Multidisciplinary expert opinion on the treatment consensus for patients with EGFR mutated NSCLC with brain metastases.

The presence of an epidermal growth factor receptor (EGFR) mutation is associated with higher incidence of brain metastases in patients with non-small cell lung cancer (NSCLC); however, patients with synchronous brain metastases at diagnosis have generally been excluded from clinical trials. As there is limited clinical evidence for managing this patient population, a multidisciplinary group of Spanish medical and radiation oncologists, and neuro-oncologist with expertise treating brain metastases in lung cancer patients met with the aim of reaching and developing an expert opinion consensus on the management of patients with EGFR mutated NSCLC with brain metastases. This consensus contains 26 recommendations and 20 conclusion statements across 21 questions in 7 areas, as well as a first-line treatment algorithm.

Factors of local recurrence and organ preservation with transoral laser microsurgery in laryngeal carcinomas; CHAID decision-tree analysis.

BACKGROUND: Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse. OBJECTIVE: To evaluate prognostic factors of local relapse and local control with TLM (LC-TLM). METHODS: Local relapse and LC-TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed. RESULTS: Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64-27.03; P < .001), paraglottic involvement (2.42, CI: 1.41-4.15; P = .001), anterior commissure involvement (2.12, CI: 1.43-3.14; P < .001), grade of differentiation (1.74, CI: 1.18-2.57; P = .005), and alcohol consumption (1.4, CI: 0.99-1.98; P = .057). Local relapse tended to inversely correlate with experience (0.73, CI: 0.51-1.03; P = .078). The most important factors for local relapse were previous radiotherapy failure and anterior commissure involvement. LC-TLM inversely correlated with previous radiotherapy failure (0.09, CI: 0.03-0.28; P < .001), paraglottic involvement (0.25, CI: 0.14-0.43; P < .001), anterior commissure involvement (0.49, CI: 0.32-0.77; P = .007), margins (0.56, CI: 0.30-1.04; P = .068), and differentiation (0.68, CI: 0.44-1.05; P = .087). LC-TLM correlated with experience (1.71, CI: 1.13-2.55; P = .010). The most important factors for LC-TLM were previous radiotherapy failure and paraglottic involvement. CONCLUSION: Previous radiotherapy failure is the most important factor for local relapse and LC-TLM. In primary treatments, anterior commissure involvement and paraglottic involvement are the most important factors for local relapse and LC-TLM, respectively.

El rol de la radioterapia holocraneal en los pacientes de mal pronóstico con metástasis cerebrales / The role of whole brain radiotherapy in poor prognosis patients with brain metastases

OBJETIVOS: En este estudio se compararon los resultados de la radioterapia holocraneal (RTHC) con el tratamiento farmacológico exclusivo (TFE) respecto del control de síntomas y la mejoría en la función neurológica en pacientes con metástasis cerebrales y con un mal pronóstico según el índice RPA. MÉTODOS: Entre diciembre de 2012 y diciembre de 2014, 100 pacientes con diagnóstico de cáncer ingresados a raíz de metástasis cerebrales sintomáticas fueron valorados por nuestro servicio. Treinta y siete pacientes fueron clasificados como RPA3. En este grupo se compararon los resultados clínicos del TFE (n=11) con los de la RTHC (n=26). RESULTADOS: La mediana de supervivencia fue de 1,2 meses, sin diferencias estadísticamente significativas entre los pacientes que recibieron TFE (0,83 meses) y aquellos tratados con RTHC (1,4 meses) (p = 0,18). No se observaron diferencias en el alivio sintomático ni en la mejoría de la función neurológica entre ambos grupos de tratamiento. En los pacientes tratados con RTHC, el alivio sintomático y la mejoría de la función neurológica no mostraron diferencias estadísticamente significativas cuando se compararon distintas dosis y fraccionamiento de radioterapia ni el tiempo transcurrido entre el diagnóstico de metástasis cerebrales y el inicio del tratamiento. CONCLUSIONES: La RTHC no produjo ningún beneficio clínico en cuanto al control sintomático ni en la mejoría de la función neurológica. No se observaron diferencias en la supervivencia entre ambos grupos de tratamiento. En los pacientes RPA3, el TFE puede ser una opción terapéutica razonable

OBJECTIVES: In this study we analysed the results of whole brain radiotherapy (WBRT) compared to exclusive pharmacologic treatment (EPT) regarding symptom control and improvement of neurological function in patients with brain mestastases and a poor prognosis (RPA3). METHODS: From December 2012 to December 2014, 100 consecutive cancer in patients with symptomatic brain mestastases were assessed in our department. We identified patients classified as RPA3 (n=37) and compared the results of patients receiving EPT (n=11) and those undergoing WBRT (n=26). RESULTS: The median survival of the entire group was 1.2 months, with no statistically significant differences between EPT (0.83 months) and WBRT (1.4 months) (P=.18). Neither were differences in symptom relief observed between the 2 groups at the last follow up. Improvement of neurological signs was poor in both treatment groups. Symptom relief and improvement of neurological function in patients undergoing WBRT showed no differences compared to radiation doses, schedules or the time from brain mestastases diagnosis to the first radiotherapy session. CONCLUSIONS: WBRT did not provide clinical benefits in control of symptoms, improvement of neurological function or survival compared with EPT. In RPA3 inpatients EPT may be a reasonable option of treatment

Pseudoprogression as an adverse event of glioblastoma therapy.

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5-fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606-7.564; P = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; P = 0.0001) but was similar for PsP and nP patients (P = 0.91). OS was shorter-though not significantly so-for PsP than nP patients (OS: 19.5 vs. 27.9 months; P = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P = 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma.

Metástasis asintomáticas de la base craneal: evolución clínica y alternativas terapéuticas / Asymptomatic skull base metastases: clinical course and therapeutic alternatives

Introducción. Las metástasis sintomáticas de la base craneal (MBC) son una progresión infrecuente, tardía y de mal pronóstico en pacientes con tumores sólidos. Sus manifestaciones clínicas pueden agruparse en cinco síndromes característicos, y su tratamiento más frecuente es la radioterapia. Gracias a los progresos tecnológicos en las pruebas de imagen y al seguimiento estrecho de los pacientes con cáncer, las MBC pueden diagnosticarse incidentalmente. En este subgrupo no se conoce la evolución clínica ni se ha establecido la mejor modalidad de tratamiento. Objetivo. Analizar las características clínicas y la evolución de los pacientes diagnosticados incidentalmente de MBC. Pacientes y métodos. Entre enero de 2012 y diciembre de 2015, 31 pacientes con una neoplasia sólida diagnosticados de MBC fueron valorados por nuestro servicio. Resultados. Las MBC se diagnosticaron por la presencia de un síndrome de base craneal (n = 24) o incidentalmente (n = 7). Los pacientes sintomáticos fueron tratados con radioterapia. Todos los pacientes diagnosticados incidentalmente permanecieron sin síntomas relacionados con la afectación de la base craneal hasta la fecha del fallecimiento, aunque frecuentemente presentaron de forma concomitante otros tipos de progresión intracraneal de mal pronóstico. Se observó una diferencia estadísticamente significativa en la supervivencia a favor de los pacientes sintomáticos (p = 0,001). Conclusiones. Las MBC diagnosticadas incidentalmente se asociaron frecuentemente a otros tipos de progresión intracraneal, limitando las opciones terapéuticas (AU)

Introduction. Skull base metastases (SBM) are an infrequent and late type of cancer progression that are associated to poor prognosis. Its clinical manifestations may be grouped in fi ve clinical syndromes and radiotherapy is its more frequent treatment. Because of the improvement in imaging tests and the close follow up of cancer patients, SBM can be diagnosed incidentally. In this group the best option of treatment has not been established. Aim. To analyze the clinical features and outcomes of patients with SBM diagnosed incidentally. Patients and methods. Between January 2012 and December 2015, 31 patients with diagnoses of SBM from solid primary tumor were reviewed. Results. SBM were diagnosed due to skull base syndromes (n = 24) or incidentally (n = 7). Symptomatic patients were treated with radiotherapy. Patients diagnosed incidentally remained without symptoms of craneal base involvement during the follow up, although they frequently had other types of intracranial progression. A statistically significant difference in survival was observed between symptomatic and asymptomatic patients (p = 0.001). Conclusions. The incidentally diagnosed SBM were frequently associated to other types of intracranial progression, limiting the options of treatment (AU)

Lesión cerebral única en pacientes con cáncer / Solitary brain lesion in patients with cancer

No disponible

Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

BACKGROUND: Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). METHODS: We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. RESULTS: One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. CONCLUSION: TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016.

Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab.

Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1ß, VHL, FIH-1, XRCC1, and XRCC5). The results were then correlated with time to progression (TTP), overall survival (OS), and toxicity (epithelitis, mucositis, and folliculitis). The median TTP and OS were better in patients with severe vs mild mucositis (17 vs 7 months, p = 0.03; and 26 vs 12 months, p = 0.016, respectively) and folliculitis (10 vs 7 months, p = 0.01, and 26 vs 10 months, p < 0.001, respectively). Patients with the HIF-1α CT/TT genotype had better OS than those with the wild-type HIF-1α CC genotype (28 vs 13 months, p = 0.035). Patients with the XRCC5 GG/AA genotype had longer TTP than patients with the XRCC5 AG genotype (11 vs 7 months, p = 0.035). Severe skin toxicity and SNPs of HIF-1α and XRCC5 were associated with different outcomes among patients treated with radiotherapy plus cetuximab.

Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: results of a phase II study.

Sunitinib is a tyrosine kinase inhibitor with direct anti-tumor and anti-angiogenesis activity targeting VEGFR 1-2, PDGFR α-ß, c-kit, bFGF, (CSF-1), FLT3 and RET. The present trial examined the activity of sunitinib in 12 patients with newly diagnosed, non-resectable glioblastoma. Patients (≤75 years of age with performance status [PS] ≥2 and minimental status [MMS] ≥25) were treated post-biopsy with sunitinib 37.5 mg daily for 8 weeks pre-radiotherapy, during radiotherapy (60 Gy, 6 weeks) and post-radiotherapy until disease progression. The primary endpoints were overall response rate (ORR; RANO criteria) after 8 weeks of sunitinib and patient tolerance. Secondary endpoints were percentage of patients free of neurological deterioration pre-radiotherapy, percentage of patients completing radiotherapy, progression-free survival (PFS), overall survival (OS), and 1-year survival. A Simon 2-stage design (12 →20) based on ORR was applied to calculate the number of patients needed to detect at least 10 % response with α error of 0.05 and ß error of 0.10. The trial was closed because it did not meet minimal activity criteria. ORR was 0 % with only 1/12 patients (8.3 %) achieving stable disease after sunitinib treatment. No patient showed reduction in gadolinium enhancement. The most frequent G3/4 toxicities were fatigue (24.9 %) and diarrhea (16.6 %); one patient died of a CNS hemorrhage; 10/12 patients (83.3 %) deteriorated neurologically before radiation therapy; median PFS was 7.7 weeks (95 % CI: 7.2-8.2); median OS was 12.8 weeks (95 % CI: 0.5-23.8 weeks); 1-year survival was 0 %. Sunitinib has no activity as monotherapy in glioblastoma, and further investigation of its efficacy in this setting is unwarranted.

Patterns of care and outcome for patients with glioblastoma diagnosed during 2008-2010 in Spain.

BACKGROUND: To assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008-2010 in Spain. METHODS: Retrospective analysis of clinical, therapeutic, and survival data collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals. RESULTS: We identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent predictor (Odds ratio [OR], 1.03; 95% confidence interval [CI],1.01-1.05; P = .006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT ≤42 days was associated with longer progression-free survival (hazard ratio [HR], 0.8; 95% CI, 0.64-0.99; P = .042) but not with overall survival (HR, 0.79; 95% CI, 0.62-1.00; P = .055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8-14.9 months), compared with 17.0 months (95% CI, 15.5-18.4 months; P = .034) among younger patients with GBM treated with the same regimen. CONCLUSIONS: In a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for chemoradiation, initiation of RT ≤42 days was associated with better progression-free survival.

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.

Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.

Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.

Implicación del patrón radiológico en el pronóstico de los tumores oligodendrogliales: correlación con el perfil genético / Implication of radiological pattern in the prognosis of oligodendroglial tumors: correlation with genetic profile

Introducción. La codeleción 1p19q (LOH1p19q) confiere a los tumores oligodendrogliales quimiosensibilidad y un mejor pronóstico en relación con otros gliomas. La investigación dirigida a identificar características radiológicas asociadas a LOH1p19q ha despertado gran interés en los últimos años. Objetivos. Confirmar la existencia de heterogeneidad regional de los parámetros moleculares en los gliomas oligodendrogliales, valorar la asociación entre el perfil genético y determinadas características radiológicas y clínicas, y analizar el valor pronóstico de éstas. Pacientes y métodos. Se incluyeron 54 pacientes tratados según un protocolo preestablecido común. Se valoraron las secuencias T1, con/sin gadolinio, y T2 de la resonancia magnética preoperatoria a ciegas de la información molecular y clínica. El análisis de LOH se efectuó sobre muestras pareadas de ADN tumoral y genómico. Resultados. La presencia de LOH1p se halló fuertemente asociada a LOH19q (p < 0,0001). LOH1p19q resultó más frecuente en los tumores situados en el lóbulo frontal (odds ratio, OR = 5,38; intervalo de confianza del 95%, IC 95% = 1,51-19,13; p = 0,007) y sin necrosis radiológica (OR = 0,17; IC 95% = 0,03-0,80; p = 0,02). La localización frontal (riesgo relativo, RR = 4,499; IC 95% = 1,027-193,708; p = 0,046), la necrosis radiológica (RR = 0,213; IC 95% = 0,065-0,700; p = 0,011) el grado de resección (RR = 9,231; IC 95% = 1,737-49,050; p = 0,009) resultaron factores pronósticos independientes de supervivencia global.Conclusiones. En los tumores oligodendrogliales, además del análisis histológico y el estudio genético-molecular, la valoración e determinadas características radiológicas puede resultar de gran utilidad para definir subgrupos de pacientes con pronóstico y respuesta al tratamiento similares. Los esfuerzos deben dirigirse, por tanto, hacia la utilización combinada de todos los recursos disponibles en cada centro (AU)

Introduction. 1p19q loss of heterozygosity (LOH1p19q) in oligodendroglial tumors has shown to be prognostic of prolonged survival and predictive of therapeutic responsiveness. During the last years, research is actively being directed to the discovery of radiological characteristics related to LOH1p19q. Aims. To confirm the existence of molecular heterogeneity in oligodendroglial tumors in relation to their anatomic distribution, and to evaluate the correlation between molecular profile and other radiological and clinical characteristics and their prognostic impact. Patients and methods. Fifty-four patients with oligodendroglial tumors managed according to a previously established protocol were included. Preoperative SE T1, T1 post-gadolinium and T2 magnetic resonance images were reviewed by two independent neuroradiologists, blinded to clinical and molecular information. LOH analysis was assessed from paired tumor-blood DNA acid samples. Results. LOH1p was highly associated with LOH19q (p < 0.0001), LOH1p (odds ratio, OR = 6.19; 95% confidence interval, 95% CI = 1.66-22.68; p = 0.004), LOH19q (OR = 7.59; 95% CI = 1.84-31.34; p = 0.006) and LOH1p19q (OR = 5.38; 95% CI = 1.51-19.13; p = 0.007) were found to be more frequent in tumors located in the frontal lobe. Frontal location (hazard ratio, HR = 4.499; 95% CI = 1.027-193.708; p = 0.046), ring enhancement (HR = 0.213; 95% CI = 0.065-0.700; p = 0.011) and extent of resection (HR = 9.231; 95% CI = 1.737-49.050; p = 0.009) resulted independent prognostic factors for overall survival in the multivariate analysis. Conclusions. Glioma classification aims to better define patients prognosis. Besides histological and immunohistochemical analyses, molecular information has become of great importance. Our results indicate that the evaluation of some MR features may also be useful. Efforts must be directed toward the use of every available resource at each institution (AU)

Validation of the new Graded Prognostic Assessment scale for brain metastases: a multicenter prospective study.

BACKGROUND: Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. METHODS: A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months. RESULTS: During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. CONCLUSIONS: Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

[Implication of radiological pattern in the prognosis of oligodendroglial tumors: correlation with genetic profile]. / Implicación del patrón radiológico en el pronostico de los tumores oligodendrogliales: correlación con el perfil genético.

INTRODUCTION: 1p19q loss of heterozygosity (LOH1p19q) in oligodendroglial tumors has shown to be prognostic of prolonged survival and predictive of therapeutic responsiveness. During the last years, research is actively being directed to the discovery of radiological characteristics related to LOH1p19q. AIMS. To confirm the existence of molecular heterogeneity in oligodendroglial tumors in relation to their anatomic distribution, and to evaluate the correlation between molecular profile and other radiological and clinical characteristics and their prognostic impact. PATIENTS AND METHODS: Fifty-four patients with oligodendroglial tumors managed according to a previously established protocol were included. Preoperative SE T1, T1 post-gadolinium and T2 magnetic resonance images were reviewed by two independent neuroradiologists, blinded to clinical and molecular information. LOH analysis was assessed from paired tumor-blood DNA acid samples. RESULTS: LOH1p was highly associated with LOH19q (p < 0.0001), LOH1p (odds ratio, OR = 6.19; 95% confidence interval, 95% CI = 1.66-22.68; p = 0.004), LOH19q (OR = 7.59; 95% CI = 1.84-31.34; p = 0.006) and LOH1p19q (OR = 5.38; 95% CI = 1.51-19.13; p = 0.007) were found to be more frequent in tumors located in the frontal lobe. Frontal location (hazard ratio, HR = 4.499; 95% CI = 1.027-193.708; p = 0.046), ring enhancement (HR = 0.213; 95% CI = 0.065-0.700; p = 0.011) and extent of resection (HR = 9.231; 95% CI = 1.737-49.050; p = 0.009) resulted independent prognostic factors for overall survival in the multivariate analysis. CONCLUSIONS: Glioma classification aims to better define patients prognosis. Besides histological and immunohistochemical analyses, molecular information has become of great importance. Our results indicate that the evaluation of some MR features may also be useful. Efforts must be directed toward the use of every available resource at each institution.

Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients.

CONCLUSIONS: Weekly paclitaxel may be an active and well tolerated chemotherapy regimen for patients with platin-resistant advanced head and neck cancer. OBJECTIVES: Weekly paclitaxel should be an active and well tolerated regimen for palliative treatment of platin-resistant patients with recurrent or metastatic carcinoma of the head and neck. We analyzed the antitumor activity and toxicity profile. PATIENTS AND METHODS: Sixty consecutive patients with advanced head and neck cancer were treated with 1 h infusion of paclitaxel, 80 mg/m(2) weekly, for 6 consecutive weeks. Patients who showed disease response or disease stabilization continued until progression of disease. RESULTS: A total of 719 doses of paclitaxel were administered to the 60 patients. No complete response was observed. Partial response and stable disease were observed in 26 (43.3%) and 9 (15%) patients, respectively. Median time to tumor progression for patients who responded to therapy was 6.2 months (SD=1.3; 95% CI, 3.7-8.6) and the overall median survival in this group of patients was 8.5 months (SD=1.4; 95% CI, 5.7-11.2). The main toxic effects were leukopenia (26.6%), anemia (43.3%), fatigue (37.4%), alopecia (18.7%), rash/desquamation (13.3%), and thrombophlebitis (6.8%).

Brain nodules with lung mass: are they always metastases?

In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

A randomized trial of the effect of training in relaxation and guided imagery techniques in improving psychological and quality-of-life indices for gynecologic and breast brachytherapy patients.

PURPOSE: The randomized study aimed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization. METHODS AND MATERIALS: Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona (Spain) were included in this study. The patients were randomly allocated to either the study group (n=32) or the control group (n=34). Patients in both groups received training regarding brachytherapy, but only study group patients received training in relaxation and guided imagery. After collection of sociodemographic data, all patients were given a set of questionnaires on anxiety and depression: the Hospital Anxiety and Depression Scale (HADS), and on quality of life: Cuestionario de Calidad de Vida QL-CA-AFex (CCV), prior to, during and after brachytherapy. RESULTS: The study group demonstrated a statistically significant reduction in anxiety (p=0.008), depression (p=0.03) and body discomfort (p=0.04) compared with the control group. CONCLUSIONS: The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety, depression and body discomfort in patients who must remain isolated while undergoing brachytherapy. This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy.State: This study has passed Ethical Committee review.

Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas.

PURPOSE: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance. The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. EXPERIMENTAL DESIGN: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. RESULTS: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. CONCLUSIONS: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.

Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial.

PURPOSE: To evaluate the safety profile and efficacy of whole brain radiotherapy (WBRT) concomitantly with temozolomide (TMZ) in patients with brain metastases (BM). METHODS AND MATERIALS: Patients with BM were randomly assigned to 30 Gy of WBRT with or without concomitant TMZ (75 mg/m(2)/d) plus two cycles of TMZ (200 mg/m(2)/d for 5 days). The primary outcome was analysis of neurologic toxicity. The primary efficacy measures were 90-day progression-free survival of BM and the radiologic response at Days 30 and 90. RESULTS: We enrolled 82 patients. No neurologic acute toxicity was observed. Grade 3 or worse hematologic toxicity was seen in 3 patients and Grade 3 or worse vomiting in 1 patient of the WBRT plus TMZ arm. The objective response rate at 30 and 90 days and overall survival were similar in both arms. The percentage of patients with progression-free survival of BM at 90 days was 54% for WBRT vs. 72% for WBRT and TMZ (p = 0.03). Death from BM was greater in the WBRT arm (69% vs. 41%, p = 0.03). CONCLUSION: The concomitant use of RT with TMZ was well tolerated and resulted in significantly better progression-free survival of BM at 90 days. Although caution should be used, these results suggest TMZ could improve local control of BM.