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Blood Cancer Journal Mar 2022Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or... (Review)
Review
Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is restricted to soft-tissue plasmacytomas that arise due to hematogenous spread and have no contact with bony structures. Typical sites of EMD vary according to the phase of MM. At diagnosis, EMD is typically found in skin and soft tissues; at relapse, typical sites involved include liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura, and pericardium. The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. In patients with newly diagnosed MM, the reported incidence ranges from 0.5% to 4.8%, while in relapsed/refractory MM the reported incidence is 3.4 to 14%. Available data demonstrate that the prognosis is poor, and considerably worse than for MM without soft-tissue plasmacytomas. Among patients with plasmacytomas, those with EMD have poorer outcomes than those with paraskeletal involvement. CNS involvement is rare, but prognosis is even more dismal than for EMD in other locations, particularly if there is leptomeningeal involvement. Available data on treatment outcomes for EMD are derived almost entirely from retrospective studies. Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Plasmacytoma; Prospective Studies; Retrospective Studies; Tumor Microenvironment
PubMed: 35314675
DOI: 10.1038/s41408-022-00643-3 -
Journal of Personalized Medicine Jun 2023Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around... (Review)
Review
A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.
Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.
PubMed: 37374005
DOI: 10.3390/jpm13061016 -
Frontiers in Oncology 2021This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell...
Comparisons Between Frontline Therapy and a Combination of Eltrombopag Plus Immunosuppression Therapy and Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Severe Aplastic Anemia: A Systematic Review.
This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the frontline treatment for severe aplastic anemia (SAA) patients. Four electronic databases and Clinicaltrials.gov were comprehensively searched from January 2010 to August 2020. Studies that aimed at evaluating the efficacy and safety of EPAG+IST or haplo-HSCT in SAA patients were included. One-/2-year overall survival (OS), complete response (CR), and overall response rates (ORRs) were indirectly compared between EPAG+IST and haplo-HSCT. A total of 447 patients involved in 10 cohort studies were found to be eligible for this study. A narrative synthesis was performed due to lack of data directly comparing the outcome of EPAG+IST and haplo-HSCT. Consistent with the analysis results in the whole population, subgroup analyses in the age-matched population showed that there was no significant difference in ORR between EPAG+IST and haplo-HSCT groups. However, the CR rate was lower in the EPAG+IST group when compared with the haplo-HSCT group. The incidence rate of clonal evolution/SAA relapse ranged at 8-14 and 19-31% in the EPAG+IST group but not reported in the haplo-HSCT group. The incidence rate for acute graft vs. host disease (aGVHD) and chronic graft vs. host disease (cGVHD) ranged at 52-57 and 12-67%, respectively, for the haplo-HSCT group. The main causes of deaths were infections in the EPAG+IST group, and GVHD and infections in the haplo-HSCT group. EPAG+IST has a comparable ORR and 1-/2-year OS but lower CR rate when indirectly compared with haplo-HSCT in the frontline treatment of patients with SAA. Patients treated with haplo-HSCT may exhibit a high incidence of GVHD, whereas patients treated with EPAG+IST may experience more relapses or clone evolution.
PubMed: 33981596
DOI: 10.3389/fonc.2021.614965 -
Cytometry. Part B, Clinical Cytometry 2010Individuals with monoclonal B-cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia... (Review)
Review
BACKGROUND
Individuals with monoclonal B-cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia (CLL), and in general populations. MBL and its relationship with CLL have been actively investigated over the last decade. This report systematically reviews the prevalence of MBL in the context of the populations studied and the evolution of laboratory methods used to define MBL.
METHODS
To identify published studies that have assessed the prevalence of MBL, we systematically searched the MEDLINE databases and consulted with members of the International MBL Study Group. We reviewed the 10 articles that were identified by this process. We abstracted information on study populations, laboratory tests, criteria for designating MBL, and the reported frequencies.
RESULTS
Three of the ten studies were published in 2009, three between 2007 and 2008, and four between 2002 and 2004. Reported prevalences varied widely, ranging from 0.12 to 18.2%. This variability was clearly associated with both the laboratory methods and the populations studied. MBL was more common among older individuals and kindred of persons with CLL. The most common MBL subtype was CLL-like MBL.
CONCLUSIONS
Large population-based studies of MBL that employ standardized laboratory methods with a consensus case definition are needed to assess prevalence and establish risk factors. These studies should include prospective follow-up of MBL cases to determine the relationship between MBL and CLL. Data from original studies should be reported in sufficient detail to allow future synthesis of information from multiple studies, such as meta-analysis.
Topics: B-Lymphocytes; Clone Cells; Female; Global Health; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocyte Count; Lymphocytosis; MEDLINE; Male; Prevalence
PubMed: 20839330
DOI: 10.1002/cyto.b.20538 -
Diagnostic Cytopathology Jun 2022In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death-1 (PD-1)/program death ligand-1... (Review)
Review
In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death-1 (PD-1)/program death ligand-1 (PD-L1) axis have become an integral part of treating advanced stage non-small cell lung carcinoma (NSCLC) and many other cancer types. Multiple monoclonal antibodies are available commercially to detect PD-L1 expression in tumor cells by immunohistochemistry (IHC). As most clinical trials initially required tumor biopsy for PD-L1 detection by IHC, many of the currently available PD-1/PD-L1 assays have been developed and validated on formalin fixed tissue specimens. The majority (>50%) of lung cancer cases do not have a surgical biopsy or resection specimen available for ancillary testing and instead must rely primarily on fine needle aspiration biopsy specimens for diagnosis, staging and ancillary tests. Review of the literature shows multiple studies exploring the feasibility of PD-L1 IHC on cytological samples. In addition, there are studies addressing various aspects of IHC validation on cytology preparations including pre-analytical (e.g., different fixatives), analytical (e.g., antibody clone, staining platforms, inter and intra-observer agreement, cytology-histology concordance) and post-analytical (e.g., clinical outcome) issues. Although promising results in this field have emerged utilizing cytology samples, many important questions still need to be addressed. This review summarizes the literature of PD-L1 IHC in lung cytology specimens and provides practical tips for optimizing analysis.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Biopsy, Fine-Needle; Humans; Immunohistochemistry; Lung Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 35293692
DOI: 10.1002/dc.24955 -
Urologic Oncology Jun 2020Following radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC), intravesical recurrence (IVR) is found in 22% to 47% of patients. Patients with...
PURPOSE
Following radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC), intravesical recurrence (IVR) is found in 22% to 47% of patients. Patients with a primary urothelial carcinoma of the bladder (UCB) have an increased risk of a future UTUC (1%-5%). Paired UTUC and UCB might represent clonally related tumors due to intraluminal seeding of tumor cells or might be separate entities of urothelial carcinoma caused by field cancerization. We systematically reviewed all the relevant literature to address the possible clonal relation of UTUC and paired UCB.
MATERIALS AND METHODS
MEDLINE, EMBASE, and COCHRANE databases were systematically searched for relevant citations published between January 2000 and July 2019. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of 5038 citations identified, 86 full papers were screened, and 9 studies met the inclusion criteria.
RESULTS
The populations studied and the molecular techniques used to assess clonality of UTUC and paired UCB differed largely over time. Eight studies reported on primary UTUC and meta- or synchronous IVR without a history of UCB. A total of 118 tumors (55 UTUC and 63 IVR) from 49 patients were included, of which 94% seemed to be clonally related. Five studies reported on primary UCB and subsequent UTUC with a total of 61 tumors (30 UCB and 31 UTUC) from 14 patients; a possible clonal origin was identified for 85% of the tumors.
CONCLUSION
Taking into account the limitations of microsatellite technology in comparison to Next Generation Sequencing and currently accepted concepts of tumor heterogeneity and evolution, this systematic review shows that most, if not all, UTUC and paired UCB likely are clonally related.
Topics: Carcinoma, Transitional Cell; Clone Cells; Humans; Kidney Neoplasms; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Ureteral Neoplasms; Urinary Bladder Neoplasms
PubMed: 32057596
DOI: 10.1016/j.urolonc.2020.01.008 -
Journal of Pharmacy & Pharmaceutical... 2020Bioluminescent imaging (BLI) is a versatile technique that offers non-invasive and real-time monitoring of tumor development in preclinical cancer research. However, the...
PURPOSE
Bioluminescent imaging (BLI) is a versatile technique that offers non-invasive and real-time monitoring of tumor development in preclinical cancer research. However, the technique may be limited by several factors that can lead to misinterpretation of the data. This review aimed to investigate the validity of current BLI tumor models and provide recommendations for future model development.
METHODS
Two major databases, MedLine and EMBASE, were searched from inception to July 2018 inclusively. Studies utilizing mouse xenograft models with demonstration of linear correlations between bioluminescent signal and tumor burden were included. Coefficients of correlation and determination were extracted along with data relating to animal model parameters.
RESULTS
116 studies were included for analysis. It was found that the majority of models demonstrate good correlation regardless of the model type. Selection of a single cell clone with highest luciferase expression resulted in a significantly better correlation. Lastly, appropriate tumor measurement techniques should be utilized when validating the BLI model.
CONCLUSIONS
In general, BLI remains a valid tool for pre-clinical assessment of tumor burden. While no single factor may be identified as a general limitation, data should be interpreted with caution.
Topics: Animals; Disease Models, Animal; Mice; Neoplasms, Experimental; Optical Imaging
PubMed: 32407285
DOI: 10.18433/jpps30870 -
British Journal of Cancer Jul 2003The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer... (Meta-Analysis)
Meta-Analysis Review
The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57-0.86) in seven studies on stages I-II NSCLC; 0.50 (0.39-0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76-1.10) in six studies on any stage NSCLC; 0.57 (0.41-0.78) in five studies on squamous cell cancer; 0.75 (0.61-0.93) and 0.71 (0.61-0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73-1.16) for four studies on small cell lung cancer; 1.26 (0.58-2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.
Topics: Clinical Trials as Topic; Gene Expression Regulation, Neoplastic; Genes, bcl-2; Humans; Lung Neoplasms; Odds Ratio; Prognosis; Proto-Oncogene Proteins c-bcl-2; Research Design; Survival
PubMed: 12838300
DOI: 10.1038/sj.bjc.6601095 -
Cells Nov 2021Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA...
Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic-pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.
Topics: B7-H1 Antigen; Humans; Lymphatic Metastasis; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis
PubMed: 34831388
DOI: 10.3390/cells10113165 -
Disease Markers 2020Recent trials have shown an overall survival (OS) benefit in 10-40% advanced cancer patients treated with programmed cell death 1 (PD-1) or programmed death-ligand 1... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Recent trials have shown an overall survival (OS) benefit in 10-40% advanced cancer patients treated with programmed cell death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. Here, we aimed to evaluate the relationship between PD-L1 expression and the therapeutic efficacy of PD-1 or PD-L1 inhibitors in patients with cancer with recurrent or metastatic disease, compared with control treatments.
METHODS
We systematically searched Medline (PubMed), Embase, and Cochrane Library databases up to Jan 2019 and pooled the treatment effects (hazard ratio or relative ratio) of PD-1/PD-L1 inhibitors in patients with different PD-L1 expression.
RESULTS
Overall, twenty-four qualifying trials with over 14,860 subjects were eligible in this study. Compared with conventional agents, anti-PD/PD-L1 drugs significantly reduced the risk of death (hazard ratio 0.72, 95% CI 0.66 to 0.78), irrespective of the tumor type. Additionally, when PD-L1 expression ≥1% was defined as positive, anti-PD-1/PD-L1 monotherapy correlated with prolonged overall survival in patients with nonsmall cell lung cancer (NSCLC) (0.72, 0.61 to 0.86) and other cancer types (0.66, 0.57 to 0.76) patients with PD-L1 positive, rather than those with PD-L1 negative (hazard ratio for NSCLC and other cancer types: 0.84 and 0.87, respectively; all > 0.05). The subgroup analyses to experimental agents, PD-1/PD-L1 inhibitors, PD-L1 antibody clone, and type of IHC scoring method validated the robustness of these findings. However, anti-PD-1/PD-L1 combination therapies can reduce the risk of death for patients with different cancer types, regardless of PD-L1 expression ( < 0.05 for all PD-L1 expression status).
CONCLUSIONS
We recommend PD-L1 expression as a predictive biomarker in patient selection for anti-PD-1/PD-L1 monotherapy, but not for combination therapies.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms
PubMed: 33488843
DOI: 10.1155/2020/6717912