P. Mancosu

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.

Volumetric Modulation Arc Radiotherapy Compared With Static Gantry Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma Tumor: A Feasibility Study

PURPOSE A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of >95% and maximal dose of <107%. For the organs at risk, the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V(5 Gy)) <60%, V(20 Gy) < 10%, mean <10.0 Gy; liver, V(30 Gy) <33%, mean <31 Gy; heart, V(45 Gy) <30%, V(50 Gy) <20%, dose received by 1% of the volume (D(1%)) <60 Gy; contralateral kidney, V(15 Gy) <20%; spine, D(1%) <45 Gy; esophagus, V(55 Gy) <30%; and spleen, V(40 Gy) <50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index. RESULTS RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 +/- 0.1 for RA and IMRT. The number of MU/2 Gy was 734 +/- 82 for RA and 2,195 +/- 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% +/- 2.6% and for RA of 95.7% +/- 1.5%. The treatment time was 3.7 +/- 0.3 min for RA and 13.4 +/- 0.1 min for IMRT. CONCLUSION RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients.

Volumetric Modulation Arc Radiotherapy With Flattening Filter-Free Beams Compared With Static Gantry IMRT and 3D Conformal Radiotherapy for Advanced Esophageal Cancer: A Feasibility Study

PURPOSE A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RESULTS RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). CONCLUSION RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time.

Critical Appraisal of Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Metastases to Abdominal Lymph Nodes

PURPOSE A planning study was performed comparing volumetric modulated arcs, RapidArc (RA), fixed beam IMRT (IM), and conformal radiotherapy (CRT) with multiple static fields or short conformal arcs in a series of patients treated with hypofractionated stereotactic body radiation therapy (SBRT) for solitary or oligo-metastases from different tumors to abdominal lymph nodes. METHODS AND MATERIALS Fourteen patients were included in the study. Dose prescription was set to 45 Gy (mean dose to clinical target volume [CTV]) in six fractions of 7.5 Gy. Objectives for CTV and planning target volume (PTV) were as follows: Dose(min) >95%, Dose(max) <107%. For organs at risk the following objectives were used: Maximum dose to spine <18 Gy; V(15Gy) <35% for both kidneys, V(36Gy) <1% for duodenum, V(36Gy) <3% for stomach and small bowel, V(15Gy) <(total liver volume--700 cm(3)) for liver. Dose-volume histograms were evaluated to assess plan quality. RESULTS Planning objectives on CTV and PTV were achieved by all techniques. Use of RA improved PTV coverage (V(95%) = 90.2% +/- 5.2% for RA compared with 82.5% +/- 9.6% and 84.5% +/- 8.2% for CRT and IM, respectively). Most planning objectives for organs at risk were met by all techniques except for the duodenum, small bowel, and stomach, in which the CRT plans exceeded the dose/volume constraints in some patients. The MU/fraction values were as follows: 2186 +/- 211 for RA, 2583 +/- 699 for IM, and 1554 +/- 153 for CRT. Effective treatment time resulted as follows: 3.7 +/- 0.4 min for RA, 10.6 +/- 1.2 min for IM, and 6.3 +/- 0.5 min for CRT. CONCLUSIONS Delivery of SBRT by RA showed improvements in conformal avoidance with respect to standard conformal irradiation. Delivery parameters confirmed logistical advantages of RA, particularly compared with IM.

Phase I-II study of hypofractionated simultaneous integrated boost using volumetric modulated arc therapy for adjuvant radiation therapy in breast cancer patients: a report of feasibility and early toxicity results in the first 50 treatments

BackgroundTo report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery.MethodsBetween September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of 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. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor.ResultsThe median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up.ConclusionsThe 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

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.

Cranio-spinal irradiation with volumetric modulated arc therapy: A multi-institutional treatment experience

PURPOSE To report the treatment of cranio-spinal irradiation (CSI) with volumetric modulated arc therapy (RapidArc) in adults and a child. MATERIALS AND METHODS Five patients from 5 institutions were treated with CSI using RapidArc technology. Patient age varied between 7 and 45 years. The lengths of the planning target volumes (PTV) and dose prescriptions ranged from 54.6 to 78.4 cm, and from 12 to 36 Gy, respectively. Different arc arrangements were used, with two or three isocentres, from two to six modulated arcs, for patient positioned either in prone (n=3) or supine position (n=2). Doses to PTV, organs at risk and non-target tissue are reported for each of the five patients. Data concerning imaging strategy and pre-treatment quality assurance are also reported. RESULTS The mean conformity index CI(95%) was 1.05 ± 0.05 (range: 1.00, 1.13). Mean doses to the lenses, lungs, heart, and kidneys were, respectively, 7.6 ± 1.6, 6.6 ± 3.0, 5.7 ± 2.3, and 6.1 ± 2.1 Gy, keeping those value acceptably low. Mean non-target tissue dose was 21.0 ± 3.8% (5.6 ± 1.8 Gy, range: 3.0-8.1 Gy). All patients were successfully planned and treated with RapidArc. CONCLUSIONS RapidArc techniques achieved highly conformal treatment plans for 5 adults or paediatric patients. Beam-on time was short, and RapidArc plans were satisfactorily delivered to all presented patients.