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Expert Review of Anticancer Therapy Jun 2023A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated... (Meta-Analysis)
Meta-Analysis
Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.
BACKGROUND
A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
METHODS
A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR).
RESULTS
Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors.
CONCLUSION
In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Lymphocytes, Tumor-Infiltrating; CD8-Positive T-Lymphocytes; Prognosis; B7-H1 Antigen
PubMed: 37114477
DOI: 10.1080/14737140.2023.2208351 -
International Journal of Molecular... Mar 2023Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor...
Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Topics: Humans; Ecosystem; Neuroma, Acoustic; Treatment Outcome; Tumor Burden; Tumor Microenvironment
PubMed: 37047498
DOI: 10.3390/ijms24076522 -
Critical Reviews in Oncology/hematology May 2023Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes... (Review)
Review
Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes have been identified in these cancers. In this systematic review, we include studies into molecular subtyping and summarize biological and clinical features of the subtypes within and across sites of origin, searching for suggestions to improve classification and prognostication. PubMed and Embase were searched for original research articles describing potential mesenchymal(-like) mRNA-based subtypes in pancreato-biliary or gynecological adenocarcinomas. Studies limited to supervised clustering were excluded. Fourty-four studies discussing cholangiocarcinomas, gallbladder, ampullary, pancreatic, ovarian, and endometrial adenocarcinomas were included. There was overlap in molecular and clinical features in mesenchymal(-like) subtypes across all adenocarcinomas. Approaches including microdissection were more likely to identify prognosis-associated subtypes. To conclude, molecular subtypes in pancreato-biliary and gynecological adenocarcinomas share biological and clinical characteristics. Furthermore, separation of stromal and epithelial signals should be applied in future studies of biliary and gynecological adenocarcinomas.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Prognosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37004743
DOI: 10.1016/j.critrevonc.2023.103982 -
Journal of Cancer Research and Clinical... Aug 2023Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target...
PURPOSE
Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers.
METHODS
We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease.
RESULTS
Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors.
CONCLUSION
It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.
Topics: HSP90 Heat-Shock Proteins; Gastrointestinal Neoplasms; Humans; Molecular Targeted Therapy; Isoxazoles; Resorcinols; Antineoplastic Agents; Clinical Trials as Topic
PubMed: 36966394
DOI: 10.1007/s00432-023-04689-z -
Scientific Reports Mar 2023The gastrointestinal tract's most commonly occurring primary mesenchymal tumor is the gastrointestinal stromal tumor (GIST). However, few cases worldwide were reported...
The gastrointestinal tract's most commonly occurring primary mesenchymal tumor is the gastrointestinal stromal tumor (GIST). However, few cases worldwide were reported associated with renal cell carcinoma (RCC). Therefore, we aimed to identify the association of genitourinary tumors in patients with GIST in our tertiary care hospital in Saudi Arabia and compare it to the literature. We identified all patients in the pathology department database with the diagnosis of GIST. We excluded duplicate and recurrent cases. We examined patients' files for the presence of RCC, adrenal tumors, or other genitourinary cancer. A systematic review of the association was conducted. From 2003 to 2020, 170 patients had a histopathologic diagnosis of primary GIST, 100 men and 70 women, median age of 57 (range 9-91) years at the time of diagnosis. The site of primary GIST was gastric 103, small bowel 43, mesenteric 5, omentum/peritoneum 7, abdomen 4, isolated adrenal 1, and other 7. Six patients had associated primary genitourinary cancer. Three patients had RCC (two clear cell RCC and one radiologic diagnosis only), and three had adrenal tumors (one adrenal carcinoma, one an isolated adrenal GIST, and one pheochromocytoma). In addition, two patients had a tumor invading the urinary bladder. Although the cohort included 63 men aged 60 or above (median 71 ± 8.7 years, range 60-94), none demonstrated clinical prostatic carcinoma. Data was compared to 69 systematic review articles. We report the rare association between GIST tumors and primary genitourinary cancer, mainly RCC and adrenal tumors. Also, we identified a secondary invasion of the urinary bladder. Unlike the reported series, none of the older male patients had clinical prostate cancer.
Topics: Humans; Male; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Gastrointestinal Stromal Tumors; Carcinoma, Renal Cell; Saudi Arabia; Kidney Neoplasms; Adrenal Gland Neoplasms
PubMed: 36922517
DOI: 10.1038/s41598-023-28060-x -
International Journal of Molecular... Feb 2023Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous... (Review)
Review
Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8 T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo.
Topics: Humans; Neoplasms; Extracellular Vesicles; Killer Cells, Natural; T-Lymphocytes; Immunotherapy; Tumor Microenvironment
PubMed: 36835438
DOI: 10.3390/ijms24044026 -
International Journal of Molecular... Feb 2023Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML)... (Meta-Analysis)
Meta-Analysis
Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in (rs1045642, rs2032582, rs1128503) and one in (rs2231142) and the imatinib plasma trough concentration (C) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the c.421 A allele showed higher imatinib plasma C with respect to the CC/CA carriers (C, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between polymorphisms and imatinib C, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between c.421C>A and imatinib plasma C in GIST and CML patients.
Topics: Humans; Adenosine Triphosphate; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Gastrointestinal Stromal Tumors; Genotype; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prospective Studies
PubMed: 36834713
DOI: 10.3390/ijms24043303 -
Journal of the National Cancer Institute May 2023A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of...
BACKGROUND
A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence.
METHODS
EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020. Trials investigating anticancer drugs for advanced disease, with superiority design and standard treatments as control were eligible. The highest level of preexisting evidence was retrieved from the main study report.
RESULTS
A total of 193 phase III trials were included, and 69 (35.8%) met their primary endpoint. Positivity rates were as follows: gastroesophageal 37%, colorectal 48%, pancreatic 17.1%, hepatocellular 20%, neuroendocrine 75%, and both biliary tract and GIST 60%. No information about preexisting evidence was found for 44 trials (22.8%). For the remaining 149, preexisting evidence consisted of phase II studies in 123 cases (82.6%) and phase I studies in 26 cases (17.4%). The probability of success was 34.1%, 35.8%, and 35.7%, respectively (P = .934). No parameter from prior studies predicted the outcome of phase III trials except β < .2 (P = .048). A numerically increased success rate was observed for phase III trials preceded by positive phase II studies (41.9% vs 18.5%, P = .2).
CONCLUSIONS
There does not appear to be an association between level of prior evidence and success of phase III gastrointestinal cancer trials. These data, along with the high phase III failure rate, highlight the need to improve the drug development process in this setting.
Topics: Humans; Antineoplastic Agents; Medical Oncology; Gastrointestinal Neoplasms; Colorectal Neoplasms; Clinical Trials, Phase III as Topic
PubMed: 36762842
DOI: 10.1093/jnci/djad030 -
Clinical & Translational Oncology :... Jun 2023Tumor microenvironment is infiltrated by many immune cells, of which Regulatory T (Treg) cells are usually considered as negative regulators of the immune responses.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumor microenvironment is infiltrated by many immune cells, of which Regulatory T (Treg) cells are usually considered as negative regulators of the immune responses. However, the effect of FOXP3 (forkhead box transcription factor 3) Treg cells infiltrated into the tumor areas on the prognosis of breast cancer is controversial. This meta-analysis aimed to dissect the potential values of FOXP3 tumor-infiltrating lymphocytes (TILs) as a prognosis predictor of breast cancer.
METHODS
After systematic retrieval of all relevant studies, 28 eligible articles were identified for meta-analysis. Odd ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) were obtained for pooled analyses of pathological complete response (pCR), overall survival (OS), and corresponding forest plots and funnel plots were plotted, respectively.
RESULTS
Pooled results revealed that patients with higher levels of FOXP3 TILs experienced better pCR (OR: 1.24, 95% CI 1.09-1.41) and OS (HR: 0.79, 95% CI 0.64-0.97). Subgroup analysis revealed that elevated FOXP3 TILs were significantly associated with improved pCR (OR: 1.20, 95% CI 1.02-1.40) and OS (HR: 0.22, 95% CI 0.06-0.88) in human epidermal growth factor receptor 2 positive (HER2) breast cancer patients. Furthermore, FOXP3 TILs in the stromal area were statistically correlated with the favorable pCR (OR: 1.22, 95% CI 1.08-1.38) and OS (HR: 0.68, 95% CI 0.49-0.96).
CONCLUSIONS
The predictive role of FOXP3 TILs in the prognosis of breast cancer is influenced by various factors such as molecular subtype of breast cancer and the location of Treg. In HER2 breast cancer and triple-negative breast cancer, FOXP3 TILs are associated with better pCR and OS. Additionally, FOXP3 TILs in stromal represent a favourable prognosis.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Lymphocytes, Tumor-Infiltrating; Triple Negative Breast Neoplasms; T-Lymphocytes, Regulatory; Forkhead Transcription Factors; Tumor Microenvironment
PubMed: 36692642
DOI: 10.1007/s12094-023-03080-1 -
Current Oncology (Toronto, Ont.) Dec 2022Background: Rectal gastrointestinal stromal tumours (GISTs) have many treatment options, but uncertainty remains regarding the best treatment regimen for this rare... (Meta-Analysis)
Meta-Analysis Review
Background: Rectal gastrointestinal stromal tumours (GISTs) have many treatment options, but uncertainty remains regarding the best treatment regimen for this rare pathology. The aim of this review is to assess the optimal management approach including timing of chemotherapy. Methods: PubMed, EMBASE, and Cochrane databases were searched for relevant articles comparing the impact of radical vs. local excision, and neoadjuvant vs. adjuvant therapy had on outcomes in the management of rectal GISTs. We specifically evaluated the influence that the aforementioned factors had on margins, recurrence, overall survival, 5-year disease-free survival, and hospital length of stay. Results: Twenty-eight studies met our predefined criteria and were included in our study, twelve of which were included in the quantitative synthesis. When comparing neoadjuvant versus adjuvant chemotherapy, our meta-analysis noted no significance in terms of margin negativity (R0) (odds ratio [OR] 2.01, 95% confidence interval [CI], 0.7−5.79, p = 0.20) or recurrence rates (OR 0.22, 95% CI, 0.02−1.91, p = 0.17). However, there was a difference in overall 5-year survival in favour of neoadjuvant therapy (OR 3.19, 95% CI, 1.37−7.40, * p = 0.007). Comparing local excision versus radical excision, our meta-analysis observed no significance in terms of overall 5-year survival (OR1.31, 95% CI, 0.81−2.12, p = 0.26), recurrence (OR 0.67, 95% CI, 0.40−1.13, p = 0.12), or 5-year disease-free survival (OR 1.10, 95% CI, 0.55−2.19, p = 0.80). There was a difference in length of hospital stay with a reduced mean length of stay in local excision group (mean difference [MD] 6.74 days less in the LE group; 95% CI, −6.92−−6.56, * p =< 0.00001) as well as a difference in R0 rates in favour of radical resection (OR 0.68, 95% CI, 0.47−0.99, * p = 0.05). Conclusion: Neoadjuvant chemotherapy is associated with improved overall 5-year survival, while local excision is associated with reduced mean length of hospital stay. Further large-volume, prospective studies are required to further define the optimal treatment regimen in this complex pathology.
Topics: Humans; Rectum; Gastrointestinal Stromal Tumors; Rectal Neoplasms; Disease-Free Survival; Combined Modality Therapy
PubMed: 36661683
DOI: 10.3390/curroncol30010034