S. Garelli

Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma

To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70–76 Gy delivered with a conformal 3-field arrangement to the prostate±seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. Late rectal toxicity was graded according to the RTOG morbidity scoring scale. Median follow up is 25.8 (range: 12–70.2 months). The 2-year actuarial likelihood of grade 2–4 rectal toxicity was 21.8±3.2%. A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2–4 late rectal toxicity. The 2-year estimates of grade 2–4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3±5.2% and 14.1±3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.

The determination of dose characteristics of ruthenium ophthalmic applicators using radiochromic film

Ruthenium ophthalmic applicators are energetic beta ray sources, supplied in several shapes and dimensions, and used in intraocular tumor therapy. Because of their small dimensions, the determination of dosimetric characteristics represents a technical challenge. We developed a semiautomatic method to define surface dose, dose distribution, and percentage depth dose of such applicators using radiochromic dosimetric media. These detectors consist of a thin (7 microns) radiation sensitive layer on polyester base (100 microns total thickness) changing color as a function of radiation exposure. Transmission images of exposed films were then grabbed with a TV-digitizer system to obtain a gray-level image from which dosimetric characteristics such as isodose distribution, dose values, and homogeneity of nuclide distribution were derived. Good agreement between experimental results and Monte Carlo simulation performed using the GEANT 3 code, appear to be a confirmation of the validity of the method. Moreover while manufacturer specifications of absolute and relative dose rates present a standard deviation error of +/- 30% on dose rate and +/- 6% on accuracy of relative dose values, the proposed method reduces the errors to +/- 10% and +/- 4%, respectively.

A biologically competitive 21 days hypofractionation scheme with weekly concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and short term late effects.

BackgroundRadiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule.MethodsBetween February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions.ResultsAll the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis.ConclusionsThe clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime.

Radiosurgery with Helical Tomotherapy Outcomes for Patients with One or Multifocal Brain Metastasis

To evaluate the feasibility and report the preliminary results for stereotactic radiosurgery (SRS) treatments of single or multiple brain metastases delivered with helical tomotherapy (HT) by means of the InterFix™ Radiosurgery kit. Between September 2010 and August 2012, thirty patients underwent SRS for treatment of 46 brain metastases with a median prescription dose of 20 Gy (range 15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic resonance imaging (MRI). Dose distribution indexes were computed and compared with published data for SRS performed with dedicated machines. After a median follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was 70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was 72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as headache and epileptic crisis occurred in only two patients. The mean values of conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50 respectively. HT-SRS for single or multiple brain metastases appears a reliable technique with encouraging clinical outcomes and competitive dosimetrical results.

Accelerated partial breast irradiation via the mammosite® catheter: Preliminary reports of a single-institution experience

Abstract:  Several studies have shown that the majority of in‐breast recurrences following lumpectomy are at or near the original tumor site while ipsilateral breast recurrences further afield occur rarely. This suggests that the radiation dose could be delivered exclusively to the tumor bed, allowing larger fractions to be used without increasing toxicity and shortening the total treatment time. We investigated the use of the MammoSite irradiation system with a view to analyzing complications, cosmesis and patient comfort. Between 2004 and 2007 intracavity brachytherapy was given to 30 patients using the MammoSite device. The reference isodose was prescribed to the lumpectomy cavity with a 1 cm margin. Geometric parameters and anatomic position of the applicator after implantation were checked via CT, x‐ray and ultrasound. Analysis was done for patient quality of life, cosmesis, early and late complications. Forty‐nine patients received a proposal for MammoSite brachytherapy. Nine declined, 40 enrolled while 10 were excluded for various reasons ( Table 5 ). A total of 30 patients were actually treated to 34 Gy (2 × 3.4 Gy) in 5 days. We observed 3 cases (10%) of infection within 3 months of implantation. Symptomatic seroma was seen in five patients (16.6%) at 6 months, in three (10%) at 12 months, and in just one patient (3.3%) at 18 months. Good to excellent cosmetic results were achieved in 75% by patient and physician ratings. Accelerated partial breast irradiation using the MammoSite catheter produces favorable short‐term outcomes, limited toxic effects on skin, and optimal cosmetic results. Patient tolerance for the treatment is very high. Critical issues may regard the importance of good cavity conformance and adequate balloon‐skin distance in avoiding possible dose excesses to the skin. For a selected patient group, this could be a valid alternative to conventional whole breast irradiation.

Novel 10-fraction breast irradiation in prone and supine position: technical, dosimetric and clinical evaluation.

Background The aim of this study was to evaluate retrospectively the planned dose distribution and acute toxicity of adjuvant hypofractionated whole breast radiotherapy (RT) delivered in the prone vs. supine position. Methods Twenty-four patients were enrolled; 12 underwent adjuvant RT with a supine setup and 12 with a prone setup. We included patients according to breast volume (≥500 mL), disease stage (≤pT2/pN1), and clinical/biological features. Patients received a regimen of 35 Gy in 10 fractions for 2.5 weeks, and a concomitant boost of 3/4 Gy in 1 fraction/week. Target coverage was assessed by volume, V90, V95, V100, V103 and V105. Heart, LADCA and ipsilateral lung doses were evaluated according to volume, maximum dose, mean dose, V14, V10 and V5. We evaluated acute skin toxicity during RT, at the end of treatment, and after 1 month according to RTOG scales. Results Radiobiological equivalence was warranted with satisfactory BED values: considering α/β = 4 for breast cancer, the 10-fraction schedule equaled 74 or 77 Gy depending on the boost dose (3 Gy vs. 4 Gy, respectively). Toxicity was low and similar for supine and prone treatments. Dose sparing was significant in the ipsilateral lung in the prone position (median Dmax: 28.7 Gy vs. 38.4 Gy; median Dmean: 0.8 Gy vs. 6.3 Gy; median V14:0.6% vs. 13.5%; median V5: 0 vs. 19.3%, p<0.001). Conclusions This novel 10-fraction schedule is feasible and well tolerated; the prone position allows better saving of OARs, with a statistically significant value for the ipsilateral lung.

The application of GEANT4 simulation code to the verification of a brachytherapy calibration procedure

The MicroSelectron High Dose Rate (HDR) system, installed at the National Institute for Cancer Research of Genova, uses a high activity Iridium-192 source which can be programmed to stay in specific positions for defined periods of time. The source consists of a cylinder of 0.6 mm of diameter and 3.5 mm length which is packed into a stainless steel tube of 1.1. mm of diameter and 5.0 mm length.

Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up.

AIMS AND BACKGROUND To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed. METHODS Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity. RESULTS Median follow-up was 80.5 months (range, 60-98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy-seven percent of the patients were satisfied with their cosmetic results. CONCLUSIONS Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis

PURPOSE This paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures. METHODS 42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement. RESULTS The average dose homogeneity index was 1.04 ± 0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ± 0.2 and 50 ± 14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity. CONCLUSIONS Homogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.

Comparison of local recurrence among early breast cancer patients treated with electron intraoperative radiotherapy vs hypofractionated photon radiotherapy An observational study

Purpose To evaluate local recurrence (LR) in women with early breast cancer (BC) who underwent intraoperative radiation therapy with electrons particles (IORT-E) or adjuvant hypofractionated external radiotherapy (HYPOFX). Materials and methods We retrospectively analyzed 470 patients with early BC treated at our center from September 2009 to December 2012. 235 women were treated with breast-conserving surgery and immediate IORT-E (21 Gy/1 fraction) while 235 patients underwent wide excision followed by hypofractionated whole-breast irradiation. Radiotherapy modality was chosen according to an individualized decision based on tumor features, stage, technical feasibility, age, and acceptance to be enrolled in the IORT-E group. Results After a median follow-up of 6 years, we observed 8 (3.4%) and 1 (0.42%) LR in the IORT-E and in the HYPOFX group (p = 0.02), respectively. The two groups differed in the prevalence of clinical characteristics (p < 0.05): age, tumor size, surgical margins, receptors, ki67, and histology. 4 and 1 woman in the IORT-E and HYPOFX group died of BC, respectively (p = 0.167). OS and DFS hazard ratio [HR] were 2.14 (95% IC, 1.10–4.15) and 2.09 (95% IC, 1.17–3.73), respectively. Conclusion Our comparison showed that IORT-E and HYPOFX are two effective radiotherapy modalities after conservative surgery in early BC. However, at 6 years a significant higher rate of LR occurred in patients submitted to IORT-E with respect to HYPOFX. This finding may be correlated to some subsets of patients who, depending on the biological characteristics of the BC, may be less suitable to IORT-E.