Isolated Splenic Metastasis of Primary Lung Cancer Presented as Metachronous Oligometastatic Disease—A Case Report

Modern oncology practice and new antitumor drugs prolonged disease-free intervals in patients with lung cancer. Patients with distant metastatic disease are treated only with palliative intent. The International Association for the Study of Lung Cancer, in the 8th edition of the TNM classification, for the first time includes oligometastatic disease as a clinical state that describes the patients with distant metastasis, limited in number and organ sites, who may have more indolent biology. In this paper, we present a case of a 56-year-old man who was admitted to our clinic regarding a radiologically diagnosed splenic lesion of uncertain nature, and who underwent a left upper lobectomy for primary lung cancer 12 years before. After a detailed radiological diagnosis, it was concluded that it is highly suspected metastatic lesion of the spleen and the patient underwent a splenectomy. While no definitive protocols exist on the management of isolated splenic metastasis from lung cancer, splenectomy, in suitable patients, with reasonable survival expectations, improves patient disease-free survival and can prevent potentially life-threatening complications, such as splenic rupture. 18F-FDG PET has very high sensitivity and specificity for differentiating benign and malignant splenic lesions especially in patients who are in the follow up protocol due to primary malignancy.

Trends in Pancreatic Cancer Incidence and Mortality in Lithuania, 1998–2015

Background: Pancreatic cancer is one of the deadliest cancers worldwide, and its incidence is increasing. The aim of this study was to examine the time trends in the incidence and mortality rates of pancreatic cancer for the period of 1998–2015 for the first time in Lithuania by sex, age, subsite, and stage. Methods: This study was based on all cases (deaths) of pancreatic cancer diagnosed between 1998 and 2015. Age-standardized incidence (mortality) rates and group-specific rates were calculated for each sex using the direct method (European Standard). TNM classification-based information reported to the cancer registry was grouped into three categories: (1) localized cancer: T1-3/N0/M0; (2) cancer with regional metastasis: any 1-3/N+/M0; (3) advanced cancer: any T/any N/M+. Joinpoint regression was used to provide annual percentage changes (APCs) and to detect points in time where statistically significant changes in the trends occurred. Results: Overall, 8514 pancreatic cancer cases (4364 in men and 3150 in women) were diagnosed and 7684 persons died from cancer of the pancreas. Pancreatic cancer incidence rates were considerably lower for women than for men, with a female:male ratio of 1:2. Incidence rates changed during the study period from 14.2 in 1998 to 15.0/100,000 in the year 2015 in men, and from 6.7 to 9.8/100,000 in women. Incidence rates over the study period were stable for men (APC = 0.1%) and increasing for women by 1.1% per year. Similarly, mortality rates increased in women by 0.9% per year, and were stable in men. During the study period, incidence and mortality rates of pancreatic cancer were close. For the entire study period, rates increased significantly in the 50–74 years age group; only cancer of the head of pancreas showed a decline by 0.9%, while tail and not-specified pancreatic cancer incidence increased by 11.4% and 4.51%, respectively. Conclusions: The increasing pancreatic cancer incidence trend in the Lithuanian population may be related to the prevalence of its main risk factors (smoking, obesity, physical inactivity, diet, and diabetes).

Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasion on PDAC. One hundred and twenty-two patients with resected PDAC were examined. We distinguished three groups: direct (per continuitatem, Nc) from the main tumour, metastasis (Nm) without any contact to the main tumour, and a mixed mechanism (Ncm). Afterwards, the prognostic power of the different groups was analysed concerning overall survival (OS). In total, 20 patients displayed direct lymph node invasion (Nc = 16.4%), 44 were classed as Nm (36.1%), and 21 were classed as Ncm (17.2%). The difference in OS was not statistically significant between N0 (no lymph node metastasis, n = 37) and Nc (p = 0.134), while Nm had worse OS than N0 (p < 0.001). Direct invasion alone had no statistically significant effect on OS (p = 0.885). Redefining the N0 stage by including Nc patients showed a more precise OS prediction among N stages (p = 0.001 vs. p = 0.002). Nc was more similar to N0 than to Nm; hence, we suggest a rethinking of TNM classification based on the mechanisms of lymph node metastases in PDAC. Overall, this novel classification is more precise.

MNCD: A New Tool for Classifying Parkinson’s Disease in Daily Clinical Practice

Background and objective: Parkinson’s disease (PD) is a clinically heterogeneous disorder in which the symptoms and prognosis can be very different among patients. We propose a new simple classification to identify key symptoms and staging in PD. Patients and Methods: Sixteen movement disorders specialists from Spain participated in this project. The classification was consensually approved after a discussion and review process from June to October 2021. The TNM classification and the National Institutes of Health Stroke Scale (NIHSS) were considered as models in the design. Results: The classification was named MNCD and included 4 major axes: (1) motor symptoms; (2) non-motor symptoms; (3) cognition; (4) dependency for activities of daily living (ADL). Motor axis included 4 sub-axes: (1) motor fluctuations; (2) dyskinesia; (3) axial symptoms; (4) tremor. Four other sub-axes were included in the non-motor axis: (1) neuropsychiatric symptoms; (2) autonomic dysfunction; (3) sleep disturbances and fatigue; (4) pain and sensory disorders. According to the MNCD, 5 stages were considered, from stage 1 (no disabling motor or non-motor symptoms with normal cognition and independency for ADL) to 5 (dementia and dependency for basic ADL). Conclusions: A new simple classification of PD is proposed. The MNCD classification includes 4 major axes and 5 stages to identify key symptoms and monitor the evolution of the disease in patients with PD. It is necessary to apply this proof of concept in a properly designed study.

Computed tomography radiomics for the prediction of thymic epithelial tumor histology, TNM stage and myasthenia gravis

Objectives To evaluate CT-derived radiomics for machine learning-based classification of thymic epithelial tumor (TET) stage (TNM classification), histology (WHO classification) and the presence of myasthenia gravis (MG). Methods Patients with histologically confirmed TET in the years 2000–2018 were retrospectively included, excluding patients with incompatible imaging or other tumors. CT scans were reformatted uniformly, gray values were normalized and discretized. Tumors were segmented manually; 15 scans were re-segmented after 2 weeks by two readers. 1316 radiomic features were calculated (pyRadiomics). Features with low intra-/inter-reader agreement (ICC<0.75) were excluded. Repeated nested cross-validation was used for feature selection (Boruta algorithm), model training, and evaluation (out-of-fold predictions). Shapley additive explanation (SHAP) values were calculated to assess feature importance. Results 105 patients undergoing surgery for TET were identified. After applying exclusion criteria, 62 patients (28 female; mean age, 57±14 years; range, 22–82 years) with 34 low-risk TET (LRT; WHO types A/AB/B1), 28 high-risk TET (HRT; WHO B2/B3/C) in early stage (49, TNM stage I-II) or advanced stage (13, TNM III-IV) were included. 14(23%) of the patients had MG. 334(25%) features were excluded after intra-/inter-reader analysis. Discriminatory performance of the random forest classifiers was good for histology(AUC, 87.6%; 95% confidence interval, 76.3–94.3) and TNM stage(AUC, 83.8%; 95%CI, 66.9–93.4) but poor for the prediction of MG (AUC, 63.9%; 95%CI, 44.8–79.5). Conclusions CT-derived radiomic features may be a useful imaging biomarker for TET histology and TNM stage.

Indication to postoperative radiotherapy for oral cavity squamous cell carcinoma: what’s new in the Depth of Infiltration (DOI) era?

Objectives: The last edition of the American Joint Committee on Cancer (AJCC eighth) has introduced the depth of infiltration (DOI) as a new prognostic parameter in oral cavity squamous cell carcinomas (OCSCCs). Aim of this study is to analyze the impact of stage migration on the indication to postoperative radiotherapy (PORT). Methods: OCSCCs treated at two Institutions between 2014 and 2019 were retrieved. Per the AJCC eighth, only pT3 primarily OCSCCs were considered; availability of the pathologic specimen was a further inclusion criterion. Risk factors considered for PORT were: pT3-pT4, nodal involvement, positive/close surgical margins, perineural and lymph vascular invasion. Results: One-hundred forty-nine patients staged as pT3 AJCC eighth were included. A four-fold increase in the number of patients staged as pT3 from the seventh to the eighth AJCC was found. Stage migration to pT3 was equally due to the downstaging from former pT4 (38%) and upstaging of former pT1-pT2 (35%). Considering the former pT1-pT2 53 patients, 13 (25%) had no risk factors for PORT other than DOI. Among 25 cases with former pT1-pT2 and negative lymph nodes no additional risk factors were found in 11 (44%). Conclusion: Ninety percent of patients had at least one risk factor besides DOI and would have received PORT also according to the AJCC seventh; notably, of former pT1-pT2N0, half of them have been upstaged to pT3 in the current TNM classification. The role of PORT in this cohort of patients has not been clarified yet. Advances in knowledge: Other-than-DOI risk factors leading to PORT indication are highly prevalent in OCSSC patients classified as pT3 per the latest AJCC TNM staging system and should therefore be considered for a comprehensive oncological assessment.

Prognostic Performance of Alternative Lymph Node Classification Systems for Patients with Medullary Thyroid Cancer: A Single Center Cohort Study

Background Lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS) have been proposed as alternative lymph node (LN) classification schemes. Various cut-off values have been defined for each system, with the question of the most appropriate for patients with medullary thyroid cancer (MTC) still remaining open. We aimed to retrospectively compare the predictive impact of different LN classification systems and to define the most appropriate set of cut-off values regarding accurate evaluation of overall survival (OS) in patients with MTC. Methods 182 patients with MTC who were operated on between 1985 and 2018 were extracted from our medical database. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 28 LNR and 28 LODDS classifications and compare them with the N category according to the 8th edition of the AJCC/UICC TNM classification in terms of discriminative power. Regression models were adjusted for age, sex, T category, focality, and genetic predisposition. Results High LNR and LODDS are associated with advanced T categories, distant metastasis, sporadic disease, and male gender. In addition, among 56 alternative LN classifications, only one LNR and one LODDS classification were independently associated with OS, regardless of the presence of metastatic disease. The C-statistic demonstrated comparable results for all classification systems showing no clear superiority over the N category. Conclusion Two distinct alternative LN classification systems demonstrated a better prognostic performance in MTC patients than the N category. However, larger scale studies are needed to further verify our findings.

575 Heart failure as the cancer for the heart: the prognostic role of the new TNM-like classification

Aims Heart failure (HF) is the pandemic of the third millennium accounting for the highest mortality rate among general population, second only to lung cancer. Beside heart, HF can affect lungs and peripheral organs, such as kidney, liver, brain, erythropoiesis, leading to multiorgan dysfunction. This is similar to spread of cancer. We proposed a new staging system of HF, named HLM, analogous to TNM classification used in oncology, which refers to heart damage (H), instead of T for tumour, lung involvement (L), instead of N for lymphnodes, and malfunction (M) of peripheral organs, instead of M for metastasis. The aim of this study was a comparison of HLM score with NYHA classes, ACC/AHA stages and HF classification by left ventricular ejection fraction (LVEF), to assess the most accurate prognosis tool for HF patients, in terms of a composite endpoint of all-cause death and hospitalization. Methods and results We performed a multicentre observational, prospective study of consecutive patients admitted for HF, or at risk for HF. All parameters for heart, lungs, and peripheral organ function were collected and examined. Each patient was classified according to HLM, NYHA, ACC/AHA scores and LVEF, at hospital admission and at discharge. The composite endpoint was all-cause death and rehospitalization; the secondary endpoints were all-cause death, cardiac death, and rehospitalization. Patients were followed up at 12 months. We enrolled 2152 patients. Among those, 1720 patients completed the 12-months follow-up. Comparing HLM with other nosologies, the area under the ROC curve (AUC) was greater for HLM score than NYHA, ACC/AHA and LVEF scores regarding the composite endpoint (HLM = 0.644; NYHA = 0.580; ACC/AHA = 0.572; EF = 0.572) and all-cause death (HLM = 0.713; NYHA = 0.596; ACC/AHA = 0.594; EF = 0.565). HLM score related AUC showed statistically significant differences compared to LVEF (P &lt; 0.001), ACC-AHA (P &lt; 0.001), and NYHA (P &lt; 0.001) scores’ AUC, in terms of all-cause death and the composite of all-cause death and rehospitalization, at 12 months follow-up. Moreover, the AIC and BIC values to predict the composite of all-cause death and rehospitalization, all-cause death, cardiac death and rehospitalization rate at 12 months follow-up were always lower for HLM model compared with the others. Conclusions According to our results, HLM score has greater prognostic power compared to other nosologies, in terms of composite outcome, rehospitalization, and all-cause death, as well as all-cause death, cardiac death, and rehospitalization, at 12 months follow-up in HF patients. HLM score overcomes the cardiocentric view of HF and it addresses the pathophysiological mechanisms underlining heart abnormalities. Such a multivariable, holistic staging system may be used in HF patients, in order to improve clinical management and to reduce healthcare costs.