What's new in thoracic oncology.

Many changes have occurred in the field of thoracic surgery over the last several years. In this review, we will discuss new diagnostic techniques for lung cancer, innovations in surgery, and major updates on latest treatment options including immunotherapy. All these have significantly started to change our approach toward the management of lung cancer and have great potential to improve the lives of our patients afflicted with this disease.

The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.

Clinical aspects of oral cancer and potentially malignant disorders in South and Southeast Asia.

BACKGROUND: Oral cancer and Oral Potentially Malignant Disorders (OPMD) are major health problems in South and Southeast Asia. AIMS: To describe and discuss the clinical aspects of Oral Cancer and OPMD in South and Southeast Asia. MATERIALS AND METHODS: Literature review of concepts and data over the last four decades. DISCUSSION: Asian countries account for about two-thirds of new cases of oral cancer (OC) globally, with the highest burden in the South and Southeast Asian countries, including Pakistan and India. Habits, dietary patterns, socioeconomic status, and access to routine dental care play a crucial role in defining the demographics and clinical presentation of OC in these regions and significantly influence the morbidity and mortality of the disease. This region sees the use of different types of tobacco with or without areca nut (AN), such as pan masala, gutka, gul, snuff, mawa, and mishri. Tobacco use is high among men in Sri Lanka, Myanmar, Maldives, Bangladesh, Nepal, India and Bhutan. Areca nut is the fourth most common addictive substance globally and is frequently used in South and Southeast Asian countries, including Southeast China, Hainan Island, India, Taiwan, and the Pacific Islands, and immigrants from these regions in Africa, Europe, and North America. The use of these products results in mucosal alterations with varied clinical presentation of Oral Potentially Malignant Disorders (OPMDs) and OC. We discuss here the different types of OPMD and OC, the diagnostic aids and their relevance in clinical practice, and factors that influence their prognosis.

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.

Prognostic impact of deep learning-based quantification in clinical stage 0-I lung adenocarcinoma.

OBJECTIVES: To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. METHODS: A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. RESULTS: The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. CONCLUSION: DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. CLINICAL RELEVANCE STATEMENT: Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. KEY POINTS: • Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). • For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. • The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.

Lymph node sampling-what are the numbers?

Lung cancer is a deadly disease. Lymph node staging is the most important prognostic factor, and lymphatic drainage of the lung is complex. Major advances have been made in this field over the last several decades, but there is much left to understand and improve upon. Herein, we review the history of the lymphatic system and the creation of lymph node maps, the evolution of tumor, node, and metastasis lung cancer classification, the importance of lung cancer staging, techniques for lymph node dissection, and our recommendations regarding a minimum number of nodes to sample during pulmonary resection.

Evaluation of the relationship of the T and M stage with the erector spinae muscle area in male lung cancer patients.

OBJECTIVES: Sarcopenia is very common due to cachexia and presents with a decrease in skeletal muscle mass. In this study, we aimed to investigate the relationship between the T, M category and the erector spinae muscle area (ESMa). MATERIAL AND METHODS: The initial first thorax and high-resolution computed tomography (CT) of patients with lung cancer between 2015 and 2019 were retrospectively screened. After exclusion criterias remaining 226 male patients constituted the study group. ESMa was measured manually in the section taken from the T12 vertebra spinous process level as previously described in the literature and its relationship with the T and M stage were evaluated. RESULTS: The mean ages of patients were 70 ± 9.57 years. The T stage was T1 in 34 (15%) patients, T2 in 46 (20.4%), T3 in 59 (26.1%), and T4 in 87 (38.5%). Metastasis was detected in 83 (36.7%) patients. The mean ESMa of the patients was 34.15 ± 7.21 mm2 and did not differ according to the T stage (p = .39). ESMa was lower in the metastatic group (mean 30.42 ± 6.38 mm2) than the non-metastatic group (mean 36.32 ± 6.78 mm2) (p = .0001). CONCLUSIONS: ESMa, one of the indicators of sarcopenia, is lower in patients with metastatic lung cancer than in nonmetastatic.

A novel nomogram and risk stratification system predicting the cancer-specific survival of patients with gastric neuroendocrine carcinoma: a study based on SEER database and external validation.

BACKGROUND: Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients. METHODS: Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P < 0.001), respectively. In 1-, 3-, and 5-year CSS prediction using DCA curves, the nomogram outperformed the AJCC staging system. The nomogram performed well in both the internal and external validation cohorts. CONCLUSION: We developed and validated a nomogram to predict 1-, 3-, and 5-year CSS for GNEC patients after surgical resection. This well-performing model could help doctors enhance the treatment plan.

Does the ypTNM-stage adequately predict long-term survival rates in gastric cancer patients receiving neoadjuvant chemotherapy followed by radical resection?

BACKGROUND: Following neoadjuvant chemotherapy (NAC) for resectable gastric cancer, the prognostic adequacy of the UICC staging system needs to be investigated. In particular to explore whether the ypTNM curves for radically resected gastric cancer patients receiving NAC follow the stage-matched survival curves of radically resected chemo-naïve patients (pTNM). Further, to disclose any interaction between the TNM-response mode to NAC and stage-specific survival rates, i.e., whether survival for a particular pathological disease stage was dependent on whether this was reached through a downstaging or as stable disease following NAC. MATERIAL AND METHODS: Retrospective study on radically resected patients ≤ 75 years of age with gastric adenocarcinoma stages I-III diagnosed during 2001-2016. The patients constitute two population-based cohorts; the SURG-group with n = 121 patients treated before 2007 when NAC was introduced, and the NAC-group with n = 126 patients diagnosed since early 2007, receiving NAC and subsequent radical resection. RESULTS: Long-term survival rates were similar when specific ypTNM-stages were compared to their corresponding pTNM chemo-naïve counterparts. The dichotomised N0 vs. N + had a substantial impact on the long-term survival rates in both groups, however, no discrepancy in long-term survival rates between pN0 vs. ypN0, and pN + vs. ypN + was found. The pathological stage determined long-term survival rates irrespective of the baseline disease stage, as no interaction between the response mode and stage-specific survival rates was found. CONCLUSIONS: Survival curves for specific ypTNM-stages following NAC did not differ from the corresponding survival curves of their chemo-naïve pTNM counterparts. The interpretation is that NAC affected the gastric cancer, lymph nodes, and micrometastases, in such a way that the final ypTNM-stage provided similar prognostic information as the chemo-naïve pTNM-stages. Survival rates were contingent on the final ypTNM-stages alone, and not influenced by the response mode to reach that particular disease stage, or predetermined by the original clinical TNM-stage.

Sensitivity to thyroid hormone indices are associated with papillary thyroid carcinoma in Chinese patients with thyroid nodules.

BACKGROUND: The association between thyroid hormone sensitivity and thyroid cancer is unknown, and we aimed to investigate the association between sensitivity to thyroid hormone indices and papillary thyroid carcinoma (PTC) in Chinese patients with thyroid nodules (TNs). METHODS: A total of 1,998 patients undergoing thyroid surgery due to TNs from Nanjing Drum Tower Hospital were included in this study. We evaluated central sensitivity to thyroid hormones, such as thyroid stimulating hormone index (TSHI), TSH T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric thyroid feedback quantile-based Index (PTFQI). Peripheral sensitivity to thyroid hormone was evaluated by FT3 to FT4 ratio. Multivariate logistic regression analysis was performed to evaluate the association between sensitivity to thyroid hormone indices and PTC risk. RESULTS: The results showed that central indices of thyroid hormone sensitivity, including TSHI, TT4RI, TFQI, and PTFQI, were positively associated with PTC risk. For each SD increase in TSHI, TT4RI, TFQI, and PTFQI, the odds ratios (OR, 95% CI) of PTC were 1.31 (1.18-1.46), 1.01 (1.01-1.02), 1.94 (1.45-2.60), and 1.82 (1.41-2.34), respectively. On the other hand, the association between peripheral sensitivity to thyroid hormone and PTC was significantly negative. For each SD increase in FT3/FT4 ratio, the OR (95% CI) of PTC was 0.18 (0.03-0.96), and a negative correlation was found between FT3/FT4 ratio and TNM staging of PTC. CONCLUSIONS: Sensitivity to thyroid hormone indices could be used as new indicators for predicting PTC in Chinese patients with TNs. Future researches are still needed to confirm our findings.

Newly proposed survival staging system for poorly differentiated thyroid cancer: a SEER-based study.

OBJECTIVE: Despite the recent release of the 8th edition TNM staging system, the risk stratification for poorly differentiated thyroid cancer (PDTC) remains controversial. STUDY DESIGN: Retrospective study. SETTING: SEER database and the First Hospital of China Medical University (FHCMU) database. METHODS: Between 2004 and 2015, 1201 PDTC patients from the SEER database were enrolled to propose a new staging system. 38 PDTC patients were included from the FHCMU. RESULTS: A retrospective analysis of 1201 PDTC cases was performed, and a new staging classification was developed as follows: stage I: age < 55 and T1/any N/M0 (n = 127, 10.57%); stage II: age < 55 and T2-4/any N/M0 or age ≥ 55 and T1-2/any N/M0 (n = 523, 43.55%); stage III: age < 55 and any T/N0/M1 or age ≥ 55 and any T3/any N/M0 (n = 239, 19.90%); stage IV: age < 55 and any T/N1/M1 or age ≥ 55 and T4/any N/M0, and T/any N/M1 (n = 312, 25.98%). The 10-year disease-specific survival rates of patients in the new stages I, II, III, and IV were 97.9%, 77.9%, 35.3%, and 12.1%, respectively. The proportion of variation explained (PVE) for disease-specific survival of the proposed system was higher than that of the 8th AJCC TNM staging (30.61% vs. 27.15%). The accuracy of the staging system was verified in 38 PDTC patients from the FHCMU. CONCLUSION: The proposed staging system provided a more accurate risk stratification for PDTC patients. The new staging model may facilitate the design of personalized treatment strategies for PDTC patients.

ypTNM staging is a potentially useful prognostic stratification tool in patients with advanced gastric cancer after preoperative chemotherapy.

PURPOSE: Although the usefulness of the ypStage in neoadjuvant chemotherapy for advanced gastric cancer (GC) has been reported, whether or not the ypStage is applicable to all GC patients who receive preoperative chemotherapy, including conversion surgery cases, is unclear. Therefore, this retrospective study evaluated the value of the ypTNM staging system in all advanced GC patients who received chemotherapy prior to gastrectomy. METHODS: A total of 66 patients who underwent chemotherapy prior to gastrectomy for advanced GC at Chiba University Hospital from January 2008 to December 2020 were enrolled in the current study. The prognostic impact of the ypStage on the overall survival (OS) and relapse-free survival (RFS) were examined via univariate and multivariate analyses. RESULTS: The 5-year OS rates for ypStage I, II, III, and IV were 87.5%, 64.7%, 52.9%, and 28.6%, respectively, while the 5-year RFS rates were 81.3%, 57.4%, 44.4%, and 28.6%, respectively. The univariate analysis revealed that the ypStage was significantly correlated with the OS (p = 0.037) and the ypT status and ypStage showed a significant correlation with the RFS (p = 0.043 and p = 0.021, respectively). The multivariate analysis demonstrated that only the ypStage was an independent prognostic factor for the OS and RFS (p = 0.024 and p = 0.018, respectively). CONCLUSION: The ypTNM stage may be a useful tool for the risk stratification of all advanced GC patients treated with chemotherapy followed by gastrectomy, including not only neoadjuvant but also conversion surgery cases.

Prognostic impact of muscle invasion in buccal mucosa squamous cell carcinoma.

OBJECTIVE: The objective of the study was to assess the prognostic value of muscle invasion (MI), a key histopathological feature of tumor aggressiveness, and construct a superior prognostic prediction model combining the current TNM staging system. MATERIALS AND METHODS: MI was analyzed in the whole-slide images from a total of 301 patients with primary buccal mucosa squamous cell carcinoma (BMSCC). Survival times of patients with/without MI were evaluated by Kaplan-Meier analysis. MI was further combined with the TNM staging system to explore its predictive value for prognosis. Moreover, 204 cases of head and neck carcinoma from the TCGA database were included. RESULTS: MI positive rate reached to 76% (229/301) in patients with BMSCC. MI was associated with poor overall survival (p = 0.012) and disease-free survival (p = 0.022). The novel system (TNM staging combined with MI) revealed strong predictive performance, with the largest area under the curve (OS: p < 0.001, DFS: p < 0.004). MI and the established classification system were also had good predictive ability in the TCGA cohort. CONCLUSIONS: MI is an independent predictor of poor prognosis of BMSCC. The inclusion of MI in prediction system can augment the risk stratification of patients with oral squamous cell carcinoma and may assist in the clinical decision-making process.

Intra- and interobserver agreement of rectal cancer staging with MRI.

BACKGROUND: Reliable preoperative staging of rectal cancers is crucial for treatment decision making. PURPOSE: To assess the intra- and inter-observer agreement of rectal cancer staging, including the sub-categories, with magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study includes 85 patients (35.3% women; mean age = 62.2 ± 11.2 years) who underwent MRI for rectal cancer staging between August 2020 and April 2021. All the stored images were evaluated independently by two radiologists with 10-15 years of experience. For intra-observer agreement, the evaluations were done two months apart. Analyses were made using kappa, prevalence and bias-adjusted kappa (PABAK), and intraclass correlation coefficient (ICC), where appropriate. RESULTS: There was a substantial inter-observer agreement for tumor localization (kappa = 0.665, PABAK = 0.682), mesorectal fascia invasion (kappa = 0.663, PABAK = 0.822), internal and external sphincter involvement (kappa 0.804 and 0.751, PABAK 0.859 and 0.929, respectively), and moderate to substantial agreement for M-staging (kappa = 0.451, PABAK = 0.742) and extramural vascular invasion (kappa = 0.569, PABAK = 0.741). There was also a good inter-observer agreement for T staging and N staging (ICC = 0.862, 95% confidence interval [CI] = 0.788-0.911; and ICC = 0.841, 95% CI = 0.595-0.922, respectively). As expected, intra-observer agreement was better than inter-observer agreement. CONCLUSION: Intra- and inter-observer agreement for MRI staging of rectal cancers using the structured reporting template is good.

Long-term outcomes following surgical treatment for thymic epithelial tumor in Japan and an analysis of prognostic factors based on the Japanese Association for Research on the Thymus nationwide database.

PURPOSE: Patients with a thymic epithelial tumor (TET), comprising thymoma, thymic carcinoma (TC), and thymic neuroendocrine neoplasm (TNEN), are rarely encountered. The present study was conducted to determine the recent outcomes of surgical treatment for TET in Japan and clarify the significance of prognostic factors by analyzing a nationwide database created by the Japanese Association for Research on the Thymus (JART). METHODS: The JART database includes records of 2471 thymoma, 285 TC, and 56 TNEN cases surgically treated between 1991 and 2010. At the time of the final follow-up examination, 439 patients had died, with tumor the cause of death in 188. The disease-specific survival was examined using the Kaplan-Meier method, with Cox's proportional hazards model utilized to determine independent prognostic factors. RESULTS: The 10-year survival rate according to TNM-based Stage I, II, IIIA, IIIB, IVA, and IVB classification was 98.7%, 76.8%, 85.0%, 68.9%, 66.2%, and 59.8%, respectively. The T factor, M factor, and tumor size were independent prognostic factors in both thymoma and thymic carcinoma cases, while the N factor had tendency to be a prognostic factor in thymoma but not in thymic carcinoma cases. The WHO histological type was an independent factor in thymoma cases. CONCLUSION: The significance of pathology and TNM classification as prognostic factors was confirmed.

Classification of early-stage colon cancer with Immunoscore®: clinical evidence and case studies.

Immunoscore® is a digital pathology diagnostic immunoassay used to complement tumor node metastasis staging for the prediction of recurrence risk in patients with early-stage colon cancer. In combination with standard clinicopathological features, Immunoscore informs adjuvant chemotherapy decision-making for patients with early-stage colon cancer. Immunoscore has been validated in patients with stage II/III colon cancer and demonstrated to be a stronger prognostic factor for survival than tumor node metastasis staging alone. Immunoscore improves the prognostic definition of patients with colon cancer, the identification of those patients at high risk of tumor recurrence, and the ability to predict which patients will derive most benefit from the use of adjuvant chemotherapy. Immunoscore has robust analytical performance characteristics which include good interlaboratory reproducibility and overall assay precision.

Plain language summary Immunoscore^® is a digital pathology diagnostic test that is used in addition to standard tools for assessing the severity and aggressiveness of tumors in patients with early-stage colon cancer. Immunoscore helps clinicians decide whether chemotherapy would be appropriate in these cases and, if so, for what duration. The test is currently used for patients with stage II or stage III colon cancer to guide treatment and is a good indicator of prognosis in colon cancers, helping to identify which patients are at a higher risk of tumor recurrence and which patients might benefit most from chemotherapy. Immunoscore is also a reliable and precise test, even when performed on different portions of a tumor sample.

Modified cancer TNM classification for localized renal cell carcinoma based on the prognostic analysis of 3748 cases from a single center.

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.

Correlations between serum levels of microRNA-148a-3p and microRNA-485-5p and the progression and recurrence of prostate cancer.

BACKGROUND: Unpredicted postoperative recurrence of prostate cancer, one of the most common malignancies among males worldwide, has become a prominent issue affecting patients after treatment. Here, we investigated the correlation between the serum miR-148a-3p and miR-485-5p expression levels and cancer recurrence in PCa patients, aiming to identify new biomarkers for diagnosis and predicting postoperative recurrence of prostate cancer. METHODS: A total of 198 male PCa cases treated with surgery, postoperative radiotherapy, and chemotherapy were involved in the presented study. Serum levels of miR-148a-3p and miR-485-5p were measured before the initial operation for the involved cases, which were then followed up for two years to monitor the recurrence of cancer and to split the cases into recurrence and non-recurrence groups. Comparison of the relative expressions of serum miR-148a-3p and miR-485-5p were made and related to other clinic pathological features. RESULTS: Pre-surgery serum levels of miR-148a-3p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly lower (P < 0.05) than levels in patients with TNM Classification of Malignant Tumors (TNM) stage cT2b and higher prostate cancer (Gleason score ≥ 7). pre-surgery serum levels of miR-485-5p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly higher (P < 0.05) than in patients with TNM stage cT2b and higher cancer (Gleason score ≥ 7). Serum miR-148a-3p level in recurrence group is higher than the non-recurrence group (P < 0.05) while serum miR-485-5p level in recurrence group is lower than non-recurrence group (P < 0.05). ROC curve analysis showed the AUCs of using miR-148a-3p, miR-485-5p, and combined detection for predicting recurrence of prostate cancer were 0.825 (95% CI 0.765-0.875, P < 0.0001), 0.790 (95% CI 0.726-0.844, P < 0.0001), and 0.913 (95% CI 0.865-0.948, P < 0.0001). CONCLUSION: Pre-surgery serum miR-148a-3p level positively correlates while miR-485-5p level negatively correlates with prostate cancer's progressing and postoperative recurrence. Both molecules show potential to be used for predicting postoperative recurrence individually or combined.

Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Combining nutritional status with TNM stage: a physiological update on gastric cancer staging for improving prognostic accuracy in elderly patients.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients. METHODS: In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups. RESULTS: Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM. CONCLUSIONS: The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients.