Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma.

PURPOSE: No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. METHODS: Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. RESULTS: From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5-20). Median re-RT dose was 24 Gy (range 18-36 Gy) for a median number of 5 fractions (range 1-6). Median regorafenib treatment duration was 12 weeks (range 3-26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6­month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9-12.7 months) and 75% (95% CI 50.9-89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7-8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand-foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. CONCLUSION: For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary.

Linear accelerator-based stereotactic arrhythmia radioablation for paroxysmal atrial fibrillation in elderly: a prospective phase II trial.

AIMS: Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. METHODS AND RESULTS: Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001). CONCLUSION: The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04575662.

Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial.

PURPOSE: Aim of this study is to evaluate safety and efficacy of SBRT in elderly patients affected by localized prostate cancer (PC). MATERIAL AND METHODS: Men aged 70 years or older were enrolled and analyzed. The SBRT schedule was 35 Gy in 5 fractions administered in 1-2 weeks. According to risk group, androgen deprivation therapy (ADT) was prescribed. Urinary symptoms were evaluated at baseline using the International Prostate Symptom Score (IPSS). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed at the end of treatment, 2 weeks after SBRT and during follow-up using the Common Terminology Criteria for Adverse Events (CTCAE). PSA values were recorded before treatment and during follow-up as biochemical response criteria. RESULTS: Between 07/2019 and 09/2021, 111 patients were enrolled. Median age was 77 years. At the end of treatment, no acute GU/GI toxicities ≥ G2 were observed. At 2-3 weeks after treatment, 3 patients reported G2 GU toxicity, while 14 patients referred G2 GI toxicity. During the last follow up, 26 and 2 patients reported, respectively, G1 and G2 GU toxicity, while 22 and 1 cases described, respectively, G1 and G2 GI toxicity. No late toxicities ≥ G3 were recorded. GU toxicity is related to absence of urethra sparing, increasing PTV volume, Dmax PTV and IPSS; GI toxicity is related to RT schedule (each other day is better than consecutive day), Dmax rectum and IPSS, At a median follow-up of 24 months, excellent biochemical disease control was achieved in all cases with median PSA of 0.5 ng/ml. CONCLUSION: SBRT in elderly patients affected by PC is feasible and well tolerated with excellent biochemical disease control. Longer follow-up is needed to assess late toxicity profile and long-term clinical outcome.

Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial.

PURPOSE: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. METHODS: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. RESULTS: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5­year disease-free survival (DFS) was 95.0% (85.9-100%) in group 1 and 93.0% (86.3-100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100-100%) in group 1 and 97.4% (92.4-100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2-99.4%) and 96.9% (91.5-100.0%), respectively. For groups 1 and 2, the 5­year outcomes were 5.0% (0.0-14.4%) and 2.3% (0.0-6.1%) for local recurrence (p = 0.51), and 6.2% (0.0-17.4%) and 7.0% (0.0-13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0-14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0-0.0%). CONCLUSION: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.

Cone-beam computed tomography for organ motion evaluation in locally advanced rectal cancer patients.

PURPOSE: Due to a reported dose-response relationship in rectal cancer radiotherapy, a greater interest in dose intensification on small boost volume arises. Considering the need of an appropriate target movements evaluation, this retrospective study aimed to use cone-beam computed tomography (CBCT) for GTV and mesorectum organ motion (OM) evaluation, in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemo-radiotherapy, in prone and supine position. METHODS: Thirty-two LARC patients were analyzed. GTV and mesorectum were delineated on MRI co-registrated with CT simulation. GTV and mesorectum OM was estimated on all CBCTs, performed during treatment, co-registrated with CT simulation. OM evaluation was obtained, as mean shift in left and right (L-R), postero-anterior (P-A) and cranio-caudal (Cr-C) directions. Volumes variability was calculated by DICE index. RESULTS: A total of 296 CBCTs were analyzed. Mean shifts of the GTV and mesorectum in prone position were - 0.16 cm and 0.15 cm in L-R direction, 0.28 cm and - 0.40 cm in P-A direction, and 0.14 cm and - 0.21 cm, in Cr-C direction; for supine position the mean shifts of the GTV were - 0.10 cm and 0.17 cm in R-L direction, 0.26 cm and - 0.23 cm in A-P direction, 0.09 cm and - 0.11 cm in Cr-C direction. Mean DICE index for GTV and mesorectum was 0.74 and 0.86, in prone position, and 0.78 and 0.89 in supine position, respectively. CONCLUSION: GTV and mesorectum OM was less than 4 mm in all directions in both positions, with a 1 mm less deviation in supine position. CBCTs resulted effective for OM assessment, and it could be an appropriate method for the implementation on an intensification treatment.

Improving Quality Assurance in a Radiation Oncology Using ARIA Visual Care Path.

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.

The Role of Telemedicine for Psychological Support for Oncological Patients Who Have Received Radiotherapy.

AIM: In our radiation departments, all patients received psycho-oncological support during RT and during follow-up. Based on the latter, the aim of this retrospective analysis was to evaluate the role of tele-visits and in-person psychological support for cancer patients after RT, and to report a descriptive analysis pointing out the needs of psychosocial intervention in a radiation department during radiation treatment. METHODS: According to our institutional care management, all patients receiving RT were prospectively enrolled to receive charge-free assessment of their cognitive, emotional and physical states and psycho-oncological support during treatment. For the whole population who accepted the psychological support during RT, a descriptive analysis was reported. For all patients who agreed to be followed up by a psycho-oncologist, at the end of RT, a retrospective analysis was conducted to evaluate the differences between tele-consultations (video-call or telephone) and on-site psychological visits. Patients were followed up by on-site psychological visit (Group-OS) or tele-consult (Group-TC) visit. For each group, to evaluate anxiety, depression and distress, the Hospital Anxiety Depression Scale (HADS), Distress Thermometer and Brief COPE (BC) were used. RESULTS: From July 2019 to June 2022, 1145 cases were evaluated during RT with structured psycho-oncological interviews for a median of 3 sessions (range 2-5). During their first psycho-oncological interview, all the 1145 patients experienced the assessment of anxiety, depression and distress levels with the following results: concerning the HADS-A scale, 50% of cases (574 patients) reported a pathological score ≥8; concerning the HADS-D scale, 30% of cases (340 patients) reported a pathological score ≥8, concerning the DT scale, 60% (687 patients) reported a pathological score ≥4. Eighty-two patients were evaluated after RT: 30 in the Group-OS and 52 in the Group-TC. During follow-up, a median of 8 meetings (range 4-28) were performed. Comparing psychological data at baseline (beginning of RT) and at the last follow-up, in the entire population, a significant improvement in terms of HADS-A, global HADS and BC was shown (p 0.04; p 0.05; and p 0.0008, respectively). Compared to baseline, statistically significant differences were observed between the two groups in terms of anxiety in favor of on-site visit: Group-OS reported a better anxiety score compared with Group-TC. In each group, a statistical improvement was observed in BC (p 0.01). CONCLUSION: The study revealed optimal compliance to tele-visit psychological support, even if the anxiety could be better controlled when patients were followed up on-site. However, rigorous research on this topic is needed.

DWI-MR and PET-CT Functional Imaging for Boost Tumor Volume Delineation in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND/AIM: T2 weighted magnetic resonance (MR) imaging is the gold standard for locally advanced rectal cancer (LARC) staging. The potential benefit of functional imaging, as diffusion-weighted MR (DWI) and positron emission tomography-computed tomography (PET-CT), could be considered for treatment intensification strategies. Dose intensification resulted in better pathological complete response (pCR) rates. This study evaluated the inter-observer agreement between two radiation oncologists, and the difference in gross tumor volume (GTV) delineation in simulation-CT, T2-MR, DWI-MR, and PET-CT in patients with LARC. PATIENTS AND METHODS: Two radiation oncologists prospectively delineated GTVs of 24 patients on simul-CT (CTGTV), T2-weighted MR (T2GTV), echo planar b1000 DWI (DWIGTV) and PET-CT (PETGTV). Observers' agreement was assessed using Dice index. Kruskal-Wallis test assessed differences between methods. RESULTS: Mean CTGTV, T2GTV, DWIGTV, and PETGTV were 41.3±26.9 cc, 25.9±15.2 cc, 21±14.8 cc, and 37.7±27.7 cc for the first observer, and 42.2±27.9 cc, 27.6±16.9 cc, 19.9±14.9cc, and 34.8±24.3 cc for the second observer, respectively. Mean Dice index was 0.85 for CTGTV, 0.84 for T2GTV, 0.82 for DWIGTV, and 0.89 for PETGTV, representative of almost perfect agreement. Kruskal-Wallis test showed a statistically significant difference between methods (p=0.009). Dunn test showed there were differences between DWIGTV vs. PETGTV (p=0.040) and DWIGTV vs. CTGTV (p=0.008). CONCLUSION: DWI resulted in smaller volume delineation compared to CT, T2-MR, and PET-CT functional images. Almost perfect agreements were reported for each imaging modality between two observers. DWI-MR seems to remain the optimal strategy for boost volume delineation for dose escalation in patients with LARC.

Phase II Trial of LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for Paroxysmal Atrial Fibrillation in Elderly: Planning and Dosimetric Point of View.

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 TrueBeamTM. 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.

Smile InTM Totems in Radiotherapy: Patients' Satisfaction with Limited Equipment and COVID-19.

BACKGROUND: We report a mono-institutional experience regarding patient-perceived quality regarding the Chieti Radiotherapy Department, through RAMSI (Radiotherapy Amica Mia-SmileINTM(SI)-My Friend RadiotherapySI) project, in critical scenarios of limited equipment and COVID-19. MATERIAL AND METHODS: Patient-reported experience measures (PREMs) were assessed as follows: Patient-centric welcome perception (PCWP), Comfort, Professional skills and Punctuality. Patients could give anonymous feedback using HappyOrNot technology through four totems located in strategic areas within the center. An internal benchmark was obtained using the feedback received after a preliminary observation period. The SI Experience Index was collected, analyzed and compared. Weekly and monthly reports were generated. RESULTS: From February 2019 to February 2022, 8924 patients accessed the department; 17,464 daily treatments were recorded and 5830 points of feedback were collected: 896, 1267, 1125 and 2542 for PCWP, Comfort, Professional skills and Punctuality, respectively. A LINAC decommissioning period was analyzed, with decreases in the SI-Index score and Smile-IN approved percentage and an improvement after this period. Additionally, the COVID-19 pandemic was analyzed with a mild evaluations decrease for PREM's Welcome, Comfort and Punctuality (Δ-value: -9%, -3% and -4%, respectively), while Professional skills were always optimal. CONCLUSION: The RAMSI project was effective for assessing treatment quality perception, allowing for improving clinical procedures with corrective actions. The RAMSI project is ongoing.

Quality of Life in Early Breast Cancer Patients: A Prospective Observational Study Using the FACT-B Questionnaire.

BACKGROUND/AIM: Quality of life (QoL) in early breast cancer (BC) treatment may be affected by acute and late toxicities. This study evaluated the impact of radiotherapy (RT) schedules, treatment-related toxicities, hormone therapy (HT) and age on QoL. PATIENTS AND METHODS: Ninety-five patients answered the FACT-B 4.0 questionnaire. Acute or late toxicities were recorded at each follow-up visit. RESULTS: The median trend of the QoL subscales was stable during all questionnaires. HT negatively impacted on Functional Assessment of Cancer Therapy-General-Total, functional and emotional wellbeing. No difference was recorded between RT schedules and toxicity. No significant differences for age were detected in QoL. CONCLUSION: RT seems not to influence QoL of BC patients, in terms of fractionation regimen or RT-related side-effects. Moreover, women having systemic HT experienced a QoL worse than patients treated with RT only. Further and long-term protocols are needed to improve the validity of the tool.

Clinical outcomes in elderly rectal cancer patients treated with neoadjuvant chemoradiotherapy: impact of tumor regression grade : Tumor regression grade after neoadjuvant chemoradiotherapy in elderly rectal cancer patients.

PURPOSE: The effect of neoadjuvant chemoradiotherapy (CRT) and the relationship between pathological complete response (pCR) with clinical outcomes has been evaluated in elderly locally advanced rectal cancer (LARC) patients. METHODS: We retrospectively analyzed 117 LARC patients treated with conformal RT and concomitant fluoropirimidine-based chemotherapy. A dose of 4500 cGy, on the pelvis, up to 5500 cGy on the tumor was delivered. Multidisciplinary evaluation, including geriatric assessment, was previously performed to identify frail patients unsuitable for combined treatment. RESULTS: The median age was 75 (range 70-88 years), and 103 (88%) patients had ECOG Performance Status (PS) = 0. All patients except one completed CRT. Ten (8.5%) patients temporarily suspended CRT for acute severe hematologic complication, diarrhea and/or proctitis and hypokalemia. Of the 103 operated patients (88%), a pCR, according to Mandard tumor regression grade (TRG) score, was obtained in 28 patients (27.2%), with TRG1-2 rate of 43.7%. The 3- and 5-year overall survival (OS) rates were 80.2% ± 4.2% and 68.0% ± 5.2%, 72.4% ± 4.5% and 57.8% ± 5.2% for disease-free survival (DFS), and 92.2% ± 2.8% and 89.5% ± 3.9% for loco-regional control. Patients with TRG1-2 had 3- and 5-year OS rates of 84.1% ± 6.6% and 84.1% ± 6.6% compared with 82.8% ± 5.5% and 67.7% ± 7.2% for patients with TRG3-5 (p = 0.012). The 3- and 5-year DFS rates for patients with TRG1-2 were 77.6% ± 7.0% and 74.2% ± 7.5% compared with 70.9% ± 6.3% and 54.7% ± 7.3% for patients with TRG3-5 (p = 0.009). CONCLUSION: Our results reported good tolerability and clinical outcomes of neoadjuvant CRT, with a benefit in patients ≥ 70 years, confirming the prognostic role of pCR on clinical outcomes.

COVID-19 and radiation oncology: the experience of a two-phase plan within a single institution in central Italy.

BACKGROUND: COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II. METHODS: The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily. RESULTS: By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed. CONCLUSION: During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.