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International Journal of Molecular... Sep 2023Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any...
Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant ( 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.
Topics: Humans; Female; Neoplasm, Residual; Neoplasm Recurrence, Local; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Oncogenes; Cystadenocarcinoma, Serous; Cell-Free Nucleic Acids
PubMed: 37762691
DOI: 10.3390/ijms241814388 -
Nature Communications Nov 2023While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL)...
While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL) has been reported, the contribution of light chain loci (IGK/IGL) remains elusive. This study is to evaluate the prognosis of IGH and IGK/IGL rearrangement-based MRD detected by next-generation sequencing in B-ALL at the end of induction (EOI) and end of consolidation (EOC). IGK/IGL rearrangements identify 5.5% of patients without trackable IGH clones. Concordance rates for IGH and IGK/IGL are 79.9% (cutoff 0.01%) at EOI and 81.0% (cutoff 0.0001%) at EOC, respectively. Patients with NGS-MRD < 0.01% at EOI or <0.0001% at EOC present excellent outcome, with 3-year event-free survival rates higher than 95%. IGH-MRD is prognostic at EOI/EOC, while IGK-MRD at EOI/EOC and IGL-MRD at EOI are not. At EOI, NGS identifies 26.2% of higher risk patients whose MRD < 0.01% by flow cytometry. However, analyzing IGK/IGL along with IGH fails to identify additional higher risk patients both at EOI and at EOC. In conclusion, IGH is crucial for MRD monitoring while IGK and IGL have relatively limited value.
Topics: Child; Humans; Genes, Immunoglobulin; Neoplasm, Residual; Immunoglobulin Heavy Chains; Precursor Cell Lymphoblastic Leukemia-Lymphoma; High-Throughput Nucleotide Sequencing
PubMed: 37978187
DOI: 10.1038/s41467-023-43171-9 -
Hepatobiliary Surgery and Nutrition Feb 2024With the development of novel active systemic therapies, the landscape of hepatocellular carcinoma (HCC) management is rapidly changing. However, HCC lacks sensitive and... (Review)
Review
Existing and emerging biomarkers in hepatocellular carcinoma: relevance in staging, determination of minimal residual disease, and monitoring treatment response: a narrative review.
BACKGROUND AND OBJECTIVE
With the development of novel active systemic therapies, the landscape of hepatocellular carcinoma (HCC) management is rapidly changing. However, HCC lacks sensitive and specific biomarkers to predict prognosis, monitor for minimal residual disease after locoregional therapy, and predict treatment response. In this review, we aim to summarize the best supporting evidence for refining existing, and development of novel biomarkers for staging, prognosis, determination of minimal residual disease and monitoring treatment response in HCC, focusing on those with evidence in clinical trials.
METHODS
PubMed and Embase databases were searched using the keywords; hepatocellular carcinoma, biomarker, minimal residual disease, surveillance, prognosis, staging, alpha-fetoprotein (AFP), liquid biopsy, treatment response, adjuvant, immunotherapy. Relevant clinical studies were included.
KEY CONTENT AND FINDINGS
AFP remains the major workhorse as the most widely used biomarker in HCC, however, its lack of wide applicability due to the high proportion of patients with HCC who are AFP negative, limits its value throughout all stages of HCC management. Significant work has been done to combine AFP with other clinical and serologic factors to increase its accuracy and utility as a biomarkers. However, it is likely that other more novel biomarkers such as those obtained through liquid biopsy will provide the prognostic power necessary for applications such as detecting recurrence and predicting treatment response. Liquid biopsy provides not only a wealth of potential biomarkers including circulating tumor cells and cell-free RNA/DNA, but also the ability to examine the mutational characteristics of the tumor with next generation sequencing. While early evidence supports the potential impact of many new biomarkers, validation in large clinical trials is lacking.
CONCLUSIONS
This review highlights the paucity of sensitive and specific, widely applicable biomarkers, throughout all phases of management of HCC and summarizes evidence on biomarkers currently in use, as well as those in development and validation. Inclusion of biomarker analysis through clinical trials in HCC is critical to development of optimal therapeutic regimens, and improve patient outcomes.
PubMed: 38322200
DOI: 10.21037/hbsn-22-526 -
Scientific Reports Jul 2023Patients with acute myeloid leukemia (AML) and nucleophosmin 1 gene mutations (NPM1) show a favorable prognosis with chemotherapy (CT) in the absence of negative...
Patients with acute myeloid leukemia (AML) and nucleophosmin 1 gene mutations (NPM1) show a favorable prognosis with chemotherapy (CT) in the absence of negative prognostic genetic abnormalities. Between 2008 and 2021 64 patients with NPM1AML received alloHSCT because of additional adverse prognostic factors (1st line), inadequate response to or relapse during or after CT (2nd line). To expand the evidence in alloTX in NPM1 AML, clinical and molecular data were retrospectively analyzed with respect to pre-transplant strategies and outcome. Patients with minimal residual disease negative (MRD-) CR at transplant had better 2-y-PFS and 2-y-OS (77% and 88%) than patients with minimal residual disease positive (MRD+) CR (41% and 71%) or patients with active disease (AD) at transplant (20% and 52%). The 2nd line patients with relapse after completing CT responded well to high dose cytarabine based salvage chemotherapy (salvage CT) in contrast to patients relapsing while still on CT (90% vs 20%, P = 0.0170). 2-y-PFS and 2-y-OS was 86% in patients who achieved a 2nd MRD- CR pre alloHSCT. Outcome in NPM1AML depends on disease burden at alloHSCT. Time and type of relapse in relation to CT are predictive for response to salvage CT.
Topics: Humans; Nuclear Proteins; Nucleophosmin; Neoplasm, Residual; Retrospective Studies; Mutation; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Prognosis; Recurrence
PubMed: 37402862
DOI: 10.1038/s41598-023-38037-5 -
Gynecologic Oncology Mar 2024Among uterine malignancies, endometrial cancer (EC) is the most common cancer of the female reproductive tract. Traditionally, risk stratification in EC is determined by...
INTRODUCTION
Among uterine malignancies, endometrial cancer (EC) is the most common cancer of the female reproductive tract. Traditionally, risk stratification in EC is determined by standard clinicopathological risk factors. Although circulating tumor DNA (ctDNA) has emerged as a prognostic biomarker in various malignancies, its clinical validity in EC remains to be established.
METHODS
In this analysis of real-world data, 267 plasma samples from 101 patients with stage I EC were analyzed using a tumor-informed ctDNA assay (Signatera™ bespoke mPCR-NGS). Patients were followed post-surgically and monitored with ctDNA testing for a median of 6.8 months (range: 0.37-19.1).
RESULTS
Patients who tested ctDNA-positive at both their first time point and longitudinally experienced inferior recurrence-free survival (RFS) (HR = 6.2; p = 0.0006 and HR = 15.5; p < 0.0001, respectively), and showed a recurrence rate of 58% and 52%, vs. 6% and 0%, respectively for the ctDNA-negative patients. Most ctDNA-positive patients had high-risk histologies or sarcoma, versus low-risk and high-intermediate risk (H-IR) EC. Furthermore, patients with high-risk histologies who were ctDNA-positive showed shorter RFS compared to those who tested negative (HR = 9.5; p = 0.007), and those who tested positive in the low/H-IR cohort (HR = 0.25; p = 0.04). Post-surgically, detectable ctDNA was highly prognostic of clinical outcome and remained the only significant risk factor for recurrence when adjusted for clinicopathological risk factors, such as histologic risk group, mismatch repair (MMR), and p53 status.
CONCLUSION
Incorporating ctDNA monitoring along with traditional known risk factors may aid in identifying patients with stage I EC who are at highest risk of recurrence, and possibly aid in treatment stratification.
Topics: Humans; Female; Prognosis; Circulating Tumor DNA; Endometrial Neoplasms; Neoplasm Recurrence, Local; Biomarkers, Tumor
PubMed: 38262240
DOI: 10.1016/j.ygyno.2023.12.025 -
Thoracic Cancer May 2024Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and...
BACKGROUND
Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA-based MRD detection to predict recurrence in a real-world cohort of primarily early-stage non-small cell lung cancer (NSCLC) patients treated with curative intent.
METHODS
Longitudinal plasma samples were collected post curative-intent treatment from 36 patients with stage I-IV NSCLC. A personalized, tumor-informed assay was used to detect and quantify ctDNA in plasma samples.
RESULTS
Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA-positivity during the MRD window were 15 times more likely to recur compared to ctDNA-negative patients (HR: 15.0, 95% CI: 1.0-253.0, p = 0.010). At any time post-curative intent treatment, ctDNA-positivity was associated with significantly poorer recurrence-free survival compared to persistently ctDNA-negative patients (p < 0.0001).
CONCLUSION
Our real-world data indicate that longitudinal, personalized, tumor-informed ctDNA monitoring is a valuable tool in patients with NSCLC receiving curative treatment to identify patients at high risk for recurrence.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Neoplasm, Residual; Male; Female; Lung Neoplasms; Aged; Middle Aged; Biomarkers, Tumor; Neoplasm Recurrence, Local; Precision Medicine; Prognosis; Aged, 80 and over; Adult
PubMed: 38558374
DOI: 10.1111/1759-7714.15281 -
Aging Sep 2023An increasing number of studies are shown how crucial a role cellular senescence plays in tumor development. In this study, we developed a senescence-related lncRNA...
BACKGROUND
An increasing number of studies are shown how crucial a role cellular senescence plays in tumor development. In this study, we developed a senescence-related lncRNA prognostic index (SRLPI) to forecast radiosensitivity and the probability of biochemical recurrence (BCR) in patients with prostate cancer (PCa).
METHODS
PCa cohorts in TCGA and GEO databases were downloaded. Senescence-and prognosis-related lncRNA with differential expression in tumor and normal samples were identified and used to establish the SRLPI score. Mutation landscape, function pathway, tumor stemness and heterogeneity and tumor immune microenvironment were also analyzed. We performed the analysis using R 3.6.3 and the appropriate tools.
RESULTS
A SRLPI score was constructed based on SNHG1 and MIAT in the TCGA cohort. Our classification of PCa patients into high- and low-risk groups was based on the median SRLPI score. When compared to the low-SRLPI group, the high-SRLPI group was more vulnerable to BCR (HR: 3.33). In terms of BCR-free survival and metastasis-free survival, the GSE116918 showed similar findings. Surprisingly, the SRLPI score demonstrated a high level of radiosensitivity for diagnosis (AUC: 0.98). Age, Gleason score, T stage, N stage, positive lymph nodes, and residual tumor were all significantly greater in patients with high SRLPI scores. Furthermore, this score was significantly related to markers of senescence. Protein secretion and androgen response were found to be substantially enriched in the low-SRLPI group, whereas E2F targets were found to be strongly enriched in the high-SRLPI group for pathway analysis. For the tumor microenvironment assessment, B cells, CD8+ T cells, immune score and TIDE score were positively related to SRLPI score while endothelial level was negatively associated with SRLPI score with statistical significance.
CONCLUSIONS
We developed a SRLPI score that was related to prognosis and radiosensitivity and might be helpful in clinical practice.
PubMed: 37742230
DOI: 10.18632/aging.204888 -
British Journal of Anaesthesia Dec 2023Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for... (Review)
Review
Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for solid organ tumours in cancer patients and is potentially curative. Cancer- and surgery-induced inflammatory processes can facilitate residual tumour cell survival, growth, and subsequent recurrence. However, it has been hypothesised that anaesthetic and analgesic techniques during surgery might influence the risk of cancer recurrence. This narrative review aims to provide an updated summary of recent observational studies and new randomised controlled clinical trials on whether certain specific anaesthetic and analgesic techniques or perioperative interventions during tumour resection surgery of curative intent materially affect long-term oncologic outcomes.
Topics: Humans; Neoplasm Recurrence, Local; Anesthesia; Anesthetics; Analgesics
PubMed: 37689540
DOI: 10.1016/j.bja.2023.07.027 -
Cell Reports. Medicine Mar 2024Drug-tolerant persisters (DTPs) are a rare subpopulation of cells within a tumor that can survive therapy through nongenetic adaptive mechanisms to develop relapse and...
Drug-tolerant persisters (DTPs) are a rare subpopulation of cells within a tumor that can survive therapy through nongenetic adaptive mechanisms to develop relapse and repopulate the tumor following drug withdrawal. Using a cancer cell line with an engineered suicide switch to kill proliferating cells, we perform both genetic screens and compound screens to identify the inhibition of bromodomain and extraterminal domain (BET) proteins as a selective vulnerability of DTPs. BET inhibitors are especially detrimental to DTPs that have reentered the cell cycle (DTEPs) in a broad spectrum of cancer types. Mechanistically, BET inhibition induces lethal levels of ROS through the suppression of redox-regulating genes highly expressed in DTPs, including GPX2, ALDH3A1, and MGST1. In vivo BET inhibitor treatment delays tumor relapse in both melanoma and lung cancer. Our study suggests that combining standard of care therapy with BET inhibitors to eliminate residual persister cells is a promising therapeutic strategy.
Topics: Humans; Neoplasm Recurrence, Local; Lung Neoplasms
PubMed: 38508142
DOI: 10.1016/j.xcrm.2024.101471 -
European Urology Focus Jan 2024Repeat transurethral resection (reTUR) is a guideline-recommended treatment strategy in high-risk non-muscle-invasive bladder cancer (NMIBC) patients treated with... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Repeat transurethral resection (reTUR) is a guideline-recommended treatment strategy in high-risk non-muscle-invasive bladder cancer (NMIBC) patients treated with transurethral resection of bladder tumor (TURBT); however, the impact of recent procedural/technological developments on reTUR outcomes has not been assessed yet.
OBJECTIVE
To assess the outcomes of reTUR for NMIBC in the contemporary era, focusing on whether temporal differences and technical advancement, specifically, photodynamic diagnosis and en bloc resection of bladder tumor (ERBT), affect the outcomes.
EVIDENCE ACQUISITION
Multiple databases were queried in February 2023 for studies investigating reTUR outcomes, such as residual tumor and/or upstaging rates, its predictive factors, and oncologic outcomes, including recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall (OS) survival. We synthesized comparative outcomes adjusting for the effect of possible confounders.
EVIDENCE SYNTHESIS
Overall, 81 studies were eligible for the meta-analysis. In T1 patients initially treated with conventional TURBT (cTURBT) in the 2010s, the pooled rates of any residual tumors and upstaging on reTUR were 31.4% (95% confidence interval [CI]: 26.0-37.2%) and 2.8% (95% CI: 2.0-3.8%), respectively. Despite a potential publication bias, these rates were significantly lower than those in patients treated in the 1990-2000s (both p < 0.001). ERBT and visual enhancement-guided cTURBT significantly improved any residual tumor rates on reTUR compared with cTURBT based on both matched-cohort and multivariable analyses. Among studies adjusting for the effect of possible confounders, patients who underwent reTUR had better RFS (hazard ratio [HR]: 0.78, 95% CI: 0.62-0.97) and OS (HR: 0.86, 95% CI: 0.81-0.93) than those who did not, while it did not lead to superior PFS (HR: 0.74, 95% CI: 0.47-1.15) and CSS (HR: 0.94, 95% CI: 0.86-1.03).
CONCLUSIONS
reTUR is currently recommended for high-risk NMIBC based on the persistent high rates of residual tumors after primary resection. Improvement of resection quality based on checklist applications and recent technical/procedural advancements hold the promise to omit reTUR.
PATIENT SUMMARY
Recent endoscopic/procedural developments improve the outcomes of repeat resection for high-risk non-muscle-invasive bladder cancer. Further investigations are urgently needed to clarify the potential impact of the use of these techniques on the need for repeat transurethral resection in the contemporary era.
Topics: Humans; Neoplasm, Residual; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Cystectomy
PubMed: 37495458
DOI: 10.1016/j.euf.2023.07.002