMATFFF. The EAR calculated based on DVH in the brain could not be reduced using FFF mode. VMATFFF improved the target coverage and homogeneity and kept the dose in the OAR similar compared to 3DCRT. In addition, delivery times were significantly reduced using VMATFFF. Therefore, for radiotherapy of ependymoma patients, VMATFFF may be considered advantageous for the combination of Elekta Synergy linac and Oncentra External Beam planning system used in this study.
Osteoarthritis of the knee is a common disease, often associated with a Baker’s cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker’s cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker’s cyst.
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process are poorly understood so far. In this study, the interaction of endothelial cells and adipose-derived stem cells in conjunction with treatment with platelet-rich plasma is investigated in the context of radiation effects. Therefore, the expression of surface-marker CD90 and CD31 was determined. Moreover, cell proliferation and viability after external radiation was analyzed with and without treatment by platelet-rich plasma.