Background: Significant advances in the molecular profiling of gliomas, led the 2016 World Health Organization (WHO) Classification to include, for the first-time, molecular biomarkers in glioma diagnosis: IDH mutations and 1p/19q codeletion. Here, we evaluated the effect of this new classification in the stratification of gliomas previously diagnosed according to 2007 WHO classification. Then, we also analyzed the impact of TERT promoter mutations, PTEN deletion, EGFR amplification and MGMT promoter methylation in diagnosis, prognosis and response to therapy in glioma molecular subgroup. Methods: A cohort of 444 adult gliomas was analyzed and reclassified according to the 2016 WHO. Mutational analysis of IDH1 and TERT promoter mutations was performed by Sanger sequencing. Statistical analysis was done using SPSS Statistics 21.0. Results: The reclassification of this cohort using 2016 WHO criteria led to a decrease of the number of oligodendrogliomas (from 82 to 49) and an increase of astrocytomas (from 49 to 98), while glioblastomas (GBM) remained the same (n = 256). GBM was the most common diagnosis (57.7%), of which 55.2% were IDH-wildtype. 1p/19q codeleted gliomas were the subgroup associated with longer median overall survival (198 months), while GBM IDH-wildtype had the worst outcome (10 months). Interestingly, PTEN deletion had poor prognostic value in astrocytomas IDH-wildtype (p = 0.015), while in GBM IDH-wildtype was associated with better overall survival (p = 0.042) as well as MGMT promoter methylation (p = 0.009). EGFR amplification and TERT mutations had no impact in prognosis. Notably, EGFR amplification predicted a better response to radiotherapy (p = 0.011) and MGMT methylation to chemo-radiotherapy (p = 0.003). Conclusion: In this study we observed that the 2016 WHO classification improved the accuracy of diagnosis and prognosis of diffuse gliomas, although the available biomarkers are not enough. Therefore, we suggest MGMT promoter methylation should be added to glioma classification. Moreover, we found two genetic/clinical correlations that must be evaluated to understand their impact in the clinical setting: i) how is PTEN deletion a favorable prognostic factor in GBM IDH wildtype and an unfavorable prognostic factor in astrocytoma IDH wildtype and ii) how EGFR amplification is an independent and strong factor of response to radiotherapy.

Background: Well-differentiated thyroid cancer (WDTC) is the most common endocrine neoplasia, and its incidence is rising. Studies have reported an increased risk of second primary cancer (SPC) in WDTC survivors, but its relationship with radioiodine treatment (RAIT) and other risk factors remains controversial. This study evaluated whether RAIT is an independent risk factor for SPC in WDTC patients. Methods: This was a retrospective single-center study. A total of 2031 patients with WDTC diagnosed between 1998 and 2009, treated and followed at the authors' tertiary cancer center, were included. Results: The median age of patients was 48 years (range 5–90 years); 83% were women and 77% underwent RAIT. The median follow-up was 8.8 years (range 5.0–17.0 years). A total of 130 SPC were diagnosed: 108/1570 (6.9%) received RAIT (RAIT+) and 22/461 (4.8%) did not (RAIT–). The most common SPC was breast cancer (31%), followed by genitourinary and gastrointestinal cancer (18% each). The 10-year cumulative incidence of SPC was 8.2% in RAIT+ and 4.5% in RAIT–. The absolute risk increase in the RAIT+ group versus the RAIT– group at 10 years of follow-up was 0.039 [confidence interval (CI) 0.011–0.067] per patient-year. The number needed to harm (NNH) was 25.6 [CI 15.0–87.2], indicating that on average during a 10-year follow-up period, there is one additional case of SPC for every 26 patients receiving RAIT. When controlling for age, sex, and familial and personal histories of cancer, there was an 84% increase in the risk of SPC in the RAIT+ group compared to the RAIT– group (p = 0.026; relative risk = 1.84 [CI 1.02–3.31]). There was an association between SPC incidence and total cumulative activity administered, which was statistically significant >200 mCi. The incidence of SPC was higher in both the WDCT and the RAIT+ cohorts compared to the general population (standardized incidence ratios = 1.32 and 1.40, respectively). Conclusion: These results indicate that in spite of the low incidence of SPC in WDTC patients, the risk is increased after RAIT, particularly for activities >200 mCi. Thus, considering the excellent survival of patients with WDTC, clinicians need to weigh the risks and benefits of RAIT, especially in patients with low-risk thyroid cancer.

The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis.

PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); p = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; p = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (−) 36%; p = 0.007; DFS HPV (+) 83% and HPV (−) 43%; p = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: p = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02–20.99; p = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation.

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratios are below &OV0556;10 000 in all evaluated outcomes, being around &OV0556;9100 per quality-adjusted life-year gained, &OV0556;6700 per life-year gained, and &OV0556;8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of &OV0556;20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

Acute erythroleukemia (AEL) is a rare disease typically associated with a poor prognosis. The median survival ranges between 3–9 months from initial diagnosis. Hypomethylating agents (HMAs) have been shown to prolong survival in patients with myelodysplastic syndromes (MDS) and AML, but there is limited data of their efficacy in AEL. We collected data from 210 AEL patients treated at 28 international sites. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method and the log-rank test was used for subgroup comparisons. Survival between treatment groups was compared using the Cox proportional hazards regression model. Eighty-eight patients were treated with HMAs, 44 front line, and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response rate (complete or partial) compared to first-line HMA (72% vs. 46.2%, respectively; p ≤ 0.001), but similar progression-free survival (8.0 vs. 9.4 months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7 months; p = 0.564), but patients with high-risk cytogenetics treated with HMA first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results support the therapeutic value of HMA in AEL.