Roberta Carbonara

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.

A 71-year-old male ex-smoker presented in October 2021 to our department with a brain and bone metastatic adenocarcinoma NSCLC. PDL1, ROS, EGFR, and ALK were negative. He underwent stereotactic radiotherapy for brain metastases. In November 2021, he started a chemotherapy (CHT) regimen with cisplatin (75 mg/m² every 21 days) and pemetrexed (500 mg/m² every 21 days), and ICI with Atezolizumab (1200 mg every 21 days). In July 2022, RT to the lung tumor and mediastinal nodal was performed with a total dose of 45 Gy in 15 fractions. He continued with immunotherapy until December 2022, when a grade 3–4 toxicity from immunotherapy was observed (hypothyroidism, psoriasis, and cystitis). He achieved a complete clinical response to the therapy. To date, the patient is alive, with a complete metabolic response, without treatment at 37 months from diagnosis.

Background/Objectives. Adult medulloblastoma (AMB) patients should receive postoperative craniospinal irradiation (CSI) as a standard treatment. Volumetric intensity-modulated arc therapy (VMAT) is a promising method for CSI. This report summarizes the repositioning and dosimetric data outcomes for six AMB patients. Methods. Complete CSI and posterior cranial fossa irradiation, or tumor bed boost irradiation with Linac-based VMAT, was performed and evaluated. Patients were immobilized in the supine position with two thermoplastic masks (head-neck and abdomen). To ensure inter-fraction reproducibility during radiotherapy (RT), a single cone-beam CT (CBCT) scan for each isocenter and real-time surface-guided RT using AlignRT^® were performed daily before and during the RT session. Match values of all three translational axes (x = lateral, y = longitudinal, z = vertical) were recorded. Results. From August 2022 to September 2023, six AMB patients were treated with CSI: three women and three men with a median age of 32 (22–42). All cases were classical MB, four were low risk, and two were defined as high risk due to the metastatic disease. All patients underwent surgery; two received a gross total resection. Low-risk patients received 36 Gy for CSI and a 54 Gy boost, while high-risk patients received 39 Gy for CSI. No significant toxicities greater than G2 were observed during RT, and only two cases reported decreased platelet counts. The dose to the organs at risk was low and acceptable. The mean dose to the heart, lungs, eyes, stomach, and thyroid were 4.4 Gy, 8.5 Gy, 12 Gy, 8.7 Gy, and 11 Gy, respectively. In terms of repositioning data, 124 CBCT scans were analyzed. Inter-fraction CBCT mean values for the study population in all translational directions were inferior to 2 mm in more than 90% of cases. Conclusions. VMAT is a convenient and effective treatment for AMB. Positioning and immobilization with masks (head and neck plus abdomen) reduce inter-fraction motion.

A 71-year-old male ex-smoker presented in October 2021 to our department with a brain and bone metastatic adenocarcinoma oncogene-negative, PDL1-negative NSCLC. He underwent stereotactic radiotherapy for brain metastases, and then chemotherapy with cisplatin and gemcitabine was administered, followed by immunotherapy with Nivolumab. In July 2022, RT to lung tumor and mediastinal nodal was performed with a total dose of 45Gy in 15 fractions. He continued with immunotherapy until December 2022, when a grade 3-4 toxicity from immunotherapy was ob-served (hypothyroidism, psoriasis, cystitis). He achieved a complete clinical response to the therapy. To date, the patient is alive, with a complete metabolic response, without treatment at 35 months from diagnosis.

Purpose: Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. Materials and Methods: The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients’ reports were categorized based on treatment years period: 2019–2020 (A); 2021 (B); and 2022–2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients’ positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5–10% in the case of zero or one major incident. Results: From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0–3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients’ photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. Conclusions: Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient’s care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents.

Purpose: Approaching treatment for elderly patients with atrial fibrillation is difficult. A prospective phase II trial evaluating LINAC-based stereotactic arrhythmia radioablation (STAR) safety in this population started in 2021. Dosimetric and planning data were reported. Materials and Methods: A vac-lock bag was used for immobilization in the supine position and a computed tomography (CT, 1 mm) was performed. The clinical target volume (CTV) was defined as the area around the pulmonary veins. An internal target volume (ITV) was added to the CTV to compensate heart and respiratory movement. The planning target volume (PTV) was defined by adding 0–3 mm to the ITV. STAR was performed during free-breathing with a PTV prescription total dose (Dp) of 25 Gy/1 fraction. Flattening filter-free volumetric-modulated arc therapy plans were generated, optimized, and delivered by TrueBeam^TM. Image-guided radiotherapy with cone-beam CT and surface-guided radiotherapy with Align-RT (Vision RT) were employed. Results: From May 2021 to March 2022, 10 elderly patients were treated. Mean CTVs, ITVs, and PTVs were 23.6 cc, 44.32 cc, and 62.9 cc, respectively; the mean prescription isodose level and D2% were 76.5% and 31.2 Gy, respectively. The average heart and left anterior descending artery (LAD) Dmean were 3.9 and 6.3 Gy, respectively; the mean Dmax for LAD, spinal cord, left and right bronchus, and esophagus were 11.2, 7.5, 14.3, 12.4, and 13.6 Gy, respectively. The overall treatment time (OTT) was 3 min. Conclusions: The data showed an optimal target coverage, sparing surrounding tissue, in 3 min of OTT. LINAC-based STAR for AF could represent a valid non-invasive alternative for elderly patients who were excluded from catheter ablation.

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.

When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors.