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BACKGROUND: The prediction of postoperative functional status in non-small cell lung cancer patients based on preoperative assessment of physical and respiratory capacity is inadequate based on recent RCTs. MATERIAL AND METHODS: Prospectively collected spirometry data and the six-minute walk test results of 57 patients treated with lobectomy for non-small cell lung cancer were analyzed. The tests were performed before surgery, and 30 and 90 days after lobectomy. All patients underwent a respiratory functional and physical capacity assessment. RESULTS: All 57 patients underwent lobectomy. Before surgery, mean FEV1 was 2.4 ± 0.7 L, corresponding to %FEV1 of 88.3 ± 17.3%. The mean absolute and expected 6MWT distance was 548 ± 74.6 m and 108.9 ± 14.5%, respectively. At the first postoperative evaluation 30 days after surgery, FEV1 and %FEV1 decreased significantly by an average of 0.5 ± 0.3 L and 15.1 ± 10.7%, while 6MWT and expected 6MWT decreased minimally by an average of 1.0 m and 0.8%, respectively. Three months after lobectomy, FEV1 and %FEV1, compared with the initial assessment, decreased by an average of 0.3 ± 0.3 l and 7.8 ± 10.0%, while 6MWT and its expected score increased to 564.6 ± 84.6 m and 112.8 ± 15.8%, respectively. CONCLUSIONS: After lobectomy, FEV1 decreased slightly and less than expected, while 6MWT increased proportionally compared to the preoperative evaluation.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Espirometría , Humanos , Espirometría/métodos , Femenino , Masculino , Neoplasias Pulmonares/cirugía , Anciano , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neumonectomía/métodos , Pruebas de Función Respiratoria/métodos , Estudios Prospectivos , Volumen Espiratorio ForzadoRESUMEN
Background: Arthroplasty is gaining more and more popularity in the treatment of osteoarthritis (OA) of the metatarsophalangeal I joint (MTP1). The aim of our study was to evaluate the early and long-term objective clinical and radiographic results, as well as the subjective results, of MTP1 arthroplasty in comparison to MTP1 arthrodesis among patients with OA and a valgus deformity of their MTP 1 joint. Methods: Patients with OA MTP1 were examined before surgery and in the 5-year period after surgery. The inclusion criteria for the study were OA of the MTP1 joint and a non-axial position of the toe in valgus between 20 and 40 degrees. Prostheses were created for the patients with higher demands for mobility of their MTP 1 joint and arthrodesis was carried out for those with lower expectations. The treatment outcomes were assessed by clinical examination, radiography, the AOFAS scale, the SEFAS scale, and using patient-related outcome measures (PROM). Results: A total of 39 people, 37 women and 2 men, aged 55 to 67 years old (average, 61 years old) participated in the study. During the follow-up period, there were no complications in the form of infection or a loosening of the implant after both arthroplasty and arthrodesis. The follow-up examination 60 months after the surgery showed an improvement in scores (>20 points) on both the AOFAS and SEFAS scales. All patients, after surgery, reported reduced pain. Conclusions: The use of a silicone prosthesis in the surgical treatment of degenerative changes in the MTPI joint, with appropriate indications and excluding cases with large hallux valgus, gives better results than arthrodesis.
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Background and Purpose: Radiation-induced lymphopenia (RIL) is a common side effect of radiotherapy (RT) that may negatively impact survival. We aimed to identify RIL predictors in patients with non-small-cell lung cancer (NSCLC) treated intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Materials and Methods: We retrospectively analysed data of 306 patients who underwent radical RT for NSCLC. Absolute lymphocyte count (ALC) loss was evaluated for each patient by fitting an exponential decay curve to data from first 45 days since treatment start, and percentage ALC loss relative to baseline was calculated based on area under the decay curve and baseline ALC. We compared IMRT and VMAT treatment plans and used linear regression to predict ALC loss. Results: ALC decreased during RT in the whole patient group, while neutrophil counts remained stable and decreased only in those treated with concurrent chemoradiotherapy (CRT). Percentage ALC loss ranged between 11 and 78 % and was more strongly than lymphocyte nadir correlated with dose-volume metrics for relevant normal structures. We found evidence for the association of high radiation dose to the lungs, heart and body with percentage ALC loss, with lung volume exposed to 20-30 Gy being most important predictors in patients treated with IMRT. A multivariable model based on CRT use, baseline ALC and first principal component (PC1) of the dose-volume predictors showed good predictive performance (bias-corrected R2 of 0.40). Conclusion: Percentage lymphocyte loss is a robust measure of RIL that is predicted by baseline ALC, CRT use and dose-volume parameters to the lungs, heart and body.
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Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology in solid tumours, specifically focusing on the impact of tumour heterogeneity and genomic patient features on systemic therapies and radiation. We also discuss the implementation of novel tools, such as next-generation sequencing and liquid biopsies, to overcome this problem.
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The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme. At evaluation after one year, both mentors and mentees scored the programme with a median score of 9 on a scale of 10. All of the mentors indicated that they wanted to participate again as mentors.
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Tutoría , Oncología por Radiación , Sociedades Médicas , Humanos , Proyectos Piloto , Oncología por Radiación/educación , Europa (Continente) , Oncología Médica/educación , Mentores , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy-induced toxicity. METHODS: We present a case of a 73-year-old woman with locally advanced polymorphous low-grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity. RESULTS: We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation-induced toxicity. CONCLUSIONS: Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.
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Adenocarcinoma , Traumatismos por Radiación , Femenino , Humanos , Anciano , Leucocitos Mononucleares/patología , Adenocarcinoma/genética , Adenocarcinoma/radioterapia , Adenocarcinoma/patología , Nasofaringe/patología , Reparación del ADN/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genéticaRESUMEN
Cardio-oncology currently faces one of the greatest challenges in the field of health care. The main goal of this discipline is to ensure that patients treated for cancer do not suffer or die from cardiovascular disease. The number of studies on the mechanisms of heart injury during cancer treatment is constantly increasing. However, there is insufficient data on heart rhythm disorders that may result from this treatment. This issue seems to be particularly important in patients with lung cancer, in whom anticancer therapy, especially radiotherapy, may contribute to the onset of cardiac arrhythmias. The observed relationship between cardiac dosimetry and radiotherapy-induced cardiotoxicity in lung cancer treatment may explain the increased mortality from cardiovascular causes in patients after chest irradiation. Further research is essential to elucidate the role of cardiac arrhythmias in this context. Conversely, recent reports have highlighted the application of stereotactic arrhythmia radioablation (STAR) in the treatment of ventricular tachycardia. This review of available studies on the epidemiology, pathogenesis, diagnosis, and treatment of arrhythmias in patients treated for lung cancer aims to draw attention to the need for regular cardiological monitoring in this group of patients. Improving cardiac care for patients with lung cancer has the potential to enhance their overall therapeutic outcomes.
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The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by the loss of Shieldin proteins can be resensitized by the constitutive association of DYNLL1 with MRE11. These results define the temporal and functional dynamics of the 53BP1-centric DNA end resection factors in cells.
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Proteína BRCA1 , Roturas del ADN de Doble Cadena , Proteína BRCA1/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , ADN/metabolismo , Reparación del ADN por Unión de Extremidades , Núcleo Celular/metabolismo , Reparación del ADNRESUMEN
BACKGROUND AND PURPOSE: Despite its increasing popularity, there are limited prospective data on stereotactic arrhythmia radioablation (STAR). In this trial, we assessed the safety and efficacy of STAR in patients with ventricular tachycardia (VT), focusing on early treatment-related grade ≥ 3 adverse events (AE). MATERIALS AND METHODS: This prospective trial was designed for adults with VT recurrence following catheter ablation (CA) despite adequate pharmacotherapy, or contraindications to CA. A single dose of 25 Gy was delivered to the arrhythmia substrate defined on electro-anatomic mapping and cardiac-gated CT. The primary endpoint was safety, defined as two or fewer treatment-related grade ≥ 3 AEs during the first three months in 11 patients. Additional endpoints included treatment efficacy, clinical and biological markers of cardiac injury, and quality of life. RESULTS: Eleven patients with a median age of 67 years, structural heart disease, and a clinically significant recurrence of VT despite adequate pharmacotherapy and 1-4 previous CAs were enrolled between 2020/09 and 2022/10. Following the treatment, one patient developed a possibly treatment-related grade ≥ 3 AE, a grade 4 heart failure exacerbation at 87 days, which resolved after conservative treatment. There was a total 84.3% reduction in VT burden in 10 evaluable patients; however, VT recurrence was eventually observed in eight, and three patients required additional CAs. Three deaths due to unrelated causes were recorded. CONCLUSIONS: STAR appears to be safe and efficient. It is a promising treatment for selected patients; however, long-term outcomes remain to be evaluated, and controlled trials comparing STAR with standards of care are missing.
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PURPOSE: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. METHODS: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). RESULTS: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). CONCLUSION: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Estudios Retrospectivos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Resultado del Tratamiento , Antígeno Prostático Específico , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Lutecio/uso terapéuticoRESUMEN
PURPOSE: Mouse and non-human primate models showed that serum miRNAs may be used to predict the biological impact of radiation doses. We hypothesized that these results can be translated to humans treated with total body irradiation (TBI), and that miRNAs may be used as clinically feasible biodosimeters. METHODS: To test this hypothesis, serial serum samples were obtained from 25 patients (pediatric and adults) who underwent allogeneic stem-cell transplantation and profiled for miRNA expression using next-generation sequencing. miRNAs with diagnostic potential were quantified with qPCR and used to build logistic regression models with lasso penalty to reduce overfitting, identifying samples drawn from patients who underwent total body irradiation to a potentially lethal dose. RESULTS: Differential expression results were consistent with previous studies in mice and non-human primates. miRNAs with detectable expression in this and two prior animal sets allowed for distinction of the irradiated from non-irradiated samples in mice, macaques and humans, validating the miRNAs as radiation-responsive through evolutionarily conserved transcriptional regulation mechanisms. Finally, we created a model based on the expression of miR-150-5p, miR-30b-5p and miR-320c normalized to two references and adjusted for patient age with an AUC of 0.9 (95%CI:0.83-0.97) for identifying samples drawn after irradiation; a separate model differentiating between high and low radiation dose achieved AUC of 0.85 (95%CI: 0.74-0.96). CONCLUSIONS: We conclude that serum miRNAs reflect radiation exposure and dose for humans undergoing TBI and may be used as functional biodosimeters for precise identification of people exposed to clinically significant radiation doses.
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MicroARNs , Exposición a la Radiación , Adulto , Humanos , Ratones , Animales , Niño , MicroARNs/genética , Irradiación Corporal Total , Relación Dosis-Respuesta en la Radiación , BiomarcadoresRESUMEN
Introduction: Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up. Materials and methods: Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT. Results: Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors. Conclusion: We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.
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Background and Objective: Lung cancer remains the leading cause of cancer-related mortality and constitutes a significant societal burden. Recent advancements in targeted therapies and immunotherapy have considerably broadened therapeutic options in lung cancer, particularly in non-small-cell lung cancer (NSCLC). However, these novel methods necessitate sophisticated molecular diagnostics. Liquid biopsy, which refers to the cytological and molecular analysis of cancer markers shed by the tumor into the body fluids, may offer an attractive diagnostic tool at the individual patient level. This approach is particularly relevant for lung cancer, as the anatomical location of tumor lesions frequently makes them inaccessible for tissue biopsy. Apart from minimal invasiveness, the major advantages of liquid biopsy include better reflection of the tumor clonal heterogeneity (spatial heterogeneity), the possibility of sequential sampling, and real-time monitoring of tumor load and its evolving mutational status (temporal heterogeneity). Methods: This article reviews the available data in this field, current applications, and future perspectives in accordance with the Narrative Review reporting rules. Key Content and Findings: We discuss the most used approaches, i.e., circulating DNA and tumor cells, but also emerging liquid biopsy techniques, such as plasma DNA methylation, plasma metabolites and RNA, extracellular vesicles, and tumor-educated platelets in NSCLC. Finally, we highlight the current limitations of liquid biopsy techniques hampering their clinical applications. Conclusions: Due to their advantages, liquid biopsy-based approaches have recently gained immense interest in oncology. Potential applications of this method include early detection, informing precision medicine-based individualized treatment, and real-time monitoring of disease evolution and treatment. The development of next-generation sequencing has vastly extended genetic profiling, thus enabling better identification of druggable alterations. However, the clinical application of liquid biopsy techniques is still limited due to their suboptimal specificity and sensitivity, lack of standardization, and relatively high costs. Addressing these issues may allow further integration of liquid biopsies in the routine clinical setting, thus making a profound and permanent change in NSCLC management.
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The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
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Ablación por Catéter , Taquicardia Ventricular , Humanos , Estudios Prospectivos , Arritmias Cardíacas , Ventrículos Cardíacos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high dose rate brachytherapy (HDR BT) on health related quality of life (HRQL) in patients with early stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: From March 2019 to February 2021, 60 patients were enrolled with early stage endometrioid endometrial carcinoma, and qualified to adjuvant treatment after hysterectomy. HRQL was assessed using the EORTC QLQ-C30 questionnaire, with the endometrial cancer-specific HRQL module EORTC QLQ-EN24. Questionnaires were completed in four timepoints during adjuvant radiotherapy. RESULTS: A significant decrease in mean global health status / quality of life (p < 0.001) and role functioning (p = 0.028) was noted, as assessed in EORTC QLQ-C30 scale. Among the EORTC QLQ-C30 symptoms scales, significant differences were noted in the fatigue scale (p = 0.003), pain scale (p = 0.001), constipation scale (p < 0.001) and diarrhea scale (p < 0.001) over time. The EORTC QRQ-EN24 analysis showed significant deterioration in the urological symptoms scale (p < 0.001), gastrointestinal symptoms scale (p < 0.001) and in the mean pain in back and pelvis scale (p = 0.003). CONCLUSIONS: Adjuvant radiotherapy in patients with early-stage endometrioid endometrial cancer after hysterectomy is associated with worse quality of life, especially due to the toxicity of the treatment in relation to the gastrointestinal tract and urinary system.
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Brain metastases (BM) are a common and devastating manifestation of breast cancer (BC). BM are particularly frequent in the HER2-positive and triple-negative breast cancer phenotypes and usually occur following the metastatic spread to extracranial sites. Several genes mediating BM and biomarkers predicting their risk in BC have been reported in the past decade. These findings have advanced the understanding of BM pathobiology and paved the way for developing new therapeutic strategies but they still warrant a thorough clinical validation. Hence, a better understanding of the mechanistic aspects of BM and delineating the interactions of tumor cells with the brain microenvironment are of utmost importance. This review discusses the molecular basis of the metastatic cascade: the epithelial-mesenchymal transition, cancer, and tumor microenvironment interaction and intravasation, priming of the metastatic niche in the brain, and survival in the new site. We also outline the postulated mechanisms of BC cells' brain tropism. Finally, we discuss advances in the field of biomarkers (both tissue-based and liquid-based) that predict BM from BC.
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Neoplasias Encefálicas , Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama Triple Negativas/patología , Biomarcadores , Neoplasias Encefálicas/secundario , Microambiente TumoralRESUMEN
A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan-Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local-regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07-1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19-6.15). Definitive local salvage therapies were feasible in the majority of the patients with local-regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients' survival compared to primary disease recurrence.
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BACKGROUND AND PURPOSE: The outcomes of conventional radiotherapy for painful vertebral haemangiomas have been improved through dose escalation at the expense of overall treatment time. We hypothesized that with the aid of precise hypofractionated radiotherapy, it is possible to safely deliver a similar biological equivalent dose over a significantly shorter course of treatment with a comparable efficacy and safety. MATERIALS AND METHODS: In this prospective, single-institution unblinded randomized clinical trial (NCT02332408) patients with painful vertebral haemangiomas were allocated one-to-one either to 25 Gy delivered in five fractions (CK) or conventionally fractionated radiotherapy up to 36 Gy (conv.). The main endpoint was pain relief at two years, measured on a subjective and numerical scale (NRS). RESULTS: The trial was finished yielding 74 evaluable patients, including 38 in the CK arm. Adverse events were infrequent and the treatment was well tolerated. The overall treatment time was significantly shorter in the CK arm (median of 13 days vs 25 days). At two years, more than half of the patients reported improvement (46; 62.2 %) , in 21 cases the pain symptoms were stable (28.4 %), and in seven cases worse (9.5 %). There were significantly more patients reporting improvement in the CK arm (73.7 % vs 50 %; p = 0.036). The median decrease in NRS was 4 (IQR 1-5) or 59 % (IQR 20-86 %), and the difference between arms was not statistically significant. CONCLUSION: Five fractions hypofractionated radiotherapy for painful vertebral haemangiomas up to a total dose of 25 Gy is a safe treatment modality, significantly shorter compared to conventional fractionation, and possibly more effective.
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Hemangioma , Dolor , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Fraccionamiento de la Dosis de Radiación , Hemangioma/radioterapiaRESUMEN
Bone metastases are the most common cause of cancer-related pain. It has been reported that radiotherapy is efficient in the palliation of pain caused by bone metastases. Half-body irradiation (HBI) is a method of palliative treatment in patients with multiple metastases to bones. The present study aimed to evaluate the efficiency of upper and lower HBI in reducing pain in patients with multiple bone metastases treated with volumetric modulated arc therapy (VMAT) HBI. A total of 22 patients received HBI based on the VMAT technique between July 2018 and July 2020. Treatment plans were subject to a dosimetric analysis. The absorbed doses ranged from 6 to 8 Gy in a single fraction. The patients rated pain on the 11-point (0-10) verbal numeric pain score (VNPS) before irradiation and after 1 month of follow-up. To assess the analgesic effect of HBI radiotherapy, data from 19 patients who attended the follow-up visit were analyzed. Before the treatment, the median VNPS of pain was 5 (IQR, 3-8); after the follow-up period, it was 3 (IQR, 1-4) (P=0.003). The median VNPS of the maximum pain within the last month before treatment was 8 (IQR, 7-10) and after irradiation it was 5 (IQR, 4-7) (P<0.001). The median VNPS of the average pain within the last month before the treatment was 5 (IQR, 4-7); after the treatment, it was 3 (IQR, 2-5) (P=0.003). In conclusion, conformal VMAT-intensity-modulated radiation therapy HBI is an effective method for reducing pain in patients with painful multiple bone metastases. Conformal techniques of radiation allow for the reduction of doses to organs at risk thus potentially reducing the toxicity of treatment.
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DNA replication is a process fundamental in all living organisms in which deregulation, known as replication stress, often leads to genomic instability, a hallmark of cancer. Most malignant tumors sustain persistent proliferation and tolerate replication stress via increasing reliance to the replication stress response. So whilst replication stress induces genomic instability and tumorigenesis, the replication stress response exhibits a unique cancer-specific vulnerability that can be targeted to induce catastrophic cell proliferation. Radiation therapy, most used in cancer treatment, induces a plethora of DNA lesions that affect DNA integrity and, in-turn, DNA replication. Owing to radiation dose limitations for specific organs and tumor tissue resistance, the therapeutic window is narrow. Thus, a means to eliminate or reduce tumor radioresistance is urgently needed. Current research trends have highlighted the potential of combining replication stress regulators with radiation therapy to capitalize on the high replication stress of tumors. Here, we review the current body of evidence regarding the role of replication stress in tumor progression and discuss potential means of enhancing tumor radiosensitivity by targeting the replication stress response. We offer new insights into the possibility of combining radiation therapy with replication stress drugs for clinical use.