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European Journal of Cancer (Oxford,... Jul 2021Soft-tissue sarcomas (STSs) are rare malignancies, accounting for approximately 1% of adult cancer. Metastatic disease carries a poor prognosis, and various efforts have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Soft-tissue sarcomas (STSs) are rare malignancies, accounting for approximately 1% of adult cancer. Metastatic disease carries a poor prognosis, and various efforts have been made to improve the prognosis of advanced STS, to date with little success. Immune checkpoint inhibitors (ICPIs) have substantially improved prognosis for many cancer types. Their role in the treatment of STS, however, remains unravelled.
OBJECTIVE
The objective of the study is to assess the activity of ICPIs in the treatment of STS.
METHODS
We performed a systematic review using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Furthermore, abstracts from European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and Connective Tissue Society Oncology (CTOS) congress were searched from 2017 until 2020. Prospective clinical trials investigating ICPIs, either monotherapy or combination therapy, in STS were available for inclusion. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and major toxicity. Cut-off for clinical activity was defined as an ORR of ≥0.15. Subgroup analysis was carried out as per treatment category, disease setting and histologic subtype, using a random effects model.
RESULTS
We identified 27 studies, including a total of 1012 patients (range 6-85) with more than 25 histologic subtypes. The pooled ORR was 0.14 (95% confidence interval [CI] 0.09-0.18), DCR was 0.55 (95% CI 0.43-0.66), mean PFS range was 1.8-11.5 months and mean OS was 6.1-34.7 months. The pooled ORR as per treatment category was 0.14 for anti-programmed cell death 1 (anti-PD1) monotherapy (95% CI 0.07-0.23), 0.16 for anti-PD1 + anti-cytotoxic T-lymphocyte-associated protein 4 (95% CI 0.06-0.29), 0.20 for anti-PD1 + tyrosine kinase inhibitor (95% CI 0.06-0.38), 0.20 for anti-PD1 + chemo (95% CI 0.06-0.38) and 0.08 for anti-PD1 + immunomodulator (95% CI 0.01-0.19). The pooled ORR as per disease setting was as follows: neoadjuvant treatment, 0.09 (0.00-0.25); advanced disease first line, 0.23 (0.15-0.32) and advanced pretreated, 0.13 (0.09-0.19). High response rates were seen in classic Kaposi sarcoma (CKS), alveolar soft part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (UPS) with ORR of 0.69 (95% CI 0.51-0.82), 0.35 (95% CI 0.27-0.44) and 0.20 (95% CI 0.15-0.27), respectively. Activity was limited in gastrointestinal stromal tumour (ORR 0.01 [95% CI 0.0-0.08]), uterine leiomyosarcoma (ORR 0.06 [95% CI 0.02-0.18]), leiomyosarcoma (ORR 0.10 [95% CI 0.06-0.17]) and liposarcoma (ORR 0.11 [95% CI 0.07-0.17]).
CONCLUSION
Clinical activity of ICPIs in STS is highly variable and depends on histologic subtype, disease setting and concomitant treatment strategy. Activity was high in CKS, ASPS and UPS. Early incorporation of ICPIs in combination with chemotherapy seems a promising strategy that warrants further interest. Translational research integrating molecular profile, biological behaviour and response to ICPIs should determine their role in treatment of STS.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Immune Checkpoint Inhibitors; Prognosis; Programmed Cell Death 1 Receptor; Progression-Free Survival; Sarcoma
PubMed: 34107450
DOI: 10.1016/j.ejca.2021.04.034 -
Pediatric Surgery International Sep 2021Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic... (Review)
Review
Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic features of pediatric GIST are not clearly defined. Clinical knowledge has been largely extrapolated from case series and adult studies. In this systematic review, we aimed to analyze the health outcome metrics of pediatric GIST. Medline and Embase databases were searched using relevant key terms. The original search retrieved 1,892 titles; 27 studies with 184 patients (68% female) were included for final review. The primary tumors were located in the stomach (165/184, 90%), small bowel (12/184, 7%), and elsewhere (7/184, 4%). Individual patient data were available in 125 cases with a median follow-up of 6.7 years. All patients underwent surgical resection, which varied from wide local excision to total gastrectomy. There were 12 deaths (10%), 65 (52%) patients were alive with no evidence of disease, and 31 cases (25%) were alive with disease. Tumor size > 5 cm, high mitotic index, and spindle morphology were predictive of mortality. Pediatric GIST has a more favorable prognosis and different characteristics versus adult tumors. There is a crucial need for international consensus and specific pediatric guidelines for the treatment of this rare tumor.
Topics: Adult; Aged; Child; Female; Gastrointestinal Stromal Tumors; Humans; Intestine, Small; Male; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 34081161
DOI: 10.1007/s00383-021-04931-0 -
Acta Obstetricia Et Gynecologica... Oct 2021Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with...
Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with different clinical and biologic features: adult GCT and juvenile GCT. Most women diagnosed with the adult GCT have a favorable prognosis, with a 5-year survival rate of 97%-98%, but adult GCT has a feature of late relapse; the recurrence time could be more than 20 years after diagnosis. Juvenile GCT has a survival rate of 97% in stage I and a 5-year survival rate of 0%-22% in advanced stage with earlier recurrence than adult GCT. Consequently, the scenario emphasizes the need for early diagnosis, standardized treatment protocols, and long-term follow up. However, there is a lack of consensus regarding accurate diagnosis of GCT and adjuvant treatment. Furthermore, GCT tends to occur in young women, which emphasizes the viability of fertility-sparing surgery. The current review performed a systematic literature review of 60 articles to summarize the latest advances in GCT, with an emphasis on the molecular pathogenesis and survival after fertility-sparing surgery. We found that young women with fertility-sparing surgery had a desirable reproductive and survival outcome compared with those undergoing radical surgery.
Topics: Female; Fertility Preservation; Granulosa Cell Tumor; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Survival Analysis
PubMed: 34027996
DOI: 10.1111/aogs.14189 -
BMC Cancer Apr 2021The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer.
METHODS
Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed.
RESULTS
TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46).
CONCLUSIONS
The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
Topics: Carcinoma, Squamous Cell; Disease-Free Survival; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Stromal Cells
PubMed: 33931044
DOI: 10.1186/s12885-021-08222-8 -
Asian Journal of Surgery Dec 2021Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility... (Meta-Analysis)
Meta-Analysis Review
Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.
Topics: Epidermal Cyst; Humans; Male; Testicular Neoplasms
PubMed: 33893031
DOI: 10.1016/j.asjsur.2021.03.016 -
Stem Cell Reviews and Reports Mar 2022Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials.
METHODS
A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed.
RESULTS
We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD - 2.40, 95 % CI -3.36 to -1.44, p < 0.001). Heterogeneity between studies was observed and included aspects of study design such as enrichment of MSC-EVs with specific anti-tumor molecules, tissue source of MSCs, method of EV isolation, characterization of MSCs and EVs, dosage and administration schedules, and tissue type and source of tumor cells studied.
CONCLUSIONS
MSC-EVs are associated with mixed effects on tumor growth in animal models of cancer. In studies where anti-tumor RNAs are packaged in EVs, a significant reduction in tumor growth was observed. Reducing heterogeneity in study design may accelerate our understanding of the potential effects of MSC-EVs on cancer. [274 words] Forest plot of MSC-EV effect on tumor growth accordinggenetic modification of EVs in animal studies identified from a systematicreview of the literature. All cohorts from studies with multiple interventiongroups are presented separately with control groups divided equally among thegroups. M, modified; H, hypoxia.
Topics: Animals; Disease Models, Animal; Extracellular Vesicles; Mesenchymal Stem Cells; Neoplasms
PubMed: 33860455
DOI: 10.1007/s12015-021-10163-5 -
Clinical Journal of Gastroenterology Aug 2021Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg...
Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg but rarely in the gastrointestinal tract. In this study, we report a case of synovial sarcoma arising in the stomach of a 59-year-old woman. Gastrointestinal endoscopy revealed an ulcerative and hemorrhagic tumor with marginal elevation in the fundus. Histological study showed that the tumor was composed of tightly packed spindle cells in bundles, and one of its component demonstrated significant mitotic activity (> 40/10 high-power fields) in several areas. The diagnosis was confirmed by the evidence of SS18 gene rearrangement, according to immunohistochemistry study, (including a novel SS18-SSX fusion-specific antibody), fluorescent in situ hybridization, and the identification of the SS18-SSX1 and SS18-SSX1/2/4 fusion transcripts using reverse-transcript polymerase chain reaction. No evidence of local recurrence or distant metastasis has been found in the more than 5 years since. Distinguishing synovial sarcoma in the digestive tract from other mesenchymal neoplasms, such as gastrointestinal stromal tumor, may be difficult, especially when spindle-shaped cell proliferation is predominant, as in our patient. Therefore, morphological, immunohistological, and molecular evaluations are important for a comprehensive diagnosis.
Topics: Adult; Biomarkers, Tumor; Female; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Sarcoma, Synovial; Stomach
PubMed: 33844129
DOI: 10.1007/s12328-021-01408-4 -
European Journal of Surgical Oncology :... Jul 2021The influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly associated with the occurrence of R1 resection and may be a confounder of R1 resection in GISTs. The present meta-analysis evaluated the real influence of R1 resection on the prognosis of GISTs by excluding the confounding effect of tumor rupture.
METHODS
The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were searched. Studies that compared R1 with negative microscopic margin (R0) resection in GIST patients and reported the time-to-event data of recurrence-free survival (RFS) or disease-free survival (DFS) were eligible for inclusion. The quality of the observational studies was assessed using the Newcastle-Ottawa scale.
RESULTS
Of the 4896 records screened, 23 retrospective studies with 6248 participants were selected. In the overall analysis, R1 resection resulted in a significantly shorter RFS/DFS than R0 resection for GISTs (HR = 1.80, 95% CI = 1.54-2.10, P < 0.001, I = 14%). However, the inferior RFS/DFS vanished when tumor rupture cases were excluded (HR = 1.34, 95% CI = 0.98-1.83, P = 0.07, I = 33%). Sensitivity analysis by high-quality studies brought about a more robust HR of 1.15 (95% CI = 0.88-1.50, P = 0.29), with low heterogeneity (I = 0%). The qualities of evidence for the outcomes were high.
CONCLUSIONS
This meta-analysis shows that R1 resection did not influence the survival outcome of GISTs. Reresection may not be necessary when positive microscopic margins exist. This analysis could provide high-quality evidence for the development of guidelines.
Topics: Gastrointestinal Stromal Tumors; Humans; Margins of Excision; Prognosis; Rupture; Survival Analysis
PubMed: 33573855
DOI: 10.1016/j.ejso.2021.01.032 -
The British Journal of Ophthalmology Jun 2022This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a 'neuroma' or...
BACKGROUND/AIMS
This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a 'neuroma' or 'microneuroma' in the human cornea using laser-scanning in vivo confocal microscopy (IVCM).
METHODS
The review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature.
RESULTS
Twenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed 'neuromas' and 'microneuromas' could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological.
CONCLUSION
These findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features.
Topics: Cornea; Corneal Stroma; Humans; Lasers; Microscopy, Confocal; Neuroma
PubMed: 33568390
DOI: 10.1136/bjophthalmol-2020-318156 -
Current Problems in Cancer Jun 2021Nilotinib has been used as a third-line drug for gastrointestinal stromal tumors (GISTs) after a failure of sunitinib. In this study, we aimed to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis
Nilotinib has been used as a third-line drug for gastrointestinal stromal tumors (GISTs) after a failure of sunitinib. In this study, we aimed to evaluate the efficacy of nilotinib in different genomic subtypes of GISTs. We searched the English articles through EMBASE, Cochrane Library and PubMed Database regarding to the use of nilotinib on GISTs, which published up to February 15, 2019. Inclusion criteria were: GISTs patients received nilotinib in a clinical trial and had detailed genetic subtype records (such as KIT exon 9, KIT exon 11, or PDGFRA mutations, or wild-type). The clinical benefit rate was used to assess the efficacy of nilotinib. A total of 3 studies involving 218 GISTs were included in this meta-analysis. The overall OR (KIT group vs WT group) was 3.26 (95% CI: 1.14-9.28; P = 0.027, P = 0.613). The overall OR in KIT exon 11 group vs WT group was 5.30 (95% CI: 1.79-15.68; P = 0.003, P = 0.409). The overall OR in KIT exon 9 group vs WT group was 0.13 (95% CI: 0.02-0.86; P = 0.035, P = 0.229). The overall OR in KIT exon 11 group vs exon 9 group was 9.96 (95% CI: 0.39-254.66; P < 0.0001, P = 0.024). Different genotypes of GISTs showed different responses to nilotinib, and KIT exon 11-mutant GISTs mostly benefited from nilotinib, followed by KIT exon 9-mutant or WT one.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Genotype; Humans; Male; Middle Aged; Proto-Oncogene Proteins c-kit; Pyrimidines; Receptor, Platelet-Derived Growth Factor alpha; Treatment Outcome; Young Adult
PubMed: 33495025
DOI: 10.1016/j.currproblcancer.2020.100705