Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study).

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

Clinical outcomes and timing on the combination of focal radiation therapy and immunotherapy for the treatment of brain metastases.

Introduction: Radiotherapy is one of the standard treatments for brain metastases (BM). Over the past years, the introduction of immunotherapy as routine treatment for solid tumors has forced investigators to review and evaluate how it would interact with radiation. Radiation and Immunotherapy have shown a synergic effect activating the host's immune system and enhancing treatment response. The combinatory effect on BM is currently under investigation. Methods: Data published on Pubmed to determine toxicity, survival, treatment characteristics and timing on the combination of radiotherapy and immunotherapy for the treatment of BM has been reviewed. Results: Mostly retrospective reviews report an improvement of intracranial progression free survival (iPFS) when combining radioimmunotherapy for BM patients. Two systematic reviews and meta-analysis and one phase II prospective trial also report a benefit on iPFS without an increase of toxicity. Among the published literature, the definition of concurrency is heterogeneous, being one month or even narrowed intervals correlated to better clinical outcomes. Toxicity due to concurrent radioimmunotherapy, specifically symptomatic radionecrosis, is also directly analyzed and reported to be low, similar to the toxicity rates secondary to stereotactic radiosurgery alone. Conclusion: Radiation combined with immunotherapy has shown in predominantly retrospective reviews a synergic effect on the treatment of BM. The concurrent combination of radioimmunotherapy is a feasible therapeutic strategy and seems to improve clinical outcomes, especially iPFS, when delivered within <30 days. Larger prospective and randomized studies are needed to establish reliable outcomes, best delivery strategies and toxicity profile.

Clinicopathological and Neuroimaging Features of Primary Gliosarcoma: A Case Series and Review of Literature.

BACKGROUND: Gliosarcoma (GS) is a rare primary high-grade brain neoplasm with a poor prognosis and challenging surgical resection. Although it is now considered a morphologic variant of IDH-wildtype glioblastoma (World Health Organization Classification of Tumours 2021), GS may display peculiarities that hamper both surgical and oncological management. METHODS: In this retrospective study, we searched our registry for histologically confirmed GS patients between 2006 and 2020. Cases were reviewed for clinical information, pathologic characteristics, imaging findings, management, and outcome. RESULTS: 21 patients with histologically confirmed GS were identified with a median age of 62 years. Twelve were men and 9 women. The temporal lobe was the most common location (9 patients, 42.9%). Nineteen patients underwent surgical resection, and only 4 (19%) demonstrated gross total resection on postsurgical MRI, with an overall median survival of 7 months (range, 0.5-37). Diagnostic MRI demonstrated heterogenous lesions with necrotic-cystic areas and a ring-enhancement pattern. Only 1 case of extracranial extension was seen in our sample, and no patient showed distant metastases. CONCLUSIONS: The rarity of primary GS and the absence of specific therapeutic guidelines represent a significant clinical challenge. Our study provides a comprehensive analysis of clinical and neuroimaging characteristics in a real-world patient cohort and compares our findings with the available literature.

Texture Analysis of the Apparent Diffusion Coefficient Focused on Contrast-Enhancing Lesions in Predicting Survival for Bevacizumab-Treated Patients with Recurrent Glioblastoma.

PURPOSE: Glioblastoma often recurs after treatment. Bevacizumab increases progression-free survival in some patients with recurrent glioblastoma. Identifying pretreatment predictors of survival can help clinical decision making. Magnetic resonance texture analysis (MRTA) quantifies macroscopic tissue heterogeneity indirectly linked to microscopic tissue properties. We investigated the usefulness of MRTA in predicting survival in patients with recurrent glioblastoma treated with bevacizumab. METHODS: We evaluated retrospective longitudinal data from 33 patients (20 men; mean age 56 ± 13 years) who received bevacizumab on the first recurrence of glioblastoma. Volumes of contrast-enhancing lesions segmented on postcontrast T1-weighted sequences were co-registered on apparent diffusion coefficient maps to extract 107 radiomic features. To assess the performance of textural parameters in predicting progression-free survival and overall survival, we used receiver operating characteristic curves, univariate and multivariate regression analysis, and Kaplan-Meier plots. RESULTS: Longer progression-free survival (>6 months) and overall survival (>1 year) were associated with lower values of major axis length (MAL), a lower maximum 2D diameter row (m2Ddr), and higher skewness values. Longer progression-free survival was also associated with higher kurtosis, and longer overall survival with higher elongation values. The model combining MAL, m2Ddr, and skewness best predicted progression-free survival at 6 months (AUC 0.886, 100% sensitivity, 77.8% specificity, 50% PPV, 100% NPV), and the model combining m2Ddr, elongation, and skewness best predicted overall survival (AUC 0.895, 83.3% sensitivity, 85.2% specificity, 55.6% PPV, 95.8% NPV). CONCLUSIONS: Our preliminary analyses suggest that in patients with recurrent glioblastoma pretreatment, MRTA helps to predict survival after bevacizumab treatment.

Persistent lymph nodes after curative chemoradiotherapy for head and neck cancer: imaging predictors of response for decision-making.

PURPOSE: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). MATERIALS AND METHODS: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. RESULTS: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048). CONCLUSIONS: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.

CO2-TOLMS for laryngeal cancer in the elderly, pushing the boundaries of partial laryngectomy.

INTRODUCTION: CO2 transoral laser microsurgery (CO2-TOLMS) has pushed the indications of partial surgery of the larynx regardless the age of the patient. OBJECTIVE: To evaluate the complications and the oncologic and functional outcomes of CO2-TOLMS in patients older and younger than 70 years. METHODS: Retrospective analysis of 1244 consecutive laryngeal carcinomas treated with CO2-TOLMS. Complications, length of hospitalization, functional and survival outcomes were evaluated. RESULTS: The mean age was 64.2 ±â€¯11.1 years (20-96). Four hundred and sixteen patients were older than 70 years and 104 older than 80 years. The main location was the glottis (912), followed by the supraglottis (332). There were no differences in pT classification between the age groups. No differences were observed in voice outcomes. A higher rate of signs of aspiration at the glottic location was observed for those older than 70 years (2.1 % vs 5 %, p = 0.027). The need for definitive gastrostomy in supraglottic tumours was higher in those older than 70 years (0 % vs 6.5 %, p: 0.001). In the glottis, no differences in tracheostomy or gastrostomy rates were observed. Five-year overall survival was lower in the older than 70 years. No differences in disease-specific survival were observed in early stages for both locations, but a lower survival was observed in stage III glottic cancer for the older than 70 years. CONCLUSIONS: CO2-TOLMS is a valid treatment for laryngeal carcinomas in the elderly, with a reduced number of complications and good functional and oncologic outcomes.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms

PurposeThis prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures.MethodsWe evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days).ResultsAt the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years.ConclusionLow dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms.

PURPOSE: This prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures. METHODS: We evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days). RESULTS: At the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years. CONCLUSION: Low dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Transoral laser microsurgery in locally advanced laryngeal cancer: Prognostic impact of anterior versus posterior compartments.

BACKGROUND: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. METHODS: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. RESULTS: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. CONCLUSIONS: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.

Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: A GORTEC internationally-reviewed HNCIG-endorsed consensus.

INTRODUCTION: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. MATERIAL AND METHODS: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. RESULTS: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. CONCLUSION: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

Succinate Pathway in Head and Neck Squamous Cell Carcinoma: Potential as a Diagnostic and Prognostic Marker.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9-100.0] vs. 16.7% [95% CI: 0.0-44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.

RNA sequencing and Immunohistochemistry Reveal ZFN7 as a Stronger Marker of Survival than Molecular Subtypes in G-CIMP-negative Glioblastoma.

PURPOSE: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials. EXPERIMENTAL DESIGN: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes. RESULTS: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes. CONCLUSIONS: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

Is anti-inflammatory radiotherapy an effective treatment in trochanteritis?

OBJECTIVE: To evaluate the analgesic efficacy of low-dose radiotherapy in refractory cases of trochanteritis. METHODS: We evaluated a total of 60 consecutive patients who received low-dose radiotherapy to achieve an anti-inflammatory and analgesic effect for recurrent trochanteritis following scarce response to conventional therapy. All patients were evaluated at baseline (prior to radiotherapy) and at 1 and 4 months after radiotherapy and then yearly thereafter for pain assessment using a visual analogue scale (VAS) and to determine the administration of analgesic treatment. RESULTS: An improvement in the symptomatology was observed in 62% of the patients with a significant reduction in the VAS (8 ± 2 vs 4 ± 2; p < 0.0001), which was largely maintained until the second evaluation at 4 months. In the cases responding to radiotherapy, the probability of maintaining improvement beyond 24 months was 70%. CONCLUSION: Low-dose anti-inflammatory radiation may be used in the treatment of the recurrent cases of relapse or no response of trochanteritis to conventional treatments, with a high probability of remission of pain. These preliminary results indicate the need for evaluating the use of radiotherapy in patients with trochanteritis refractory to conventional treatment in a long-term controlled study. Advances in knowledge: Radiotherapy provides effective analgesic treatment for patients refractory to standard treatment for trochanteritis.

Increased signal intensity in FLAIR sequences in the resection cavity can predict progression and progression-free survival in gliomas / La hiperseñal en la cavidad posquirúrgica en secuencias FLAIR puede predecir la progresión y la supervivencia en gliomas

OBJECTIVE: To determine if hyperintense fluid in the postsurgical cavity on follow-up fluid-attenuated inversion recovery (FLAIR) sequences can predict progression in gliomas. MATERIAL AND METHODS: Observational study of magnetic resonance imaging signal of fluid within the post-surgical cavity in patients with glioma (grade II-IV), with surgery and follow-up between 2007 and 2012. Qualitative comparison between the signal of fluid in the cavity and of the ventricular cerebrospinal fluid (CSF) was performed on FLAIR sequences. Fluid in the cavity was classified as isointense or hyperintense compared to CSF. Double-blind reading was performed. The signal intensity was correlated with tumour progression, assessed using Response Assessment in Neuro-Oncology criteria. RESULTS: A total of 107 patients were included, of whom 90 had high-grade gliomas. Inter-rater agreement was excellent, and intra-rater complete (k = 0.94 and 1, p < .001). Hyperintense fluid in the resection cavity occurred more commonly (58.9% versus 29.4%, p = .025) and earlier (mean 4.5 versus 9.9 months, p < .001) in high-grade than in low-grade gliomas. Hyperintense fluid was associated with progression in high-grade gliomas, with a sensitivity of 65.7% (95% CI, 54.3-75.6%) and a specificity of 70.6% (95% CI, 46.6-87%), and in low-grade gliomas with a sensitivity of 50% (95% CI, 18.7-81.2%), and a specificity of 81.8% (95% CI, 51.1-96%). The positive predictive value of this sign was 90.6% (95% CI, 79.3-96.3%) for high-grade gliomas, and was higher for grade IV (93.2%, 95% CI, 87.3-99.1%) and lower for grade III (77.8%, 95% CI, 59.6-96%), and low-grade gliomas (60%, 95% CI, 22.9-88.4%). False-positives were identified in 7 patients, due to bleeding or infection. Hyperintense fluid in high-grade gliomas preceded progression in 22 patients (30.1%), with a mean of 4.1 months (SD 2.1, 95% CI, 3.2-5), and associated with poorer progression-free survival (mean 6.8 versus 11.7 months, p = .004). CONCLUSIONS: Hyperintense fluid in the resection cavity on follow-up FLAIR sequences occurs more frequently and earlier in high-grade gliomas, and is associated with poorer progression-free survival. Hyperintense fluid is associated with disease progression, and can predict the progression of resected gliomas. False-positives due to bleeding and infection can be observed, and are easily recognizable

OBJETIVO: Analizar si la hiperseñal en la cavidad posquirúrgica en secuencia FLAIR puede predecir la progresión en gliomas. MATERIAL Y MÉTODOS: Estudio observacional de la señal en resonancia magnética de la cavidad posquirúrgica en pacientes con glioma (gradoII-IV), con cirugía y seguimiento entre 2007 y 2012. La comparación cualitativa entre la señal del líquido en la cavidad y del líquido cefalorraquídeo (LCR) normal se realizó en las secuencias FLAIR. El líquido en la cavidad se clasificó como isointenso o hiperintenso en comparación con el LCR. Se utilizó una lectura doble ciego. La intensidad de la señal se correlacionó con la progresión tumoral evaluada según los criterios RANO. RESULTADOS: Se incluyeron 107 pacientes, 90 con gliomas de alto grado. La correlación entre los lectores fue excelente, y la intralector, completa (k = 0,94 y 1, p < 0,001). La hiperseñal en la cavidad de resección ocurrió con mayor frecuencia (58,9% versus 29,4%, p = 0,025) y más temprano (media 4,5 frente a 9,9 meses, p < 0,001) en los gliomas de alto grado que en los de bajo grado. La hiperseñal se asoció a la progresión en los gliomas de alto grado con una sensibilidad del 65,7% (IC 95%, 54,3-75,6%) y una especificidad del 70,6% (IC 95%, 46,6-87%), y en los gliomas de bajo grado con una sensibilidad del 50% (IC 95%, 18,7-81,2%) y una especificidad del 81,8% (IC 95%, 51,1-96%). El valor predictivo positivo de este signo fue del 90,6% (IC 95%, 79,3-96,3%) para los gliomas de alto grado, más alto (93,2%, IC 95%, 87,3-99,1%) para los de grado IV y bajo (77,8%, IC 95%, 59,6-96%) para los de grado III y para gliomas de bajo grado (60%, IC95%, 22,9-88,4%). En 7 pacientes se identificaron falsos positivos debidos a sangrado o infección. La hiperseñal en la cavidad en gliomas de alto grado precedió la progresión en 22 pacientes (30,1%), con una media de 4,1meses (DE 2,1, IC 95%, 3,2-5), y se asoció a peor supervivencia libre de progresión (media 6,8 frente a 11,7 meses, p = 0,004). CONCLUSIONES: La hiperseñal en la cavidad de resección en secuencias FLAIR ocurre con más frecuencia y más temprano en gliomas de alto grado, y se asocia a peor supervivencia libre de progresión. La hiperseñal en la cavidad se asocia a la progresión de la enfermedad y puede predecir la progresión de los gliomas operados. Pueden darse falsos positivos debidos a hemorragia e infección, y son fácilmente reconocibles

Increased signal intensity in FLAIR sequences in the resection cavity can predict progression and progression-free survival in gliomas.

OBJECTIVE: To determine if hyperintense fluid in the postsurgical cavity on follow-up fluid-attenuated inversion recovery (FLAIR) sequences can predict progression in gliomas. MATERIAL AND METHODS: Observational study of magnetic resonance imaging signal of fluid within the post-surgical cavity in patients with glioma (grade II-IV), with surgery and follow-up between 2007 and 2012. Qualitative comparison between the signal of fluid in the cavity and of the ventricular cerebrospinal fluid (CSF) was performed on FLAIR sequences. Fluid in the cavity was classified as isointense or hyperintense compared to CSF. Double-blind reading was performed. The signal intensity was correlated with tumour progression, assessed using Response Assessment in Neuro-Oncology criteria. RESULTS: A total of 107 patients were included, of whom 90 had high-grade gliomas. Inter-rater agreement was excellent, and intra-rater complete (k=0.94 and 1, p<.001). Hyperintense fluid in the resection cavity occurred more commonly (58.9% versus 29.4%, p=.025) and earlier (mean 4.5 versus 9.9 months, p<.001) in high-grade than in low-grade gliomas. Hyperintense fluid was associated with progression in high-grade gliomas, with a sensitivity of 65.7% (95%CI, 54.3-75.6%) and a specificity of 70.6% (95%CI, 46.6-87%), and in low-grade gliomas with a sensitivity of 50% (95%CI, 18.7-81.2%), and a specificity of 81.8% (95%CI, 51.1-96%). The positive predictive value of this sign was 90.6% (95%CI, 79.3-96.3%) for high-grade gliomas, and was higher for grade IV (93.2%, 95%CI, 87.3-99.1%) and lower for grade III (77.8%, 95%CI, 59.6-96%), and low-grade gliomas (60%, 95%CI, 22.9-88.4%). False-positives were identified in 7 patients, due to bleeding or infection. Hyperintense fluid in high-grade gliomas preceded progression in 22 patients (30.1%), with a mean of 4.1 months (SD 2.1, 95% CI, 3.2-5), and associated with poorer progression-free survival (mean 6.8 versus 11.7 months, p=.004). CONCLUSIONS: Hyperintense fluid in the resection cavity on follow-up FLAIR sequences occurs more frequently and earlier in high-grade gliomas, and is associated with poorer progression-free survival. Hyperintense fluid is associated with disease progression, and can predict the progression of resected gliomas. False-positives due to bleeding and infection can be observed, and are easily recognizable.

Daily schedule for high-dose-rate brachytherapy in postoperative treatment of endometrial carcinoma.

PURPOSE: To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicity in the postoperative treatment of endometrial carcinoma (EC). MATERIALS AND METHODS: From January 2007 to September 2010, 112 patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48-IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid and 23/112 other types. Radiotherapy patients were divided into two groups-Group 1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of 5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy). Toxicity evaluation RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and Fisher exact tests. RESULTS: With a mean follow-up of 29.52 months (range 9.60-53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1); late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9 % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had G1-G2 as vaginal scores for late problems. CONCLUSIONS: (1) Daily HDRBT using two fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment was a safe regime. (2) Group 1 showed a higher incidence of late vaginal toxicity.

Impact of radiotherapy delay on survival in glioblastoma.

BACKGROUND: Previous studies in glioblastoma have concluded that there is no decrease in survival with increasing time to initiation of RT up to 6 weeks after surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6 weeks is not small in some countries. The aim of our study was to evaluate the effect of RT delay beyond 6 weeks on survival of patients who have undergone completed resection of a glioblastoma. METHODS: We reviewed 107 consecutive glioblastoma patients who had a complete surgical resection at our hospital. Clinical data, including delay in initiation of RT, were prospectively collected. The impact of single parameters on overall survival was determined by univariate and multivariate analyses. RESULTS: According to univariate analysis, variables that had a prognostic influence on survival were age (p = 0.036), KPS (p = 0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before 42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance scale, additional treatment with chemotherapy, and initiation of RT before 6 weeks after surgery were favorable, independent prognostic factors of survival. CONCLUSIONS: Survival is significantly reduced in glioblastoma patients if RT is not initiated within the 6 weeks after complete resection of the tumor.

Correlation between clinical findings and magnetic resonance imaging for the assessment of local response after standard treatment in cervical cancer.

BACKGROUND: The aim of our study is to evaluate the correlation between gynecological examination and magnetic resonance (MRI) findings for the assessment of local response in cervical cancer patients treated with radiotherapy/chemotherapy (RT/ChT). PATIENTS AND METHODS: This study is a retrospective review of 75 consecutive cervical cancer patients from April 2004 to November 2009 treated with RT/ChT. Clinical and radiological data were subsequently analyzed. Patient's median age was 51 with a FIGO stage from Ib to IVb. Individualized RT/ChT was administered with a median dose of 45 Gy. Sixty-three patients received a complementary brachytherapy. Seventy-one patients received chemotherapy on a weekly basis. Gynecological exam was performed 3 months and 6 months after treatment and these findings were compared to MRI results at the same time. STATISTIC ANALYSIS: We used the Spearman's Rho test to determine the correlation level between the clinical and radiological methods. RESULTS: A correlation of 0.68 (60%) was observed between the clinical and MRI findings at 3 months with a further increase of up to 0.86 (82.6%) at 6 months. In the few cases with a poor correlation, the subsequent assessment and the natural history of the disease showed a greater value of the clinical exam as compared with the MRI findings. CONCLUSIONS: Physical exam remains an essential tool to evaluate the local response to RT/ChT for cervical cancer. The optimal clinical radiological correlation found at 6 months after treatment suggests that the combination of gynecological examination and MRI are probably adequate in patient monitoring.

Endometrial stromal sarcoma. Is there a place for radiotherapy?

OBJECTIVES: The optimal approach in the management of endometrial stromal sarcoma (ESS) remains unclear. The aim of the present study was to retrospectively report the outcome of patients treated for ESS in our hospital over a 27-year period in order to evaluate the treatment results and the role of radiotherapy. PATIENTS AND METHODS: From 1979 to 2006, 13 patients with ESS were treated at the Hospital Clínic of Barcelona. Patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. The 1989 FIGO classification for endometrial carcinoma was used in this retrospective study. Seven patients presented stage I (6 IB and 1 IC), 1 stage II, 3 stage III and 2 stage IV. Nine patients had high-grade tumours with an infiltration of the outer 50% of the myometrium. Postoperative radiotherapy was administered in 10 patients. RESULTS: The mean follow-up of the patients was 54.6 months (range between 3 and 190). Patients with stage IB had a better outcome in comparison to more advanced stages. Five of the six patients with stage IB received adjuvant radiotherapy and none developed local recurrence, while one patient who received no treatment with radiotherapy had a relapse. Seven of the 13 patients had stages over IB: 5 who had received radiotherapy after surgery had locoregional control and 2 who did not receive radiotherapy had local relapse. Nine patients had high-grade tumours, 6 received radiotherapy after surgery and only one had local relapse. Of the three who did not receive radiotherapy, 2 relapsed locally. Local control rate of the patients who received adjuvant radiotherapy was higher than in the patients who did not (88.9% vs. 50%). CONCLUSIONS: Our data reveal that deep myometrial invasion and stage over IB are significantly associated with poor overall survival and this finding is similar to those of studies in patients with endometrial cancer. The present study showed that the local control was higher in patients receiving radiotherapy.

Whole abdominal radiotherapy in ovarian cancer.

OBJECTIVES: The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer. MATERIAL AND METHODS: Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40-70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42-45 Gy in the pelvis. RESULTS: The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery. CONCLUSIONS: Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.