Letizia Laera

Background/Objectives: Hypofractionated radiation therapy (Hypo-RT) schedules may offer radiobiological, patient convenience, and healthcare resource advantages over standard fractionated radiation therapy (S-RT) for glioblastoma (GBM). Additionally, simulated integrated boost (SIB) Hypo-RT is proven to be an effective and safe treatment. We report on our experience regarding progression-free survival (PFS), overall survival (OS), and RT-related toxicities in GBM patients treated with Hypo-RT and S-RT. Methods: Patients with IDH-wildtype GBM received either Hypo-RT (40.05-52.5 Gy/15 fractions) or S-RT (60-70 Gy/30 fractions). Volumetric modulated arc therapy was performed for all patients. Concomitant temozolomide (75 mg/m²/day) and adjuvant chemotherapy (TMZ 150-200 mg/m² for 5 days every 28 days) were administered. OS and PFS were estimated using the Kaplan-Meier method. Results: Ninety-five patients were treated (Hypo-RT: 52, S-RT: 43). With a median follow-up of 25 months (range 9-63), the median age was 65 and 54 years for the Hypo-RT and S-RT groups, respectively. All patients tolerated the treatment well; no significant adverse effects were observed in either group. No acute or late neurological side effects of grade ≥ 2 were reported during RT. Grade 3-4 hematologic toxicity occurred in five cases, all of which interrupted concomitant TMZ (all occurring in the S-RT arm). The time to progression for the S-RT and Hypo-RT groups was 13.7 and 11.1 months, respectively (p=0.243). Regarding OS, the S-RT group had a median OS of 28.8 months compared to 17.5 months in the Hypo-RT group (p=0.007). Conclusions: Although further investigations are ongoing, a statistically significant difference exists in OS between Hypo-RT and S-RT. Hypo-RT could potentially become the standard of care not only for elderly patients but also for those with poor prognosis. Additional investigation with more data is necessary in this context to determine the best standard approach.

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/Methods: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2–3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15–36 Gy), and median fractions was 5 (range 1–6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6–56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3–4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. Conclusion. Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed.

Background: Glioblastoma (GBM) is a very poor-prognosis brain tumor. To date, maximal excision followed by radiochemotherapy, in 30 fractions, is the standard approach. Limited data are present in the literature about hypofractionated radiotherapy (hypo-RT) in GBM poor prognosis patients. Thus, this retrospective study was conducted to evaluate efficacy and toxicity of hypo-RT with simultaneous integrated boost (SIB) in association with temozolomide (TMZ) in this patient setting. Methods: Poor-prognosis GBM patients underwent surgery (complete, subtotal or biopsy) followed by SIB-hypo-RT and concomitant/adjuvant TMZ. The prescription dose was 40.05 Gy (15 fractions) with a SIB of 52.5 Gy (3.5 Gy/fraction) on surgical cavity/residual/macroscopic disease. Volumetric modulated arc therapy was performed. Results: From July 2019 to July 2021, 30 poor-prognosis patients affected by GBM were treated by SIB-hypo-RT; 25 were evaluated in the present analysis due to a minimum follow up of 6 months. The median age and KPS were 65 years and 60%, respectively. At the median follow-up time of 15 months (range 7–24), median and 1-year overall survival and progression-free survival were 13 months and 54%, and 8.4 months and 23%, respectively. No acute or late neurological side effects of grade ≥ 2 were reported. Grade 3–4 hematologic toxicity occurred in three cases. Conclusion: SIB-hypo-RT associated with TMZ in poor-prognosis patients affected by GBM is an effective and safe treatment. Prospective studies could be warranted.

Opinion statement Pancreatic neuroendocrine tumours (PNETs) are a rare and heterogeneous group of tumours with various clinical manifestations and biological behaviours. They represent approximately 2–4% of all pancreatic tumours, with an incidence of 2–3 cases per million people. PNETs are classified clinically as non-functional or functional, and pancreatic resection is recommended for lesions greater than 2 cm. The surgical approach can involve “typical” and “atypical” resections depending on the number, size and location of the tumour. Typical resections include pancreaticoduodenectomy, distal pancreatectomy enucleation and, rarely, total pancreatectomy. Atypical resections comprise central pancreatectomies or enucleations. Minimally invasive pancreatic resection has been proven to be technically feasible and safe in high-volume and specialized centres with highly skilled laparoscopic surgeons, with consolidated benefits for patients in the postoperative course. However, open and minimally invasive pancreatic surgery remains to have a high rate of complications; there is no specific technical contraindication to minimally invasive pancreatic surgery, but an appropriate patient selection is crucial to obtain satisfactory clinical and oncological outcomes.

In the treatment of advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors have shown remarkable results. However, not all patients with NSCLC respond to this drug treatment or receive durable benefits. Thus, patient stratification and selection, as well as the identification of predictive biomarkers, represent pivotal aspects to address. In this framework, metabolomics can be used to support the discrimination between responders and non-responders. Here, metabolomics was used to analyze the sera samples from 50 patients with NSCL treated with immune checkpoint inhibitors. All the samples were collected before the beginning of the treatment and were analyzed by NMR spectroscopy and multivariate statistical analyses. Significantly, we show that the metabolomic fingerprint of serum acts as a predictive “collective” biomarker to immune checkpoint inhibitors response, being able to predict individual therapy outcome with > 80% accuracy. Metabolomics represents a potential strategy for the real-time selection and monitoring of patients treated with immunotherapy. The prospective identification of responders and non-responders could improve NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.