A. Tozzi

Is Stereotactic Body Radiation Therapy an Attractive Option for Unresectable Liver Metastases? A Preliminary Report From a Phase 2 Trial

PURPOSE To evaluate the feasibility of high-dose stereotactic body radiation therapy (SBRT) in the treatment of unresectable liver metastases. METHODS AND MATERIALS Patients with 1 to 3 liver metastases, with maximum individual tumor diameters less than 6 cm and a Karnofsky Performance Status of at least 70, were enrolled and treated by SBRT on a phase 2 clinical trial. Dose prescription was 75 Gy on 3 consecutive days. SBRT was delivered using the volumetric modulated arc therapy by RapidArc (Varian, Palo Alto, CA) technique. The primary end-point was in-field local control. Secondary end-points were toxicity and survival. RESULTS Between February 2010 and September 2011, a total of 61 patients with 76 lesions were treated. Among the patients, 21 (34.3%) had stable extrahepatic disease at study entry. The most frequent primary sites were colorectal (45.9%) and breast (18%). Of the patients, 78.7% had 1 lesion, 18.0% had 2 lesions, and 3.3% had 3 lesions. After a median of 12 months (range, 2-26 months), the in-field local response rate was 94%. The median overall survival rate was 19 months, and actuarial survival at 12 months was 83.5%. None of the patients experienced grade 3 or higher acute toxicity. No radiation-induced liver disease was detected. One patient experienced G3 late toxicity at 6 months, resulting from chest wall pain. CONCLUSIONS SBRT for unresectable liver metastases can be considered an effective, safe, and noninvasive therapeutic option, with excellent rates of local control and a low treatment-related toxicity.

Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments

PurposeTo test feasibility and safety of clinical usage of Flattening Filter Free (FFF) beams for delivering ablative stereotactic body radiation therapy (SBRT) doses to various tumor sites, by means of Varian TrueBeam™ (Varian Medical Systems).Methods and MaterialsSeventy patients were treated with SBRT and FFF: 51 lesions were in the thorax (48 patients),10 in the liver, 9 in isolated abdominal lymph node, adrenal gland or pancreas. Doses ranged from 32 to 75 Gy, depending on the anatomical site and the volume of the lesion to irradiate. Lung lesions were treated with cumulative doses of 32 or 48 Gy, delivered in 4 consecutive fractions. The liver patients were treated in 3 fractions with total dose of 75 Gy. The isolated lymph nodes were irradiated in 6 fractions with doses of 45 Gy. The inclusion criteria were the presence of isolated node, or few lymph nodes in the same lymph node region, in absence of other active sites of cancer disease before the SBRT treatment.ResultsAll 70 patients completed the treatment. The minimum follow-up was 3 months. Six cases of acute toxicities were recorded (2 Grade2 and 2 Grade3 in lung and 2 Grade2 in abdomen). No patient experienced acute toxicity greater than Grade3. No other types or grades of toxicities were observed at clinical evaluation visits.ConclusionsThis study showed that, with respect to acute toxicity, SBRT with FFF beams showed to be a feasible technique in 70 consecutive patients with various primary and metastatic lesions in the body.

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.

Stereotactic body radiation therapy for liver tumours using flattening filter free beam: dosimetric and technical considerations.

PurposeTo report the initial institute experience in terms of dosimetric and technical aspects in stereotactic body radiation therapy (SBRT) delivered using flattening filter free (FFF) beam in patients with liver lesions.Methods and MaterialsFrom October 2010 to September 2011, 55 consecutive patients with 73 primary or metastatic hepatic lesions were treated with SBRT on TrueBeam using FFF beam and RapidArc technique. Clinical target volume (CTV) was defined on multi-phase CT scans, PET/CT, MRI, and 4D-CT. Dose prescription was 75 Gy in 3 fractions to planning target volume (PTV). Constraints for organs at risk were: 700 cc of liver free from the 15 Gy isodose, Dmax < 21 Gy for stomach and duodenum, Dmax < 30 Gy for heart, D0.1 cc < 18 Gy for spinal cord, V15 Gy < 35% for kidneys. The dose was downscaled in cases of not full achievement of dose constraints. Daily cone beam CT (CBCT) was performed.ResultsForty-three patients with a single lesion, nine with two lesions and three with three lesions were treated with this protocol. Target and organs at risk objectives were met for all patients. Mean delivery time was 2.8 ± 1.0 min. Pre-treatment plan verification resulted in a Gamma Agreement Index of 98.6 ± 0.8%. Mean on-line co-registration shift of the daily CBCT to the simulation CT were: -0.08, 0.05 and -0.02 cm with standard deviations of 0.33, 0.39 and 0.55 cm in, vertical, longitudinal and lateral directions respectively.ConclusionsSBRT for liver targets delivered by means of FFF resulted to be feasible with short beam on time.

Clinical outcome of hypofractionated stereotactic radiotherapy for abdominal lymph node metastases.

PURPOSE We report the medium-term clinical outcome of hypofractionated stereotactic body radiotherapy (SBRT) in a series of patients with either a solitary metastasis or oligometastases from different tumors to abdominal lymph nodes. METHODS AND MATERIALS Between January 2006 and June 2009, 19 patients with unresectable nodal metastases in the abdominal retroperitoneal region were treated with SBRT. Of the patients, 11 had a solitary nodal metastasis and 8 had a dominant nodal lesion as part of oligometastatic disease, defined as up to five metastases. The dose prescription was 45 Gy to the clinical target volume in six fractions. The prescription had to be downscaled by 10% to 20% in 6 of 19 cases to keep within dose/volume constraints. The first 11 patients were treated with three-dimensional conformal techniques and the last 8 by volumetric intensity-modulated arc therapy. Median follow-up was 1 year. RESULTS Of 19 patients, 2 had a local progression at the site of SBRT; both also showed concomitant tumor growth at distant sites. The actuarial rate of freedom from local progression was 77.8% ± 13.9% at both 12 and 24 months. Eleven patients showed progressive local and/or distant disease at follow-up. The 12- and 24-month progression-free survival rates were 29.5% ± 13.4% and 19.7% ± 12.0%, respectively. The number of metastases (solitary vs. nonsolitary oligometastases) emerged as the only significant variable affecting progression-free survival (p < 0.0004). Both acute and chronic toxicities were minimal. CONCLUSIONS Stereotactic body radiotherapy for metastases to abdominal lymph nodes was shown to be feasible with good clinical results in terms of medium-term local control and toxicity rates. Even if most patients eventually show progressive disease at other sites, local control achieved by SBRT may be potentially significant for preserving quality of life and delaying further chemotherapy.

Stereotactic body radiation therapy for abdominal targets using volumetric intensity modulated arc therapy with RapidArc: Feasibility and clinical preliminary results

Abstract Purpose. To report early clinical experience in stereotactic body radiation therapy (SBRT) delivered using volumetric intensity modulated arc therapy with RapidArc (RA) in patients with primary or metastatic tumours at abdominal sites. Material and methods. Thirty-seven consecutive patients were treated using RA. Of these, 16 had primary or metastatic liver tumours, nine had pancreatic cancer and 12 a nodal metastasis in the retro-peritoneum. Dose prescription varied from 45 to 75 Gy to the Clinical Target Volume in 3 to 6 fractions. The median follow-up was 12 months (6–22). Early local control and toxicity were investigated and reported. Results. Planning objectives on target volumes and organs at risk were met in most cases. Delivery time ranged from 2.8 ± 0.3 to 9.2 ± 2.4 minutes and pre-treatment plan verification resulted in a Gamma Agreement Index from 95.3 ± 3.8 to 98.3 ± 1.7%. At the time of analysis, local control (freedom from progression) at six months, was assessable in 24 of 37 patients and was achieved in 19 patients with a crude rate of 79.2%. Seven patients experienced treatment-related toxicity. Three patients experienced a mild and transient G1 enteritis and two showed a transient G1 liver damage. Two had late toxicity: one developed chronic enteritis causing G1 diarrhoea and G1 abdominal pain and one suffered at three months a G3 gastric bleeding. No patients experienced G4 acute toxicity. Conclusions. SBRT for abdominal targets delivered by means of RA resulted to be feasible with good early clinical results in terms of local control rate and acute toxicity profile. RA allowed to achieve required target coverage as well as to keep within normal tissue dose/volume constraints.

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.

Cone beam CT pre‐ and post‐daily treatment for assessing geometrical and dosimetric intrafraction variability during radiotherapy of prostate cancer

The purpose of this study was to quantify the relationship between treatment time and dose uncertainty due to intrafraction organ motion in prostate cancer radiotherapy (RT). Ten consecutive patients with prostate cancer treated by radical RT by volumetric modulated arc therapy (RapidArc) were considered. For each patient, pre‐ and post‐treatment cone beam computed tomography (CBCT) was performed in 10 fractions. The prostate, rectum and bladder were contoured on each CBCT. The change in organ position, volume and dosimetric uncertainty induced by organ motion were evaluated. Interval time between the two CBCTs ranged between 4 and 16 min (mean 7.3±0.7 min). Treatment with intrafraction prostate motion > 3 mm and > 5 mm were 24% and 5%, respectively. Regarding change in centroid position and volume, a poor time correlation was found for target and rectum, while a constant increase was obtained for bladder. The agreement index was highly correlated to time (r=−0.89 for bladder, r=−0.95 for rectum, and r=−0.84 for prostate). In terms of difference in dose volume histogram between pre‐ and post‐CBCT, the dose uncertainties for the targets and rectum amplified with the increasing time. The increasing intrafraction dose uncertainty with time requires the use of an RT technique with minimization of treatment time to improve confidence in planning dose distribution. PACS number: 87.55.tm

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.