Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Brain metastases and next-generation anticancer therapies: a survival guide for clinicians.

Historically, patients with brain metastases (BMs) have been characterized by few systemic treatment options and poor prognosis. The recent introduction of next-generation anticancer therapies such as molecular targeted agents and immunotherapy have revolutionized the clinical decision-making process of this sub-population, posing new challenges to physicians. In this review, current evidence for the use of checkpoint inhibitors and targeted therapies in patients with BMs are discussed, with a focus on lung cancer, breast cancer, melanoma and renal cell carcinoma, providing suggestions and potential workflows for daily clinical practice. Several other on-going and future challenges, such as clinical trials design, ways to improve CNS penetration of novel drugs and unique molecular characteristics of BMs, are also discussed. The aim is producing an updated and easy-to-read guide for physicians, to improve decision-making in clinical practice.

Stereotactic radiation therapy for oligometastatic esophagogastric adenocarcinoma: outcome and prognostic factors.

OBJECTIVE: The aim of this study was to evaluate clinical results and prognostic factors in a cohort of patient with oligometastatic esophagogastric adenocarcinoma treated with stereotactic radiation therapy (SRT). METHODS: This retrospective study included patients affected by 1-3 metastases treated with SRT from 2013 to 2021. Local control (LC), overall survival (OS), progression-free survival (PFS), time to polymetastatic dissemination (TTPD) and time to systemic therapy change/initiation (TTS) were evaluated. RESULTS: Between 2013 and 2021, 55 patients were treated with SRT on 80 oligometastatic sites. Median follow-up was 20 months. Nine patients had local progression. 1 and 3 years LC was respectively 92 and 78%. 41 patients experienced further distant disease progression, median PFS was 9.6 months, 1 and 3 years PFS was respectively 40 and 15%. 34 patients died, median OS was 26.6 months, 1 and 3 years OS was respectively 78 and 40%. During follow-up, 24 patients changed or initiated a new systemic therapy; median TTS time was 9 months. 27 patients experienced poliprogression, 44% after 1 year and 52% after 3 years. Median TTPD was 8 months. The best local response (LR), tyming of metastases and PS were related with prolonged PFS on multivariate analysis. LR was correlated with OS at multivariate analysis. CONCLUSION: SRT represents a valid treatment for oligometastatic esophagogastric adenocarcinoma. CR correlated with PFS and OS, while metachronous metastasis and a good PS correlated with a better PFS. ADVANCES IN KNOWLEDGE: In selected gastroesopagheal oligometastatic patients, SRT can prolong OS Local response to SRT, metachronous timing of metastases and better PS improve PFS.Local response correlates with OS.

Stereotactic radiosurgery for the treatment of brainstem metastases: a multicenter retrospective study.

BACKGROUND: Brainstem metastases (BSM) are associated with a poor prognosis and their management represents a therapeutic challenge. BSM are often inoperable and, in absence of randomized trials, the optimal radiation treatment of BSM remains to be defined. We evaluated the efficacy and toxicity of linear accelerator (linac)-based stereotactic radiosurgery (SRS) and hypofractionated steretotactic radiotherapy (HSRT) in the treatment of BSM in a series of patients treated in different clinical centers. METHODS: We conducted a multicentric retrospective study of patients affected by 1-2 BSM from different histologies who underwent SRS/HSRT. Freedom from local progression (FLP), cancer-specific survival (CSS), overall survival (OS), and treatment-related toxicity were evaluated. In addition, predictors of treatment response and survivals were evaluated. RESULTS: Between 2008 and 2021, 105 consecutive patients with 111 BMS who received SRS or HSRT for 1-2 BSM were evaluated. Median follow-up time was 10 months (range 3-130). One-year FLP rate was 90.4%. At the univariate analysis, tumor volume ≤ 0.4 cc, and concurrent targeted therapy were associated with longer FLP, with combined treatment that remained a significant independent predictor [0.058, HR 0.139 (95% CI 0.0182-1.064]. Median OS and CSS were 11 months and 14.6 months, respectively. At multivariate analysis, concurrent targeted therapy administration was significantly associated with longer OS [HR 0.514 (95%CI 0.302-0.875); p = 0.01]. Neurological death occurred in 30.4% of patients, although this was due to local progression in only 3 (2.8%) patients. CONCLUSION: Linac-based SRS/HSRT offers excellent local control to patients with BSM, with low treatment-related toxicity and no apparent detrimental effects on OS. When treated with ablative intent, BSM are an uncommon cause of neurological death. The present results indicates that patients with BSM should not be excluded a priori from clinical trials.

Current status and recent advances in reirradiation of glioblastoma.

Despite aggressive management consisting of maximal safe surgical resection followed by external beam radiation therapy (60 Gy/30 fractions) with concomitant and adjuvant temozolomide, approximately 90% of WHO grade IV gliomas (glioblastomas, GBM) will recur locally within 2 years. For patients with recurrent GBM, no standard of care exists. Thanks to the continuous improvement in radiation science and technology, reirradiation has emerged as feasible approach for patients with brain tumors. Using stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT), either hypofractionated or conventionally fractionated schedules, several studies have suggested survival benefits following reirradiation of patients with recurrent GBM; however, there are still questions to be answered about the efficacy and toxicity associated with a second course of radiation. We provide a clinical overview on current status and recent advances in reirradiation of GBM, addressing relevant clinical questions such as the appropriate patient selection and radiation technique, optimal dose fractionation, reirradiation tolerance of the brain and the risk of radiation necrosis.

Post-operative management of brain metastases: GRADE-based clinical practice recommendations on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: To perform a systematic review of the current level of evidence on post-operative management following brain metastasectomy (namely: adjuvant stereotactic radiosurgery, whole brain radiotherapy or observation), and to propose a GRADE-based dedicated recommendation to inform Radiation Oncologists' clinical practice. METHODS: A panel of expert Radiation Oncologists from the Italian Association of Radiotherapy and Clinical Oncology had defined the search question per the PICO methodology. Electronic databases were independently screened; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted. The individual and pooled hazard ratios with 95% confidence intervals (CI), as well as the pooled risk ratio (RR) were calculated using a fixed- or random-effects model. RESULTS: Eight full-texts were retrieved: six retrospective studies and two randomized clinical trials. Outcomes of benefit and damage were analyzed for SRS + observation (PICO A) and SRS + WBRT. SRS allowed for increased rates of local control when compared to both observation and WBRT, while evidence was less conclusive for distant brain control, leptomeningeal disease control and overall survival. In the SRS, the incidence of severe radionecrosis was higher as compared to WBRT, despite neurocognitive deterioration rates were lower. Overall, SRS seems to favorably compare with observation and whole brain RT, despite the level of evidence for the recommendation was low and very low, respectively. CONCLUSION: Despite low level of evidence, the panel concluded that the risk/benefit ratio probably favors adjuvant SRS as compared to the observation and whole brain RT as adjuvant treatments following brain metastasectomy (5 votes/5 participants, 100% attendance).

Association of supratotal resection with progression-free survival, malignant transformation, and overall survival in lower-grade gliomas.

BACKGROUND: Supratotal resection is advocated in lower-grade gliomas (LGGs) based on theoretical advantages but with limited verification of functional risk and data on oncological outcomes. We assessed the association of supratotal resection in molecularly defined LGGs with oncological outcomes. METHODS: Included were 460 presumptive LGGs; 404 resected; 347 were LGGs, 319 isocitrate dehydrogenase (IDH)-mutated, 28 wildtype. All patients had clinical, imaging, and molecular data. Resection aimed at supratotal resection without any patient or tumor a priori selection. The association of extent of resection (EOR), categorized on volumetric fluid attenuated inversion recovery images as residual tumor volume, along with postsurgical management with progression-free survival (PFS), malignant (M)PFS, and overall survival (OS) assessed by univariate, multivariate, and propensity score analysis. The study mainly focused on IDH-mutated LGGs, the "typical LGGs." RESULTS: Median follow-up was 6.8 years (interquartile range, 5-8). Out of 319 IDH-mutated LGGs, 190 (59.6%) progressed, median PFS: 4.7 years (95% CI: 4-5.3). Total and supratotal resection obtained in 39% and 35% of patients with IDH1-mutated tumors. In IDH-mutated tumors, most patients in the partial/subtotal group progressed, 82.4% in total, only 6 (5.4%) in supratotal. Median PFS was 29 months (95% CI: 25-36) in subtotal, 46 months (95% CI: 38-48) in total, while at 92 months, PFS in supratotal was 94.0%. There was no association with molecular subtypes and grade. At random forest analysis, PFS strongly associated with EOR, radiotherapy, and previous treatment. In the propensity score analysis, EOR associated with PFS (hazard ratio, 0.03; 95% CI: 0.01-0.13). MPFS occurred in 32.1% of subtotal total groups; 1 event in supratotal. EOR, grade III, previous treatment correlated to MPFS. At random forest analysis, OS associated with EOR as well. CONCLUSIONS: Supratotal resection strongly associated with PFS, MPFS, and OS in LGGs, regardless of molecular subtypes and grade, right from the beginning of clinical presentation.

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

Critical Re-Evaluation of a Failure Mode Effect Analysis in a Radiation Therapy Department After 10 Years.

PURPOSE: Failure mode effect analysis (FMEA) is a proactive methodology that allows one to analyze a process, regardless of whether an adverse event occurs. In our radiation therapy (RT) department, a first FMEA was performed in 2009. In this paper we critically re-evaluate the RT process after 10 years and present it in terms of a lesson learned. METHODS AND MATERIALS: A working group (WG), led by a qualified clinical risk engineer, which included radiation oncologists, physicists, a radiation therapist, and a nurse, evaluated the possible failure modes (FMs) of the RT process. For each FM, the estimated frequency of occurrence (O, range 1-4), the expected severity of the damage (S, range 1-5), and the detectability lack (D, range 1-4) were scored. A risk priority number (RPN) was obtained as RPN = OxSxD. The data were compared with the 2009 edition. RESULTS: In the 2020 analysis, 67 FMs were identified (27 in the 2009 series). The absolute risk values of the previous 3 highest FMs were generally reduced. The patient identification risk (highest value in the 2009 analysis) was reduced from 48.0 to 6.9, becoming the 51st RPN score, thanks to a patient barcode recognition within the bunker. The 2020 highest risk values regarded: (i-2020) the patient's inadequate recollection and reporting of his/her medical history (ie, anamnesis) during the first medical examination and (ii-2020) the incorrect interpretation of tumor and normal tissue in computed tomography images. The WG proposed corrective actions. CONCLUSIONS: In this single institution experience, the 10-year FMEA analysis showed a reduction in the previous higher RPN values thanks to the corrective actions taken. The new FMs and subsequent RPNs reveal the need for a continuous iterative improvement process.

Prognostic factors and outcome of HER2+ breast cancer with CNS metastases.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

Role of stereotactic body radiation therapy for lung metastases from radio-resistant primary tumours.

OBJECTIVES: A retrospective analysis was performed on patients treated for lung oligo-metastatic disease from radio-resistant histology groups. METHODS: The primary end point was local control (LC), secondary end points were overall survival (OS) and progression free survival (PFS). Toxicity was scored according to CTCAE 4.03. RESULTS: 200 patients were analyzed: 49.5% of the cases derived from colorectal primary tumors, 20.5% from sarcomas, 12.0% from renal cell carcinoma and the rest from other mixed origin. The mean follow-up was 24.2 months. LC at 1 and 2 years was 91, 84.9%. Primary histology and the presence of extra-pulmonary disease had a significant impact on LC. OS at 1 and 2 years was 88.7, 65.4%. Primary histology, disease free interval, presence of extra-pulmonary disease, number of irradiated lung lesions and age showed a correlation with prognosis at univariate analysis. PFS at 1 and 2 years was 84, 57.7%. The presence of extra-pulmonary disease and the number of irradiated lung lesions correlated with prognosis. Treatment was well tolerated with no G3-4 acute or late toxicity recorded. CONCLUSION: Colorectal metastases showed a higher rate of local relapse. However, the factors mostly influencing prognosis were the presence of extra-pulmonary disease and the number of lung lesions.

Phase II trial of hypofractionated VMAT-based treatment for early stage breast cancer: 2-year toxicity and clinical results.

BACKGROUND: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. METHODS: Patients presenting early-stage breast cancer were enrolled in a phase II trial. ELIGIBILITY CRITERIA: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor. RESULTS: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24-55 months). Median age was 62 years old (range 30-88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases. CONCLUSIONS: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Volumetric modulated arc therapy for thoracic node metastases: a safe and effective treatment for a neglected disease.

PURPOSE: To evaluate the outcome of Stereotactic Body Radiation Therapy (SBRT) with Volumetric Modulated Arc Therapy (VMAT) for thoracic node metastases. RESULTS: 18 out of 29 patients presented with isolated thoracic node metastases with no other sites of disease. Median prescribed dose was 45Gy (range 30-60Gy).Acute toxicity was recorded as G0 in 28 patients, while one patient was scored as G1. Late toxicity was G0 in 26 patients, one patient was scored G1, one as G2, and one as G4 presented acute myocardial infarction.During follow up, the best local response was complete remission in 14 patients and partial remission in 11 patients. With a median follow up of 12 months (range 2-35) 9 patients died from disease progression, 10 were still alive with distant metastases, 5 had a locally controlled disease and 5 patients were disease free.The median OS estimated was 18 months (76%, 49% at one, two years). The median PFS was 9 months (28%, 17% at one, two years). MATERIALS AND METHODS: Twenty-nine patients with 32 thoracic nodes metastases were treated with SBRT in our institution. Toxicities and response were assessed. Overall Survival (OS) and Progression Free Survival (PFS) were evaluated. CONCLUSIONS: SBRT is an efficient treatment for thoracic node metastases.

Treatment: Outcome and Toxicity of Volumetric Modulated Arc Therapy in Oropharyngeal Carcinoma.

BACKGROUND/AIM: Radiotherapy is a common approach for treating squamous cell carcinoma (SCC) of the oropharynx. We aimed to analyze toxicity and outcome of patients affected by oropharyngeal SCC treated with volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Fifty-four patients presenting advanced orophayngeal carcinoma who were treated with radical radiotherapy were analyzed. All patients were treated with VMAT-RapidArc, with simultaneous integrated boost in 33 fractions for a dose of 69.96 Gy to the high-risk, and of 54.45 Gy to the low-risk volume. RESULTS: Median follow-up was 23 months. In eight cases, locoregional relapse was observed (median time to relapse=10.7 months). Four among eight local recurrences appeared in the high-dose target volume. The 1- and 2-year actuarial disease-free survival rates were 88% and 80%, respectively. The 1- and 2-year actuarial overall survival rates were 94% and 87%, respectively. CONCLUSION: VMAT for oropharyngeal SCC treatment is effective and safe, with interesting rates of control of disease and survival.

Toxicity profile and early clinical outcome for advanced head and neck cancer patients treated with simultaneous integrated boost and volumetric modulated arc therapy.

BACKGROUND: Shortening the overall treatment time without increasing acute reactions is one of the major aims in radiotherapy for head and neck cancer (HNC). Volumetric modulated arc therapy (VMAT) with Simultaneous Integrated Boost (SIB) showed improvements in outcome and pattern of toxicity. Patients with stage III-IV HNC treated with VMAT-SIB have been analysed, and doses were correlated to limiting structures and toxicity. METHODS: One hundred two patients treated from December 2008 to August 2014 were analysed. Patients were treated with VMAT (RapidArc) and SIB in 33 fractions for a total dose of 69.96 and 54.45Gy, respectively. For organs at risk, D1/3 V, D1/2 V, D2/3 V, the mean dose, VD with D = 10,20,30,40,50,70 Gy were analysed. For targets, D98%, D2%, and V95%, V107%, conformity and homogeneity indexes were calculated. Toxicity was graded according to CTCAE3. RESULTS: Oral cavity V30Gy, V40Gy, and V70Gy, were found correlated with mucosal toxicity grading. Concerning salivary glands, significant was only D2/3V for one of the two parotids. Almost all analysed parameters of the inferior constrictor muscle were significant while no correlations were found for middle and superior constrictors. With median follow-up of 19 months, Overall Survival (OS) at 3 and 5 years was 83 % ± 4 % and 73 % ± 10 %. Mean OS was 51 ± 3 months. Disease Free Survival (DFS) at 3 and 5 years was 71 % ± 7 %, and 34 % ± 16 %. Mean DFS was 43 ± 3 months. CONCLUSIONS: RapidArc technology and SIB with 1.65 and 2.12Gy/fraction for 33 fractions showed a good toxicity profile and encouraging trend for OS and DFS for patients with stage III-IV HNC.

Evaluation of a synthetic single-crystal diamond detector for relative dosimetry on the Leksell Gamma Knife Perfexion radiosurgery system.

PURPOSE: To evaluate the new commercial PTW-60019 synthetic single-crystal microDiamond detector (PTW, Freiburg, Germany) for relative dosimetry measurements on a clinical Leksell Gamma Knife Perfexion radiosurgery system. METHODS: Detector output ratios (DORs) for 4 and 8 mm beams were measured using a microDiamond (PTW-60019), a stereotactic unshielded diode [IBA stereotactic field detector (SFD)], a shielded diode (IBA photon field detector), and GafChromic EBT3 films. Both parallel and transversal acquisition directions were considered for PTW-60019 measurements. Measured DORs were compared to the new output factor reference values for Gamma Knife Perfexion (0.814 and 0.900 for 4 and 8 mm, respectively). Profiles in the three directions were also measured for the 4 mm beam to evaluate full width at half maximum (FWHM) and penumbra and to compare them with the corresponding Leksell GammaPlan profiles. RESULTS: FWHM and penumbra for PTW-60019 differed from the calculated values by less than 0.2 and 0.3 mm, for the parallel and transversal acquisitions, respectively. GafChromic films showed FWHM and penumbra within 0.1 mm. The output ratio obtained with the PTW-60019 for the 4 mm field was 1.6% greater in transverse direction compared to the nominal value. Comparable differences up to 0.8% and 1.0% for, respectively, GafChromic films and SFD were found. CONCLUSIONS: The microDiamond PTW-60019 is a suitable detector for commissioning and routine use of Gamma Knife with good agreement of both DORs and profiles in the three directions.

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly.

OBJECTIVE: To report about clinical outcome of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in elderly patients. METHODS: Patients with 1-4 inoperable metastases were treated with SBRT. Dose prescription ranged from 40 to 75 Gy in 3-8 fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and disease-specific survival (DSS). RESULTS: 82 patients with 111 total metastases were treated. Median age was 79 years. 64 patients (78%) had a single lesion; the remaining patients had 2-4 lesions. 16 (14.4%) lesions were localized in the abdomen, 50 (45.0%) in the liver and 45 (40.5%) in the lungs. Local response was observed for 87 lesions (78.4%) while local progression was observed in 24 lesions (21.6%). Actuarial 1-year LC was 86.8% ± 3.3%. Actuarial 1-year OS was 93.6% ± 2.7%. 2-year findings were 76.3% ± 4.4% and 72.0% ± 5.6%, respectively. Actuarial 1- and 2-year DSS results were 97.5% ± 2.0% and 81.6% ± 4.9%, respectively. Treatment-related Grade 2-3 toxicity was observed in five patients (4.2%); Grade 1 toxicity in seven patients (5.9%) and no toxicity was observed in 85.4% of the cases. CONCLUSION: SBRT is a safe and effective therapeutic option for the treatment of oligometastatic disease in the elderly with acceptable rates of LC and low treatment-related toxicity. ADVANCES IN KNOWLEDGE: The use of SBRT for oligometastatic disease in the elderly can be considered as a valuable approach, particularly for patients with fragile status or refusing other approaches.

Plan robustness in field junction region from arcs with different patient orientation in total marrow irradiation with VMAT.

BACKGROUND: The cranial-caudal (CC) maximum LINAC couch shift is usually around 130-150 cm; therefore total marrow (and lymph-nodes) irradiation (TMI-TMLI) requires two different plans, one with patient head-first-supine ("body plan" - skull-thighs) and a second feet-first-supine ("legs plan" - feet-femurs head). A challenging planning is required to manage the region in which the radiation come from the two plans (that cannot be automatically optimized together). We studied a robust way to produce a plan sum in this field junction region without creating under/over dosage on PTV and hotspots out. MATERIAL AND METHODS: Twenty-one patients candidates to bone marrow transplantation were treated with TMI-TMLI on TrueBeam using RapidArc technique. All body bones were defined as PTV and, for TMLI, lymph-nodes and spleen were included, too. The two plans according to ALARA principle were optimized. In particular, in the overlapping region (PTVJ), two specular sigmoid dosimetric shapes were adopted for obtaining homogeneous integral dose. Furthermore, 144 plans from four patients were calculated to evaluate plan robustness. RESULTS: In all patients, 95% of the prescription dose covered >99% of PTVJ. Regarding the robustness study, differences <1% were found for mean doses to PTVJ and surrounding healthy tissue (HT) for 5 mm shifts. Maximum dose increased up to 21.4% for 10 mm shifts in CC. PTVJ V95% decreased of around 9% (range -3.4% to 24.3%) revealing possible target under-dosage. CONCLUSIONS: Dosimetric field junction from two different plans is possible for TMI-TMLI with optimal target coverage. The correct repositioning between the two plans is fundamental, in particular in CC direction.

On the pre-clinical validation of a commercial model-based optimisation engine: application to volumetric modulated arc therapy for patients with lung or prostate cancer.

PURPOSE: To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to advanced lung cancer and to low risk prostate carcinoma patients. METHODS AND MATERIALS: Two sets each of 27 previously treated patients, were selected to train models for the prediction of dose-volume constraints. The models were validated on the same sets of plans (closed-loop) and on further two sets each of 25 patients not used for the training (open-loop). RESULTS: Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. In the pass-fail analysis, the rate of criteria not fulfilled was reduced in the lung patient group from 11% to 7% in the closed-loop and from 13% to 10% in the open-loop studies; in the prostate patient group it was reduced from 4% to 3% in the open-loop study. CONCLUSIONS: Plans were optimised using a knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data, particularly in the sparing of organs at risk. The data suggest that the new engine is reliable and could encourage its application to clinical practice.

Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy.

BACKGROUND: To appraise the role of volumetric modulated arc (RapidArc, RA) in the treatment of anal canal carcinoma (ACC). METHODS: A retrospective analysis has been conducted on 36 patients treated with RA since 2009 comparing outcome against a group of 28 patients treated with conformal therapy (CRT). RA treatments were prescribed with SIB technique with 59.4 Gy to the primary tumor and nodes and 49.5 Gy to the elective nodes. CRT was sequentially delivered with 45 Gy to the pelvic target and a boost of 14.4 Gy to the primary tumor. RESULTS: Median age of patients was 65 yrs for RA (59 yrs for CRT); 90% had Stage II-III (93% in the CRT group). No statistically significant differences were observed concerning survival or control. 5 yrs disease specific survival was 85.7% and 81.2%, loco-regional control was of 78.1% and 82.1% for RA and CRT respectively. RA treatments lead to lower incidence of higher grade of toxicity events (all retrospectively retrieved from charts as worse events). Grade 2-3 toxicity, compared to CRT, reduced from 89% to 68% for GI, from 39% to 33% for GU and from 82% to 75% for the skin. Late toxicity was as follows: 5/36 (14%) and 3/36 (8%) patients had G1 or G2 GI toxicity in the RA group (1/28 (4%) and 4/28 (14%) in the CRT group). GU late toxicity was observed only in 4/28 (14%) patients of the CRT group: 3/28 (11%) had G2 and 1/28 (4%) had G1. CONCLUSIONS: RA treatments of ACC patients proved to be equally effective than CRT but it was associated to a reduction of toxicity.