Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study.

BACKGROUND: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. PATIENTS AND METHODS: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. RESULTS: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3-4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3-77.4) and 85.9% (95% CI: 80.2-90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0-13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5-26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3-5 were significantly associated with worse PFS, OS and metastasis-free survival. CONCLUSIONS: Preoperative IMRT-SIB with the moderate dose intensification of 52.5-57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

Radiotherapy during COVID-19 pandemic. How to create a No fly zone: a Northern Italy experience.

BACKGROUND: SARS-CoV-2 pandemic represents a troubling health emergency but also a main challenge for the clinical governance of the system. Discontinuation of radiation treatments is not desirable and potentially life-threatening. On the other hand, accesses to hospital expose cancer patients to an increased risk of COVID-19 infection. We report our extended protocol, draft to manage clinical activities in our radiotherapy department, by minimizing contagion risks. METHODS: We used telephonic screening to assess the need for patient admission. A telephonic triage was performed to identify the presence of COVID-19 infection risk factors or symptoms. New treatments were stratified according to priority codes. A reserved entrance to radiotherapy department was assured for patients and staff. Surgical disposable mask was required for patients and caregivers. The activities were distributed during the whole workday, avoiding overlap to reduce aggregation. RESULTS: From 1st February 2020 to 31 March 2020, we reported an increase in the number of first medical examinations and treatments, compared to the same period of the previous year. Outpatients first medical examinations have been spread over the 12 working hours. No COVID-19 cases were detected. CONCLUSION: During COVID-19 pandemic, we introduced procedures that allowed us to ensure the continuity in oncological cares, with limited risks of infection for patients and staff.

Effects of high-energy photon beam radiation therapy on Jarvik 2000 LVAD: in vitro evaluation.

PURPOSE: Left ventricular assist device (LVAD) is considered a standard care for patients with advanced heart failure. The aim of this work was to study in vitro the effects of direct exposure of the Jarvik 2000 LVAD to 10-MV photon beams. METHODS: Jarvik 2000 pump was immersed in a siliconized box filled with deionized water. A 30 × 30 × 15 cm RW3 slabs were added forth and back to the box. A treatment plan consisting of a single direct 10 × 10 cm2 field size beam was used to deliver 1000 MU at the center of the pump. During irradiation, the external Flow Maker controller and the lithium battery were positioned away from the beam. Pump parameter data (included voltage, current and frequency) were measured, recorded and analyzed for changes in pump function among baseline, pre-irradiation, during irradiation, post-irradiation and after 6 months. The whole session lasted 6 months. The Mann-Whitney U test was used to compare the repeated measurements. X-ray radiation attenuation was also studied. RESULTS: The parameters investigated remained stable over the 6 months; that is, no pump stops, alarms, events, operational changes or abnormalities during the discharge rate of the connected power sources, were encountered, confirmed by the Mann-Whitney U test applied to all sessions (p > 0.1). The measured X-ray attenuation differed from the calculated one by TPS by 34%. CONCLUSION: The Jarvik 2000 resulted stable under direct X-ray beam of 10-MV energy. Its strong attenuation, however, can affect dose deposition in the pump in TPS, and it must be taken into account.

Inter-observer variability of clinical target volume delineation in definitive radiotherapy of neck lymph node metastases from unknown primary. A cooperative study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Group.

BACKGROUND: This study, promoted by Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Group, aimed to assess the current national practice of target volume delineation on a case of neck lymph node metastases from unknown primary evaluating inter-observer variability, in a setting of primary radiotherapy. MATERIALS AND METHODS: A case of metastatic neck lymph node from occult primary was proposed to 17 radiation oncologists. A national reference RT center was identified and considered as benchmark. Participants were requested to delineate target volumes. A structured questionnaire was administered. A comparison between following parameters of the CTVs was performed: centroids distances, Dice similarity index (DSI), Jaccard index and mean distance to agreement (MDA). Volume expressed in cubic centimeters and CTVs cranio-caudal extension were evaluated. RESULTS: Sixteen of 17 radiation oncologists recommended three CTVs dose levels. (CTV HD, CTV ID and CTV LD); CTV ID was not delineated by one of the participants and by the reference center. The distance between the reference centroid and the mean centroid of CTVs HD was 1.09 cm (0.36-3.99 cm); for CTV LD, a mean centroids distance of 2.45 (0.27-4.83 cm) was found, and for CTV HD, mean DSI is 0.48 and mean Jaccard index is 0.32 and MDA was 8.89 mm. CTV LD showed a mean DSI of 0.46, mean Jaccard index of 0.31 and MDA of 14.87 when compared to the reference. CONCLUSION: Many aspects concerning treatment optimization of cervical nodes metastases from occult primary remain unclear, and we found a notable heterogeneity of global radiotherapy management reporting discordances both in target volume delineation and volume prescription.

Hippocampal sparing approach in fractionated stereotactic brain VMAT radio therapy: A retrospective feasibility analysis.

Volumetric Modulated Arc Therapy (VMAT) techniques for fractioned stereotactic brain radiotherapy (FSBRT) can achieve highly conformal dose distribution to intracranial lesions. However, they can potentially increase the dose to hippocampus (H) causing neurocognitive toxicity during the first four months after irradiation. The purpose of this study was to assess the feasibility of hippocampal-sparing (HS) treatment plans in 22 patients with brain metastasis treated with VMAT technique. Firstly, we retrospectively analyzed hippocampal doses in all 22 VMAT original (not hippocampal-sparing, NHS) plans. Plans with hippocampal dose exceeding constraints (9 out of 22) were re-planned considering dose constraints on the hippocampus (H) and on hippocampal avoidance zone (HAZ) generated using 5 mm isotropic margin to the hippocampus. Conformity (CI) and homogeneity indexes (HI) on the target and MUs, were maintained as close as possible to the original plans. Mean CINHS and CIHS obtained were: 0.79 ± 0.11 and 0.81 ± 0.10, respectively (P = 0.75); mean HINHS and HIHS were 1.05 ± 0.02 and 1.04 ± 0.01 respectively (P = 0.72). In both sets of plans, the mean MU values were similar: 1033 ± 275 and 1022 ± 234 for NHS and HS respectively. In HS plans, the mean hippocampal dose was decreased by an average of 35%. After replanning, the Dmax (21.3 Gy) for HAZ and H was met by 45% (4/9) and 78% (7/9) of the NHS plans, respectively. The worst results were obtained for cases with target volumes extention closer than 12 mm to H, because of the difficulty to spare hippocampus without compromising target coverage. After replanning D40% constraint value (7.3 Gy) was met by all the 9 NHS plans. In conclusion, this study suggests that an hippocampal-sparing approach to FSBRT is feasible resulting in a decrease in the dose to the hippocampus without any loss in conformity or increase in treatment time.

Development of a contouring guide in three different head set-ups for hippocampal sparing radiotherapy: a practical approach.

BACKGROUNDS: Irradiation of the hippocampus plays a role in neurocognitive toxicity. Its delineation is complex and in practice different head position can vary hippocampus morphology on axial images; so atlas in a single standard position can result ineffective to describe different hippocampal morphologies in different head set-up. The purpose of our study was to develop a guide based on magnetic resonance imaging for hippocampus delineation in three different head set-ups. MATERIALS AND METHODS: Three patients were selected to elaborate our guide. Patients were submitted to a planning computed tomography of the brain district in different head positions: 1° patient in neutral, 2° patient in over-extended and 3° patient in head hypo-extended position; axial images of 2-mm thickness were obtained. Computed tomography images were fused with diagnostic brain magnetic resonance images; then hippocampus was delineated according to RTOG atlas. Contours were revised by two neuro-radiologists with >5-year expertise in neuroimaging. RESULTS: A guide was developed for each of three head positions considered. RTOG atlas provided an easy and reliable guide for hippocampus delineation in neutral position of the head. Discrepancies were observed in cranial and caudal limit in case of head over/hypo-extension, as well as in hippocampal morphology near the encephalic trunk where hippocampus takes an oblong shape in over-extended set-up, and short and stocky in hypo-extension. CONCLUSION: Our guide can represent a useful tool for hippocampal delineation in clinical practice and for different anatomic variations due to different head positions. Certainly, it should be validated in practice.