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Frontiers in Genetics 2023Minimal residual disease (MRD) refers to a very small number of residual tumor cells in the body during or after treatment, representing the persistence of the tumor and... (Review)
Review
Minimal residual disease (MRD) refers to a very small number of residual tumor cells in the body during or after treatment, representing the persistence of the tumor and the possibility of clinical progress. Circulating tumor DNA (ctDNA) is a DNA fragment actively secreted by tumor cells or released into the circulatory system during the process of apoptosis or necrosis of tumor cells, which emerging as a non-invasive biomarker to dynamically monitor the therapeutic effect and prediction of recurrence. The feasibility of ctDNA as MRD detection and the revolution in ctDNA-based liquid biopsies provides a potential method for cancer monitoring. In this review, we summarized the main methods of ctDNA detection (PCR-based Sequencing and Next-Generation Sequencing) and their advantages and disadvantages. Additionally, we reviewed the significance of ctDNA analysis to guide the adjuvant therapy and predict the relapse of lung, breast and colon cancer et al. Finally, there are still many challenges of MRD detection, such as lack of standardization, false-negatives or false-positives results make misleading, and the requirement of validation using large independent cohorts to improve clinical outcomes.
PubMed: 37636270
DOI: 10.3389/fgene.2023.1172108 -
Cancers Oct 2023(1) Background: Endometrial cancer (EC) is a common gynecological malignancy, often diagnosed at an early stage with a high overall survival rate. Surgical treatment is... (Review)
Review
(1) Background: Endometrial cancer (EC) is a common gynecological malignancy, often diagnosed at an early stage with a high overall survival rate. Surgical treatment is the primary approach, guided by pathological and molecular characteristics. Stage IVB EC, characterized by intra and/or extra-abdominal metastasis, presents a significant challenge with no clear consensus on optimal management. (2) Methods: A systematic literature review was conducted from January to May 2023, covering studies from 2000 to 2023. Eligible studies included retrospective case series, prospective trials, and randomized clinical trials. (3) Results: Of 116 studies identified, 21 were deemed relevant: 7 on primary surgery, 10 on neoadjuvant chemotherapy (NACT), and 4 on adjuvant treatment. Notably, the impact of residual tumor after primary surgery was a critical factor affecting survival. The use of NACT followed by interval debulking surgery showed promise, particularly in cases deemed unresectable. Adjuvant treatment, combining radiotherapy and chemotherapy, demonstrated improved survival but lacked consensus regarding its role. (4) Conclusions: Stage IVB EC poses a complex challenge with limited evidence to guide management. Optimal cytoreduction remains crucial, and NACT should be considered for unresectable cases. Multimodality adjuvant therapy may benefit patients, even with disease spread beyond the pelvis. Future advances in molecular classification and targeted therapies are expected to enhance treatment strategies.
PubMed: 37958299
DOI: 10.3390/cancers15215123 -
Journal of Clinical Medicine Nov 2023Low-grade myofibroblastic sarcoma (LGMS) is a rare tumor entity which occurs in the subcutaneous and deep soft tissues; it is less common in the bone with a predilection... (Review)
Review
INTRODUCTION
Low-grade myofibroblastic sarcoma (LGMS) is a rare tumor entity which occurs in the subcutaneous and deep soft tissues; it is less common in the bone with a predilection for the extremities and the head and neck region. As confirming the diagnosis is difficult and treatment strategies are not standardized, we aimed to identify patient and tumor characteristics, and to summarize treatment strategies and their clinical outcomes to guide surgeons.
METHODS
Included were full articles reporting patients with histology of LGMS in the extremities, excluding tumors of the trunk. All patients underwent surgery but with different extend, from marginal to wide resection. Included studies should inform about local recurrence, metastasis, or evidence of disease, depending on the surgical treatment. We conducted a structured search using MEDLINE (via PubMed), Web of Science, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies on low-grade myofibroblastic sarcoma of the extremities. Study designs like randomized controlled trials, systematic reviews, prospective trials, retrospective studies, and case reports were included. Prospective studies and comparative studies were not available at all. Therefore, meta-analysis was not possible and statistical analysis was purely descriptive.
RESULTS
Of the 789 studies identified from our initial search, 17 studies including 59 cases reported LGMS of the extremities with the surgical treatment and clinical outcome and were therefore analyzed. In addition, we present the rare case and surgical management of a 28-year-old male patient with residual LGMS of the thumb after an initial incomplete resection. The current literature suggests that a wide excision with R0 margins should be considered the standard treatment for LGMS. In cases where surgery leads to significant functional impairment, individual options like free tissue transfer from a donor site have to be considered. Therefore, we also present an illustrative case. For all selected case series and case reports, a high risk of confounding, selection bias, information bias, and reporting bias must be anticipated. Nevertheless, this systematic review provides a comprehensive overview on surgical treatment and clinical outcomes in LGMS surgery of the extremities.
PubMed: 38002641
DOI: 10.3390/jcm12227027 -
Surgical Oncology Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients... (Meta-Analysis)
Meta-Analysis Review
Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.
METHODS
We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI).
RESULTS
We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA.
CONCLUSION
Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.
Topics: Humans; Prognosis; Circulating Tumor DNA; Proto-Oncogene Proteins p21(ras); Mutation; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Biomarkers, Tumor
PubMed: 37852124
DOI: 10.1016/j.suronc.2023.102007 -
Cells Oct 2023Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and... (Meta-Analysis)
Meta-Analysis Review
Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27-4.28, < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53-10.04, < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13-19.17, < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.
Topics: Humans; Circulating Tumor DNA; Biomarkers; Combined Modality Therapy; Liver Neoplasms; Colorectal Neoplasms
PubMed: 37947598
DOI: 10.3390/cells12212520 -
Cancers Feb 2024The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the... (Review)
Review
The study cohort consisted of 83 patients with a mean age of 49.55 (SD 13.72) with a female preponderance (60 patients). Here, 32.14% of patients had primary LTS; the remaining were metastases. Clinical presentation included nonspecific back pain (57.83%), weakness (21.69%) and radicular pain (18.07%). History of uterine neoplasia was found in 33.73% of patients. LTS preferentially affected the thoracic spine (51.81%), followed by the lumbar (21.67%) spine. MRI alone was the most common imaging modality (33.33%); in other cases, it was used with CT (22.92%) or X-ray (16.67%); 19.23% of patients had Resection/Fixation, 15.38% had Total en bloc spondylectomy, and 10.26% had Corpectomy. A minority of patients had laminectomy and decompression. Among those with resection, 45.83% had a gross total resection, 29.17% had a subtotal resection, and 16.67% had a near total resection. Immunohistochemistry demonstrated positivity for actin (43.37%), desmin (31.33%), and Ki67 (25.30). At a follow-up of 19.3 months, 61.97% of patients were alive; 26.25% of 80 patients received no additional treatment, 23.75% received combination radiotherapy and chemotherapy, only chemotherapy was given to 20%, and radiotherapy was given to 17.5%. Few (2.5%) had further resection. For an average of 12.50 months, 42.31% had no symptoms, while others had residual (19.23%), other metastasis (15.38%), and pain (7.69%). On follow-up of 29 patients, most (68.97%) had resolved symptoms; 61.97% of the 71 patients followed were alive.
PubMed: 38398139
DOI: 10.3390/cancers16040748 -
Annals of Surgical Oncology Jan 2024The tumor microenvironment (TME) plays a crucial role in therapy response and modulation of immunologic surveillance. Adjuvant immunotherapy has recently been introduced... (Review)
Review
Potential Predictive Immune and Metabolic Biomarkers of Tumor Microenvironment Regarding Pathological and Clinical Response in Esophageal Cancer After Neoadjuvant Chemoradiotherapy: A Systematic Review.
INTRODUCTION
The tumor microenvironment (TME) plays a crucial role in therapy response and modulation of immunologic surveillance. Adjuvant immunotherapy has recently been introduced in post-surgery treatment of locally advanced esophageal cancer (EC) with residual pathological disease after neoadjuvant chemoradiotherapy (nCRT). F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) remains a valuable imaging tool to assess therapy response and to visualize metabolic TME; however, there is still a paucity in understanding the interaction between the TME and nCRT response. This systematic review investigated the potential of TME biomarkers and F-FDG-PET/CT features to predict pathological and clinical response (CR) after nCRT in EC.
METHODS
A literature search of the Medline and Embase electronic databases identified 4190 studies. Studies regarding immune and metabolic TME biomarkers and F-FDG-PET/CT features were included for predicting pathological response (PR) and/or CR after nCRT. Separate analyses were performed for F-FDG-PET/CT markers and these TME biomarkers.
RESULTS
The final analysis included 21 studies-10 about immune and metabolic markers alone and 11 with additional F-FDG-PET/CT features. High CD8 infiltration before and after nCRT, and CD3 and CD4 infiltration after nCRT, generally correlated with better PR. A high expression of tumoral or stromal programmed death-ligand 1 (PD-L1) after nCRT was generally associated with poor PR. Moreover, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) of the primary tumor were potentially predictive for clinical and PR.
CONCLUSION
CD8, CD4, CD3, and PD-L1 are promising immune markers in predicting PR, whereas TLG and MTV are potential F-FDG-PET/CT features to predict clinical and PR after nCRT in EC.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Neoadjuvant Therapy; B7-H1 Antigen; Tumor Microenvironment; Chemoradiotherapy; Esophageal Neoplasms; Biomarkers, Tumor; Radiopharmaceuticals; Tumor Burden; Retrospective Studies
PubMed: 37777688
DOI: 10.1245/s10434-023-14352-z -
Digestive and Liver Disease : Official... Dec 2023There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence.
METHODS
Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs.
RESULTS
Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79).
CONCLUSION
Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence.
Topics: Humans; Ileum; Prognosis; Neoplasm Recurrence, Local; Cecum; Crohn Disease; Margins of Excision; Recurrence; Retrospective Studies
PubMed: 36658042
DOI: 10.1016/j.dld.2022.12.021 -
Alimentary Pharmacology & Therapeutics May 2024The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting... (Review)
Review
BACKGROUND
The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection.
AIM
To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening.
METHODS
The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria.
RESULTS
A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes.
CONCLUSIONS
This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.
Topics: Humans; Early Detection of Cancer; Colorectal Neoplasms; Rectum; MicroRNAs; Hemoglobins; Occult Blood; Biomarkers; Feces; Mass Screening
PubMed: 38534182
DOI: 10.1111/apt.17947 -
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