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Craniopharyngiomas continue to present a challenge in clinical practice due to their heterogeneity and unpredictable adherence to vital neurovascular structures, particularly the hypothalamus. This results in different degrees of hypothalamus-pituitary axis dysfunction and a lack of uniform consensus and treatment guidelines regarding optimal management. MRI and CT are complementary techniques in the preoperative diagnostic phase, enabling the precise definition of craniopharyngioma size, shape, and consistency, as well as guiding classification into histopathological subtypes and topographical categories. Meanwhile, MRI plays a crucial role in the immediate postoperative period and follow-up stages by identifying treatment-related changes and residual tumors. This pictorial essay aims to provide an overview of the role of imaging in identifying variables indicative of the adherence degree to the hypothalamus, hypothalamic-pituitary dysfunction, the extent of surgical excision, and prognosis. For a more comprehensive assessment, we choose to distinguish the following two scenarios: (1) the initial diagnosis phase, where we primarily discuss the role of radiological variables predictive of adhesions to the surrounding neurovascular structures and axis dysfunction which may influence the choice of surgical resection; (2) the early post-treatment follow-up phase, where we discuss the interpretation of treatment-related changes that impact outcomes.
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The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by MRI. However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAM) are abundant in GBM tumor microenvironment (TME) and are found in peripheral blood (PB). FKBP51 expression, with its canonical and spliced isoforms, is constitutive in immune cells and aberrant in GBM. Spliced FKBP51s supports M2 polarization. To find an immunologic signature that combined with MRI could advance in diagnosis, we immunophenotyped the macrophages of TME and PB from 37 patients with GBM using FKBP51s and classical M1-M2 markers. We also determined the tumor levels of FKBP51s, PD-L1, and HLA-DR. Tumors expressing FKBP51s showed an increase in various M2 phenotypes and regulatory T cells in PB, indicating immunosuppression. Tumors expressing FKBP51s also activated STAT3 and were associated with reduced survival. Correlative studies with MRI and tumor/macrophages cocultures allowed to interpret TAMs. Tumor volume correlated with M1 infiltration of TME. Cocultures with spheroids produced M1 polarization, suggesting that M1 macrophages may infiltrate alongside cancer stem cells. Cocultures of adherent cells developed the M2 phenotype CD163/FKBP51s expressing pSTAT6, a transcription factor enabling migration and invasion. In patients with recurrences, increased counts of CD163/FKBP51s monocyte/macrophages in PB correlated with callosal infiltration and were accompanied by a concomitant decrease in TME-infiltrating M1 macrophages. PB PD-L1/FKBP51s connoted necrotic tumors. In conclusion, FKBP51s identifies a GBM subtype that significantly impairs the immune system. Moreover, FKBP51s marks PB macrophages associated with MRI features of glioma malignancy that can aid in patient monitoring. SIGNIFICANCE: Our research suggests that by combining imaging with analysis of monocyte/macrophage subsets in patients with GBM, we can enhance our understanding of the disease and assist in its treatment. We discovered a similarity in the macrophage composition between the TME and PB, and through association with imaging, we could interpret macrophages. In addition, we identified a predictive biomarker that drew more attention to immune suppression of patients with GBM.
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Neoplasias Encefálicas , Glioblastoma , Isoformas de Proteínas , Proteínas de Ligação a Tacrolimo , Microambiente Tumoral , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/diagnóstico por imagem , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Prognóstico , Feminino , Microambiente Tumoral/imunologia , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Pessoa de Meia-Idade , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Imageamento por Ressonância Magnética , AdultoRESUMO
MRI plays a key role in the evaluation of post-treatment changes, both in the immediate post-operative period and during follow-up. There are many different treatment's lines and many different neuroradiological findings according to the treatment chosen and the clinical timepoint at which MRI is performed. Structural MRI is often insufficient to correctly interpret and define treatment-related changes. For that, advanced MRI modalities, including perfusion and permeability imaging, diffusion tensor imaging, and magnetic resonance spectroscopy, are increasingly utilized in clinical practice to characterize treatment effects more comprehensively. This article aims to provide an overview of the role of advanced MRI modalities in the evaluation of treated glioblastomas. For a didactic purpose, we choose to divide the treatment history in three main timepoints: post-surgery, during Stupp (first-line treatment) and at recurrence (second-line treatment). For each, a brief introduction, a temporal subdivision (when useful) or a specific drug-related paragraph were provided. Finally, the current trends and application of radiomics and artificial intelligence (AI) in the evaluation of treated GB have been outlined.
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Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as 'protein-philin' (Greek 'philin' = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor's intrinsic properties. Among the members of the immunophilin family, the FKBP5 gene was the only one identified to have a splicing variant. Cancer cells impose unique demands on the splicing machinery, thus acquiring a particular susceptibility to splicing inhibitors. This review article aims to overview the current knowledge of the FKBP5 gene functions in human cancer, illustrating how cancer cells exploit the scaffolding function of canonical FKBP51 to foster signaling networks that support their intrinsic tumor properties and the spliced FKBP51s to gain the capacity to evade the immune system.
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Neoplasias , Proteínas de Ligação a Tacrolimo , Humanos , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/química , Proteínas de Ligação a Tacrolimo/metabolismo , Neoplasias/genética , Transdução de SinaisRESUMO
PURPOSE: Regorafenib is a multikinase inhibitor, approved as a preferred regimen for recurrent glioblastoma (rGB). Although its effects on prolonging survival could seem modest, it is still unclear whether a subset of patients, potentially identifiable by imaging biomarkers, might experience a more substantial positive effect. Our aim was to evaluate the potential value of magnetic resonance imaging-derived parameters as non-invasive biomarkers to predict response to regorafenib in patients with rGB. METHODS: 20 patients with rGB underwent conventional and advanced MRI at diagnosis (before surgery), at recurrence and at first follow-up (3 months) during regorafenib. Maximum relative cerebral blood volume (rCBVmax) value, intra-tumoral susceptibility signals (ITSS), apparent diffusion coefficient (ADC) values, and contrast-enhancing tumor volumes were tested for correlation with response to treatment, progression-free survival (PFS), and overall survival (OS). Response at first follow-up was assessed according to Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: 8/20 patients showed stable disease at first follow-up. rCBVmax values of the primary glioblastoma (before surgery) significantly correlated to treatment response; specifically, patients with stable disease displayed higher rCBVmax compared to progressive disease (p = 0.04, 2-group t test). Moreover, patients with stable disease showed longer PFS (p = 0.02, 2-group t test) and OS (p = 0.04, 2-group t test). ITSS, ADC values, and contrast-enhancing tumor volumes showed no correlation with treatment response, PFS nor OS. CONCLUSION: Our results suggest that rCBVmax of the glioblastoma at diagnosis could serve as a non-invasive biomarker of treatment response to regorafenib in patients with rGB.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Biomarcadores , Estudos RetrospectivosRESUMO
MRI is undoubtedly the cornerstone of brain tumor imaging, playing a key role in all phases of patient management, starting from diagnosis, through therapy planning, to treatment response and/or recurrence assessment. Currently, neuroimaging can describe morphologic and non-morphologic (functional, hemodynamic, metabolic, cellular, microstructural, and sometimes even genetic) characteristics of brain tumors, greatly contributing to diagnosis and follow-up. Knowing the technical aspects, strength and limits of each MR technique is crucial to correctly interpret MR brain studies and to address clinicians to the best treatment strategy. This article aimed to provide an overview of neuroimaging in the assessment of adult primary brain tumors. We started from the basilar role of conventional/morphological MR sequences, then analyzed, one by one, the non-morphological techniques, and finally highlighted future perspectives, such as radiomics and artificial intelligence.
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BACKGROUND: The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended to offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). The aim of the present paper is to describe our nMTB, to evaluate its impact on clinical management decisions, and to assess the role of neuroradiologists. METHODS: The retrospective evaluation of the cases discussed at our nMTB from March 2017 to March 2020. From the electronic records, we extracted epidemiological, clinical and other specific data of nMTB. From the radiological records, we calculated data relating to the number, time for revision, and other specifications of MRI re-evaluation. Statistical analysis was performed. RESULTS: a total of 447 discussions were analyzed, representing 342 patients. The requests for case evaluations came from radiation oncologists (58.8%) and neurosurgeons (40.5%), and were mainly addressed to the neuroradiologist (73.8%). The most frequent questions were about the treatment's changes (64.4%). The change in patient treatment was reported in 40.5% of cases, 76.8% of these were based on the neuroradiologic assessment. A total of 1514 MRI examinations were re-evaluated, employing approximately 67 h overall. The median of the MRI exams reviewed per patient was 3 (min-max 1-12). CONCLUSIONS: Our study supported that the multidisciplinary approach to patient care can be particularly effective in managing brain tumors. A review by an expert neuroradiologist impacts patient management in the context of nMTBs, but has costs in terms of the time and effort spent preparing for it.
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Despite Glioblastoma (GBM) frequently expressing programmed cell death ligand-1 (PD-L1), treatment with anti-programmed cell death-1 (PD1) has not yielded brilliant results. Intratumor variability of PD-L1 can impact determination accuracy. A previous study on mouse embryonic fibroblasts (MEFs) reported a role for cyclin-D in control of PD-L1 expression. Because tumor-cell growth within a cancer is highly heterogeneous, we looked at whether PD-L1 and its cochaperone FKBP51s were influenced by cell proliferation, using U251 and SF767 GBM-cell-lines. PD-L1 was measured by Western blot, flow cytometry, confocal-microscopy, quantitative PCR (qPCR), CCND1 by qPCR, FKBP51s by Western blot and confocal-microscopy. Chromatin-Immunoprecipitation assay (xChIp) served to assess the DNA-binding of FKBP51 isoforms. In the course of cell culture, PD-L1 appeared to increase concomitantly to cyclin-D on G1/S transition, to decrease during exponential cell growth progressively. We calculated a correlation between CCND1 and PD-L1 gene expression levels. In the temporal window of PD-L1 and CCND1 peak, FKBP51s localized in ER. When cyclin-D declined, FKBP51s went nuclear. XChIp showed that FKBP51s binds CCND1 gene in a closed-chromatin configuration. Our finding suggests that the dynamism of PD-L1 expression in GBM follows cyclin-D fluctuation and raises the hypothesis that FKBP51s might participate in the events that govern cyclin-D oscillation.
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Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/metabolismo , Ciclina D/metabolismo , Glioblastoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Fibroblastos/metabolismo , Citometria de Fluxo/métodos , HumanosRESUMO
Brain biopsy is the gold standard in order to establish the diagnosis of unresectable brain tumors. Few studies have investigated the long-term outcomes of biopsy patients. The aim of this single-institution-based study was to assess the concordance between radiological and histopathological diagnoses, and the long-term patient outcome. Ninety-three patients who underwent brain biopsy in the last 5 years were analyzed. We included patients treated with stereotactically guided needle, open, and neuroendoscopic biopsies. Most patients (86%) received needle biopsy. Gliomas and primary brain lymphomas comprised 88.2% of cases. The diagnostic yield was 95.7%. Serious complication and death rates were 3.2% and 2.1%, respectively. The concordance rate between radiological and histological diagnoses was 93%. Notably, the positive predictive value of radiological diagnosis of lymphoma was 100%. Biopsy allowed specific treatment in 72% of cases. Disease-related neurological worsening was the main reason that precluded adjuvant treatment. Adjuvant treatment, in turn, was the strongest prognostic factor, since the median overall survival was 11 months with vs. 2 months without treatment (p = 0.0002). Finally, advanced molecular evaluations can be obtained on glioma biopsy specimens to provide integrated diagnoses and individually tailored treatments. We conclude that, despite the huge advances in imaging techniques, biopsy is required when an adjuvant treatment is recommended, particularly in gliomas.
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Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s- had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.
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Neoplasias Encefálicas , Citometria de Fluxo , Glioblastoma , Imageamento por Ressonância Magnética , Monócitos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Antígeno B7-H1/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Feminino , Glioblastoma/sangue , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Superfície Celular/sangue , Proteínas de Ligação a Tacrolimo/sangueRESUMO
The treatment of recurrent high-grade gliomas remains a major challenge of daily neuro-oncology practice, and imaging findings of new therapies may be challenging. Regorafenib is a multi-kinase inhibitor that has recently been introduced into clinical practice to treat recurrent glioblastoma, bringing with it a novel panel of MRI imaging findings. On the basis of the few data in the literature and on our personal experience, we have identified the main MRI changes during regorafenib therapy, and then, we defined two different patterns, trying to create a simple summary line of the main changes of pathological tissue during therapy. We named these patterns, respectively, pattern A (less frequent, similar to classical progression disease) and pattern B (more frequent, with decreased diffusivity and decrease contrast-enhancement). We have also reported MR changes concerning signal intensity on T1-weighted and T2-weighted images, SWI, and perfusion imaging, derived from the literature (small series or case reports) and from our clinical experience. The clinical implication of these imaging modifications remains to be defined, taking into account that we are still at the dawn in the evaluation of such imaging modifications.
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BACKGROUND: The survival benefit in maximizing resection in glioblastomas (GBMs) has been demonstrated by numerous studies. The true limit of infiltration of GBMs has been an overwhelming obstacle, and several technological advances have been introduced to improve the identification of residual tumors. OBJECTIVE: To evaluate whether the integration of 5-aminolevulinic acid (5-ALA) with microbubble contrast-enhanced ultrasound (CEUS) improves residual tumor identification and has an impact on the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS). METHODS: A total of 230 GBM procedures were retrospectively studied. Cases were stratified according to the surgical procedure into 4 groups: 5-ALA- and CEUS-guided surgeries, 5-ALA-guided surgeries, CEUS-guided surgeries, and conventional microsurgical procedures. RESULTS: Patients undergoing conventional microsurgical procedures showed the worst EORs compared to the assisted techniques (5-ALA and CEUS procedures). Both 5-ALA and CEUS techniques improved the EOR compared to conventional microsurgical procedures. However, their combination gave the best results in terms of the EOR (P = .0003). The median EOR% and the number of supramarginal resections are hence superior in the 5-ALA + CEUS + group compared to the others; this observation had consequences on PFS and OS in our series. CONCLUSION: In terms of the EOR, the best results can be achieved through a combination of both techniques, where the 5-ALA-guided procedure is followed by a final survey with CEUS. Compared with other intraoperative imaging techniques, CEUS is a real-time, readily repeatable, safe, and inexpensive technique that provides valuable information to the surgeon before, during, and after resection.
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Neoplasias Encefálicas/cirurgia , Meios de Contraste , Glioblastoma/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Ácidos Levulínicos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Seguimentos , Glioblastoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/cirurgia , Estudos Retrospectivos , Adulto Jovem , Ácido AminolevulínicoRESUMO
PURPOSE: Susceptibility-weighted imaging (SWI) is useful for glioma grading and discriminating between brain tumor categories in adults, but its diagnostic value for pediatric brain tumors is unclear. Here we evaluated the usefulness of SWI for pediatric tumor grading and differentiation by assessing intratumoral susceptibility signal intensity (ITSS). METHODS: We retrospectively enrolled 96 children with histopathologically diagnosed brain tumors, who underwent routine brain MRI exam with SWI (1.5 T scanner). Each tumor was assigned an ITSS score by a radiology resident and an experienced neuroradiologist, and subsequently by consensus. Statistical analyses were performed to differentiate between low-grade (LG) and high-grade (HG) tumors, histological categories, and tumor locations. Inter-reader agreement was assessed using Cohen's kappa (κ). RESULTS: The interobserver agreement was 0.844 (0.953 between first reader and consensus, and 0.890 between second reader and consensus). Among all tumors, we found a statistically significant difference between LG and HG for ITSS scores of 0 and 2 (p = 0.002). This correlation was weaker among astrocytomas alone, and became significant when considering only off-midline astrocytomas (p = 0.05). Scores of 0 and 2 were a strong discriminating factor (p = 0.001) for astrocytomas (score 0) and for embryonal, choroid plexus, germ-cell, pineal, and ependymoma tumors (score 2). No medulloblastoma showed a score of 0. CONCLUSIONS: Our preliminary ITTS results in pediatric brain tumors somewhat differed from those obtained in adult populations. These findings highlight the potential valuable role of ITSS for tumor grading and discriminating between some tumor categories in the pediatric population.
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Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Gradação de Tumores , Estudos RetrospectivosAssuntos
Analgésicos não Narcóticos , Dexmedetomidina , Região Lombossacral , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Analgésicos não Narcóticos/administração & dosagem , Dexmedetomidina/administração & dosagem , Humanos , Infusões Intravenosas , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/cirurgiaRESUMO
Dysplasia epiphysealis hemimelica is a rare osteocartilaginous overgrowth syndrome of bone epiphysis, mostly encountered in the lower limbs of immature skeleton patients. We report a case of proximal humerus presentation in an adult male, with neither articular involvement nor clinical dysfunction. This case highlights the importance of stratification into intra- and extra-articular lesions, as this distinction ultimately influences both symptoms and treatment outcome. In addition, the case highlights the importance of specific imaging modalities, such as CT and MR images, which provide excellent anatomic location of the lesion, adequate extension of cartilaginous components, exact status of articular cartilage, and accurate assessment of neighboring structures, such as vessels, nerves, ligaments, tendons, and muscles. The imaging features are described, the relevant literature is reviewed, and salient features are discussed.
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Acral metastases in the hand are exceedingly rare. We present the unusual case of a metastatic tumor of the hand of unknown primary site in a 77-year-old man with no known cancer history. The patient presented with pain and swelling in the tip of the left ring finger, which had previously been diagnosed as gout at another clinic. Laboratory tests, including white blood cell count, erythrocyte sedimentation rate/C-reactive protein, and uric acid were all within normal limits. Excisional biopsy was taken by amputation of the distal phalanx of the left ring finger through the distal third of the middle phalanx. Pathology confirmed the presence of a moderately differentiated adenocarcinoma of unknown primary site. Roentgenographic examination of the chest revealed no pathologic findings. The patient refused further investigation and adequate treatment. He died 4 months later. The current description confirms the rarity of metastatic malignancy of the hand and its poor prognosis.
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OBJECTIVE: We studied the correlation of magnetic resonance imaging (MRI) findings with the prognosis of patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) who had undergone percutaneous balloon compression (PBC). To the best of our knowledge, no studies have previously reported on this topic. We also performed a review of pertinent studies. METHODS: From a surgical series of 82 patients with TN who had undergone PBC from January 2013 to June 2017, we identified 16 patients with MS (mean age, 54.81 ± 8.51 years; mean follow-up, 38.12 ± 19.86 months). Using brain MRI, we evaluated the presence of a lesion in the trigeminal nerve root entry zone and trigeminal nuclei. With other clinical and procedure-related factors, we studied its effect on acute pain relief (pain free at hospital discharge) and pain-free survival (PFS). RESULTS: Of the 16 patients, 15 (93.75%) reported acute pain relief; 8 patients (50.00%) experienced a recurrence of pain. At the latest follow-up visit, an excellent outcome (Barrow Neurological Institute grade 1-2) was obtained for 75% of patients and a good outcome (Barrow Neurological Institute grade 3) for 25%. No patient experienced uncontrolled pain. The presence of a pear-like balloon shape during surgery (P = 0.0053) and a MRI detectable lesion in the trigeminal pathway (P = 0.049) were associated with greater PFS. CONCLUSIONS: PBC can be efficient in treating MS-related TN. Some factors, such as a pear-like balloon shape during surgery and evidence of a MRI-detectable lesion in the trigeminal pathway were associated with longer PFS.
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Imageamento por Ressonância Magnética , Esclerose Múltipla/cirurgia , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Oclusão com Balão/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Dor/diagnóstico , Manejo da Dor , Prognóstico , Estudos Retrospectivos , Neuralgia do Trigêmeo/complicações , Neuralgia do Trigêmeo/diagnósticoRESUMO
BACKGROUND: To assess the oncologic outcomes of hypofractionated whole breast irradiation (Hypo-WBI). METHODS: Eligible patients had undergone breast conservative surgery for early breast cancer (pTis-2) and none/limited nodal involvement. Hypo-WBI consisted of 34 Gy in 10 daily fractions over 2 weeks to the whole breast three-dimensional conformal radiotherapy (3DCRT), followed by a single fraction of 8 Gy to the tumor bed after 1 week (electrons). Primary endpoint is freedom from ipsilateral breast tumor recurrence (IBTR). Minimum follow up for living & event-free patients is 3 yrs.; median follow up time of the whole analyzed patient population is 5.4 yrs. (range: 1.8-11.4 yrs). RESULTS: Two hundred fifty-one patients were accrued from 2004 to 2013. All patients underwent local excision of the primary tumor to negative margins. Four patients failed in the ipsilateral breast after a median time of 3.2 years (range: 1.7-5.7 yrs) for a 5-year IBTR-free survival of 98.7% (95%CI: 97.3%-100%). IBTR-free survival was significantly higher for patients with invasive cancer than for patients with intraductal carcinoma (p = 0.036). Within patients with invasive tumors, no clear trends or associations were detected between IBTR and age, grading, molecular subtype, pT or pN stage. At 5 years, the actuarial rates of GR2 fibrosis and GR2+ teleangectasia are 2.4% (95%CI: 0-6.5%) and 7.1% (95%CI: 0.4-13.7%), respectively. Cosmesis was scored as excellent/good by ≈95% of patients and ≈60% of clinicians. CONCLUSIONS: Hypo-WBI in 3 weeks allows excellent oncologic outcomes for invasive breast cancer after conservative surgery. Patients with intraductal carcinoma should be treated with Hypo-WBI only within a controlled study. TRIAL REGISTRATION: IRE-IFO Ethical and Scientific Committee (cod. RS61/04).