The value of computer aided detection system FOR mammography in the breast cancer screening: single-center, prospective, randomized clinical trial

Purpose. To assess the influence of mammography mapping with the help of computer-aided detection system (CAD) MammCheck II of our own design on the relapse-free survival (RFS) in breast cancer (BC) patients detected during the combined (mammographic and ultrasound [US]) screening. Materials and methods. 10732 women aged 40-87 years old (mean age: 52.20±8.63) who performed mammography were randomized to the standard screening group (mammography → US of the dense breasts) or to the group of CAD-assisted screening (mammography → CAD → targeted US of suspicious CAD markings, as well as the standard US of the dense breasts; CAD group). The primary endpoint was the 3-years RFS. Results. Totally, in the standard screening group we identified 230 BCs (4.29%), in the CAD group — 248 BCs (4.62%; p>0.05), including 49 (21.20%) и 88 (35.48%) 0-I stage BCs, respectively (p<0.05). Median of the primary tumor size was significantly lower in the CAD group (18 mm) compared to the standard screening group (25 mm; р<0.05). 3-years RFS was significantly higher (87.90%) in the CAD group compared to the standard screening group (81.20%; р<0.05). Conclusion. Breast US after the previous mammography CAD mapping significantly increases the 3-years RFS of women with combined screening-detected BC.

Predictive and Prognostic Effects of Primary Tumor Size on Colorectal Cancer Survival

BackgroundPathologic staging is crucial in colorectal cancer (CRC). Unlike the majority of solid tumors, the current staging model does not use tumor size as a criterion. We evaluated the predictive and prognostic impact of primary tumor size on all stages of CRC.MethodsUsing the National Cancer Database (NCDB), we conducted an analysis of CRC patients diagnosed between 2010 and 2015 who underwent resection of their primary cancer. Univariate and multivariate analyses were used to identify predictive and prognostic factors, Kaplan-Meier analysis and Cox proportional hazards models for association between tumor size and survival.ResultsAbout 61,000 patients met the inclusion criteria. Median age was 63 years and majority of the tumors were colon primary (82.7%). AJCC stage distribution was: I - 20.1%; II - 32.1%; III - 34.7% and IV - 13.1%. The prognostic impact of tumor size was strongly associated with survival in stage III disease. Compared to patients with tumors &lt;2cm; those with 2-5cm (HR 1.33; 1.19-1.49; p&lt;0.001), 5-10cm (HR 1.51 (1.34-1.70; p&lt;0.001) and &gt;10cm (HR 1.95 (1.65-2.31; p&lt;0.001) had worse survival independent of other variables. Stage II treated without adjuvant chemotherapy had comparable survival outcomes (HR 1.09; 0.97-1.523; p=0.148) with stage III patients who did, while Stage II patients who received adjuvant chemotherapy did much better than both groups (HR 0.76; 0.67-0.86; p&lt;0.001). Stage III patients who did not receive adjuvant chemotherapy had the worst outcomes among the non-metastatic disease subgroups (HR 2.66; 2.48-2.86; p&lt;0.001). Larger tumors were associated with advanced stage, MSI high, non-rectal primary and positive resection margins.ConclusionsFurther studies are needed to clarify the role of tumor size in prognostic staging models, and how to incorporate it into therapy decisions.

Clinicopathological and Ultrasound Features as Risk Stratification Predictors of Clinical and Pathological Nodal Status in Papillary Thyroid Carcinoma: A Study of 748 Patients

Background: Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid malignancy that tends to metastasize to cervical lymph nodes. In the present study, we aimed to investigate which clinicopathologic and ultrasound features of PTC are associated with clinical lymph node metastasis (LNM) and numbers of pathological LNM.Methods: From January 2016 to December 2018, we identified a cohort of patients with PTC who underwent cervical ultrasonography and were diagnosed through operation and pathology. Clinical N1(cN1) and >5 pathologic N1(pN1) was performed in accordance with a standardized protocol. A model to determine the intermediate risk stratification of the 2015 ATA was established using the outcomes of univariate and multivariate analyses. Results: we collected 748 PTC patients in the final inclusion criteria. From the analyses, primary tumor size >21mm, capsule contact, extrathyroidal extensions (ETE), postsurgical radioiodine (RAI) treatment and central LNM remained independent risk factors for cN1 in PTC patients. Multifocality, primary tumor size >21mm, capsule contact, ETE and RAI treatment are significant independent risk factors for >5 pN1. Primary tumor size >21mm, capsule contact, ETE and RAI treatment were independent risk factors for both cN1 and >5 pN1.Conclusions: We conclude that primary tumor size >21mm, capsule contact, ETE and RAI treatment were independent predictors of for intermediate risk of recurrence in patients with PTC. Ultrasonography is a good technique for the preoperative lymph node staging of PTC and is helpful for detecting LNM.

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels

Serum thyrotropin (TSH) level after thyroid surgery affects the prognosis of differentiated thyroid cancer (DTC). However, the effects of preoperative serum TSH levels on the prognosis of DTC remain contradictory. In this study, to better understand the relationship between preoperative TSH levels and the prognosis of DTC, we performed pattern analysis of prognostic factors of DTC according to preoperative serum TSH levels. We retrospectively reviewed the clinical records of patients who were diagnosed and treated for DTC at the Samsung Medical Center, between 1994 and 2016. We reviewed preoperative serum TSH levels and performed a pattern analysis with prognostic risk factors for DTC. For pattern analysis, TSH was divided into 10 groups of equal fractions (TSH decile). We found a linear association between preoperative TSH levels and extra-thyroidal extension and lymph node metastasis. However, primary tumor size and initial distant metastasis showed a bimodal peak, which was similar to the pattern of overall and disease-specific death. We found that preoperative TSH range which showed the lowest mortality rate was about 0.8 to 1.59 mIU/L, which are slightly lower normal TSH levels. Although there was no linear trend, the primary tumor size, initial distant metastasis, and mortality of DTC were closely related with preoperative TSH decile and they showed a bimodal pattern. The results obtained in this study provide additional information for understanding the association between preoperative TSH levels and DTC prognosis.

Metastatic Risk Profile of Microscopic Lymphatic and Venous Invasion in Medullary Thyroid Cancer

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients with medullary thyroid cancer who had≥5 lymph nodes removed at initial thyroidectomy, microscopic lymphatic and venous invasion were significantly associated with greater primary tumor size (27.6 vs. 14.5 mm, and 30.8 vs. 16.2 mm) and more frequent lymph node metastasis (97.0 vs. 25.9%, and 85.2 vs. 39.5%) and distant metastasis (25.0 vs. 5.1%, and 32.8 vs. 7.3%). Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (97.0 vs. 32.8%) and positive predictive value (58.4 vs. 39.2%); comparable regarding negative predictive value (98.5 vs. 90.5%) and accuracy (80.4 vs. 85.1%); and worse regarding specificity (74.1 vs. 92.7%). On multivariable logistic regression, microscopic lymphatic invasion predicted lymph node metastasis better (odds ratio [OR] 65.6) than primary tumor size (OR 4.6 for tumors>40 mm and OR 2.7 for tumors 21–40 mm, relative to tumors≤20 mm), whereas primary tumor size was better in predicting distant metastasis (OR 8.3 for tumors>40 mm and OR 3.9 for tumors 21–40 mm, relative to tumors≤20 mm) than microscopic venous invasion (OR 3.2). These data show that lymphatic invasion predicts lymph node metastases better in medullary thyroid cancer than venous invasion heralds distant metastases.

The prognostic significance of primary tumor size in squamous cell carcinoma of the penis

Background To evaluate the association of primary tumor size with clinicopathologic characteristics and survival of patients with squamous cell carcinoma of the penis (SCCP). Methods This study analyzed the data of 1001 patients with SCCP, obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. The Kaplan–Meier method and the Cox proportional hazards regression model were used to analyze the effects of primary tumor size on overall survival (OS) and penile carcinoma-specific survival (PCSS). Results Advanced T stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P = 0.001) were more frequently associated with SCCP patients with tumor size ≥ 3 cm than those with tumor size < 3 cm. In Kaplan–Meier analyses, the patients with large tumors (≥ 3 cm) exhibited an inferior OS and PCSS than those with small tumors (< 3 cm). Moreover, tumor size was identified to be an independent prognostic factor for OS [hazard ratio (HR) 1.665, P < 0.001] and PCSS (HR 2.076, P = 0.003) of patients with SCCP in multivariate analyses. Conclusions Large tumor size is associated with adverse clinicopathological characteristics of patients with SCCP. Besides, tumor size represents an independent prognostic factor for OS and PCSS. Therefore, clinical assessment of tumor size as a crucial prognostic factor might be highly beneficial for early intervention in patients with SCCP.

The Gut Microbiome as a Promising Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of various diseases, including cancer. As such, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively and prospectively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were retrospectively performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.

Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Management of Synchronous Extrathoracic Oligometastatic Non-Small Cell Lung Cancer

Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state—≤5 extrathoracic metastatic lesions in ≤3 organs—is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12–29%), and the five-year OS was 36% (95% CI, 27–50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03–1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06–2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24–0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02–1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05–3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10–3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.