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BACKGROUND: Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment. METHODS: We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT. RESULTS: A total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0-2, 3, and 4-5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001). CONCLUSIONS: Male sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT.
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Neoplasias Encefálicas , Irradiación Craneana , Cuidados Paliativos , Radiocirugia , Humanos , Masculino , Femenino , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/mortalidad , Radiocirugia/métodos , Anciano , Cuidados Paliativos/métodos , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Irradiación Craneana/métodos , Adulto , Estado de Ejecución de KarnofskyRESUMEN
BACKGROUND: In the treatment of nonsmall cell lung cancer (NSCLC), a disease-free survival of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a disease-free survival of 5 years (late recurrent brain metastasis [LRBM]). METHODS: We reviewed 1281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included. RESULTS: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC. CONCLUSIONS: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Supervivencia sin Enfermedad , Adulto , Anciano , Craneotomía , Mutación , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT). METHODS: Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed. RESULTS: The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage. CONCLUSION: The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.
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Gliosarcoma (GS), a morphological variant of glioblastoma, pathologically shows a biphasic pattern with gliomatous and sarcomatous components. It has been reported that GS has much higher metastatic capacity than glioblastoma. A few reports on the pathology of the extracranial metastasis of GS have shown that metastatic lesions had a sarcomatous component alone or a mixture of gliomatous and sarcomatous ones. Therefore, it is considered that GS tends to disseminate hematogenously due to its mesenchymal sarcomatous component. Herein, we report an autopsy case of GS with multiple extracranial metastases treated by craniotomy, radiotherapy, and bevacizumab. In this case, metastatic lesions at autopsy contained a gliomatous component alone, but no sarcomatous component. In addition, the sarcomatous component disappeared from the intracranial lesion at autopsy after the administration of bevacizumab. In this report, we discuss the clinical course and pathological findings at the initial state, recurrence, and autopsy, including the results of whole-genome analysis.
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Neoplasias Encefálicas , Glioblastoma , Gliosarcoma , Humanos , Gliosarcoma/tratamiento farmacológico , Gliosarcoma/genética , Gliosarcoma/patología , Bevacizumab/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Perfil Genético , Neoplasias Encefálicas/patologíaRESUMEN
Primary intraosseous meningioma (PIM) is a rare tumor that arises in the skull. Histopathologically, it is generally described as a slow-growing, benign lesion. However, on rare occasions, PIM presents as a malignancy with high proliferative ability, which requires maximal resection, adjuvant radiotherapy, and subsequent careful follow-up. Because of the rarity of such cases, they present a diagnostic challenge with unusual pathological findings. Herein, we report a case of a primary intraosseous anaplastic meningioma with extensive invasion inside and outside the skull, along with the results of whole-genome analysis. Histopathological diagnosis was a World Health Organization grade 3 anaplastic meningioma. In the literature, only two cases of anaplastic PIM have been reported, so its characteristics and treatment are poorly understood. Our patient was successfully treated with tumor resection, followed by intensity-modulated radiation therapy. Follow-up imaging studies revealed no recurrence or distant metastasis, including to lung, liver, and bone, at 8 months after the surgery.
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Background: Cerebrospinal fluid (CSF) cytology remains the gold standard approach for diagnosing of leptomeningeal metastases (LM), but has clinical problems due to its low sensitivity. This systemic review and meta-analysis evaluated the diagnostic accuracy of the novel CSF biomarkers of liquid biopsy and magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers. Methods: A systematic search of electronic databases was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI since January 2000 with registration for PROSPERO (#CRD42022301988). Articles were selected based on pre-defined inclusion and exclusion criteria following the PRISMA 2020 statement. Results: The search yielded 3790 citations, and 10 studies with 668 patients were included in the final analysis. The pooled prevalence of LM was 50.9% (340/668). The respective sensitivity and specificity for index tests were as follows: circulating tumor cells (CTC), 87.0% (95% confidence interval [CI] 77.9-92.6%) and 93.8% (86.9-97.2%); cell-free tumor DNA, 97.9% (19.3-100%) and 89.0% (25.3-99.5%); MRI 59.4% (60.7-76.9%) and 97.6% (77.3-99.8%); cytology, 71.9% (54.7-82.9%) and 100%. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI. Conclusion: Novel CSF liquid biopsies and MRI may offer improved diagnostic accuracy for LM from solid cancers; however, further research is required to specify the threshold values and to construct standards for individual primary cancers.
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PURPOSE: The initial brain metastasis velocity (iBMV) was recently reported as a survival predictor after brain metastases (BM) in patients treated by stereotactic radiosurgery. In this study, we validated whether iBMV is a prognostic tool, regardless of treatment modality, in patients with non-small cell lung cancer (NSCLC) with metachronous BM. METHODS: We retrospectively reviewed consecutive 3,792 new lung cancer cases in which no BM was found on magnetic resonance (MR) screening between February 2014 and December 2019, and enrolled 176 NSCLC patients with subsequent BM. Overall survival (OS) was calculated from the date of MR to identify the time from BM to death. RESULTS: The median iBMV score was 1.9. We used an iBMV score of 2.0 as the cutoff level, as previously reported. An iBMV score ≥ 2.0 was significantly associated with older age, high neutrophil-to-lymphocyte ratio, and Stage IV (P = 0.04, 0.02, and 0.02, respectively). The median OS was 0.92 years. The median OS for patients with iBMV score ≥ 2.0 and < 2.0 were 0.59 years and 1.33 years, respectively (P < 0.001). Multivariate analysis showed that an iBMV score ≥ 2.0, ECOG performance status score of 1-3, Stage IV, and non-adenocarcinoma histology were independent poor prognostic factors (hazard ratio (HR), 1.94; P = 0.0001; HR, 1.53; P = 0.04; HR, 1.45; P = 0.04; and HR, 1.14; P = 0.03, respectively). Patients with iBMV scores of < 2.0 were more likely to undergo craniotomy or stereotactic irradiation. CONCLUSIONS: An iBMV score ≥ 2.0 is an independent predictor of survival in NSCLC patients with metachronous BM, regardless of the treatment modality.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , PronósticoRESUMEN
BACKGROUND: Linac-based fractionated stereotactic radiotherapy (fSRT) and stereotactic radiosurgery (SRS) are increasingly being used to manage patients with multiple metastases. This retrospective cohort study aimed to compare the outcomes after linac-based fSRT and SRS between three patient groups classified based on the number of brain metastases (BMs): 1 BM, 2-4 BM, 5-10 BM. METHODS: The data of consecutive patients with 1-10 BMs treated with fSRT or SRS between July 2016 and June 2018 at a single institution were collected. Patients with previous whole-brain radiotherapy (WBRT), concurrent use of WBRT, or surgical resection were excluded from the analysis. A total of 176 patients were classified into three groups according to the number of BMs: 78, 67, and 31 patients in 1 BM, 2-4 BM, and 5-10 BM, respectively. The Kaplan-Meier method was used to estimate overall survival (OS) curves, and the cumulative incidence with competing risks was used to estimate local control (LC), distant intracranial failure (DIF), and radiation necrosis (RN). RESULTS: Median OS was 19.8 months (95% confidence interval [CI] 10.2-27.5), 7.3 months (4.9-11.1), and 5.1 months (4.0-9.0) in 1 BM, 2-4 BM, and 5-10 BM, respectively. Compared to 2-4 BM, 1 BM had significantly better OS (hazard ratio [HR] 0.59, 95% CI 0.40-0.87; p = 0.0075); however, 5-10 BM had comparable OS (HR 1.36, 95% CI 0.85-2.19; p = 0.199). There was no significant difference in LC, DIF, and RN between tumor number groups, but DIF was lower in 1 BM. RN of grade 2 or higher occurred in 21 patients (13.5%); grade 4 and 5 RN were not observed. CONCLUSIONS: The linac-based fSRT and SRS for patients with 5-10 BMs is comparable to that for patients with 2-4 BMs in OS, LC, DIF, and RN. It seems reasonable to use linac-based fSRT and SRS in patients with 5-10 BMs.
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Neoplasias Encefálicas , Traumatismos por Radiación , Radiocirugia , Humanos , Radiocirugia/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Factibilidad , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/secundario , Traumatismos por Radiación/etiologíaRESUMEN
BACKGROUND: The safety and effectiveness of neoadjuvant fractionated stereotactic radiotherapy (FSRT) before piecemeal resection of brain metastasis (BM) remains unknown. METHODS: We retrospectively reviewed 20 consecutive patients with BM who underwent neoadjuvant FSRT followed by piecemeal resection between July 2019 and March 2021. The prescribed dose regimens were as follows: 30 Gy (n = 11) or 35 Gy (n = 9) in five fractions. RESULTS: The mean follow-up duration was 7.8 months (range 2.2-22.3). The median age was 67 years (range 51-79). Fourteen patients were male. All patients were symptomatic. All tumors were located in the supratentorial compartment. The median maximum diameter and volume were 3.7 cm (range 2.6-4.9) and 17.6 cm3 (range 5.6-49.7), respectively. The median time from the end of FSRT to resection was 4 days (range 1-7). Nausea (CTCAE Grade 2) occurred in one patient and simple partial seizures (Grade 2) in two patients during radiation therapy. Gross total removal was performed in seventeen patients and sub-total removal in three patients. Postoperative complications were deterioration of paresis in two patients. Local recurrence was found in one patient (5.0%) who underwent sub-total resection at 2 months after craniotomy. Distant recurrence was found in six patients (30.0%) at a median of 6.9 months. Leptomeningeal disease recurrence was found in one patient (5.0%) at 3 months. No radiation necrosis developed. CONCLUSIONS: Neoadjuvant FSRT appears to be a safe and effective approach for patients with BM requiring piecemeal resection. A multi-institutional prospective trial is needed.
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Neoplasias Encefálicas , Radiocirugia , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Abnormal hypertrophic arachnoid membranes are often observed in the brain-meningioma interface during microsurgery. They contain fibrosis and tumor cell clusters; however, preservation of the membranes does not always cause recurrence from the brain surface, and the optimal treatments in the interface remain unclear. We investigated the incidence of recurrence on the brain surface following extra-arachnoid dissection with an approach emphasizing preservation of the arachnoid membranes in meningiomas of World Health Organization (WHO) Grade I. The features of dissection cleavages in the interface were prospectively recorded at surgery. The patients were followed up with MR imaging regularly. In total, 111 patients were included. The median follow-up time was 97.0 (interquartile range [IQR] 70.0-124.0) months. The cleavages in the interface were classified into three subgroups: the Extra-H group (n = 56) with extra-arachnoid resection and preservation of hypertrophic arachnoid membranes, the Extra-N group (n = 39) with extra-arachnoid resection having normal membranes, and the Subpial resection group (n = 16). Tumors recurred in 13 (11.7%) patients at both the brain and dura mater (n = 1) or at the dura mater alone (n = 12). The median recurrence-free survival (RFS) of all recurrences was significantly related to the Simpson grades (P <0.01). For brain surface recurrence, the median RFS was not related to the subgroups. The Karnofsky Performance Scores (KPSs) significantly improved in the patients except for the Subpial group at 3 months after surgery. This study revealed that hypertrophic arachnoid membranes preserved on the brain surface rarely caused recurrence from the brain in WHO Grade I meningiomas after a long-term follow-up.
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Neoplasias Meníngeas , Meningioma , Encéfalo/patología , Niño , Estudios de Seguimiento , Humanos , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
Project High-tech Omics-based Patient Evaluation (HOPE), which used whole-exome sequencing and gene expression profiling, was launched in 2014. A total of ~2,000 patients were enrolled until March 2016, and the survival time was observed up to July 2019. In our previous study, a tumor microenvironment immune type classification based on the expression levels of the programmed death-ligand 1 (PD-L1) and CD8B genes was performed based on four types: A, adaptive immune resistance; B, intrinsic induction; C, immunological ignorance; and D, tolerance. Type A (PD-L1+ and CD8B+) exhibited upregulated features of T helper 1 antitumor responses. In the present study, survival time analysis at 5 years revealed that patients in type A had a better prognosis than those in other categories [5 year survival rate (%); A (80.5) vs. B (73.9), C (73.4) and D (72.6), P=0.0005]. Based on the expression data of 293 immune response-associated genes, 62 specific genes were upregulated in the type A group. Among these genes, 18 specific genes, such as activated effector T-cell markers (CD8/CD40LG/GZMB), effector memory T-cell markers (PD-1/CD27/ICOS), chemokine markers (CXCL9/CXCL10) and activated dendritic cell markers (CD80/CD274/SLAMF1), were significantly associated with a good prognosis using overall survival time analysis. Finally, multivariate Cox proportional hazard regression analyses of overall survival demonstrated that four genes (GZMB, HAVCR2, CXCL9 and CD40LG) were independent prognostic markers, and GZMB, CXCL9 and CD40LG may contribute to the survival benefit of patients in the immune type A group.
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BACKGROUND/AIM: The enzyme-linked immunospot (ELISPOT) assay is a well-established method used to evaluate the strength of T cell-mediated immune activity, and accepted as a standard functional immunological assay. Cytokine activity is a novel parameter reflecting spot size and intensity, which has not been used in ELISPOT assay before. MATERIALS AND METHODS: In the present study, from 113 ELISPOT assay data derived from previous clinical trials with dendritic cell vaccines, both spot number count and cytokine activity data for IFN-γ secretion were obtained using an ELISPOT reader. Comparing the new parameter cytokine activity with the existing parameter spot number, the feasibility of cytokine activity was investigated. RESULTS: There were no significant differences in sensitivity and specificity between spot number and cytokine activity among ELISPOT assay data from CMVpp65 and other antigen peptide-stimulated cytotoxic T lymphocytes. CONCLUSION: Although cytokine activity is a novel parameter unreported so far, it did not show any advantages in the evaluation T cell immune responses compared to the existing spot number parameter.
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Citocinas/metabolismo , Ensayo de Immunospot Ligado a Enzimas/métodos , Neoplasias/inmunología , Glioblastoma/inmunología , Humanos , Interferón gamma/metabolismo , Leucocitos Mononucleares/inmunología , Melanoma/inmunología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Objectives In EGFR-mutated non-small cell lung cancer (NSCLC) patients, approximately 80-90% of leptomeningeal metastasis (LM) develops after failed initial treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI). However, the efficacy of rechallenging with previously administered EGFR-TKIs in patients with EGFR-mutated NSCLC and the LM that develops following EGFR-TKI treatment failure remains unknown. Materials and methods We retrospectively reviewed medical records of patients with EGFR-mutated NSCLC and LM, from November 2011 to August 2019. The patients were classified according to the LM treatment type: switched to previously unadministered EGFR-TKIs (Switch-TKI) or rechallenge with previously administered EGFR-TKIs (Rechallenge-TKI). Results In total, 50 patients treated with EGFR-TKI after LM diagnosis were included; 35 were treated with Switch-TKI and 15 with Rechallenge-TKI. The median overall survival (OS) from the time of LM diagnosis was 6.2 months in all study patients. According to the treatment type, the median OS from the time of LM diagnosis was 6.9 months in Switch-TKI patients and 4.9 months in Rechallenge-TKI patients. There was no significant difference in the OS between the Switch-TKI and Rechallenge-TKI groups (P = 0.864). Thirty-five patients were treated with erlotinib and 15 with osimertinib; Regardless of the type for EGFR-TKI, there was no significant difference in OS between patients treated with Switch-TKI and those treated with Rechallenge-TKI. Conclusion Rechallenge of previously administered EGFR-TKIs may be a therapeutic option for LM development after EGFR-TKI treatment failure in patients with EGFR-mutated NSCLC, not only switching to previously unadministered EGFR-TKIs.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Carcinomatosis Meníngea/secundario , Persona de Mediana Edad , Estudios Retrospectivos , Factores SexualesRESUMEN
PURPOSE: While leptomeningeal metastasis (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER + HER2-ABC) has a poor prognosis, the details of ER + HER2-LM are unclear. We therefore retrospectively investigated patients with LM from ER + HER2-ABC. METHODS: ER + HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group). RESULTS: Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group. CONCLUSION: Management of LM from ER + HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.
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Neoplasias Encefálicas , Neoplasias de la Mama , Carcinomatosis Meníngea , Neoplasias de la Mama/terapia , Femenino , Humanos , Pronóstico , Receptor ErbB-2/genética , Estudios RetrospectivosRESUMEN
This study aimed to identify the elderly generation with the worst prognoses for high-grade astrocytoma and find independent predictors of good outcomes. We conducted a retrospective analysis of 91 patients, ≥65 years old, with anaplastic astrocytoma or glioblastoma. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using log-rank test or multivariate Cox regression analysis. We included 21 (23%) and 70 (77%) patients aged 65-69 years and ≥70 years. In the two generations, significant differences were found in the Charlson comorbidity index, extent of resection, chemoradiotherapy (CRT) as adjuvant therapy, and radiation dose (all P < 0.05). The median PFS was 9.9 and 6.9 months in patients aged 65-69 and ≥70 years (P = 0.10). The median OS was 22.8 and 11.6 months in patients aged 65-69 and ≥70 years (P = 0.009). In the multivariate analyzes in patients ≥70 years, only postoperative Karnofsky performance status (KPS) scores ≥70 were significantly related to prolonged PFS (hazard ratio [HR]: 0.48, P = 0.04), and postoperative KPS, CRT as adjuvant therapy, and salvage therapy were significantly related to prolonged OS (HR: 0.45, P = 0.03, HR: 0.38, P = 0.002, and HR: 0.43, P = 0.01, respectively). In conclusion, in patients ≥70 with high-grade astrocytoma, OS was significantly shorter compared to those aged 65-69. Postoperative KPS score was significantly related to prolonged PFS and OS. Postoperative CRT and salvage therapy at recurrence may be effective in the selected elderly.
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Astrocitoma/cirugía , Astrocitoma/terapia , Anciano , Astrocitoma/mortalidad , Astrocitoma/radioterapia , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Terapia Recuperativa/métodosRESUMEN
BACKGROUND: The incidence of leptomeningeal metastasis (LM) is underestimated because of its non-specific signs and the low sensitivity of clinical diagnostic modalities. Cerebrospinal magnetic resonance (MR) imaging with and without contrast enhancement (CE) is a gold standard for the neuroradiological assessment of patients with suspected LM. Previous studies suggested that some LM cases show changes of the brainstem surface on non-contrast MR images without or before the appearance of abnormalities on CE images. We assessed the features of this non-contrast MR finding in a cohort of LM patients in this retrospective single-institution study. METHODS: We reviewed head MR images and clinical data of 142 consecutive patients in whom the final diagnosis was LM. RESULTS: We found that 11 of these 142 patients (7.7%) with LM had band-like hyperintensity on the brainstem surface on non-enhanced FLAIR images, which looked like bloomy rind on cheese. Three of seven patients who were examined using diffusion-weighted imaging showed restricted diffusion in the corresponding lesion site. The above-mentioned 11 patients included 10 women and 1 man, with a median age of 61 years. All 11 patients had primary lung adenocarcinoma. Seven patients had symptomatic hydrocephalus. Ten patients had EGFR-mutated and one had ALK-rearrangement adenocarcinomas. Before the diagnosis of LM, 10 patients had undergone systemic therapy with EGFR-TKI or pemetrexed, and 1 patient with ALK inhibitor and bevacizumab. CONCLUSIONS: We present a series of patients with bloomy rind sign that is non-enhancing LM reliably detected by FLAIR hyperintensity on the brainstem surface. This finding is rare, but may reflect the spread of cancer cells in both the leptomeningeal membrane and the surface of the brain parenchyma specifically in patients with lung adenocarcinomas. Further study is needed to determine the clinical significance of this sign, and the pathophysiological factors associated with it may be clarified by analyzing serial MR images in a larger cohort of patients treated for LM.
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Adenocarcinoma del Pulmón/patología , Tronco Encefálico/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/secundario , Anciano , Femenino , Humanos , Aumento de la Imagen , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of the INI1 gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT.
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Neoplasias Encefálicas/patología , Neoplasias Primarias Secundarias/patología , Tumor Rabdoide/patología , Proteína SMARCB1/genética , Adulto , Neoplasias Encefálicas/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Niño , Progresión de la Enfermedad , Humanos , Masculino , Neoplasias Primarias Secundarias/genética , Tumor Rabdoide/genéticaRESUMEN
BACKGROUND/AIM: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy. PATIENTS AND METHODS: Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients. RESULTS: The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients. CONCLUSION: Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.