E. Rondi

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes

Background The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression‐free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Patients and Methods Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3‐month PSA decrease from pre‐SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Results Median follow‐up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In‐field progression occurred in 12 lesions (9.7%). Two‐year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. Conclusion SBRT is safe and offers good in‐field control. At 2 years after SBRT, 1 of 3 patients is progression‐free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD. Micro‐Abstract Stereotactic body radiotherapy is being investigated in nodal oligometastatic prostate cancer recurrences as an alternative to systemic treatment. This approach yields excellent in‐field control and a low toxicity profile. In selected cases, this approach might also defer palliative androgen deprivation therapy.

Prospective Study on the Dose Distribution to the Acoustic Structures during Postoperative 3D Conformal Radiotherapy for Parotid Tumors Dosimetric and Audiometric Aspects

Background and Purpose:To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT).Methods and Materials:A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose–volume histograms were plotted.Results:Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy).Conclusion:Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings.Hintergrund und Ziel:Dosisverteilungsanalyse im Hörorgan für Patienten mit 3-dimensionaler konformaler Radiotherapie (3D-CRT) nach Parotidektomie.Patienten und Methoden:17 Patienten erhielten eine 3D-CRT nach radikaler Parotidektomie (mittlere Dosis: 63 Gy). Die audiometrische Evaluierung umfasste Tonaudiometrie und Tympanometrie vor, 3, 6 und 24 Monate nach der Radiotherapie. Die Ohrstrukturen wurden im Planungscomputertomogramm konturiert. Die mittleren und maximalen Gesamtstrahlendosen wurden berechnet und die Dosis-Volumen-Histogramme ausgewertet.Ergebnisse:Vor Radiotherapie waren die medianen audiometrischen Ausgangsgrenzwerte normal. 3 Monate nach der RT zeigten sich bei 3 Patienten Unterdruck im Mittelohr und/oder Effusion, die nach 6 Monaten vollständig verschwanden. Während des 2-jährigen Follow-up zeigte keines der Ohren perzeptive Hörverluste bei Sprachfrequenzen. Die mittleren Dosen im äußeren ipsilateralen Gehörgang, in Mastoidzellen, im Trommelfell, in der Eustachischen Röhre, in Bogengängen und Cochlea waren 44,8 Gy, 39,0 Gy, 30,9 Gy, 33,0 Gy, 19,6 Gy und 19,2 Gy. Die Dosen im kontralateralen Ohr waren vernachlässigbar, abgesehen von der Eustachischen Röhre (bis zu 28,2 Gy).Schlussfolgerung:3D-CRT nach Parotidektomie ist mit relativ geringen Dosen im Hörorgan verbunden. Audiometrie nach der RT zeigte keine Hörschäden an. Längere Folgestudien und größere Patientenserien sind gerechtfertigt, um diese vorläufigen Ergebnisse zu bestätigen.

Rationale and protocol of AIRC IG-13218, short-term radiotherapy for early prostate cancer with concomitant boost to the dominant lesion.

Introduction Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options. Methods The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome). Results The study is ongoing, and we expect to complete recruitment by the end of 2016. Conclusions Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective. Trial registration ClinicalTrials.gov identifier: NCT01913717.

Prospective study on the dose distribution to the acoustic structures during postoperative 3D conformal radiotherapy for parotid tumors

Background and Purpose:To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT).Methods and Materials:A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose–volume histograms were plotted.Results:Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy).Conclusion:Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings.Hintergrund und Ziel:Dosisverteilungsanalyse im Hörorgan für Patienten mit 3-dimensionaler konformaler Radiotherapie (3D-CRT) nach Parotidektomie.Patienten und Methoden:17 Patienten erhielten eine 3D-CRT nach radikaler Parotidektomie (mittlere Dosis: 63 Gy). Die audiometrische Evaluierung umfasste Tonaudiometrie und Tympanometrie vor, 3, 6 und 24 Monate nach der Radiotherapie. Die Ohrstrukturen wurden im Planungscomputertomogramm konturiert. Die mittleren und maximalen Gesamtstrahlendosen wurden berechnet und die Dosis-Volumen-Histogramme ausgewertet.Ergebnisse:Vor Radiotherapie waren die medianen audiometrischen Ausgangsgrenzwerte normal. 3 Monate nach der RT zeigten sich bei 3 Patienten Unterdruck im Mittelohr und/oder Effusion, die nach 6 Monaten vollständig verschwanden. Während des 2-jährigen Follow-up zeigte keines der Ohren perzeptive Hörverluste bei Sprachfrequenzen. Die mittleren Dosen im äußeren ipsilateralen Gehörgang, in Mastoidzellen, im Trommelfell, in der Eustachischen Röhre, in Bogengängen und Cochlea waren 44,8 Gy, 39,0 Gy, 30,9 Gy, 33,0 Gy, 19,6 Gy und 19,2 Gy. Die Dosen im kontralateralen Ohr waren vernachlässigbar, abgesehen von der Eustachischen Röhre (bis zu 28,2 Gy).Schlussfolgerung:3D-CRT nach Parotidektomie ist mit relativ geringen Dosen im Hörorgan verbunden. Audiometrie nach der RT zeigte keine Hörschäden an. Längere Folgestudien und größere Patientenserien sind gerechtfertigt, um diese vorläufigen Ergebnisse zu bestätigen.

Set-up errors in head and neck cancer patients treated with intensity modulated radiation therapy: Quantitative comparison between three-dimensional cone-beam CT and two-dimensional kilovoltage images

OBJECTIVES To compare the patient set-up error detection capabilities of three-dimensional cone beam computed tomography (3D-CBCT) and two-dimensional orthogonal kilovoltage (2D-kV) techniques. METHODS 3D-CBCT and 2D-kV projections were acquired on 29 head-and-neck (H&N) patients undergoing Intensity Modulated Radiotherapy (IMRT) on the first day of treatment (time 0) and after the delivery of 40 Gy and 50 Gy. Set-up correction vectors were analyzed after fully automatic image registration as well as after revision by radiation oncologists. The dosimetric effects of the different sensitivities of the two image guidance techniques were assessed. RESULTS A statistically significant correlation among detected set-up deviations by the two techniques was found along anatomical axes (0.60 < ρ < 0.72, p < 0.0001); no correlation was found for table rotation (p = 0.41). No evidence of statistically significant differences between the indications provided along the course of the treatment was found; this was also the case when full automatic versus manually refined correction vectors were compared. The dosimetric effects analysis revealed slight statistically significant differences in the median values of the maximum relative dose to mandible, spinal cord and its 5 mm Planning Organ at Risk Volume (0.95%, 0.6% and 2.45%, respectively), with higher values (p < 0.01) observed when 2D-kV corrections were applied. CONCLUSION A similar sensitivity to linear set-up errors was observed for 2D-kV and 3D-CBCT image guidance techniques in our H&N patient cohort. Higher rotational deviations around the table vertical axis were detected by the 3D-CBCT with respect to the 2D-kV method, leading to a consistent better sparing of organs at risk.

What is the price of functional surgical organ preservation in local-regionally advanced supraglottic cancer? Long-term outcome for partial laryngectomy followed by radiotherapy in 32 patients

AIMS AND BACKGROUND To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor. METHODS AND STUDY DESIGN A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied. RESULTS The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy. CONCLUSIONS We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects.

Prone breast radiotherapy in a patient with early stage breast cancer and a large pendulous breast.

In women with large and pendulous breasts postoperative radiotherapy in the supine position could represent a technical challenge because of the resulting dose inhomogeneity and the large amount of lung and heart receiving a high percentage of the prescribed dose. Breast-conserving surgery is therefore relatively contraindicated in these patients. Alternative positions for radiation therapy treatment have been proposed, and prone breast irradiation in particular has been recognized as a useful alternative to conventional treatment in the supine position. We report the case of a large-breasted patient treated in prone position in our radiation therapy division.

Multimodal image registration for the identification of dominant intraprostatic lesion in high-precision radiotherapy treatments

PURPOSE The integration of CT and multiparametric MRI (mpMRI) is a challenging task in high-precision radiotherapy for prostate cancer. A simple methodology for multimodal deformable image registration (DIR) of prostate cancer patients is presented. METHODS CT and mpMRI of 10 patients were considered. Organs at risk and prostate were contoured on both scans. The dominant intraprostatic lesion was additionally delineated on MRI. After a preliminary rigid image registration, the voxel intensity of all the segmented structures in both scans except the prostate was increased by a specific amount (a constant additional value, A), in order to enhance the contrast of the main organs influencing its position and shape. 70 couples of scans were obtained by varying A from 0 to 800 and they were subsequently non-rigidly registered. Quantities derived from image analysis and contour statistics were considered for the tuning of the best performing A. RESULTS A = 200 resulted the minimum enhancement value required to obtain statistically significant superior registration results. Mean centre of mass distance between corresponding structures decreases from 7.4 mm in rigid registration to 5.3 mm in DIR without enhancement (DIR-0) and to 2.7 mm in DIR with A = 200 (DIR-200). Mean contour distance was 2.5, 1.9 and 0.67 mm in rigid registration, DIR-0 and DIR-200, respectively. In DIR-200 mean contours overlap increases of +13 and +24% with respect to DIR-0 and rigid registration, respectively. CONCLUSION Contour propagation according to the vector field resulting from DIR-200 allows the delineation of dominant intraprostatic lesion on CT scan and its use for high-precision radiotherapy treatment planning. Advances in knowledge: We investigated the application of a B-spline, mutual information-based multimodal DIR coupled with a simple, patient-unspecific but efficient contrast enhancement procedure in the pelvic body area, thus obtaining a robust and accurate methodology to transfer the functional information deriving from mpMRI onto a planning CT reference volume.

Validation of a pretreatment delivery quality assurance method for the CyberKnife Synchrony system

PURPOSE To evaluate the geometric and dosimetric accuracies of the CyberKnife Synchrony respiratory tracking system (RTS) and to validate a method for pretreatment patient-specific delivery quality assurance (DQA). METHODS An EasyCube phantom was mounted on the ExacTrac gating phantom, which can move along the superior-inferior (SI) axis of a patient to simulate a moving target. The authors compared dynamic and static measurements. For each case, a Gafchromic EBT3 film was positioned between two slabs of the EasyCube, while a PinPoint ionization chamber was placed in the appropriate space. There were three steps to their evaluation: (1) the field size, the penumbra, and the symmetry of six secondary collimators were measured along the two main orthogonal axes. Dynamic measurements with deliberately simulated errors were also taken. (2) The delivered dose distributions (from step 1) were compared with the planned ones, using the gamma analysis method. The local gamma passing rates were evaluated using three acceptance criteria: 3% local dose difference (LDD)/3 mm, 2%LDD/2 mm, and 3%LDD/1 mm. (3) The DQA plans for six clinical patients were irradiated in different dynamic conditions, to give a total of 19 cases. The measured and planned dose distributions were evaluated with the same gamma-index criteria used in step 2 and the measured chamber doses were compared with the planned mean doses in the sensitive volume of the chamber. RESULTS (1) A very slight enlargement of the field size and of the penumbra was observed in the SI direction (on average <1 mm), in line with the overall average CyberKnife system error for tracking treatments. (2) Comparison between the planned and the correctly delivered dose distributions confirmed the dosimetric accuracy of the RTS for simple plans. The multicriteria gamma analysis was able to detect the simulated errors, proving the robustness of their method of analysis. (3) All of the DQA clinical plans passed the tests, both in static and dynamic conditions. No statistically significant differences were found between static and dynamic cases, confirming the high degree of accuracy of the Synchrony RTS. CONCLUSIONS The presented methods and measurements verified the mechanical and dosimetric accuracy of the Synchrony RTS. Their method confirms the fact that the RTS, if used properly, is able to treat a moving target with great precision. By combining PinPoint ion chamber, EBT3 films, and gamma evaluation of dose distributions, their DQA method robustly validated the effectiveness of CyberKnife and Synchrony system.

Electron Beam Intraoperative Radiotherapy (ELIOT) in Pregnant Women with Breast Cancer: From in Vivo Dosimetry to Clinical Practice

Background: The aim of this study was to confirm our preliminary results with in vivo dosimetry in non-pregnant breast cancer patients receiving electron beam intraoperative radiotherapy (ELIOT) and to report on the first treatment in a pregnant woman. Patients and Methods: Following our previous experience, 5 non-pregnant patients receiving ELIOT to the tumor bed after breast-conserving surgery (BCS) were studied with thermoluminescent dosimeters positioned in the subdiaphragmatic region, within the uterus, and in the ovarian region. In December 2011, the first pregnant breast cancer patient underwent BCS and ELIOT (21 Gy at 90% isodose) during the 15th week of gestation. Results: The mean dose to the subdiaphragmatic external region in the 5 non-pregnant patients was 5.57 mGy, while pelvic measurements were below 1 mGy. The actual dosimetry of the pregnant patient showed a mean subdiaphragmatic dose of 4.34 mGy, a mean suprapubic dose of 1.64 mGy, and mean ovarian doses of 1.48 mGy (right-sided) and 1.44 mGy (left-sided). The expected dose to the fetus was estimated as 0.84 mGy (0.004% of the prescribed dose). Conclusion: ELIOT as an anticipated boost to the breast could be considered in pregnant women in the early second trimester, postponing whole-breast irradiation after delivery.