Search

Supplemental material, Supplementary_Materials for Dose prescription in SBRT for early-stage non-small cell lung cancer: are we all speaking the same language? by Anna Merlotti, Pierluigi Bonomo, Riccardo Ragona, Marco Trovò, Filippo Alongi, Rosario Mazzola, Riccardo Vigna Taglianti, Luca Gianello, Alessia Reali, Fabrizio Bergesio, Francesco Lucio, Alberto Boriano, Adriano De Maggi and Elvio Russi in Tumori Journal

Patient-specific quality assurance in volumetric modulated arc therapy (VMAT) brain stereotactic radiosurgery raises specific issues on dosimetric procedures, mainly represented by the small radiation fields associated with the lack of lateral electronic equilibrium, the need of small detectors and the high dose delivered (up to 30 Gy). GafchromicTM EBT2 and EBT3 films may be considered the dosimeter of choice, and the authors here provide some additional data about uniformity correction for this new generation of radiochromic films.A new analysis method using blue channel for marker dye correction was proposed for uniformity correction both for EBT2 and EBT3 films. Symmetry, flatness, and field-width of a reference field were analyzed to provide an evaluation in a high-spatial resolution of the film uniformity for EBT3. Absolute doses were compared with thermoluminescent dosimeters (TLD) as baseline. VMAT plans with multiple noncoplanar arcs were generated with a treatment planning system on a selected pool of eleven patients with cranial lesions and then recalculated on a water-equivalent plastic phantom by Monte Carlo algorithm for patient-specific QA. 2D quantitative dose comparison parameters were calculated, for the computed and measured dose distributions, and tested for statistically significant differences.Sensitometric curves showed a different behavior above dose of 5 Gy for EBT2 and EBT3 films; with the use of inhouse marker-dye correction method, the authors obtained values of 2.5% for flatness, 1.5% of symmetry, and a field width of 4.8 cm for a 5×5 cm2 reference field. Compared with TLD and selecting a 5% dose tolerance, the percentage of points with ICRU index below 1 was 100% for EBT2 and 83% for EBT3. Patients analysis revealed statistically significant differences (p0.05) between EBT2 and EBT3 in the percentage of points with gamma values1 (p=0.009 and p=0.016); the percent difference as well as the mean difference between calculated and measured isodoses (20% and 80%) were found not to be significant (p=0.074, p=0.185, and p=0.57).Excellent performances in terms of dose homogeneity were obtained using a new blue channel method for marker-dye correction on both EBT2 and EBT3 GafchromicTM films. In comparison with TLD, the passing rates for the EBT2 film were higher than for EBT3; a good agreement with estimated data by Monte Carlo algorithm was found for both films, with some statistically significant differences again in favor of EBT2. These results suggest that the use of GafchromicTM EBT2 and EBT3 films is appropriate for dose verification measurements in VMAT stereotactic radiosurgery; taking into account the uncertainty associated with Gafchromic film dosimetry, the use of adequate action levels is strongly advised, in particular, for EBT3.

The authors have evaluated the accuracy, in absolute and relative dose measurements, of the Gafchromic EBT film in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value of less than 0.1 mGy/pulse. However, very high dose-per-pulse electron beams are employed in certain linear accelerators dedicated to intraoperatory radiation therapy (IORT). In this study, the absorbed dose measurements with Gafchromic EBT in both low (less than 0.3 mGy per pulse) and high (30 and 70 mGy per pulse) dose-per-pulse electron beams were compared with ferrous sulfate chemical Fricke dosimetry (operated by the Italian Primary Standard Dosimetry Laboratory), a method independent of the dose per pulse. A summary of Gafchromic EBT in relative and absolute beam output determination is reported. This study demonstrates the independence of Gafchromic EBT absorption as a function of dose per pulse at different dose levels. A good agreement (within 3%) was found with Fricke dosimeters for plane-base IORT applicators. Comparison with a diode detector is presented for relative dose measurements, showing acceptable agreement both in the steep dose falloff zone and in the homogeneous dose region. This work also provides experimental values for recombination correction factor (Ksat) of a Roos (plane parallel) ionization chamber calculated on the basis of theoretical models for charge recombination.

The Gafchromic EBT was recently introduced in film dosimetry for external beam therapy (EBT). The high spatial resolution, weak energy dependence, and near-tissue equivalence of EBT films make them suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). Starting with a sensitometric curve and dose uncertainty relative to the flatbed scanner, the goal of this study was to find an efficient method of correcting for light scattering, and to compare dose distribution supplied by Gafchromic EBT with the distribution obtained with a 2D ion-chamber detector system. Light scattering was analyzed for different levels of dose, and was found to depend on the red-scale value as well as the position of the pixel on the scanner. Many "uniform" films were exposed at different levels of dose to create a two-dimensional matrix correction to take this effect into account. The dose distribution obtained for three clinical beams (10 x 10, 15 x 15 cm open fields and 12 x 12 cm wedge 60 degrees field) were in agreement with those supplied by the 2D array. Gamma index1 (using 5 mm distance and 5% dose as constraints) for the three fields considered was reached in an average of 98% of the points.

Current quality assurance regulation stresses the basic role of in vivo dosimetry. Our study evaluates the usefulness and reliability of semiconductor diodes in determining the electron absorbed dose.P-type EDE semiconductor detectors were irradiated with electron beams of different energies produced by a CGR Saturn Therac 20. The diode and ionization chamber response were compared, and effect of energy value, collimator opening, source skin distance and gantry angle on diode response was studied.Measurements show a maximum increment of about 20% in diode response increasing the beam energy (6-20 MeV). The response also increases with: collimator opening, reaching 5% with field sizes larger than 10x10 cm2 (with the exception of 20 MeV energy); SSD increase (with a maximum of 8% for 20 MeV); transversal gantry incidence, compared with the diode longitudinal axis; it does not affect the response in the interval of +/- 45 degrees. Absorbed dose attenuation at dmax, due to the presence of diode on the axis of the beam as a function of electron energy was also determined : the maximum attenuation value is 15% in 6 MeV electron beams. A dose calculation algorithm, taking into account diode response dependence was outlined. In vivo dosimetry was performed in 92 fields for 80 patients, with an agreement of +/-4 % (1 SD) between prescribed and measured dose.It is possible to use the EDE semiconductor detectors on a quality control program of dose delivery for electron beam therapy, but particular attention should be paid to the beam incidence angle and diode dose attenuation.

The value of prognostic factors in patients with advanced cervix carcinoma treated by radiotherapy was assessed in a retrospective study.From January 1977 through December 1990, 261 patients (average age 60 years) were treated at the Radiotherapy Department of the University of Turin. Distribution by stage was: 142 T2b (54%), 8 T3a (3%), 98 T3b (38%) and 13 T4 (5%). 83% of the patients underwent radiotherapy alone; the total dose was 45-88 Gy in 91 patients (42%) with poor clinical conditions, 60-75 Gy in 121 (56%) and 75-80 Gy in 5 cases. 17% of the patients was treated by surgery combined with radiotherapy. The median follow-up was 50 months (minimum 2, maximum 177 months).The 5-year NED survival and local control were 42% (52% for T2b, 33% for T3 and 15% for T4). The severe (G3-G4) complication rate was very low (1.9%).In our series, the prognostic factors which significantly influenced survival in the uni-variate analysis were: advanced T stage, contemporary infiltration of parametrium and vagina, nodal status, non squamous neoplasm, younger age and the absence of brachytherapy in the radiotherapy alone protocol.

Today there is increased need for an objective comparison between the various post-total laryngectomy phonatory rehabilitation techniques. This survey involves 20 patients who, after total laryngectomy, underwent rehabilitation using the esophageal voice (n = 10) or through the application of a secondary tracheal-esophageal prosthesis (n = 10). The multivariate analysis indicated that the only phonatory parameter which differed significantly between the two types of voice was the maximum phonation time (MPT) (p0.01). The MPT was markedly longer in patients with the tracheal-esophageal prosthesis. In patients with prosthesis, the Mann-Whitney test highlighted better figures for the following parameters: MPT (p = 0.0003), GP (maximum number of words that can be read in one breath) (p = 0.009), maximum intensity level (MIL) (p = 0.019), Shimmer (p = 0.008) and noise-to harmonics ratio (NHR) (p = 0.049). Furthermore, the Spearman test proved there is a relationship between MIL and GP, and between Pitch and Shimmer. Therefore, the tracheal-esophageal prosthesis seems to offer better phonatory energy and phonatory duration for every breath. However, these methods of objective inquiry need to be further developed so that comparison-among the different authors and among the different rehabilitation methods-can be made easier than it is now.

January, 1977, to December, 1990, 311 patients with stage IB-IIA cervix carcinoma were treated at the Radiotherapy Department of the University of Turin. The distribution by stage was: 232 T1b (74.6%) and 79 T2a (25.4%). One hundred and eighty-nine patients (77% T1b-23% T2a) underwent preoperative radiotherapy, 63 patients (58% T1b-42% T2a) radiotherapy alone and 59 (85% T1b-15% T2a) postoperative radiotherapy. The first group of patients was treated according to three treatment protocols, based on different surgical procedures. During the median follow-up period of 86 months (82.6% of the patients underwent a minimum 3-year follow-up), 55 locoregional relapses (17%) and 21 extrapelvic metastases (7%) were observed. The 5-year NED survival rate and local control was 80%. The prognostic factors which significantly influenced survival in the univariate analysis, were: disease stage (p.01), age (p.05), the period between first symptom and therapy (p = .01), treatment protocols (radiotherapy combined with surgery versus radiation therapy alone: p.05), residual disease after brachytherapy (p.01), nodal status (p.00001). In the radiotherapy alone group, the total dose influence on survival was not statistically significant (p = .12). In our series, histology and surgical procedures did not seem to influence prognosis. In the multivariate analysis, treatment protocol, age and residual disease after brachytherapy did not influence the prognosis, whereas the total dose of radiotherapy, pain (as first symptom) and Wertheim-Meigs surgery approach are prognostic factors. Severe late-effects were 17: 13 in the radiotherapy plus surgery protocol and 4 in the radiotherapy alone protocol. The incidence of major complications seems to correlate with surgical impact.

A carcinoma of the base of the tongue is diagnosed with difficulty and therapy offers a poor clinical prognosis. Between November 1988 and April 1993 45 patients were evaluated (38 men and 7 women, mean age 60 years). These patients were in poor clinical conditions and advanced clinical stage. Surgical treatment alone or in association with radiotherapy was employed in 17 patients. In the remaining patients radiation therapy alone or associated with chemotherapy was employed. Three-year overall actuarial survival was 39.5% and 3-year NED survival was 21%. Certain prognostic factors were evaluated: T stage, lymph nodes, TNM staging, extension to near anatomical areas and treatment. A Cox multivariate regression analysis revealed that clinical N stage was significant for prognosis (3-year overall actuarial survival was 76.9% for NO and 28% in subjects with clinical nodes). Subjects with neoplasm extension to pharyngo-laryngeal area could have better prognosis and, a finally, patients treated with surgery alone or in association with other treatment would achieve better local control than others.

Cholangiocarcinoma at the confluence of the hepatic ducts (Klatskin tumor) is a slowly growing malignancy with early onset of symptoms and poor outcome since surgery allows radical resection in only a minority of cases. Percutaneously placed biliary stents offer a good palliation, but tend to obstruct after 6-8 months; then, retreatment requires exchange of the endoprosthesis or establishment of a permanent external-internal biliary drainage which offers, in some patients, a relatively long survival. Percutaneous intraluminal HDR brachytherapy might be a valid alternative as a definitive therapy or as a method to keep metallic stents patent for a long time. Five patients with hilar cholangiocarcinoma, diagnosed by means of ultrasound, Computed Tomography, percutaneous transhepatic cholangiography and transluminal biopsy, underwent double percutaneous external-internal biliary drainage. Dummy sources were introduced into the drainage catheters to allow dose distribution planning. The stepwise progression of the miniaturized high activity Iridium source inside the applicators, introduced into the drainage catheters, was controlled and monitored by a computer equipped with dedicated software. In the radiotherapy bunker, using the remote loading technique, percutaneous intracavitary high dose rate brachytherapy was delivered at the rate of 750 cGy per fraction, prescribed at 1 cm from the center of the catheter, once a week, for 4 weeks. Nevertheless, only 4 of 5 patients underwent the complete treatment. In one case, radiation treatment was discontinued after the first session because of digestive bleeding from a duodenal ulcer, supposingly as a consequence of the decubitus of a catheter tip. CT demonstrated rapid progression of the disease with neoplastic spread to the omentum and gallbladder wall thickening; a gallbladder malignancy was then suspected and the patient was no more eligibile for brachytherapy. Subsequently, Carey-Coons endoprostheses were inserted to prevent post-actinic strictures and removed after three months. After completing radiation therapy, control cholangiograms demonstrated in all cases improvement of neoplastic strictures. The first two patients we treated show no signs of tumor recurrence at 4 and 1 months, respectively, after endoscopic removal of the stents. The third patient is still bearing 2 Carey-Coons endoprostheses to be removed after 3 months. The last patient with supposingly partial success of bracytherapy, was treated with two Strecker nitinol stents.

Between 1985 and 1989, 19 patients with mycosis fungoides were treated by Total Skin Electron Therapy (TSET). Overall and disease-free survival at 3 years were 72% and 40%. The complete remission (CR) rate was 100% in patients with plaque and 33.3% in those with tumor masses; patients with negative nodes had a 90% CR rate whereas in those with adenopathy the rate was 55%. Overall and disease free survivals were also correlated with these factors.

The authors report their experience on the treatment of carcinoma of the oral tongue and floor of the mouth with interstitial brachytherapy, alone or in combination with external irradiation. One hundred and fifty patients were treated; among these, 116 with brachytherapy alone, 34 with combined treatment. The five years local control in those patients treated with brachytherapy alone was 72.5% in T1, 61.2% in T2 and 35% in T3; in those patients treated with external irradiation and brachytherapy the global five years control was 42.5%. The global five years survival was 64% in the patients treated with brachytherapy alone and 48% in the patients treated with combined therapy.

Dose distribution in mantle fields irradiated with 18 MeV photons has been studied in an Alderson-Rando phantom with thermoluminescent dosimeters. The treatment was also simulated on an RT-plan 7000 computer; calculated and measured doses in anatomical sites of major interest were compared. Doses in all significant points were within +/- 7% of the doses at the reference point. Calculated and measured doses agreed within +/- 5% except points situated near unhomogeneous tissues. The authors discuss their results and present conclusions about algorithms for computer dose calculation in irregular field treatments.

Total body irradiation (TBI) is used in our Institution in the conditioning regimen for bone marrow transplantation. The fractionation pattern consists of two daily fractions of 1.65 Gy repeated for 4 days (total dose 13.20 Gy in 8 fractions). Lung dose is reduced by means of lead custom shaped shields directly strapped to the patient surface. TBI is delivered by a THERAC 20 linear accelerator with two opposing AP-PA photon beams with a maximum energy of 18 MeV. Treatment distance is 340 cm and the patient is treated in a semi-standing position. Dosimetry studies in a homogeneous phantom were performed in the treatment geometry and consisted in the determination of: tissue maximum ratios (TMR) at different depths, absorbed dose along the median axis and the diagonal of the field, variation of the absorbed dose in the prescription point with different volumes of scattering material, and transmission of shielding and compensating material. A semi-empiric formula for the calculation of absorbed dose in a point has been obtained. A subsequent study in a Rando phantom with termoluminescent dosimeters (TLD) has shown a +/- 5% agreement between calculated and measured values and a +/- 7% homogeneity.

The authors conducted a retrospective study on 99 patients with malignant tumors of the major salivary glands, who had been treated by radiotherapy between 1976 and 1986: 86 cases of parotid tumors and 13 cases of submandibular gland tumors. Only 28 tumors (28%) were T1-T2, N0-N1. Local control, 3-5 and 8-year survival rates, and complications were considered. Radiation therapy alone was performed on 19 patients (19%), while combined surgical and radiation therapy was performed on 80 patients (80%). The results of radiation therapy alone and combined with surgery are discussed. Loco-regional disease control was obtained in 9 out of 19 patients (47%) by irradiation alone, and by combined irradiation and surgery in 60 out of 80 cases (75%). Distant metastases developed in 23 out of 99 patients (23%). Loco-regional metastases were the most frequent cause of death (20 out of 55 cases: 36%). Severe complications were extremely rare. The results demonstrate not only the advantages of combined treatment but also the value of radiotherapy alone in the treatment of tumors of the major salivary glands.

After a brief review of the literature, the results of the treatment by radiation therapy in 218 patients with tonsillar region carcinoma are reported. The patients were treated at the Turin University Radiotherapy Department (131 cases) and at the Radiotherapy Department of the Ospedale Maggiore, Novara (87 cases) from 1976 through 1984. The series included 29 T1, 88 T2, 64 T3 and 37 T4; 86 patients (40%) were N0. Only 49 patients were stages I and II (1/4 of the total). The local control (T) rate at the end of therapy was 63.5% for the overall series (139/218) ranging from 100% in T1, 72.6% T2, 54.6% T3 to 30% T4; the regional control (N) for patients with cervical lymphadenopathy was 66% (88/132). The overall 5-year survival was 38%; the 5-year disease-free survival was 35%. The 5-year survival according to T-stage was 52% for limited cases (T1-T2) in comparison to 22% for advanced ones (T3-T4). The 5-year survival for N0 stage was 55%; when neck nodes were present (N # 0) the survival was 29% after 5 years. Complications included 6 cases of trismus and 2 osteonecroses of the mandible. Second primary malignant diseases were seen in 17 cases (7.8%). The most common cause of death was failure in primary tumour control (80% of cases). In this series the results of radiotherapy of early stage tonsillar carcinomas are quite good; patients with large tumour masses fare less satisfactorily. Better results should be obtained in the future by identifying prognostic factors, monitoring potential causes of treatment failure and optimizing the radiotherapeutic treatment plan and technique.