Search

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation.

68 Ga-DOTATOC represents a useful tool in tumor contouring for radiosurgery planning. We present a case series of patients affected by meningiomas on who we performed 68 Ga-DOTATOC positron emission tomography (PET)/CT pre-operatively, a subgroup of which also underwent a post-operative 68 Ga-DOTATOC PET/CT to evaluate the standardized uptake value (SUV) modification after Gamma Knife ICON treatment in single or hypofractionated fractions. Twenty patients were enrolled/included in this study: ten females and ten males. The median age was 52 years (range 33-80). The median tumor diameter was 3.68 cm (range 0.12-22.26 cm), and the median pre-radiotherapy maximum SUV value was 11 (range 2.3-92). The average of the relative percentage changes between SUVs at baseline and follow up was -6%, ranging from -41% to 56%. The SUV was reduced in seven out of 12 patients (58%), stable in two out of 12 (17%), and increased in three out of 12 (25%), suggesting a biological response of the tumor to the Gamma Knife treatment in most of the cases. 68 Ga-DOTATOC-PET represents a valuable tool in assessing the meningioma diagnosis for primary radiosurgery; it is also promising for follow-up assessment.

Nucleophosmin ( NPM1 ) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented NPM1 mutations in around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with NPM1 -mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing NPM1 -mutated MNs with blast count <20%, since NPM1 -mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to NPM1 -mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether NPM1 mutations may become sufficient to diagnose AML, irrespective of blast percentage.

BRAF exon 15 mutations are the most common molecular alterations found in papillary thyroid carcinoma (PTC). To date, there is no information regarding BRAF alterations in the thyroid parenchyma surrounding the tumor. To explore the early events associated with the development of PTC, we used massively parallel sequencing to investigate BRAF exon 15 in 30 PTCs and in 100 samples from the thyroid parenchyma surrounding the tumor. BRAF p.V600E was identified in 19/30 PTCs (63.3%). BRAF p.V600E mutations were identified in the tissue adjacent the PTC only in samples containing psammoma bodies. The other samples were either BRAF wild type (WT) or carried BRAF non p.V600E mutations. Specifically, BRAF p.G593D, -p.A598T, -p.V600M, -p.R603Q, -p.S607F, and -p.S607P were identified in 4 of 36 (11.1%) samples with follicular cell atypia, in 2 of 16 (12.5%) with follicular cell hyperplasia, and in 1 of 33 (3.0%) histologically normal samples-only in tissue surrounding BRAF p.V600E mutated PTCs. These mutations are predicted to affect protein function in silico but, in vitro, have kinase activity and BRAF phosphorylation levels similar to BRAF WT. No BRAF exon 15 mutations were identified in samples adjacent to PTCs that were BRAF WT. A mutagenic process affecting BRAF exon 15 occurs in a subset of thyroid glands that develop BRAF p.V600E mutated PTCs., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.