Tumor deposits in axillary adipose tissue in patients with breast cancer:Do they matter?

Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.

Risk factors predict microscopic extranodal tumor deposits in advanced stage Ⅲ colon cancer patients

BACKGROUND Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant metastases.Pericolonic tumor deposits(TDs)are considered prognostically distinct from lymph node metastases.AIM To investigate risk factors for extranodal TDs in stage III colon cancer.METHODS This was a retrospective cohort study.We selected 155 individuals diagnosed with stage III colon cancer from the database of the Cancer Registry of the Tri-Service General Hospital.The patients were allocated into the groups with/without N1c.Multivariate Cox regression analysis and Kaplan-Meier method were done.The primary outcomes investigate the association between the covariates and extranodal TDs,and prognostic significance of the covariates regarding the survival.RESULTS There were 136 individuals in the non-N1c group and 19 individuals in the N1c group.Patients with lymphovascular invasion(LVI)had a higher risk of TDs.Overall survival rates of patients with and without LVI were 6.64 years and 8.61 years,respectively(P=0.027).The N1c patients without LVI had higher overall survival than those who with LVI(7.73 years vs 4.42 years,P=0.010).CONCLUSION Patients having stage III colon cancer with LVI have a higher probability of having TDs than those with stage III colon cancer without LVI.Stage III colon cancer patients with TDs and LVI could have poor prognosis and outcome.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer

BACKGROUND The current prognostic significance of perigastric tumor deposits(TDs)in gastric cancer(GC)remains unclear.AIM To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC.METHODS This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1,2012 to December 31,2017 at the Chinese PLA General Hospital.According to the presence of perigastric TDs or not,the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching.The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling.The Kaplan-Meier method was used to plot survival curves.Multivariate Cox regression modeling and the log-rank test were used to analyze the data.RESULTS Perigastric TDs were found to be positive in 339(5.09%)of the 6672 patients with GC,among whom 237 were men(69.91%)and 102 were women(30.09%)(2.32:1).The median age was 59 years(range,27 to 78 years).Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients(P<0.05).The 1-,3-,and 5-year overall survival rates of GC patients with TDs were 68.3%,19.6%,and 11.2%,respectively,and these were significantly poorer than those without TDs of the same stages.There was significant variation in survival according to TD locations among the GC patients(P<0.05).A new TNM staging framework for GC was formulated according to TD location.When TDs appear in the gastric body,the original stages T1,T2,and T3 are classified as T4a with the new framework,and the original stages T4a and T4b both are classified as T4b.When TDs appear in the lesser curvature,the previous stages N0,N1,N2,and N3 now both are classified as N3.When TDs appear in the greater curvature or the distant tissue,the patient should be categorized as having M1.With the new GC staging scheme including TDs,the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs.CONCLUSION TDs are a poor prognostic factor for patients with primary GC.The location of TDs is associated with the prognosis of patients with primary GC.Accordingly,we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

Development and validation of a nomogram for preoperative prediction of tumor deposits in colorectal cancer

BACKGROUND Based on the clinical data of colorectal cancer(CRC)patients who underwent surgery at our institution,a model for predicting the formation of tumor deposits(TDs)in this patient population was established.AIM To establish an effective model for predicting TD formation,thus enabling clinicians to identify CRC patients at high risk for TDs and implement personalized treatment strategies.METHODS CRC patients(n=645)who met the inclusion criteria were randomly divided into training(n=452)and validation(n=193)cohorts using a 7:3 ratio in this retrospective analysis.Least absolute shrinkage and selection operator regression was employed to screen potential risk factors,and multivariable logistic regression analysis was used to identify independent risk factors.Subsequently,a predictive model for TD formation in CRC patients was constructed based on the independent risk factors.The discrimination ability of the model,its consistency with actual results,and its clinical applicability were evaluated using receiveroperating characteristic curves,area under the curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Thirty-four(7.5%)patients with TDs were identified in the training cohort based on postoperative pathological specimens.Multivariate logistic regression analysis identified female sex,preoperative intestinal obstruction,left-sided CRC,and lymph node metastasis as independent risk factors for TD formation.The AUCs of the nomogram models constructed using these variables were 0.839 and 0.853 in the training and validation cohorts,respectively.The calibration curve demonstrated good consistency,and the training cohort DCA yielded a threshold probability of 7%-78%.CONCLUSION This study developed and validated a nomogram with good predictive performance for identifying TDs in CRC patients.Our predictive model can assist surgeons in making optimal treatment decisions.

Radiomics for differentiating tumor deposits from lymph node metastasis in rectal cancer

BACKGROUND Tumor deposits(TDs)are not equivalent to lymph node(LN)metastasis(LNM)but have become independent adverse prognostic factors in patients with rectal cancer(RC).Although preoperatively differentiating TDs and LNMs is helpful in designing individualized treatment strategies and achieving improved prognoses,it is a challenging task.AIM To establish a computed tomography(CT)-based radiomics model for preoperatively differentiating TDs from LNM in patients with RC.METHODS This study retrospectively enrolled 219 patients with RC[TDs+LNM-(n=89);LNM+TDs-(n=115);TDs+LNM+(n=15)]from a single center between September 2016 and September 2021.Single-positive patients(i.e.,TDs+LNM-and LNM+TDs-)were classified into the training(n=163)and validation(n=41)sets.We extracted numerous features from the enhanced CT(region 1:The main tumor;region 2:The largest peritumoral nodule).After deleting redundant features,three feature selection methods and three machine learning methods were used to select the best-performing classifier as the radiomics model(Rad-score).After validating Rad-score,its performance was further evaluated in the field of diagnosing double-positive patients(i.e.,TDs+LNM+)by outlining all peritumoral nodules with diameter(short-axis)>3 mm.RESULTS Rad-score 1(radiomics signature of the main tumor)had an area under the curve(AUC)of 0.768 on the training dataset and 0.700 on the validation dataset.Rad-score 2(radiomics signature of the largest peritumoral nodule)had a higher AUC(training set:0.940;validation set:0.918)than Radscore 1.Clinical factors,including age,gender,location of RC,tumor markers,and radiological features of the largest peritumoral nodule,were excluded by logistic regression.Thus,the combined model was comprised of Rad-scores of 1 and 2.Considering that the combined model had similar AUCs with Rad-score 2(P=0.134 in the training set and 0.594 in the validation set),Rad-score 2 was used as the final model.For the diagnosis of double-positive patients in the mixed group[TDs+LNM+(n=15);single-positive(n=15)],Rad-score 2 demonstrated moderate performance(sensitivity,73.3%;specificity,66.6%;and accuracy,70.0%).CONCLUSION Radiomics analysis based on the largest peritumoral nodule can be helpful in preoperatively differentiating between TDs and LNM.

Isolated axillary tumor deposit consistent with primary breast carcinoma:A case report

BACKGROUND We all know that lymph-node metastasis is an important factor for poor clinical outcome in breast cancer prognosis.Tumor deposit refers to a discrete collection of cancer cells that is found in the lymph nodes or other tissues adjacent to the primary tumor site.These tumor deposits are separate from the primary tumor and are often considered as a manifestation of lymph node metastasis.In gastric and colorectal cancer,tumor deposits in the lymph node drainage area have been included as independent prognostic factors.The question arises whether tumor deposits should also be considered as prognostic factors in breast cancer patients.This article aims to provoke some thoughts on this matter through a case study and literature review.CASE SUMMARY A 70-year-old female patient was found to have a right breast lump for over 2 years.On January 3,2023,a core needle biopsy of the right breast lump was performed,and the pathology report indicated invasive carcinoma.Subsequently,on January 17,2023,the patient underwent right breast-conserving surgery,sentinel lymph node biopsy,and right axillary lymph node dissection.The postoperative pathological staging was determined as stage IIB.The patient received chemotherapy,radiotherapy,and endocrine therapy.At present,nearly one year after the surgery,no obvious signs of metastasis have been observed in the follow-up examinations,but the long-term prognosis is still unknown.CONCLUSION There is a need for increased focus on the matter of tumor deposits in the lymph node drainage region,as well as a requirement for further clinical investigation to ascertain the relevance of tumor deposits in the prognosis of individuals with breast carcinoma.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Development and validation of a prognostic nomogram for colorectal cancer after surgery

BACKGROUND A nomogram is a diagram that aggregates various predictive factors through multivariate regression analysis,which can be used to predict patient outcomes intuitively.Lymph node(LN)metastasis and tumor deposit(TD)conditions are two critical factors that affect the prognosis of patients with colorectal cancer(CRC)after surgery.At present,few effective tools have been established to predict the overall survival(OS)of CRC patients after surgery.AIM To screen out suitable risk factors and to develop a nomogram that predicts the postoperative OS of CRC patients.METHODS Data from a total of 3139 patients diagnosed with CRC who underwent surgical removal of tumors and LN resection from 2010 to 2015 were collected from the Surveillance,Epidemiology,and End Results program.The data were divided into a training set(n=2092)and a validation set(n=1047)at random.The Harrell concordance index(C-index),Akaike information criterion(AIC),and area under the curve(AUC)were used to assess the predictive performance of the N stage from the American Joint Committee Cancer tumor-node-metastasis classification,LN ratio(LNR),and log odds of positive lymph nodes(LODDS).Univariate and multivariate analyses were utilized to screen out the risk factors significantly correlating with OS.The construction of the nomogram was based on Cox regression analysis.The C-index,receiver operating characteristic(ROC)curve,and calibration curve were employed to evaluate the discrimination and prediction abilities of the model.The likelihood ratio test was used to compare the sensitivity and specificity of the final model to the model with the N stage alone to evaluate LN metastasis.RESULTS The predictive efficacy of the LODDS was better than that of the LNR based on the C-index,AIC values,and AUC values of the ROC curve.Seven independent predictive factors,namely,race,age at diagnosis,T stage,M stage,LODDS,TD condition,and serum carcinoembryonic antigen level,were included in the nomogram.The C-index of the nomogram for OS prediction was 0.8002(95%CI:0.7839-0.8165)in the training set and 0.7864(95%CI:0.7604-0.8124)in the validation set.The AUC values of the ROC curve predicting the 1-,3-,and 5-year OS were 0.846,0.841,and 0.825,respectively,in the training set and 0.823,0.817,and 0.835,respectively,in the validation test.Great consistency between the predicted and actual observed OS for the 1-,3-,and 5-year OS in the training set and validation set was shown in the calibration curves.The final nomogram showed a better sensitivity and specificity than the nomogram with N stage alone for evaluating LN metastasis in both the training set(-4668.0 vs-4688.3,P<0.001)and the validation set(-1919.5 vs-1919.8,P<0.001)through the likelihood ratio test.CONCLUSION The nomogram incorporating LODDS,TD,and other risk factors showed great predictive accuracy and better sensitivity and specificity and represents a potential tool for therapeutic decision-making.