Elisabetta Ponti

Standard or hypofractionated radiotherapy in the postoperative treatment of breast cancer: a retrospective analysis of acute skin toxicity and dose inhomogeneities

BackgroundTo identify predictive factors of radiation-induced skin toxicity in breast cancer patients by the analysis of dosimetric and clinical factors.Methods339 patients treated between January 2007 and December 2010 are included in the present analysis. Whole breast irradiation was delivered with Conventional Fractionation (CF) (50Gy, 2.0/day, 25 fractions) and moderate Hypofractionated Schedule (HS) (44Gy, 2.75Gy/day, 16 fractions) followed by tumour bed boost. The impact of patient clinical features, systemic treatments and, in particular, dose inhomogeneities on the occurrence of different levels of skin reaction has been retrospectively evaluated.ResultsG2 and G3 acute skin toxicity were 42% and 13% in CF patients and 30% and 7.5% in HS patients respectively. The retrieval and revaluation of 200 treatment plans showed a strong correlation between areas close to the skin surface, with inhomogeneities >107% of the prescribed dose, and the desquamation areas as described in the clinical records.ConclusionsIn our experience dose inhomogeneity underneath G2 – G3 skin reactions seems to be the most important predictor for acute skin damage and in these patients more complex treatment techniques should be considered to avoid skin damage. Genetic polymorphisms too have to be investigated as possible promising candidates for predicting acute skin reactions.

Salvage Stereotactic Body Radiotherapy for Patients With Prostate Cancer With Isolated Lymph Node Metastasis: A Single-Center Experience

OBJECTIVE The study objective was to evaluate the efficacy of salvage stereotactic body radiation therapy (SBRT) as a treatment modality in patients with oligometastatic prostate cancer. METHODS A total of 16 patients with 18 isolated lymph nodes with recurrent prostate cancer were treated between 2008 and 2013. All patients underwent [(11)C] choline-positron emission tomography/computed tomography before SBRT. Two patients were treated in different sessions for metachronous metastases. Ten patients received androgen deprivation therapy concomitant to SBRT (total dose range, 12-35 Gy, delivered in 1-5 daily fractions). RESULTS The mean and median follow-up periods were 29.35 and 29.38 months, respectively (range, 6.3-68.8 months). Local disease control and a decrease in serum prostate-specific antigen were obtained in 15 of 16 patients (94%); only 1 patient had an in-field progression. In the 6 patients without androgen deprivation therapy at the time of SBRT, the mean time of deferment of palliative androgen deprivation therapy was 23.7 months (range, 2.5-51 months). At last follow-up, 8 patients had active prostate cancer disease; biochemical progression was observed after a mean time of 7.9 months from the completion of SBRT. One patient died of disease. Overall survival was 94%. The 2-year biochemical relapse-free survival was 44%. Late toxicity (gastrointestinal) was observed in 1 patient who had a G3 toxicity. CONCLUSIONS SBRT seems to be safe, effective, and minimally invasive in the eradication of limited nodal recurrence from oligometastatic prostate cancer. SBRT is well tolerated by patients with low toxicity and yielded a local control of the disease.

Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for brain metastases

BackgroundTo assess interfraction translational and rotational setup errors, in patients treated with image-guded hypofractionated stereotactic radiotherapy, immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates.Methods37 patients with 47 brain metastases were treated with hypofractionated stererotactic radiotherapy. All patients were immobilized with a combination of a thermoplastic mask and a bite-block fixed to a stereotactic frame support. Daily cone-beam CT scans were acquired for every patient before the treatment session and were matched online with planning CT images, for 3D image registration. The mean value and standard deviation of all translational (X, Y, Z) and rotational errors (θx, θy, θz) were calculated for the matching results of bone matching algorithm.ResultsA total of 194 CBCT scans were analyzed. Mean +/- standard deviation of translational errors (X, Y, Z) were respectively 0.5 +/- 1.6 mm (range -5.7 and 5.9 mm) in X; 0.4 +/- 2.7 mm (range -8.2 and 12.1 mm) in Y; 0.4 +/- 1.9 mm (range -7.0 and 14 mm) in Z; median and 90th percentile were respectively within 0.5 mm and 2.4 mm in X, 0.3 mm and 3.2 mm in Y, 0.3 mm and 2.2 mm in Z. Mean +/- standard deviation of rotational errors (θx, θy, θz) were respectively 0.0 degrees+/- 1.3 degrees (θx) (range -6.0 degrees and 3.1 degrees); -0.1 degrees +/- 1.1 degrees (θy) (range -3.0 degrees and 2.4 degrees); -0.6 degrees +/- 1.4 degrees (θz) (range -5.0 degrees and 3.3 degrees). Median and 90th percentile of rotational errors were respectively within 0.1 degrees and 1.4 degrees (θx), 0.0 degrees and 1.2 degrees (θy), 0.0 degrees and 0.9 degrees (θz). Mean +/- SD of 3D vector was 3.1 +/- 2.1 mm (range 0.3 and 14.9 mm); median and 90th percentile of 3D vector was within 2.7 mm and 5.1 mm.ConclusionsHypofractionated stereotactic radiotherapy have the significant limitation of uncertainty in interfraction repeatability of the patient setup; image-guided radiotherapy using cone-beam computed tomography improves the accuracy of the treatment delivery reducing set-up uncertainty, giving the possibility of 3-dimensional anatomic informations in the treatment position.

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy

CONTEXT Stereotactic body radiotherapy (SBRT) is emerging as a treatment option in patients affected by oligorecurrent prostate cancer disease limited to lymph nodes, a subgroup of patients who would otherwise be treated only with androgen deprivation therapy (ADT). OBJECTIVE To perform a systematic review of SBRT for oligorecurrent prostate cancer limited to lymph nodes. EVIDENCE ACQUISITION We performed a systematic review of PubMed/Medline in October 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). We searched for studies reporting on biochemical or clinical progression and/or toxicity or complications of SBRT. Reports were excluded if these end points could not be ascertained or separately analyzed, or if insufficient details were provided. EVIDENCE OF SYNTHESIS A total of 363 patients from nine studies were collected. Of these patients, 211 were treated with SBRT for a total of 270 lymph nodes. With an alpha-beta ratio of 3 Gy, the biologically effective dose in fractionated SBRT was >100 Gy in all studies (range, 88-216 Gy). With a median follow-up of 19.23 mo, local control was achieved in 98.1% of patients. Median progression-free survival (defined as biochemical and/or radiological progression) was 22.5 mo (range, 11-30 mo). Information about ADT during SBRT was available in 281 patients, of whom 114 (40.5%) were on ADT during SBRT, and the duration of hormone therapy ranged from 1 to 17.5 mo. Median ADT-free survival was 32.8 mo (range, 25-44 mo). About toxicity, Common Terminology Criteria for Adverse Events toxicity scale was most used. Acute and/or late grade ≥2 toxicity was reported in only 5.6% of patients, and no patient developed grade 4 toxicity. CONCLUSIONS SBRT seems to be promising in lymph node oligorecurrent prostate cancer, although there is a weak level of evidence to support such investigational treatment, which is currently based on retrospective studies of single-institution or pooled experiences. ADT-free survival is an interesting end point, which needs to be investigated. PATIENT SUMMARY We performed a systematic review to assess outcomes and toxicity of stereotactic body radiotherapy (SBRT) for patients affected by oligorecurrent prostate cancer limited to lymph nodes. We concluded that SBRT is a promising therapy in this setting, but it needs to be validated in randomized controlled trials.

Oligometastatic cancer: stereotactic ablative radiotherapy for patients affected by isolated body metastasis

Abstract Background: To evaluate the outcome of patients affected by a single isolated body metastasis treated with stereotactic body radiotherapy (SBRT). Material and methods: Seven-eight patients were treated with SBRT for isolated body metastasis. The most frequent primary tumor was prostate cancer (28.2%), followed by colorectal cancer (23.1%) and lung cancer (20.5%). Median age at diagnosis of oligometastatic disease was 70 years (range 47–88). Median Karnofsky Performance Status (KPS) was 90 (range 70–100). The most common SBRT fractionation scheme was 5 × 7 Gy (total dose 35 Gy). Response to radiotherapy was determined according to RECIST criteria v1.1. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The survival analysis was performed with the Kaplan–Meier method. The correlation between time actuarial incidence and clinical parameters was studied, and the Kaplan–Meier method of log-rank test was applied. Results: With a median follow-up of 22.68 months, local control was achieved in 89.7% of the cases. The two-year overall survival (OS) and progression-free survival (PFS) were 68% and 42%, respectively. On univariate analysis, KPS ≥80 is predictive for improved OS (p = .001) and PFS (p = .001). Acute toxicity of grade ≥2 occurred in eight (10.2%) patients and late grade ≥2 toxicity in five (6.4%) patients. Conclusions: Ablative radiotherapy in ‘early oligometastatic state’ is a safe, effective and minimally invasive treatment modality. A good performance status (KPS ≥80) seems to influence the clinical outcome.

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular, we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V60 and V50 (p = 0.001) and in bladder V70 and V65 (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.

Acute and Late Toxicity after Three-Dimensional Conformal Image-Guided Radiotherapy for Localized Prostate Cancer

We evaluated the clinical impact of a high definition micro-multileaf collimator and a linac-integrated cone-beam computed tomography in 142 patients treated with conformal radiotherapy for localized prostate cancer to a total dose of 76 Gy. Details on treatment toxicity and tumour control were collected. The 3 years biochemical relapse-free survival was 90%. Acute and late gastrointestinal toxicities were low (3-year actuarial late toxicity of 11.2%). Acute genitourinary toxicity was relatively high, the 3-year actuarial genitourinary late toxicity was 12%. Conformal image-guided radiotherapy for localized prostate cancer leads to low rates of late toxicity with a high rate of tumor control.

Intra-parotid facial nerve schwannoma with intra-temporal extension; a case report. Is there a role for stereotactic radiotherapy?☆

Facial nerve schwannoma (FNS) is an extremely rare benign tumour that may arise anywhere along the course of the facial nerve; the standard treatment is total removal via microsurgery. Stereotactic radiotherapy has been shown to be effective in the treatment of skull base tumours, in particular for acoustic neuromas; it is interesting to notice that also the few data existing in literature about the use of radiotherapy for non acoustic schwannomas show an excellent local control rate and few adverse effects. Here we report a case of facial nerve neuroma, involving the nerve sheath from the geniculate ganglion to the parotid gland, treated with fractionated stereotactic radiotherapy after debulking surgery.

Intensity-modulated and 3D-conformal radiotherapy in hypofractionated prostate cancer treatment using Elekta Beam ModulatorTM micro-MLC: A dosimetric analysis

External beam radiotherapy is a therapeutic option for the radical treatment of localized prostate cancer [1]. High-dose conformal radiotherapy with conventional 2 Gy daily fractions to a total dose of 74–80 Gy is the standard of care, with an overall treatment time of 7–8 weeks [2]. However, hypofractionated radiation therapy (HFRT) for localized prostate cancer is becoming very attractive and several phase 3 randomized controlled trials have demonstrated the safety of moderate hypofractionation [3–8]. Many of these trials employed intensity-modulated radiation therapy (IMRT) with image-guidance in order to deliver the hypofractionated treatment [4,6,8]. However, three-dimensional conformal radiotherapy (3DCRT) has been used too [3,5,7]. Respect to 3DCRT, IMRT increases the dose gradient near the structures maximizing the dose to the tumor while sparing normal tissue. However, it requires more time for planning and for daily treatment delivery. Micro-multi-leaf collimators (micro-MlCs) offer the potential to improve target dose distribution and normal tissues sparing both in 3DCRT and in IMRT [9,10]. The Elekta beam ModulatorTM is a high definition multileaf collimator (4 mm leaf width at the isocenter) integrated on the Elekta synergy s linear accelerator (Elekta Oncology systems, Crawley, UK) [11]. The purpose of this dosimetric study is to evaluate the impact of the Elekta beam ModulatorTM micro-MlC in the development of IMRT and 3DCRT plans, using two different hypofractionation schedules for prostate cancer radiotherapy.

Is the in vivo dosimetry with the OneDosePlusTM system able to detect intra-fraction motion? A retrospective analysis of in vivo data from breast and prostate patients

BackgroundThe OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer.MethodsAn Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2).ResultsThe ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session.ConclusionsThe method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements.