Estrogen-related genes for thyroid cancer prognosis, immune infiltration, staging, and drug sensitivity.

BACKGROUND: Thyroid cancer (THCA) has become increasingly common in recent decades, and women are three to four times more likely to develop it than men. Evidence shows that estrogen has a significant impact on THCA proliferation and growth. Nevertheless, the effects of estrogen-related genes (ERGs) on THCA stages, immunological infiltration, and treatment susceptibility have not been well explored. METHODS: Clinicopathological and transcriptome data of patients with THCA from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were cleaned before consensus clustering. Differential expression analysis was performed on the genes expressed between THCA and paraneoplastic tissues in TCGA, and Wayne analysis was performed on the ERGs obtained from the Gene Set Enrichment Analysis MsigDB and differentially expressed genes (DEGs). Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were used to identify the set of estrogen-related differentially expressed genes (ERDEGs) associated with progression-free intervals (PFI) and to establish a prediction model. Receiver operating characteristic curves were plotted to calculate the risk scores and PFI status to validate the predictive effect of the model. Enrichment analyses and immune infiltration analyses were performed to analyze DEGs between the high- and low-risk groups, and a nomogram plot was used in the risk model to predict the PFI of THCA. RESULTS: The expression of 120 ERDEGs differed significantly between the two groups (P < 0.05). Five (CD24, CAV1, TACC1, TIPARP, and HSD17B10) of the eight ERDEGs identified using univariate Cox and LASSO regression were validated via RT-qPCR and immunohistochemistry analysis of clinical tissue samples and were used for clinical staging and drug sensitivity analysis. Risk-DEGs were shown to be associated with immune modulation and tumor immune evasion, as well as defense systems, signal transduction, the tumor microenvironment, and immunoregulation. In 19 of the 28 immune cells, infiltration levels differed between the high- and low-risk groups. High-risk patients in the immunotherapy dataset had considerably shorter survival times than low-risk patients. CONCLUSION: We identified and confirmed eight ERDEGs using a systematic analysis and screened sensitive drugs for ERDEGs. These results provide molecular evidence for the involvement of ERGs in controlling the immunological microenvironment and treatment response in THCA.

A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma.

This study aimed to explore the prognostic and predictive value of autophagy-related lncRNAs in papillary thyroid carcinoma (PTC). The expression data of autophagy-related genes and lncRNAs of the PTC patients were obtained from TCGA database. Autophagy-related-differentially expressed lncRNAs (DElncs) were identified and used to establish the lncRNAs signature predicting patients' progression-free interval (PFI) in the training cohort. Its performance was assessed in the training cohort, validation cohort, and entire cohort. Effects of the signature on I-131 therapy were also explored. We identified 199 autophagy-related-DElncs and constructed a novel six-lncRNAs signature was constructed based on these lncRNAs. This signature had a good predictive performance and was superior to TNM stages and previous clinical risk scores. I-131 therapy was found to be associated with favorable prognosis in patients with high-risk scores but not those with low-risk scores. Gene set enrichment analysis suggested that a series of hallmark gene sets were enriched in the high-risk subgroup. Single-cell RNA sequencing analysis suggested that the lncRNAs were mainly expressed in thyroid cells but not stromal cells. In conclusion, our study constructed a well-performed six-lncRNAs signature to predict PFI and I-131 therapy benefits in PTC.

A cell cycle-related lncRNA signature predicts the progression-free interval in papillary thyroid carcinoma.

The cell cycle plays a vital role in tumorigenesis and progression. Long non-coding RNAs (lncRNAs) are key regulators of cell cycle processes. Therefore, understanding cell cycle-related lncRNAs (CCR-lncRNAs) is crucial for determining the prognosis of papillary thyroid carcinoma (PTC). RNA-seq and clinical data of PTC were acquired from The Cancer Genome Atlas, and CCR-lncRNAs were selected based on Pearson's correlation coefficients. According to univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses, a five-CCR-lncRNA signature (FOXD2-AS1, LOC100507156, BSG-AS1, EGOT, and TMEM105) was established to predict the progression-free interval (PFI) in PTC. Kaplan-Meier survival, time-dependent receiver operating characteristic curve, and multivariate Cox regression analyses proved that the signature had a reliable prognostic capability. A nomogram consisting of the risk signature and clinical characteristics was constructed that effectively predicted the PFI in PTC. Functional enrichment analyses indicted that the signature was involved in cell cycle- and immune-related pathways. Furthermore, we also analyzed the correlation between the signature and immune cell infiltration. Finally, we verified the differential expression of CCR-lncRNAs in vitro using quantitative real-time polymerase chain reaction. Overall, the newly developed prognostic risk signature based on five CCR-lncRNAs may become a marker for predicting the PFI in PTC.

Interfering with ITGB1-DT expression delays cancer progression and promotes cell sensitivity of NSCLC to cisplatin by inhibiting the MAPK/ERK pathway.

Long non-coding RNA ITGB1-DT is involved in the regulation of cancer growth and metastasis. However, the roles of ITGB1-DT in non-small cell lung cancer (NSCLC) progression and sensitivity to cisplatin has not been elucidated. ITGB1-DT expression in NSCLC tissues, and the relationship between ITGB1-DT expression with NSCLC diagnosis, prognosis, clinicopathological features, and immune cell infiltration were investigated in The Cancer Gene Atlas (TCGA) database. The roles and mechanisms of ITGB1-DT in cell growth, migration, and drug sensitivity of NSCLC cells were explored in the cell model. The prognostic nomograms of ITGB1-DT-related genes were evaluated using bioinformatics. ITGB1-DT was overexpressed in NSCLC. Elevated ITGB1-DT expression was related to the late T stage, N stage, M stage, short overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of NSCLC patients. ITGB1-DT was the independent risk factors for poor prognosis, and had diagnostic value for NSCLC patients. Interfering with the ITGB1-DT expression can inhibit the proliferation, migration, and invasion of A549, H1299, and drug-resistant A549/DDP, possibly due to the inhibition of p38 MAPK and ERK phosphorylation levels. ITGB1-DT expression was correlated with the levels of NSCLC immune infiltration cells, such as the TReg, Th, and NK cells. ITGB1-DT-related gene nomograms were associated with the prognosis, and were expected to evaluate the prognosis of NSCLC patients. In conclusion, inhibition of ITGB1-DT expression delayed the growth and metastasis of NSCLC using the MAPK/ERK signaling mechanism and enhanced the sensitivity of NSCLC to cisplatin drugs. These results indicate that ITGB1-DT might be a biomarker for evaluating the diagnosis and prognosis of NSCLC patients.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment.

Centrosome and spindle pole-associated protein (CSPP1) is a centrosome and microtubule-binding protein that plays a role in cell cycle-dependent cytoskeleton organization and cilia formation. Previous studies have suggested that CSPP1 plays a role in tumorigenesis; however, no pan-cancer analysis has been performed. This study systematically investigates the expression of CSPP1 and its potential clinical outcomes associated with diagnosis, prognosis, and therapy. CSPP1 is widely present in tissues and cells and its aberrant expression serves as a diagnostic biomarker for cancer. CSPP1 dysregulation is driven by multi-dimensional mechanisms involving genetic alterations, DNA methylation, and miRNAs. Phosphorylation of CSPP1 at specific sites may play a role in tumorigenesis. In addition, CSPP1 correlates with clinical features and outcomes in multiple cancers. Take brain low-grade gliomas (LGG) with a poor prognosis as an example, functional enrichment analysis implies that CSPP1 may play a role in ferroptosis and tumor microenvironment (TME), including regulating epithelial-mesenchymal transition, stromal response, and immune response. Further analysis confirms that CSPP1 dysregulates ferroptosis in LGG and other cancers, making it possible for ferroptosis-based drugs to be used in the treatment of these cancers. Importantly, CSPP1-associated tumors are infiltrated in different TMEs, rendering immune checkpoint blockade therapy beneficial for these cancer patients. Our study is the first to demonstrate that CSPP1 is a potential diagnostic and prognostic biomarker associated with ferroptosis and TME, providing a new target for drug therapy and immunotherapy in specific cancers.

Alpha-L-Fucosidase Has Diagnostic Value in Prostate Cancer With "Gray-Zone PSA" and Inhibits Cancer Progression via Regulating Glycosylation.

BACKGROUND: This study aimed to explore the diagnostic value of alpha-l-fucosidase (AFU) in prostate cancer (PCa) patients with "gray-zone PSA" and to investigate the correlation between AFU expression and clinicopathological characteristics of PCa patients. METHODS: The level of AFU and other necessary clinicopathological variables of patients were retrieved from electronic medical records. The transcriptome profiling and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The protein level of AFU in tissue was assessed by immunohistochemistry (IHC). All the data were processed by appropriate analysis methods. The p-value of <0.05 was considered statistically significant. RESULTS: AFU showed ideal diagnostic value for PCa with prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/ml, and its optimal cutoffs were 19.5 U/L. Beyond this, low AFU expression was associated with high pathological grade, T stage and N stage, more postoperative residual tumors, and poor primary therapy outcome, as well as shorter progression-free interval. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis illustrated that FUCA1/FUCA2 exerted tumor-suppressive function by regulating the glycosylation. CONCLUSIONS: AFU (<19.5 U/L) could effectively distinguish the PCa from the patients with "gray-zone PSA", and low expression of AFU was an independent unfavorable predictor for the clinicopathological characteristics of PCa patients.

Interferon-lambda (IFNL) germline variations and their significance for HCC and PDAC progression: an analysis of The Cancer Genome Atlas (TCGA) data.

BACKGROUND: Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are malignancies with a leading lethality. With reference to interferons (IFNs) known to mediate antitumor activities, this study investigated the relationship between germline genetic variations in type III IFN genes and cancer disease progression from The Cancer Genome Atlas (TCGA) data. The genetic variations under study tag a gain-or-loss-of-function dinucleotide polymorphism within the IFNL4 gene, rs368234815 [TT/ΔG]. METHODS: The entirety of the TCGA sequencing data was used to assess genotypes of 187 patients with HCC and of 162 patients with PDAC matched for ethnicity. Stratified for IFNL genotypes, both cohorts were subjected to time-to-event analyses according to Kaplan-Meier with regard to the length of the specific progression free interval (PFI) and the overall survival (OS) time as two clinical endpoints for disease progression. RESULTS: Logrank analysis revealed a significant relationship between IFNL genotypes and disease outcome for PDAC. This relationship was not found for HCC. A multiple Cox regression analysis employing patients' age, tumor grade and tumor stage as further covariates proved IFNL genotypes to be independent predictors for PDAC disease outcome. CONCLUSION: This repository-based approach unveiled clinical evidence suggestive for an impact of IFNL germline variations for PDAC progression with an IFNL haplotype predisposing for IFNL4 expression being favorable.

The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 29 million people and has caused more than 900,000 deaths worldwide as of September 14, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. We found that ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-ß, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. These results suggest that ACE2 is a potential protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.

CpG-methylation-based risk score predicts progression in colorectal cancer.

Aim: To identify patients with colorectal cancer (CRC) who are at a truly higher risk of progression, which is key for individualized approaches to precision therapy. Materials & methods: We developed a predictor associated with progression-free interval (PFI) using The Cancer Genome Atlas CRC methylation data. Results: The risk score was associated with PFI in the whole cohort (p < 0.001). A nomogram consisting of the risk score and other significant clinical features was generated to predict the 3- and 5-year PFI in the whole set (area under the curve: 0.79 and 0.71, respectively). Conclusion: The risk score based on 23 DNA-methylation sites may serve as the basis for improved prediction of progression in patients with CRC in future clinical practice.

Progression Risk Assessment of Post-surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms.

Background: Accurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circular RNAs (circRNAs) via the ceRNA mechanism could help establish a novel assessment tool. Methods: ceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. least absolute shrinkage and selection operator (LASSO)-Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC. Results: Six hub DE-mRNAs, namely, CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC, and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the American Thyroid Association risk stratification system and distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size (MACIS) score American Joint Committee on Cancer staging system. Conclusions: Based on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus.

PURPOSE: Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma. METHODS: After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement). RESULTS: Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy. CONCLUSIONS: To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.

Survival correlation of immune response in human cancers.

BACKGROUND: The clinical benefit of immune response is largely unknown. We systematically explored the correlation of immune response with patient outcome in human cancers. RESULTS: The global immune gene signature was primarily located on the plasma membrane with a high gene density at 6p21 and 1q23-1q24. Immune responses varied with a wide range in human cancers. A total of 11 cancer types exhibited significant correlation of immune response with overall survival. Higher immune response was significantly associated with longer overall survival in 7 types and with shorter overall survival in 4 types. In addition, 11 cancer types exhibited significant correlation of immune response with progression-free interval. Higher immune response was significantly associated with longer progression-free interval in 7 types and with shorter progression-free interval in 4 types. METHODS: The Ingenuity Knowledge Base and human genome assembly GRCh38 were used to annotate the immune gene signature by cellular components and genomic coordinates, respectively. We devised an mRNA-based metric of pre-existing immune conditions by using the gene signature, and calculated the metric for 10,062 The Cancer Genome Atlas tumor samples across 32 different cancer types. The Kaplan-Meier method was used to evaluate the overall survival and progression-free interval differences between dichotomic groups stratified by the median metric for each cancer type. CONCLUSIONS: Immune responses have different impacts on patient outcome in different human cancers. Prospective verification is needed before the findings can be applied for clinical trial development.

Identification of a Five-Gene Signature and Establishment of a Prognostic Nomogram to Predict Progression-Free Interval of Papillary Thyroid Carcinoma.

Background: The incidence of papillary thyroid carcinoma (PTC) is high and increasing worldwide. Although prognosis is relatively good, it is important to select the minority of patients with poorer prognosis to avoid side effects associated with unnecessary over-treatment in low-risk patients; this requires accurate prognostic predictions. Materials and Methods: Six PTC expression datasets were obtained from the gene expression omnibus (GEO) database. Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) database. Through integrated analysis of these datasets, highly reliable differentially-expressed genes (DEGs) between tumor and normal tissue were identified and lasso Cox regression was applied to identify DEGs related to the progression-free interval (PFI) and to establish a prognostic gene signature. The performance of a five-gene signature was evaluated based on a Kaplan-Meier curve, receiver operating characteristic (ROC), and Harrell's concordance index (C-index). Multivariate Cox regression analysis was used to identify factors associated with PTC prognosis. Finally, a prognostic nomogram was established based on the TCGA-THCA dataset. Results: A novel five-gene signature was established to predict the PTC PFI, which included PLP2, LYVE1, FABP4, TGFBR3, and FXYD6, and the ROC curve and C-index showed good performance in both training and validation datasets. This could classify patients into high- and low-risk groups with distinct PFIs and differentiate PTC tumors from normal tissue. Univariate Cox regression revealed that this signature was an independent prognostic factor for PTC. The established nomogram, incorporating the prognostic gene signature and clinical parameters, was able to predict the PFI with high efficiency. The gene signature-based nomogram was superior to the American Thyroid Association (ATA) risk stratification to predict PTC PFI. Conclusions: Our study identified a five-gene signature and established a prognostic nomogram, which were reliable in predicting the PFI of PTC; this could be beneficial for individualized treatment and medical decision making.

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting. OBJECTIVES: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value. ANIMALS: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib. METHODS: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs. RESULTS: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics.

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.

Specific immunotypes of canine T cell lymphoma are associated with different outcomes.

Canine lymphoma is a heterogeneous disease with many different subtypes. Lymphoma of T cell type in particular is variable in outcome, and includes subtypes with non-progressive, slowly- and rapidly-progressive disease course. Association of immunotype with disease course is incompletely defined. Here, results of flow cytometric immunotyping of 127 canine T cell lymphomas were analyzed in relation to survival and progression free interval. Samples originated from 101 multicentric, 8 mediastinal, 6 cutaneous, 5 hepatosplenic, 5 gastrointestinal and 2 other anatomic subtypes of T cell lymphoma. Compared to multicentric T cell lymphoma, gastrointestinal lymphoma had shorter survival and progression free interval, and hepatosplenic lymphoma had shorter survival. Among dogs with multicentric T cell lymphoma, immunotypes of CD4+/CD8-/MHCII+, CD4-/CD8+/MHCII+ and CD4-/CD8+/MHCII- were associated with longer survival times than the immunotype of CD4+/CD8-/MHCII-, and immunotypes of CD4+/CD8-/MHCII+, CD4-/CD8+/MHCII-, and CD4-/CD8-/MHCII+ were associated with longer progression free intervals. Dogs with multicentric T cell lymphoma and concurrent leukemia had shorter survival but similar progression free interval compared to those without leukemia. Body weight, sex, hypercalcemia, cell size, expression of CD3 and use of combination or single agent chemotherapy did not significantly affect outcome of multicentric TCL.

Liposomal doxorubicin: Effective treatment for pediatric desmoid fibromatosis.

Efficacy of liposomal doxorubicin (LD) in treating desmoid fibromatosis (DF) in children has not been well evaluated. This retrospective case series examines five children with progressive DF, treated with LD. We report progression-free intervals (PFIs) and radiographic as well as clinical responses for each medication received. LD was well tolerated, with an average 4.5% reduction in tumor size and median PFI of 29 months. Treatment with LD conferred the longest PFI of all medical therapies pursued. Thus, LD is an important treatment option for DF in pediatrics.

Surgery for meningioma in the elderly and long-term survival: comparison with an age- and sex-matched general population and with younger patients.

OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into "elderly" (age ≥ 65 years, n = 162) and "younger" (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75-8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70-1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23-144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23-50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09-6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.

Redistribution of resistance and sensitivity to platinum during the observation period following treatment of epithelial ovarian cancer.

The standard postoperative chemotherapy for epithelial ovarian cancer is a combination therapy including platinum and taxanes. The aim this study was to investigate the degree of platinum sensitivity in patients with relapsed epithelial ovarian cancer according to the treatment-free interval (TFI) and the histological tumor type. The medical records of 405 patients diagnosed with stage III/IV ovarian cancer, including 107 patients who relapsed after attaining a clinical complete response with first-line treatment, were retrospectively reviewed. The degree of platinum sensitivity was assessed by comparing the progression-free survival (PFS) following the second-line treatment. In patients with serous/endometrioid adenocarcinoma who were treated with platinum following relapse, there were significant differences in the PFS between the following groups of patients: those who relapsed within 6 months and those who relapsed between 6 and 12 months; those who relapsed between 6 and 12 months and those who relapsed between 12 and 18 months; and those who relapsed between 12 and 18 months and those who relapsed after 18 months. By contrast, in patients with clear cell/mucinous adenocarcinoma who were treated with platinum following a relapse, there were no significant differences in the PFS between patients who relapsed within 6 months and those who relapsed between 6 and 12 months, while there were significant differences in the PFS between those who relapsed between 6 and 12 months and those who relapsed after 12 months. With regard to the patients who relapsed after 12 months, the PFS of those with clear cell/mucinous adenocarcinoma was significantly shorter compared with the PFS of those with serous/endometrioid adenocarcinoma. Therefore, we considered it justified to classify patients with clear cell/mucinous adenocarcinoma who relapsed within 12 months as platinum-resistant and those who relapsed after 12 months as platinum-sensitive.