Potential value of detection of minimal residual disease in colorectal cancer following radical resection

Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment regimen.One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care.Due to its dynamic,effective,and non-invasive benefits over tissue biopsy,the detection of minimal or molecular residual lesions(MRD)based on circulating tumor DNA(ctDNA)is beneficial to the clinical development of drugs for patients with CRC after radical treatment,as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution.The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions(upgrade or downgrade treatment)in CRC,stratify the risk of clinical recurrence more precisely,and predict the risk of recurrence in advance of imaging examination,according to a large number of observational or prospective clinical studies.With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA,which also improves the accuracy of clinical recurrence risk assessment for CRC.Therefore,it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized,stratified precision therapy;however,additional confirmation will require subsequent high-quality,prospective,large-scale randomized controlled studies.This article will provide an overview of the definition and clinical significance of MRD,the primary indications and technological challenges for MRD detection,along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.

Liquid biopsy and blood-based minimal residual disease evaluation in multiple myeloma

Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient management.Bone marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are possible.Liquid biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour DNA.This approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients.

Can trastuzumab emtansine be replaced by additional chemotherapy plus targeted therapy for HER2-overexpressing breast cancer patients with residual disease after neoadjuvant chemotherapy?

Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients.Given that neoadjuvant chemotherapy(NAC)has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits,many patients,especially those with more advanced tumors,prefer NAC and generally will not receive additional chemotherapy after surgery,irrespective of the pathological response.However,achieving pathological complete response to NAC is strongly correlated with prognosis,especially in triple-negative and HER2-overexpressing breast cancer.Therefore,postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes.The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC.In addition,chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions.Therefore,can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer?At present,no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer.The KATHERINE study revealed that trastuzumab emtansine(T-DM1)can reduce the risk of recurrence or death by 50%compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy.T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine,and thus,to an extent,T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy.However,high cost and low accessibility limit its use especially in low-and middle-income countries and regions.Hence,we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1.Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable.However,further clinical research on the selection of chemotherapeutic agents is warranted.

Prognostic relevance of minimal residual disease in colorectal cancer

Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on survival.Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC.Analysis of circulating tumor cells(CTC)in the blood is increasingly used in clinical practice for disease monitoring of CRC patients.In this review article the role of CTC,disseminated tumor cells(DTC)in the bone marrow and micrometastases and isolated tumor cells(ITC)in the lymph nodes will be discussed,including literature published until September 2013.Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood,DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes.Minimal residual disease could be used in the future to identify patient groups at risk,who might benefit from individualized treatment options.

Coexisting opportunities and challenges:In which scenarios can minimal/measurable residual disease play a role in advanced non-small cell lung cancer?

Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.

CLINICAL SIGNIFICANCE OF THE DETECTION OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD B-ALL BY FLOW CYTOMETRY

Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses were performed after remission induction therapy.Four-color combinations of fluorochrome labeled monoclonal antibodies against lymphocyte lineage related phenotypes were used to analyze leukemic cells with flow cytometry.The cells from normal bone marrow were used as controls.The combinations of phenotypes that reflect the antigen expression differences between leukemic and normal bone marrow cells on flow cytometry were considered to be the effective phenotype combinations in the first step screening.The effective phenotype combinations were then used to monitor MRD during the disease course after therapy began. Results 58 cases of childhood B-ALL were screened for MRD effective phenotype combinations.The effective phenotype combinations were identified in 89.7% of B-ALL cases in this study.Four-color phenotype combinations were composed of CD10/CD34/CD19 plus another effective marker such as CD38,CD58,CD66c,CD21.The senstitivity of this method was 0.01%,much higher than that of microscopic inspection.In 8 cases,their bone marrow microscopic inspection results showed no remaining leukemic cells;but with flow cytometry,the percentage of leukemic cells were 5.66%,0.36%,1.43%,0.069%,1.55%,2.7%,0.028% and 0.015%,respectively.In risk stratification,all these MRD positive cases were classified into high risk group for relapse and 1 case showed early relapse within 6 months. Conclusion The application of flow cytometry in MRD measurement can significantly improve the sensitivity of detection of remained leukemic cells in childhood B-ALL,and can provide more accurate information on disease progression as well as the efficacy of therapy,thus facilitate future treatment decisions and follow ups.

DETECTION AND ITS CLINICAL VALUE OF MINIMAL RESIDUAL DISEASES IN ACUTE PROMYELOCYTIC LEUKEMIA

Objective: To detect the minimal residual diseases (MRD) in acute promyelocytic leukemia (APL) after complete remission (CR) and to analyze its clinical value in prognosis. Methods: Reverse transcription Polymerase chain reaction (RT/PCR) was used to detect MRD of patients with APL. Results: MRD positive rate in patients with APL was 92.8% (39/42) before treatment and 56.7 (21/37) immediately after the ATRA or chemotherapy-induced CR. Furthermore, MRD positive rate was related to the relapse in APL patients and could be considered as a marker to predict the relapse of patients with APL after CR. The MRD detection could also be applied to direct the consolidation therapy to prevent relapses. Conclusion: RT-PCR is valuable to monitor MRD and can be used as a marker to predict relapses.

Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.

Circulating tumor DNA(ctDNA)-based minimal residual disease in non-small cell lung cancer

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related fatalities,with non-small cell lung cancer(NSCLC)accounting for 85%of all lung cancers.Over the past forty years,patients with NSCLC have had a 5-year survival rate of only 16%,despite improvements in chemotherapy,targeted therapy,and immunotherapy.Circulating tumor DNA(ctDNA)in blood can be used to identify minimal residual disease(MRD),and ctDNA-based MRD has been shown to be of significance in prognostic assessment,recurrence monitoring,risk of recurrence assessment,efficacy monitoring,and therapeutic intervention decisions in NSCLC.The level of MRD can be obtained by monitoring ctDNA to provide guidance for more precise and personalized treatment,the scientific feasibility of which could dramatically modify lung cancer treatment paradigm.In this review,we present a comprehensive review of MRD studies in NSCLC and focus on the application of ctDNA-based MRD in different stages of NSCLC in current clinical practice.

Outcomes of Adults with Acute Lymphoblastic Leukemia After Autologous Hematopoietic Stem Cell Transplantation and the Significance of Pretransplantation Minimal Residual Disease： Analysis from a Single Center of China

Background：The postremission therapics for adult patients generally contain consolidation chemotherapy,allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation （auto-HSCT）.Because of the various results from different centers,the optimal therapy for adult acute lymphoblastic leukemia （ALL） patients is still uncertain.This study aimed to better understand predictive factors and role of auto-HSCT in the postremission thcrapy for adult ALL patients.Methods：The outcomes of 135 adult patients with ALL,who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital,Chinese Academy of Medical Sciences from January 1,1994 to February 28,2014,were retrospectively analyzed.Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.Results：Overall survival （OS） and disease-free survival （DFS） at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%,respectively.The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%.For both OS and DFS,acute T-cell lymphoblastic leukemia,high lactate dehydrogenase （LDH） at diagnosis,blast cell proportion ≥5% on the 15th day of induction therapy,and extramedullary infiltration before HSCT were the poor prognosis factors.In addition,age ≥35 years predicted poor DFS.Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model.For 44 patients who had results of pretransplantation minimal residual disease （MRD）,positive MRD （MRD ≥0.01%） indicated poor OS （P =0.044） and DFS （P =0.008）.Furthermore,for the standard risk group,the patients with negative MRD （MRD 〈0.01%） had better results （OS at 18 months was 90.0 ± 9.5%,while for the patients with positive MRD OS was 50.0 ± 35.4%,P =0.003;DFS at 18 months was 90.0 ± 9.5%,while for the positive MRD group DFS was 0%,P 〈 0.001）.Conclusions：This study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.

Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

A female patient diagnosed with acute myelocytic leukemia M5a （AML-M5a） relapsed 986 days after her allogeneic peripheral blood stem cell transplantation （alIo-PBSCT） from an unrelated male donor with matched human leukocyte antigen （HLA）. Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer （CIK） cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion （DLI） and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

Presence of extensive intraductal component in patients undergoing breast conservative surgery predicts presence of residual disease in subsequent completion mastectomy

Background Local recurrence remains a serious problem among patients undergoing breast conservative surgery. This study aimed at identifying risk factors for residual disease after breast conservative surgery. Methods This retrospective study was based on patients with invasive breast cancer who have received breast conservative surgery and subsequent completion mastectomy. All patients had a clear resection margin in the initial operation. We analyzed the association between the presence of residual disease during completion mastectomy and the following risk factors： T staging, young age, and presence of extensive intraductal component （EIC）, a close margin, lymphovascular permeation （LVP）, positivity of estrogen receptor, progesterone receptor, and c-erbB-2. Results Residual disease was encountered in 21 （45.7%） of 46 patients; EIC was present in 28 patients （60.9%）, of whom 17 had residual disease. Presence of EIC during breast conservation surgery was associated with a higher risk of residual disease during completion mastectomy （P=0.011）. Other variables were not statistically significant risk factors for presence of residual disease. No local recurrence was recorded in our cohort, and the disease-free survival and overall survival after completion mastectomy were similar for patients who had residual disease and those who had not. Conclusions The presence of EIC is a significant risk factor for residual disease in patients after breast conservative surgery. Our findings may suggest the indicated value of completion mastectomy in patients with EIC during initial breast conservative surgery to decrease the risk of subsequent local failure.

Drug resistance and minimal residual disease in multiple myeloma

Great progress has been made in improving survival in multiple myeloma(MM)patients over the last 30 years.New drugs have been introduced and complete responses are frequently seen.However,the majority of MM patients do experience a relapse at a variable time after treatment,and ultimately the disease becomes drug-resistant following therapies.Recently,minimal residual disease(MRD)detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response.MRD can be considered as a surrogate for both progression-free and overall survival.In this perspective,the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals.The present review gives an overview of drug resistance in MM,i.e.,mutation ofβ5 subunit of the proteasome;upregulation of pumps of efflux;heat shock protein induction for proteasome inhibitors;downregulation of CRBN expression;deregulation of IRF4 expression;mutation of CRBN,IKZF1,and IKZF3 for immunomodulatory drugs and decreased target expression;complement protein increase;sBCMA increase;and BCMA down expression for monoclonal antibodies.Multicolor flow cytometry,or next-generation flow,and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5.Sustained MRD negativity is related to prolonged survival,and it is evaluated in all recent clinical trials as a surrogate of drug efficacy.

Research Progress on Postoperative Minimal/Molecular Residual Disease Detection in Lung Cancer

Lung cancer is the leading cause of cancer-related deaths worldwide.Approximately 10%-50%of patients experience relapse after radical surgery,which may be attributed to the persistence of minimal/molecular residual disease(MRD).Circulating tumor DNA(ctDNA),a common liquid biopsy approach,has been demonstrated to have significant clinical merit.In this study,we review the evidence supporting the use of ctDNA for MRD detection and discuss the potential clinical applications of postoperative MRD detection,including monitoring recurrence,guiding adjuvant treatment,and driving clinical trials in lung cancer.We will also discuss the problems that prevent the routine application of ctDNA MRD detection.Multi-analyte methods and identification of specific genetic and molecular alterations,especially methylation,are effective detection strategies and show considerable prospects for future development.Interventional prospective studies based on ctDNA detection are needed to determine whether the application of postoperative MRD detection can improve the clinical outcomes of lung cancer patients,and the accuracy,sensitivity,specificity,and robustness of different detection methods still require optimization and refinement.

Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions,MET exon skipping or de novo MET amplification

Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains unknown.This prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET amplification.We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,respectively.Detectable MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,respectively.Patients with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations.Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

Analysis of the function of D279N mutation of VP2 of infectious bursal disease virus

Infectious bursal disease virus（IBDV）is responsible for the highly contagious infectious bursal disease of chickens.Further understanding the gene-function is necessary to design the tailored vaccine.The amino acid residue 279,located on strand P_F of VP2,is one of the three residues that have been reported to be involved in cell-tropism but with some inconsistency.In this study,to further clarify the amino acids involved in the cell tropism of IBDV,a series of mutations about residue 279were introduced into the VP2 of vv IBDV Gx strain.With the reverse genetic system,we found single mutation of D279N,double mutations of D279N/A284T or Q253H/D279N were not enough to adapt IBDV to chicken embryo fibroblast（CEF）cell.To evaluate whether residue 279 could influence the replication and virulence of IBDV,the virus r Gx HT-279 with three mutations（Q253H/D279N/A284T）was rescued and evaluated.Results showed that the mutation of residue 279 in VP2had no efficient effects on both the replication efficiency in vitro and the virulence to SPF chickens of IBDV.In summary,the results demonstrated that residue 279 of VP2 did not contribute efficiently to cell tropism,replication efficiency,and virulence of IBDV at least in some strains.These findings provided further information for understanding the gene function of IBDV.

Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

MRD-directed and risk-adapted individualized stratified treatment of AML

Measurable residual disease(MRD)has been widely recognized as a biomarker for deeply evaluating complete remission(CR),predicting relapse,guiding pre-emptive interventions,and serving as an endpoint surrogate for drug testing.However,despite the emergence of new technologies,there remains a lack of comprehensive understanding regarding the proper techniques,sample materials,and optimal time points for MRD assessment.In this review,we summarized the MRD methods,sample sources,and evaluation frequency according to the risk category of the European Leukemia Net(ELN)2022.Additionally,we emphasize the importance of properly utilizing and combining these technologies.We have also refined the flowchart outlining each time point for preemptive interventions and intervention paths.The evaluation of MRD in acute myeloid leukemia(AML)is sophisticated,clinically applicable,and technology-dependent,and necessitates standardized approaches and further research.

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.