[TNM Classification of malignant tumours - Eighth edition: which news?] / Classificazione TNM dei tumori maligni ­ VIII edizione: quali novità?

The eighth edition of TNM classification of malignant tumours has been published by the Union for International Cancer Control in January 2017. As for the previous editions - from the third on - it has been translated into Italian and recently published in our Country. This article explains the main changes from the previous edition: new classifications, some major revisions of cancer staging rules, the introduction of a grid of prognostic factors for each neoplasia and the addition of two chapters. These two chapters are about the essential TNM and the paediatric tumours, and have been developed in order to facilitate the use of data by Cancer Registries.

Is Ovarian Cancer Being Managed According to Clinical Guidelines? Evidence From a Population-Based Clinical Audit.

BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.

Cancer incidence in people with AIDS in Italy.

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex- and age-standardized IR and age-specific IR were estimated. The standardized IR for Kaposi sarcoma and non-Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non-AIDS-defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3-17.0) and lung (IR ratio = 1.8, 95% CI: 1.0-3.2). Age-specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non-AIDS-defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer-prevention strategies, notably smoking cessation and screening programs, in middle-aged HIV-patients.

[TNM classification of malignant tumours, VII edition 2009. Changes and practical effects on cancer epidemiology]. / Classificazione TNM dei tumori maligni, VII edizione 2009. Novità e ricadute pratiche per l'epidemiologia dei tumori.

The seventh edition of TNM classification of malignant tumours has been published by the International Union against Cancer in late 2009 and it is now available also in Italian language. This new edition introduces some major revisions and several updates of cancer staging rules. New criteria based on pathological details, biological assessment of lesions and new prognostic groupings have been established. Clinicians, pathologists, epidemiologists have now the chance to get familiar with those novelties, that are expected to be of great help in a moment like the present one, when strong evolutions occur in the strategies of diagnosis and of treatment of cancer.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). METHODS: A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. RESULTS: Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. CONCLUSIONS: Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Misclassification of breast cancer as cause of death in a service screening area.

OBJECTIVE: The aim of this study was to assess the misclassification of cause of death for breast cancer cases, and to evaluate the differential misclassification between cases detected in an organized screening program and cases found in current clinical practice. METHODS: All deaths occurring between 1999 and 2002 within breast cancer cases were linked to hospital discharge records. Death certificates and latest available hospital discharge notes were classified into various categories. We created a classification algorithm defining which combinations of categories (of death certificates and hospital discharge notes) suggested the probability of misclassification and the need for an in-depth diagnostic review. Questionable cases were reviewed by a team of experts in order to reach a consensus on cause of death. Based on our algorithmic classification and diagnostic review results, the agreement between original cause of death and that resulting from the assessment process was analyzed stratifying for every variable of interest. RESULTS: According to death certificates, breast cancer was the cause of death in 66.9% of subjects, and after assessment this figure changed to 65.7%. The misclassification rate was 4.3% and did not differ significantly between screen-detected (4.7%) and non-screen-detected (4.3%) cases. Higher misclassification rates in favor of false positivity (cause of death wrongly attributed to breast cancer in death certificates) was observed for subjects with multiple cancers (6.5% vs. 1.9%), with no admission in the year before death (4.6% vs. 2.4%) and with an unknown cancer stage (4.9% vs 2.4% or 2.3%). CONCLUSIONS: The cause of death misclassification rate is modest, causing a slight overestimate of deaths attributed to breast cancer, and is not affected by modality of diagnosis. The study confirmed the validity of using cause-specific mortality for service screening evaluation.

Prognostic Characterization of Higher-Grade Meningiomas: A Histopathological Score to Predict Progression and Outcome.

Higher-grade meningiomas (WHO grade II and III) represent a diagnostic and prognostic challenge. We assessed the pathological and molecular characteristics of 94 higher-grade meningiomas (85 grade II, 9 grade III) to identify novel prognostic parameters. Higher mitotic count (p = 0.018), diffuse (≥50%) prominent nucleoli (p < 0.001), and sheeting (p < 0.001) were associated with recurrence. Lower SSTR2a-positive cells median rate (p = 0.048) and TERT promoter mutations (p = 0.014) were associated with recurrence and patient death, respectively; further analyses did not identify other outcome associations. Presence of Ki67 hot spots was associated with a shorter progression-free survival (PFS), independently of WHO grade at multivariate analysis (HR = 3.35, p = 0.008). Necrosis was related to a poorer overall survival (OS) at univariate (focal: HR = 4.55, p = 0.041 and diffuse: HR = 7.38, p = 0.020) and Kaplan-Meier analyses. A prognostic score was designed based on previous results: Presence of diffuse (≥50%) prominent nucleoli (0/1 point), diffuse (≥50%) sheeting (0/1 point), focal (<50%) or diffuse (≥50%) necrosis (0/1/2 points), and Ki67 hot spots (0/1 point). A total score ≥4 predicted poorer PFS and OS by Kaplan-Meier (PFS: 1.7 vs 6.4 years, p < 0.001 and OS: 5.2 vs 10.8 years, p = 0.001) and multivariate (PFS: HR = 5.98, p < 0.001 and OS: HR = 2.99, p = 0.048) analyses. These results were confirmed in an independent series of 58 grade II meningiomas (PFS: HR = 7.22, p = 0.002 and OS: HR = 9.69, p = 0.003). These associations and the integrated score could complement WHO grading.

Early diagnosis, not differential treatment, explains better survival in service screening.

Italian population-based breast cancer screening programmes with 2-year, high-quality mammography started in the cities of Florence and Turin in the early 1990s. Breast cancer cases from the local Tumour Registry were classified by method of detection and tumour characteristics (size, nodal-status and grade). Follow-up was at December 2001. In total, 4444 breast cancer cases were analysed. The Hazard Ratio comparing before and after-invitation breast cancer cases indicated a 27% reduction (HR=0.73; 95%CI: 0.61-0.87) in the risk of dying for the disease. After adjustment for tumour characteristics, survival rate was comparable by invitation status, whereas the proportion of early cancer was 33.7% and 46.6% in the before and after-invitation group. Survival rates by tumour characteristic subgroups was comparable by invitation status. Late stage and grade 3 were indicators of poor prognosis. Adjustment for tumour characteristics confirmed screening and not differential treatment as the most important reason for the observed survival benefit. The survival analysis by specific subgroups did not support the hypothesis that the difference in prognosis was attributable to differential treatment.