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BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).
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The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1-3. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.
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Evolución Molecular , Inmunoterapia , Neoplasias Pulmonares , Platino (Metal) , Carcinoma Pulmonar de Células Pequeñas , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Células Clonales/efectos de los fármacos , Células Clonales/metabolismo , Células Clonales/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Genes myc/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Mutación , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Recurrencia , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/inmunología , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/terapiaRESUMEN
PURPOSE: The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with exclusively high-risk disease for whom prospective trials are limited, aiming to induce minimal residual disease (MRD) negativity. METHODS: This academic, investigator-initiated, multicenter, phase II trial enrolled patients with high-risk NDMM (HRNDMM) defined by mandatory International Staging System stage II/III combined with del17p, t(4;14), t(14;16), or more than three 1q21 copies as high-risk cytogenetic aberrations (HRCAs). Patients received Isa-KRd induction/consolidation and Isa-KR maintenance. TE patients received high-dose melphalan. TNE patients received two additional Isa-KRd cycles postinduction. This prespecified interim analysis (IA) reports the primary end point, MRD negativity (<10-5, next-generation flow), at the end of consolidation. The secondary end point was progression-free survival (PFS). RESULTS: Among 125 patients with HRNDMM (TE-intention-to-treat [ITT]-IA, 99; TNE-ITT, 26) of the IA population for the primary end point, the median age was 58 (TE-ITT-IA) and 74 (TNE-ITT) years. Del17p was the most common HRCA (TE, 44.4%; TNE, 42.3%); about one third of evaluable TE/TNE patients presented two or more HRCAs, respectively. The trial met its primary end point with MRD negativity rates after consolidation of 67.7% (TE) and 54.2% (TNE) of patients. Eighty-one of 99 TE-ITT-IA patients reached MRD negativity at any time point (81.8%). MRD negativity was sustained for ≥1 year in 62.6% of patients. With a median follow-up of 44 (TE) and 33 (TNE) months, median PFS was not reached in either arm. CONCLUSION: Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.
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Mieloma Múltiple , Humanos , Persona de Mediana Edad , Mieloma Múltiple/terapia , Lenalidomida/uso terapéutico , Lenalidomida/farmacología , Estudios Prospectivos , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ⧠rs1473473D ⧠rs3729931D: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.
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Neoplasias de la Mama , Melatonina , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Melatonina/genética , Melatonina/metabolismo , Teorema de Bayes , Polimorfismo de Nucleótido Simple , Modelos Logísticos , Estudios de Casos y Controles , Predisposición Genética a la EnfermedadRESUMEN
OBJECTIVE: Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker. RESULTS: TERT and MYC status was analyzed using digital PCR (dPCR) in tumor and adjacent non-tumor tissue samples of 114 lung cancer patients. The difference between tumor and non-tumor samples were statistically significant (p < 0.0001) for TERT and MYC. Using a predefined specificity of 99% a sensitivity of 41% and 51% was observed for TERT and MYC, respectively. For the combination of TERT and MYC the overall sensitivity increased to 60% at 99% specificity. We demonstrated that a combination of markers increases the performance in comparison to individual markers. Additionally, the determination of CNV using dPCR might be an appropriate tool in precision medicine.
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Neoplasias Pulmonares , Telomerasa , Humanos , Variaciones en el Número de Copia de ADN/genética , Dosificación de Gen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Reacción en Cadena de la Polimerasa/métodos , Telomerasa/genética , Telomerasa/análisis , Telomerasa/metabolismoRESUMEN
BACKGROUND: To include the patient perspective in the assessment of adverse events in oncology, a patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) was developed by the US National Cancer Institute, the so called PRO-CTCAE. The objective of this study was the development of disease-specific PRO-CTCAE item sets for patients with breast cancer (BC), multiple myeloma (MM), and prostate cancer (PC). METHODS: The cross-sectional survey was conducted at three German outpatient cancer centers. Prevalence and importance of the 78 PRO-CTCAE symptoms were assessed using a patient questionnaire. To select the most relevant PRO-CTCAE items for each tumor entity, symptoms were ranked based on patient answers. RESULTS: 101 patients with BC, 107 with MM, and 66 with PC participated. The final item sets contained 21 symptoms (BC) or 19 symptoms (MM and PC), respectively. Eight symptoms (fatigue, muscle pain, insomnia, joint pain, general pain, dizziness, shortness of breath, and swelling) were represented in all three item sets. Fatigue was the symptom with the highest ranking across item sets followed by insomnia. Symptoms with the highest rankings represented in only one item set were symptoms affecting the urogenital system in the PC item set, blurred vision in the BC item set, and decreased appetite in the MM item set. CONCLUSIONS: Individual PRO-CTCAE item sets for a German patient population were developed for the three tumor entities on the basis of patients' differences in symptom profiles and perceptions. The quality and psychometric criteria of the newly compiled item sets should be evaluated in validation studies.
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Neoplasias de la Mama , Mieloma Múltiple , Neoplasias , Neoplasias de la Próstata , Trastornos del Inicio y del Mantenimiento del Sueño , Masculino , Humanos , Estudios Transversales , Pacientes Ambulatorios , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/diagnóstico , Medición de Resultados Informados por el Paciente , DolorRESUMEN
Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07-2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08-1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.
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Neoplasias de la Mama , ADN Helicasas , Humanos , Femenino , Neoplasias de la Mama/genética , ADN Helicasas/genética , Neoplasias de la Mama Triple Negativas/genética , Predisposición Genética a la EnfermedadRESUMEN
Noninvasive detection of aberrant DNA methylation could provide invaluable biomarkers for earlier detection of triple-negative breast cancer (TNBC) which could help clinicians with easier and more efficient treatment options. We evaluated genome-wide DNA methylation data derived from TNBC and normal breast tissues, peripheral blood of TNBC cases and controls and reference samples of sorted blood and mammary cells. Differentially methylated regions (DMRs) between TNBC and normal breast tissues were stringently selected, verified and externally validated. A machine-learning algorithm was applied to select the top DMRs, which then were evaluated on plasma-derived circulating cell-free DNA (cfDNA) samples of TNBC patients and healthy controls. We identified 23 DMRs accounting for the methylation profile of blood cells and reference mammary cells and then selected six top DMRs for cfDNA analysis. We quantified un-/methylated copies of these DMRs by droplet digital PCR analysis in a plasma test set from TNBC patients and healthy controls and confirmed our findings obtained on tissues. Differential cfDNA methylation was confirmed in an independent validation set of plasma samples. A methylation score combining signatures of the top three DMRs overlapping with the SPAG6, LINC10606 and TBCD/ZNF750 genes had the best capability to discriminate TNBC patients from controls (AUC = 0.78 in the test set and AUC = 0.74 in validation set). Our findings demonstrate the usefulness of cfDNA-based methylation signatures as noninvasive liquid biopsy markers for the diagnosis of TNBC.
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Ácidos Nucleicos Libres de Células , Neoplasias de la Mama Triple Negativas , Humanos , Metilación de ADN , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Biomarcadores de Tumor/genética , ADN , Ácidos Nucleicos Libres de Células/genética , Marcadores Genéticos , Biopsia Líquida , Proteínas Asociadas a Microtúbulos/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: The aim of this study was to examine the validity of PET/CT scans in the preoperative identification of lymph node metastases (LNM) and compare them with postoperative outcomes. METHODS: In this retrospective study, we included 87 patients with a solitary lung nodule or biopsy-proven non-small cell lung cancer treated in our institution from 2009 to 2015. Patients were divided into two groups and four subgroups, depending on pre- and postoperative findings. RESULTS: According to our analysis, PET/CT scan has a sensitivity of 50%, a specificity of 88.89%, a positive predictive value of 63.16%, and a negative predictive value of 82.35%. Among the patients, 13.8% were downstaged in PET-CT, while 8% were upstaged. In 78.2% of cases, the PET/CT evaluation was consistent with the histology. Metastases without extracapsular invasion were seldom recognized on PET/CT. CONCLUSIONS: This analysis showed the significance of extracapsular tumor invasion, which causes an inflammatory reaction, on LNM, which is probably responsible for preoperative false-positive findings. In conclusion, PET/CT scans are very effective in identifying patients without tumors. Furthermore, it is highly probable that patients with negative findings are free of disease.
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Chronic obstructive pulmonary disease (COPD) is a major risk factor for the development of lung adenocarcinoma (AC). AC often develops on underlying COPD; thus, the differentiation of both entities by biomarker is challenging. Although survival of AC patients strongly depends on early diagnosis, a biomarker panel for AC detection and differentiation from COPD is still missing. Plasma samples from 176 patients with AC with or without underlying COPD, COPD patients, and hospital controls were analyzed using mass-spectrometry-based proteomics. We performed univariate statistics and additionally evaluated machine learning algorithms regarding the differentiation of AC vs. COPD and AC with COPD vs. COPD. Univariate statistics revealed significantly regulated proteins that were significantly regulated between the patient groups. Furthermore, random forest classification yielded the best performance for differentiation of AC vs. COPD (area under the curve (AUC) 0.935) and AC with COPD vs. COPD (AUC 0.916). The most influential proteins were identified by permutation feature importance and compared to those identified by univariate testing. We demonstrate the great potential of machine learning for differentiation of highly similar disease entities and present a panel of biomarker candidates that should be considered for the development of a future biomarker panel.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Biomarcadores , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Proteómica , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
Background: Idiopathic recurrent cervical swelling may be caused by lymphatic abnormalities. Methods: Ten patients (9 females, mean age 51.2 ± 7) with idiopathic recurrent cervical swelling underwent MR-lymphangiography (MRL). MR-lymphangiograms were evaluated regarding lymphatic anatomy and flow. Individualized treatment was recommended according to MRL-findings. Results: 8/10 patients presented with left-sided, 2/10 with right-sided swelling. Pathological lymph-flow was identified in all cases: thoracic duct dilatation in patients with left-sided and right lymphatic duct dilatation in right-sided swelling, accessory thoracic lymphatics in 7/10 and reflux in 8/10 cases. In two cases, a lymphatic thrombus was identified.After treatment, symptoms resolved completely in 6/10 cases and partially in 1/10 cases. The remaining three patients have intermittent swellings but have no treatment wish. Conclusion: Idiopathic recurrent cervical swelling can be caused by lymphatic anomalies. MRL displays impaired lymphatic drainage, lymphatic vessel dilatation, and chylolymphatic reflux as hallmarks of this condition and may aid in targeted treatment planning.
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BACKGROUND: To evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy. METHODS: This is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients' medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI). The risks were analyzed before and after start of cancer therapy. Severe toxicity during antineoplastic therapy was captured from medical records according to the Common Terminology Criteria for Adverse Events (CTCAE). The association between grade ≥ 3 toxicity and medication risks was evaluated by univariate as well as multivariate regression adjusted by ECOG and age. RESULTS: The study cohort comprised 136 patients (50% female, mean age 77 years, 42% hematological malignancies). Before the start of cancer therapy, patients took on average 5 drugs as long-term medication and 52% of patients were exposed to polymedication. More than half of patients used at least one PIM. Approximately one third of patients exhibited rPDDI. The prevalence of medication risks increased after start of cancer therapy. rPDDI were significantly associated with severe overall toxicity (OR, 5.07; p = 0.036; 95% Confidence Interval (CI) 1.11-23.14; toxicity in patients with rPDDI 94.1% (32/34) vs 75.9% (60/79) in patients without rPDDI) and hematological toxicity (OR, 3.95; p = 0.010; 95% CI 1.38-11.29; hematological toxicity in patients with rPDDI 85.3% (29/34) vs 59.5% (47/79) in patients without rPDDI). In the multivariate analysis adjusted by ECOG and age, only the association for rPDDI with hematological toxicity remained statistically significant (OR, 4.51; p = 0.007; 95% CI 1.52-13.38). These findings should be further investigated in larger studies. CONCLUSION: Medication risks are common in older patients with cancer and might be associated with toxicity. This raises the need for tailored interventions to ensure medication safety in this patient cohort.
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Antineoplásicos , Neoplasias , Anciano , Antineoplásicos/efectos adversos , Femenino , Humanos , Prescripción Inadecuada , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Polifarmacia , Lista de Medicamentos Potencialmente Inapropiados , Estudios Prospectivos , Factores de RiesgoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin ProgresiónRESUMEN
Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors' institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2-6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.
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Neoplasias Encefálicas , Epilepsia , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Epilepsia/etiología , Epilepsia/cirugía , Libertad , Humanos , Necrosis , Procedimientos Neuroquirúrgicos , Calidad de Vida , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: A shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC). METHODS: Leukocyte subtype-specific unmethylated/methylated CpG sites were selected, and methylation levels at these sites were used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls. RESULTS: The mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66-4.29), all Padj. < 1e-04). A higher neutrophil ratio and lower ratios of NK cells, CD4 + T cells, CD8 + T cells, monocytes, and B cells were associated with TNBC. The strongest association was observed with decreased NK cell ratio (OR range (1.28-1.42), all Padj. < 1e-04). The NK cell ratio was also significantly lower in pre-diagnostic samples of TNBC cases compared with controls (P = 0.019). CONCLUSION: This immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention.
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Recuento de Leucocitos/estadística & datos numéricos , Neoplasias de la Mama Triple Negativas/genética , Adulto , Estudios de Casos y Controles , Metilación de ADN/genética , Metilación de ADN/inmunología , Epigenómica/métodos , Epigenómica/estadística & datos numéricos , Femenino , Humanos , Recuento de Leucocitos/clasificación , Recuento de Leucocitos/métodos , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/inmunologíaRESUMEN
OBJECT: Intra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS). METHODS: Between 2013 and 2018, 357 patients with BM were surgically treated at the authors' neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation. RESULTS: 122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS. CONCLUSIONS: The present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.
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BACKGROUND: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). METHODS: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors' institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). RESULTS: The median overall survival (mOS) was 11 months (95% CI 8.2-13.8). An age > 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (>48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. CONCLUSIONS: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.
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OBJECT: In the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM. METHODS: Between 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI). RESULTS: A total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected "multiple intracranial metastases" (p=0.001), "infratentorial localization" (p=0.011), "preoperative CRP >5 mg/l" (p=0.01) and "frailest patients (mFI ≥ 0.27)" (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM. CONCLUSIONS: In this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.
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Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients' physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM. Between 2013 and 2018, 141 patients were surgically treated for BM from NSCLC at the authors' institution. The preoperative physical condition was assessed by the temporal muscle thickness (TMT) as a surrogate parameter for sarcopenia and the modified frailty index (mFI). For the ≥65 aged group, median overall survival (mOS) significantly differed between patients classified as 'frail' (mFI ≥ 0.27) and 'least and moderately frail' (mFI < 0.27) (15 months versus 11 months (p = 0.02)). Sarcopenia revealed significant differences in mOS for the <65 aged group (10 versus 18 months for patients with and without sarcopenia (p = 0.036)). The present study confirms a predictive value of preoperative frailty and sarcopenia with respect to OS in patients with NSCLC and surgically treated BM. A combined assessment of mFI and TMT allows the prediction of OS across all age groups.