BackgroundTriple-negative breast cancers (TNBCs) are a group of heterogeneous diseases with various morphology, prognosis, and treatment response. Therefore, it is important to identify valuable biomarkers to predict the therapeutic response and prognosis for TNBCs. Tumor-infiltrating lymphocytes (TILs) may have predictive value to pathological complete response (pCR) in neoadjuvant treated TNBCs. However, absence of standardized methodologies for TILs measurement has limited its evaluation and application in practice. In 2014, the International TILs Working Group formulated the recommendations of pathologic evaluation for TILs in breast cancers.MethodsTo evaluate the predictive value of TILs scored by methods recommended by International TILs Working Group 2014, we performed a retrospective study of TILs in 166 core needle biopsy specimens of primary invasive TNBCs with neoadjuvant chemotherapy (NAC) in a Chinese population. Intratumoral TILs (iTILs) and stromal TILs (sTILs) were scored respectively. The associations between TILs and pCR were analyzed.ResultsBoth sTILs (p = 0.0001) and iTILs (P = 0.001) were associated with pCR in univariate logistic regression analysis. Multivariate logistic regression analysis indicated that both sTILs (P = 0.006) and iTILs (P = 0.04) were independent predictors for pCR. Receiver operating characteristics (ROC) curve analysis was used to identify the optimal thresholds of TILs. TNBCs with more than 20% sTILs (P = 0.001) or with more than 10% iTILs (P = 0.003) were associated with higher pCR rates in univariate analysis. Multivariate analysis showed that a 20% threshold of sTILs (P = 0.005) was an independent predictive factor for pCR.ConclusionsOur study indicated that TILs scored by recommendations of International TILs Working Group 2014 in pre-NAC core needle biopsy specimens was significantly correlated with pCR in TNBCs, higher TILs scores predicting higher pCR rate. Both sTILs and iTILs were independent predictors for pCR in TNBCs. A 20% threshold for sTILs may be feasible to predict pCR to NAC in TNBCs.
BackgroundStromal tumor-infiltrating lymphocytes (sTILs) have been identified as a predictive biomarker for response to neoadjuvant chemotherapy (NAC) and prognosis in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. However, standardized scoring methods for use in clinical practice need to be established, and the optimal threshold of sTILs to predict pathological complete response (pCR) and prognosis in HER2+ breast cancers has not yet been defined.ObjectiveThe predictive and prognostic values of sTILs in patients with HER2-positive breast cancer treated with NAC were evaluated, with the aim to explore the optimal thresholds of sTILs and to investigate the feasibility of scoring methods in clinical practice.Patients and MethodsA total of 143 core needle biopsy specimens of HER2-positive invasive breast cancers obtained from Chinese patients who had been treated with trastuzumab-based NAC followed by surgery between 2009 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. sTIL levels in the pre-NAC core needle biopsy specimens were scored using methods recommended by the International TILs Working Group 2014. The associations between sTILs and pCR, disease-free survival (DFS), and overall survival (OS) were evaluated, and the optimal thresholds for predictive and prognostic values of sTILs were analyzed.ResultsFirst, sTILs were associated with a higher pCR rate in HER2-positive breast cancers. Univariate (per 10% sTILs: odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08, p = 0.001) and multivariate regression analyses (per 10% sTILs: OR 1.04, 95% CI 1.00–1.07, p = 0.034) indicated that sTILs as a continuous variable were a significant predictor of pCR in HER2-positive breast cancers. Receiver operating characteristics (ROC) curve analysis showed that a 20% threshold best distinguished the pCR subgroup from the non-pCR subgroup. The dichotomized sTILs with a threshold set at 20% was a strong predictor of pCR in the univariate (OR 0.25, 95% CI 0.12–0.52, p < 0.001) and multivariate analyses (OR 0.35, 95% CI 0.14–0.87, p = 0.024). Second, sTILs were associated with better prognosis in HER2-positive breast cancers. Univariate (DFS: hazard ratio [HR] 0.91, 95% CI 0.88–0.95, p < 0.001; OS: HR 0.88, 95% CI 0.83–0.94, p < 0.001), and multivariate analyses (DFS: HR 0.93, 95% CI 0.90–0.97, p < 0.001; OS: HR 0.92, 95% CI 0.86–0.98, p = 0.009) suggested that sTILs as a continuous variable had a strong predictive value for improved DFS and OS. As a binary variable with a threshold of 20%, univariate (DFS: HR 6.60, 95% CI 2.91–14.95, p < 0.001; OS: HR 10.29, 95% CI 2.37–44.66, p = 0.002) and multivariate analyses (DFS: HR 3.87, 95% CI 1.65–9.12, p = 0.002; OS: HR 4.74, 95% CI 1.02–22.01, p = 0.047) indicated that patients with ≥ 20% sTILs had a significantly better prognosis than the patients with < 20% sTILs.ConclusionsOur study indicates that baseline sTILs scored by methods recommended by the International TILs Working Group in pre-NAC core needle ...
PurposeTo analyze the potential variables affecting the survival of patients undergoing primary surgery for hypopharyngeal squamous cell carcinoma.Patients and methodsBetween August 2007 and December 2016, 93 patients with primary hypopharyngeal squamous cell carcinomas undergoing radical surgery at Fudan University Shanghai Cancer Center were reviewed. The clinicopathological features were analyzed retrospectively. The optimal cutoff values were determined based on the receiver operating characteristic curve analysis. Pearson correlation coefficients were used to assess the correlations between variables. The Kaplan–Meier and Cox proportional hazard methods were used to evaluate the impact of variables on overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).ResultsCox multivariate analysis revealed that a depth of invasion (DOI) ≥ 4.3 mm was correlated with inferior OS (P=0.045), DSS (P=0.046), and DFS (P=0.046). A primary tumor volume (PTV) ≥0.36 mL was related to poor OS (P=0.018), DSS (P=0.026), and DFS (P=0.036). A lymph node density (LND) ≥0.07 was also associated with worse OS (P=0.014) and DSS (P=0.045). Moreover, additional prognostic value was observed in the combined use of PTV and LND.ConclusionThe DOI, PTV, and LND obtained from the surgical specimens could provide additional valuable information for prognostic stratification and allowed the more appropriate selection of suitable candidates for more aggressive adjuvant therapy.
A 37-year-old Polish immigrant presented with unilateral hip pain and difficulty weight-bearing. Plain radiography and magnetic resonance imaging (MRI) revealed a lytic lesion in the acetabulum, with abnormal serum electrophoresis and bone marrow biopsy. The patient was diagnosed with two rare conditions presenting synchronously - Gaucher disease and plasmacytoma. He was treated with enzyme therapy and radiotherapy, but subsequently developed a recurrence of plasmacytoma in the right femur, confirmed with bone marrow biopsy. This was also treated with radiotherapy, followed by a retrograde femoral nail to reduce the risk of pathological fracture. The patient went on to develop multiple lytic lesions in the ribs and vertebra, seen on MRI. Further bone marrow biopsy confirmed dissemination of the plasmacytoma into multiple myeloma, for which he was treated with systemic chemotherapy. In patients presenting with refractory bone or joint pain, haematological and histological investigations should be considered to exclude less common diagnoses.
Background To analyze the prognostic value of the clinicopathological parameters of primary lesions for predicting cervical lymph node metastasis in patients with hypopharyngeal and/or supraglottic carcinoma. Methods We enrolled 127 patients with squamous cell carcinomas originating in the hypopharyngeal and/or supraglottic regions. Results Multivariate analysis identified the tumor depth as an independent predictive factor for lymph node metastasis (odds ratio, 4.959; 95% confidence interval, 2.290‐10.739; P < 0.0001) with a predictive value of 0.966. A cutoff value of 4.5 mm was determined. Conclusion The tumor depth of the primary lesion is a potent predictor of cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. In cases with clinically negative nodal status, elective neck dissection should be adopted for patients with a tumor depth reaching 4.5 mm. Regular outpatient follow‐up is recommended for patients with a tumor depth less than 1.0 mm. Close follow‐up or preventative therapy should be considered between 1.0 and 4.5 mm.
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