Impact of Salvage Cytotoxic Chemotherapy on Prognosis in Patients with Recurrence After Radical Cystectomy: A Multi-Institutional Retrospective Study

Background In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. Methods In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient’s performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). Results Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR]: 2.13; 95% confidence interval [CI]: 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR: 1.92; 95% CI: 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1–2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. Conclusions The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

A Clinical–Radiomics Model for Predicting Axillary Pathologic Complete Response in Breast Cancer With Axillary Lymph Node Metastases

PurposeTo develop a clinical–radiomics model based on radiomics features extracted from MRI and clinicopathologic factors for predicting the axillary pathologic complete response (apCR) in breast cancer (BC) patients with axillary lymph node (ALN) metastases.Materials and MethodsThe MR images and clinicopathologic data of 248 eligible invasive BC patients at the Peking University First Hospital from January 2013 to December 2020 were included in this study. All patients received neoadjuvant chemotherapy (NAC), and the presence of ALN metastases was confirmed through cytology pre-NAC. The data from January 2013 to December 2018 were randomly divided into the training and validation sets in a ratio of 7:3, and the data from January 2019 to December 2020 served as the independent testing set. The following three types of prediction models were investigated in this study. 1) A clinical model: the model was built by independently predicting clinicopathologic factors through logistic regression. 2) Radiomics models: we used an automatic segmentation model based on deep learning to segment the axillary areas, visible ALNs, and breast tumors on post-NAC dynamic contrast-enhanced MRI. Radiomics features were then extracted from the region of interest (ROI). Radiomics models were built based on different ROIs or their combination. 3) A clinical–radiomics model: it was built by integrating radiomics signature and independent predictive clinical factors by logistic regression. All models were assessed using a receiver operating characteristic curve analysis and by calculating the area under the curve (AUC).ResultsThe clinical model yielded AUC values of 0.759, 0.787, and 0.771 in the training, validation, and testing sets, respectively. The radiomics model based on the combination of MRI features of breast tumors and visible ALNs yielded the best AUC values of 0.894, 0.811, and 0.806 in the training, validation, and testing sets, respectively. The clinical–radiomics model yielded AUC values of 0.924, 0.851, and 0.878 in the training, validation, and testing sets, respectively, for predicting apCR.ConclusionWe developed a clinical–radiomics model by integrating radiomics signature and clinical factors to predict apCR in BC patients with ALN metastases post-NAC. It may help the clinicians to screen out apCR patients to avoid lymph node dissection.

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

Background: Invasive lobular carcinoma (ILC) is more likely to be bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompany by bone metastasis. Methods: We evaluated the women with bone-only metastasis of defined IDC or ILC, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's chi-squared test was used to compare the difference of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-special survival (CSS). Results: Overall, 3647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older, lower histological grade and higher proportion of HR+/HER2- subtype. But less treatment was applied to ILC than IDC, such as surgery of the breast, radiation and chemotherapy. Compared patients with IDC, the patients with ILC showed worse OS (median OS 36 and 42 months respectively, p<0.001) and CSS (median CSS 39 and 45 months respectively, p<0.001), especially in subgroups with HR+/HER2- subtype [OS (Hazard ration: 1.501, 95% CI [1.270-1.773], p<0.001); CSS (Hazard ration: 1.529, 95% CI [1.281-1.825], p<0.001)], lower histological grade (Ⅰ-Ⅱ) [OS (Hazard ration: 1.411, 95% CI [1.184-1.683], p<0.001); CSS (Hazard ration: 1.488, 95% CI [1.235-1.791], p<0.001)] or tumor burden, such as T0-2 [OS (Hazard ration: 1.693, 95% CI [1.368-2.096], p<0.001); CSS (Hazard ration: 1.76, 95% CI [1.405-2.205], p<0.001)] and N1-2 [OS (Hazard ration: 1.451, 95% CI [1.171-1.799], p=0.001); CSS (Hazard ration: 1.488, 95% CI [1.187-1.865], p=0.001)]. Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients. Conclusion: The patients with ILC have worse outcomes compared with that of IDC when bone-only metastasis occurred to them, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors (CDKs), new targeted drugs, etc.

Diagnostic Value of Cytokeratin 17 during Oral Carcinogenesis: An Immunohistochemical Study

Background. Little is known about the role of cytokeratin 17 (CK17) during oral carcinogenesis. CK17 expression in oral leukoplakia (OL), the most encountered oral potentially malignant disorders and oral squamous cell carcinoma (OSCC), remains very limited. To determine the role of CK17 during oral carcinogenesis and its potential diagnostic marker in oral premalignant and malignant lesions, this study evaluated CK17 expression in OL without dysplasia, OL with dysplasia, and OSCC. CK17 expression in these tissues was compared with those of normal oral mucosa (NOM). Additionally, the relationship between CK17 expression and clinicopathologic factors of OSCC was investigated. Methods. CK17 expression was evaluated in 186 samples consisting of 12 NOM, 33 OL without dysplasia, 58 OL with dysplasia, and 83 OSCC using immunohistochemistry. The proportion of positively immunostained cells was evaluated and scored. Results. CK17 was expressed in 8.3%, 54.5%, 74.1%, and 90.4% of NOM, OL without dysplasia, OL with dysplasia, and OSCC, respectively. NOM had a significantly lower CK17 score than OL with dysplasia ( p = 0.0003 ) and OSCC ( p < 0.0001 ). A significant association between CK17 expression and histopathologic differentiation of OSCC was found. Tumors with well differentiation had high CK17 expression compared with those of moderate and poor differentiation. Conclusion. CK17 was overexpressed in OL with dysplasia and OSCC, suggesting that CK17 plays a pivotal role in the development of premalignant lesions and OSCC. Of clinical significance, CK17 may be a good diagnostic marker for oral premalignant lesions and OSCC. Additionally, CK17 could be used as an objective tool to classify histopathologic grade in OSCC. The findings that CK17 expression is high in OSCC but low in NOM imply that CK17 may serve as a potential therapeutic target for OSCC.

Preoperative prealbumin-to-fibrinogen ratio predict Survival Outcomes in hepatocellular carcinoma patients after hepatic resection

Objective: This study aims to evaluate the clinical application of preoperative prealbumin-to-fibrinogen ratio (PFR) in the clinical diagnosis and prognostic value of hepatocellular carcinoma (HCC) patients. Methods: The clinical and laboratory data of 269 HCC patients undergoing surgical treatment from January 2012 to January 2017 in Taizhou Hospital were retrospectively analyzed. The Cox regression model was used to analyze the correlation between PFR and other clinicopathologic factors in overall survival (OS) and disease-free survival (DFS). Results: Cox regression analysis showed that PFR (hazard ratios [HR] = 2.123; 95% confidence interval [95% CI], 1.271–3.547; P = 0.004)was independent risk factors affecting the OS of HCC patients. Furthermore, a nomogram was built based on these risk factors. The C indices statistics for the OS nomogram was 0.715. Conclusion: Nomograms based on PFR can be recommended as the correct and actual model to evaluate prognosis for patients with HCC.

Resection Status Does Not Impact Recurrence in Well-Differentiated Liposarcoma of the Extremity

Background Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status. Methods A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS. Results 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection. Discussion In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Embryonal Rhabdomyosarcoma with Posttherapy Cytodifferentiation and Aggressive Clinical Course

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. Embryonal rhabdomyosarcoma (ERMS), its most common subtype, is a malignant soft tissue tumor with morphologic and immunophenotypic features of embryonic skeletal muscle. The histologic findings in ERMS typically include a range of differentiation in rhabdomyoblasts from primitive to terminally differentiated forms, and the latter become more prominent after chemotherapy-induced cytodifferentiation. Several reports have shown therapy-related cytodifferentiation to portend a good prognosis in ERMS. We discuss the case of a pediatric patient who presented with ERMS of the orbit. Although her tumor showed extensive posttreatment cytodifferentiation and several other good prognostic clinicopathologic factors, it pursued an aggressive course, resulting in early metastasis and death. This case represents an unusual course and may be instructive as to the clinicopathologic features impacting prognostication, and ultimately the biology, of this aggressive family of tumors.

Clinicopathologic Factors Related to Post-Operative Outcome of Pituitary Adenoma: a Meta-Analysis

Purpose: About 30% to 40% of patients with pituitary adenoma require surgery. About 25% to 40% of those who have had surgery will have an aggressive outcome. The purpose of this study was to see if certain clinicopathologic factors such as size, type/subtype, invasiveness, proliferative (ki-67, mitotic rate, and p53), and grade influenced the aggressiveness of postoperative pituitary adenomas. Methods: The factors mentioned in the research objectives were examined as independent variables. Ten studies out of 736 were chosen. The 10 studies had 2727 participants and 632 cases. The monitoring lasted 3-11 years. The studies' quality ranged from fair to excellent. Results: The results of the meta-analysis were: size ≥10mm OR 1,79 (1,29-2,48), corticotroph OR 1,91 (1,41-2,58), invasive OR 3,67 (1,95-6,90), proliferative OR 4,78(3,61-6,32), Ki-67 ≥ 3% OR 4,13 (2,94-5,81), mitotic rate > 2 OR 3,91 (2,74-5,57), p53 positive OR 1,92 (1,28-2,90), and grade 2b OR 4,56 (3,0-6,91). Conclusions: Size, type/subtype, invasiveness, proliferative (ki-67, mitotic rate, and p53), and grade of postoperative pituitary adenoma influenced the postoperative aggressiveness outcome.