E. Clerici

Volumetric modulated arc therapy with flattening filter free (FFF) beams for stereotactic body radiation therapy (SBRT) in patients with medically inoperable early stage non small cell lung cancer (NSCLC)

PURPOSE To assess the impact of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams for stereotactic body radiotherapy (SBRT) in inoperable stage I NSCLC. Current data were compared against a cohort of patients previously treated with advanced conformal techniques (3DCRT) based on conformal arcs. METHODS AND MATERIALS From July 2006 to December 2011 132 patients underwent SBRT, 86 by 3DCRT with flattened beams (FF), while the last 46 with VMAT RapidArc and unflattened beams (FFF). All patients were treated with 48 Gy in four fractions of 12 Gy each. Patients underwent follow-up. Clinical outcome was evaluated with thoracic and abdominal CT scan and 18FDG-CTPET before and after treatment. RESULTS Both techniques achieved adequate dose conformity to the target but with a statistically significant reduction of ipsilateral lung doses in RapidArc plans and also of Beam-on-Time (BOT) with FFF mode. The median follow up was 16 months (range 2-24 months). At 1 year, local control rate was 100% with FFF beams compared with 92.5% with FF beams (p=0.03). CONCLUSIONS SBRT with FFF beams permitted us a safe delivery of high dose per fraction in a short treatment time and resulted in an earlier radiological response compared with FF beams.

Long-term local control achieved after hypofractionated stereotactic body radiotherapy for adrenal gland metastases: A retrospective analysis of 34 patients

Abstract Aims and background. To describe feasibility, tolerability and clinical outcomes of stereotactic body radiation therapy (SBRT) in the treatment of adrenal metastases in 34 consecutive cancer patients. Material and methods. Between March 2004 and July 2010, a total of 34 consecutive patients, accounting for 36 adrenal metastatic lesions, were treated with SBRT. SBRT treatments were delivered by a Linac Varian 600 with microMLC (3DLine, Elekta, Stockholm, Sweden) and a Linac ELEKTA Precise (Elekta). All 34 patients were clinically and radiologically evaluated during and after completion of SBRT. Following outcomes were taken into account: best clinical response at any time, local control, time to systemic progression, time to local progression, overall survival and toxicity. Survival was estimated by the Kaplan-Meier method and factor potentially affecting outcomes were analyzed with Cox regression analysis. Results. Total RT doses ranged from 20 Gy in 4 fractions to 45 Gy in 18 fractions (median dose: 32 Gy; median number of fractions: 4). All doses were prescribed to the 95% isodose line. No cases of Grade ≥ 3 toxicity were recorded. At a median follow-up time of 41 months (range, 12–75) 22 patients were alive. Three of 28 lesions (11%) showed complete response, 13/28 (46%) partial response, 10/28 (36%) stable disease and 2/28 (7%) progressed in the treated area. Local failure was observed in 13 cases. Actuarial local control rates at one and two years were 66% and 32%, respectively. Median time to local progression was 19 months. Median survival was 22 months. Conclusion. SBRT in adrenal gland metastasis is feasible without significant acute and late toxicities, with a good rate of local control. New SBRT fractionation schemes and the possibility to combine new systemic approaches should be investigated in order to further increase local control and reduce systemic disease progression.

Stereotactic body radiation therapy (SBRT) for adrenal metastases : a feasibility study of advanced techniques with modulated photons and protons.

Purpose:To compare advanced treatment techniques with photons and protons as a stereotactic body radiation therapy (SBRT) for adrenal glands metastases.Materials and Methods:Planning computer tomographic (CT) scans of 10 patients were selected. A total dose of 45 Gy in 7.5 Gy fractions was prescribed. Organs at risk (OAR) were liver and kidneys. Dose–volume metrics were defined to quantify quality of plans assessing target coverage and sparing of organs at risk. Plans for RapidArc, intensity-modulated radiotherapy (IMRT), dynamic conformal arcs, 3D conformal static fields, and intensity modulated protons were compared. The main planning objective for the clinical target volume (CTV) was to cover 100% of the volume with 95% (V95% = 100%) and to keep the maximum dose below 107% of the prescribed dose (V107% = 0%). Planning objective for planning target volume (PTV) was V95% > 80%. For kidneys, the general planning objective was V15Gy < 35% and for liver V15Gy < (liver volume–700 cm3).Results:All techniques achieved the minimum and maximum dose objective for CTV and PTV, D5–95% ranged from 1 Gy (protons) to 1.6 Gy (conformal static fields) on CTV. Maximal organ at risk sparing was achieved by protons. RapidArc presented the second lowest dose bath (V10Gy and integral dose) after protons and the best conformality together with IMRT.Conclusions:Stereotactic body radiation therapy (SBRT) to adrenal glands metastases is achievable with several advanced techniques with either photons or protons. The intensity modulated approaches using either static fields, dynamic arcs or protons are superior to the other conformal solutions. For their simplicity, IMRT or RapidArc should be considered as the first option radiation treatment for those patients not eligible for proton treatment.Ziel:Diese Studie vergleicht fortgeschrittene Bestrahlungstechniken mit Photonen und Protonen bei der stereotaktischen Körperbestrahlung von Metastasen in Nebennieren.Material und Methodik:Es wurden Planungs-CTs von 10 Patienten ausgewählt und eine Dosis von 45 Gy mit einer Fraktionierungsdosis von 7.5 Gy verschrieben. Die Leber und die Nieren wurden als kritische Organe eingezeichnet. Es wurde eine Dosis-Volumen-Metrik zur Quantifizierung der Planqualität in Bezug auf die Zielvolumenabdeckung und die Schonung der kritischen Organe erstellt. RapidArc-, IMRT-, dynamisch konformale Rotations-, 3D konformale Pläne und intensitätsmodulierte Protonenpläne wurden verglichen. Die Planungsvorgaben für das CTV war die 100%ige Abdeckung des Volumens mit 95% der Verschreibungsdosis (V95% = 100%) und die Einhaltung einer maximalen Dosis unterhalb von 107% der Verschreibungsdosis (V107% = 0%). Die Planungsvorgabe für das PTV war V95% > 80%., für die Nieren V15Gy < 35% und für die Leber V15Gy < (Lebervolumen–700 cm3).Ergebnisse:Alle Bestrahlungstechniken erfüllten die minimalen und maximalen Dosisvorgaben für das CTV und das PTV.D5–95% reichten von 1 Gy (Protonen) bis zu 1,6 Gy (konformale statische Felder) beim CTV. Die maximale Schonung der kritischen Organe wurde mit der Protonentechnik erzielt. Die RapidArc-Technik zeigte das zweitniedrigste Dosisbad (V10Gy und integrale Dosis) nach den Protonen und die beste Konformität zusammen mit der IMRT-Technik.Schlussfolgerung:Die stereotaktische Körperbestrahlungstherapie von Metastasen in Nebennieren ist mit mehreren fortgeschrittenen Bestrahlungstechniken mit Photonen oder Protonen durchführbar. Die intensitätsmodulierten Methoden, entweder mit statischen Einstrahlrichtungen, dynamischen Rotationen oder Protonen, sind den anderen konformalen Techniken überlegen. Dank ihrer Einfachheit sollte die IMRT- oder die RapidArc-Technik als erste Option bei der Bestrahlung von Patienten, welche für eine Protonenbehandlung nicht in Frage kommen, berücksichtigt werden.

Stereotactic Body Radiation Therapy (SBRT) for adrenal metastases

Purpose:To compare advanced treatment techniques with photons and protons as a stereotactic body radiation therapy (SBRT) for adrenal glands metastases.Materials and Methods:Planning computer tomographic (CT) scans of 10 patients were selected. A total dose of 45 Gy in 7.5 Gy fractions was prescribed. Organs at risk (OAR) were liver and kidneys. Dose–volume metrics were defined to quantify quality of plans assessing target coverage and sparing of organs at risk. Plans for RapidArc, intensity-modulated radiotherapy (IMRT), dynamic conformal arcs, 3D conformal static fields, and intensity modulated protons were compared. The main planning objective for the clinical target volume (CTV) was to cover 100% of the volume with 95% (V95% = 100%) and to keep the maximum dose below 107% of the prescribed dose (V107% = 0%). Planning objective for planning target volume (PTV) was V95% > 80%. For kidneys, the general planning objective was V15Gy < 35% and for liver V15Gy < (liver volume–700 cm3).Results:All techniques achieved the minimum and maximum dose objective for CTV and PTV, D5–95% ranged from 1 Gy (protons) to 1.6 Gy (conformal static fields) on CTV. Maximal organ at risk sparing was achieved by protons. RapidArc presented the second lowest dose bath (V10Gy and integral dose) after protons and the best conformality together with IMRT.Conclusions:Stereotactic body radiation therapy (SBRT) to adrenal glands metastases is achievable with several advanced techniques with either photons or protons. The intensity modulated approaches using either static fields, dynamic arcs or protons are superior to the other conformal solutions. For their simplicity, IMRT or RapidArc should be considered as the first option radiation treatment for those patients not eligible for proton treatment.Ziel:Diese Studie vergleicht fortgeschrittene Bestrahlungstechniken mit Photonen und Protonen bei der stereotaktischen Körperbestrahlung von Metastasen in Nebennieren.Material und Methodik:Es wurden Planungs-CTs von 10 Patienten ausgewählt und eine Dosis von 45 Gy mit einer Fraktionierungsdosis von 7.5 Gy verschrieben. Die Leber und die Nieren wurden als kritische Organe eingezeichnet. Es wurde eine Dosis-Volumen-Metrik zur Quantifizierung der Planqualität in Bezug auf die Zielvolumenabdeckung und die Schonung der kritischen Organe erstellt. RapidArc-, IMRT-, dynamisch konformale Rotations-, 3D konformale Pläne und intensitätsmodulierte Protonenpläne wurden verglichen. Die Planungsvorgaben für das CTV war die 100%ige Abdeckung des Volumens mit 95% der Verschreibungsdosis (V95% = 100%) und die Einhaltung einer maximalen Dosis unterhalb von 107% der Verschreibungsdosis (V107% = 0%). Die Planungsvorgabe für das PTV war V95% > 80%., für die Nieren V15Gy < 35% und für die Leber V15Gy < (Lebervolumen–700 cm3).Ergebnisse:Alle Bestrahlungstechniken erfüllten die minimalen und maximalen Dosisvorgaben für das CTV und das PTV.D5–95% reichten von 1 Gy (Protonen) bis zu 1,6 Gy (konformale statische Felder) beim CTV. Die maximale Schonung der kritischen Organe wurde mit der Protonentechnik erzielt. Die RapidArc-Technik zeigte das zweitniedrigste Dosisbad (V10Gy und integrale Dosis) nach den Protonen und die beste Konformität zusammen mit der IMRT-Technik.Schlussfolgerung:Die stereotaktische Körperbestrahlungstherapie von Metastasen in Nebennieren ist mit mehreren fortgeschrittenen Bestrahlungstechniken mit Photonen oder Protonen durchführbar. Die intensitätsmodulierten Methoden, entweder mit statischen Einstrahlrichtungen, dynamischen Rotationen oder Protonen, sind den anderen konformalen Techniken überlegen. Dank ihrer Einfachheit sollte die IMRT- oder die RapidArc-Technik als erste Option bei der Bestrahlung von Patienten, welche für eine Protonenbehandlung nicht in Frage kommen, berücksichtigt werden.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

BackgroundSBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients.MethodsBetween October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan.ResultsAll dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded.ConclusionsData of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes.

Investigation on the role of integrated PET/MRI for target volume definition and radiotherapy planning in patients with high grade glioma

PURPOSE To evaluate the impact of fluid-attenuated-inversion-recovery MRI (FLAIR/MRI) and Carbon-11-labeled-methionine PET (11C-MET-PET) on high grade glioma (HGG) tumor volume delineation for radiotherapy planning. MATERIAL AND METHODS Sixty-nine patients with HGG were evaluated. The clinical target volumes (CTV1, generated by adding a 10mm margin to FLAIRMRI area, CTV2 by adding a 20mm margin to enhanced T1MRI) and biological target volume (BTV) were delineated on pre-operative MRI images and 11CMETPET respectively. RESULTS The overlap between CTV1 and CTV2 showed a low correlation between the two volumes with CTV1 not always fully included into the CTV2. In all cases the whole BTV was included into the CTV1, while in 35/69 patients (50%) part of BTV was outside the CTV2 despite larger margins were added. In all cases recurrences were within the CTV1 volume and in 19/38 (50%) partially outside the CTV2. In all patients relapse corresponded to the BTV area. CONCLUSIONS Our data suggest that the target volume definition using FLAIR-MRI is more adequate compared to enhanced T1MRI. 11C-METPET uptake could help identify microscopic residual areas.

Clinical Outcome of Stereotactic Ablative Body Radiotherapy for Lung Metastatic Lesions in Non-small Cell Lung Cancer Oligometastatic Patients

AIMS The aim of this observational study was the evaluation of toxicity, local control and overall survival in non-small cell lung cancer (NSCLC) oligometastatic patients who had undergone stereotactic ablative body radiotherapy (SABR) for lung metastatic lesions. MATERIALS AND METHODS SABR was carried out in oligometastatic patients with controlled primary tumour (adequate pulmonary function). We adopted the following dose prescriptions according to the site and the maximum diameter of the lung lesions: 60 Gy in three fractions for peripheral lesions with diameter ≤ 2 cm, 48 Gy in four fractions for peripheral lesions between 2 and 5 cm and 60 Gy in eight fractions for central lesions. A radiological response was defined according to RECIST criteria. Toxicity was recorded according to the Common Toxicity Criteria version 4.0. RESULTS Between October 2010 and December 2014, 60 NSCLC patients with 90 lung lesions in total were treated at our institution. A radiological response was obtained in most patients. No pulmonary toxicity grade 4, chest pain or rib fracture occurred. The median follow-up from diagnosis was 28 months (range 5.4-104.5 months). The local control at 2 years was 88.9%. Overall survival at 1 and 2 years was 94.5 and 74.6%, respectively. CONCLUSION SABR is well tolerated with a good radiological response and toxicity profile. Discussion within a multidisciplinary team is crucial to identify the oligometastatic patients who would probably benefit from ablative local therapy.

Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study

Purpose: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. Materials and Methods: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. Results: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate (P < .03) and multivariate analyses (P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size (P < .001) and freedom from local progression (P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression (P < .035), tumor diameter (P < .002), and computed tomography before stereotactic body radiotherapy (P < .001) were significantly correlated with overall survival from diagnosis. Conclusion: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

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.

Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A New Challenge

Purpose The aim of this study was to evaluate outcomes of hypofractionated stereotactic radiation therapy (HSRT) in patients re-treated for recurrent high-grade glioma. Materials and Methods From January 2006 to September 2013, 25 patients were treated. Six patients underwent radiation therapy alone, while 19 underwent combined treatment with surgery and/or chemotherapy. Only patients with Karnofsky Performance Status (KPS) > 70 and time from previous radiotherapy greater than 6 months were re-irradiated. The mean recurrent tumor volume was 35 cm3 (range, 2.46 to 116.7 cm3), and most of the patients (84%) were treated with a total dose of 25 Gy in five fractions (range, 20 to 50 Gy in 5-10 fractions). Results The median follow-up was 18 months (range, 4 to 36 months). The progression-free survival (PFS) at 1 and 2 years was 72% and 34% and the overall survival (OS) 76% and 50%, respectively. No severe toxicity was recorded. In univariate and multivariate analysis extent of resection at diagnosis significantly influenced PFS and OS (p < 0.01). Patients with smaller recurren tumor volume treated had better local control and survival. Indeed, the 2-year PFS was 40% (≤ 50 cm3) versus 11% (p=0.1) and the 2-year OS 56% versus 33% (> 50 cm3), respectively (p=0.26). Conclusion In our experience, HSRT could be a safe and feasible therapeutic option for recurrent high grade glioma even in patients with larger tumors. We believe that a multidisciplinary evaluation is mandatory to assure the best treatment for selected patients. Local treatment should also be considered as part of an integrated approach.