Flavia Serafini

Sooner or Later? Outcome Analysis of 431 Prostate Cancer Patients Treated With Postoperative or Salvage Radiotherapy

PURPOSE To evaluate the outcome of postoperative radiotherapy (PORT) and salvage RT (SART) using a three-dimensional conformal two-dynamic arc (3D-ART) or 3D six-field technique in 431 prostate cancer patients. METHODS AND MATERIALS Of the 431 patients, 258 underwent PORT (started <6 months after radical prostatectomy) and 173 underwent SART because of biochemical failure after radical prostatectomy. The median patient age, preoperative prostate-specific antigen level, and Gleason score was 66 years, 9.4 ng/mL, and 7, respectively. The median radiation dose was 70 Gy in 35 fractions for both PORT and SART. The 3D six-field and 3D-ART techniques were used in 25.1% and 74.9% of patients, respectively. Biochemical failure was defined as a post-RT prostate-specific antigen nadir plus 0.1 ng/mL. RESULTS Acute toxicity included rectal events (PORT, 44.2% and 0.8% Grade 1-2 and Grade 3, respectively; SART, 42.2% and 1.2% Grade 1-2 and Grade 3, respectively) and urinary events (PORT, 51.2% and 2.3% Grade 1-2 and Grade 3-4, respectively; SART, 37.6% and 0% Grade 1-2 and Grade 3, respectively). Late toxicity also included rectal events (PORT, 14.7% and 0.8% Grade 1-2 and Grade 3-4, respectively; SART, 15.0% and 0.6% Grade 1-2 and Grade 3, respectively) and urinary events (PORT, 28.3% and 3.7% Grade 1-2 and Grade 3-4, respectively; SART, 19.3% and 0.6% Grade 1-2 and Grade 3, respectively). After a median follow-up of 48 months, failure-free survival, including biochemical and clinical failure, was significantly longer in the PORT patients (79.8% vs. 60.5%, p < 0.0001). Multivariate analysis showed that a prostate-specific antigen level postoperatively but before RT of >/=0.2 ng/mL (p < 0.001), Gleason score >6 (p = 0.025) and use of preoperative androgen deprivation (p = 0.002) correlated significantly with shorter failure-free survival. Multivariate analysis showed that PORT and the 3D-ART technique correlated with greater late urinary toxicity. CONCLUSION PORT and early referral for SART offer better disease control after radical prostatectomy. The greater urinary toxicity occurring after PORT and 3D-ART requires further investigation to improve the therapeutic index.

CORRELATION BETWEEN ACUTE AND LATE TOXICITY IN 973 PROSTATE CANCER PATIENTS TREATED WITH THREE-DIMENSIONAL CONFORMAL EXTERNAL BEAM RADIOTHERAPY

PURPOSE To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. METHODS AND MATERIALS Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. RESULTS Multivariate analysis showed that age </=65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). CONCLUSION The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation

OBJECTIVES To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. MATERIALS AND METHODS One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. RESULTS All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT (P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT (P = 0.001) and higher PSA (P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. CONCLUSIONS The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.

A double-blind, randomised, vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin: interim analysis

Our aim was to assess the efficacy of MAS065D, a non-steroidal water-in-oil cream, in preventing and limiting skin reactions caused by radiation therapy (RT). 40 women treated with conservative breast cancer surgery followed by radiotherapy, were randomised to receive MAS065D (22 pts) or vehicle (18 pts). Radiotherapy was delivered in 20 fractions: 2.25 Gy to the whole breast plus a concomitant boost of 0.25 Gy to the tumour bed up to a total dose of 50 Gy. Evaluations of skin toxicity, erythema, and subjective symptoms were carried out weekly and 3 weeks after treatment completion. A statistically significant difference between vehicle and MAS065D groups was recorded regarding the maximum severity of skin toxicity (p < 0.0001), burning within the radiation field (p = 0.039) and desquamation (p = 0.02), in favour of the latter. We conclude that MAS065D may be considered a safe and effective treatment in the prevention and minimization of skin reactions and associated symptoms.

Deep inspiration breath‐hold technique guided by an opto‐electronic system for extracranial stereotactic treatments

The purpose of this work was to evaluate the intrapatient tumor position reproducibility in a deep inspiration breath‐hold (DIBH) technique based on two infrared optical tracking systems, ExacTrac and ELITETM, in stereotactic treatment of lung and liver lesions. After a feasibility study, the technique was applied to 15 patients. Each patient, provided with a real‐time visual feedback of external optical marker displacements, underwent a full DIBH, a free‐breathing (FB), and three consecutive DIBH CT‐scans centered on the lesion to evaluate the tumor position reproducibility. The mean reproducibility of tumor position during repeated DIBH was 0.5±0.3mm in laterolateral (LL), 1.0±0.9mm in anteroposterior (AP), and 1.4±0.9mm in craniocaudal (CC) direction for lung lesions, and 1.0±0.6mm in LL, 1.1±0.5mm in AP, and 1.2±0.4mm in CC direction for liver lesions. Intra‐and interbreath‐hold reproducibility during treatment, as determined by optical markers displacements, was below 1 mm and 3 mm, respectively, in all directions for all patients. Optically‐guided DIBH technique provides a simple noninvasive method to minimize breathing motion for collaborative patients. For each patient, it is important to ensure that the tumor position is reproducible with respect to the external markers configuration. PACS numbers: 87.53.Ly, 87.55.km

Physical and clinical implications of radiotherapy treatment of prostate cancer using a full bladder protocol

PurposeTo assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA).Patients and MethodsA total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose–volume histograms (DVH).ResultsCTV shifts were negligible in the laterolateral and superior–inferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior–posterior direction (95% CI, 0.83–4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95–99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose–volume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge.ConclusionHaving a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.ZusammenfassungZielEvaluierung der dosimetrischen und klinischen Implikationen bei Anwendung des Gefüllte-Blase-(FB-)Protokolls für die Behandlung des lokalisierten Prostatakarzinoms (PCA).Patienten und Methoden26 Patienten wurden für die vorliegende Studie ausgewählt. Sie unterzogen sich zwei Serien von CT-Scans: am Tag der Simulation und nach der Strahlendosis von 40 Gy. Jede Serie bestand aus zwei aufeinanderfolgenden Scans: mit gefüllter (FB) und mit leerer Blase (EB). Die Konturierung der CTVs und OARs wurden verglichen, um die Organbewegung abzuschätzen. Die Behandlungspläne wurden hinsichtlich Dosis und DVH verglichen.ErgebnisseDie CTV-Verschiebungen waren vernachlässigbar in laterolateraler und superior-inferiorer Richtung (maximale Verschiebung: 1,85 mm). Größere Verschiebungen wurden in anterior-posteriorer Richtung dokumentiert (0,83–4,41 mm; 95%-CI). In dosimetrischer Hinsicht sind die Verschiebungen geringfügig: Die minimale CTV-Dosis lag bei 98,5% (95– 99%, Median, 95% -CI). Der potentielle Vorteil hinsichtlich der GU-Toxizität bei Anwendung des FB-Behandlungsprotokolls war messbar: Das Verhältnis der Dosis-Volumen-Punkte (aus unserem Protokoll) bei gefüllter bzw. leerer Blase lag unter 0,61, mit Ausnahme der höheren Dosisbereiche, wo die DVHs konvergieren.SchlussfolgerungFB während der Strahlentherapie hat keinen Einfluss auf die Wirksamkeit der Behandlung, bewirkt jedoch günstigere DVHs und niedrigere GU-Toxizität.

Physikalische und klinische Implikationen der Behandlung bei gefüllter Blase in der Strahlentherapie des Prostatakarzinoms

PurposeTo assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA).Patients and MethodsA total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose–volume histograms (DVH).ResultsCTV shifts were negligible in the laterolateral and superior–inferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior–posterior direction (95% CI, 0.83–4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95–99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose–volume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge.ConclusionHaving a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.ZusammenfassungZielEvaluierung der dosimetrischen und klinischen Implikationen bei Anwendung des Gefüllte-Blase-(FB-)Protokolls für die Behandlung des lokalisierten Prostatakarzinoms (PCA).Patienten und Methoden26 Patienten wurden für die vorliegende Studie ausgewählt. Sie unterzogen sich zwei Serien von CT-Scans: am Tag der Simulation und nach der Strahlendosis von 40 Gy. Jede Serie bestand aus zwei aufeinanderfolgenden Scans: mit gefüllter (FB) und mit leerer Blase (EB). Die Konturierung der CTVs und OARs wurden verglichen, um die Organbewegung abzuschätzen. Die Behandlungspläne wurden hinsichtlich Dosis und DVH verglichen.ErgebnisseDie CTV-Verschiebungen waren vernachlässigbar in laterolateraler und superior-inferiorer Richtung (maximale Verschiebung: 1,85 mm). Größere Verschiebungen wurden in anterior-posteriorer Richtung dokumentiert (0,83–4,41 mm; 95%-CI). In dosimetrischer Hinsicht sind die Verschiebungen geringfügig: Die minimale CTV-Dosis lag bei 98,5% (95– 99%, Median, 95% -CI). Der potentielle Vorteil hinsichtlich der GU-Toxizität bei Anwendung des FB-Behandlungsprotokolls war messbar: Das Verhältnis der Dosis-Volumen-Punkte (aus unserem Protokoll) bei gefüllter bzw. leerer Blase lag unter 0,61, mit Ausnahme der höheren Dosisbereiche, wo die DVHs konvergieren.SchlussfolgerungFB während der Strahlentherapie hat keinen Einfluss auf die Wirksamkeit der Behandlung, bewirkt jedoch günstigere DVHs und niedrigere GU-Toxizität.

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.

Image-guided radiotherapy for prostate cancer using 3 different techniques: localization data of 186 patients

Aims and Background This study evaluates 3 different imaging modalities—ultrasound (US), stereoscopic X-ray imaging of implanted markers (Visicoils) (X-ray), and kV cone-beam computed tomography (CBCT)—to assess interfraction and intrafraction localization error during conformal radiation therapy of prostate cancer. Methods and Study Design The study population consisted of 186 consecutive prostate cancer patients treated with an image-guided radiotherapy (IGRT) hypofractionated protocol using 3 techniques: 32 with X-ray, 30 with CBCT, and 124 with US. Treatment dose of 70.2 Gy was delivered in 26 fractions with a conformal dynamic arcs technique. Interfraction prostate localization errors were determined for the 3 techniques. Moreover, interfraction and intrafraction prostate motion in terms of translations and rotations, as well as residual errors, were determined with X-ray. Results The systematic and random components of the prostate localization errors were as follows: (1) with X-ray 3.0 ± 3.4, 2.3 ± 2.7, 1.8 ± 2.3 mm in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions and 1.8° ± 1.2°, 2.3° ± 1.5°, 2.7° ± 3.1°, for the yaw, roll, and pitch rotations; (2) with CBCT3.5 ± 4.2, 3.3 ± 3.3, 2.5 ± 3.1 mm in AP, SI, and LR directions; (3) with US 3.7 ± 4.7, 3.4 ± 4.3, 2.3 ± 3.5 mm in AP, SI, and LR directions. Residual errors with X-ray were less than 1 mm in all directions. Intrafraction prostate motion of less than 0.5 mm in LR and of the order of 1 mm in AP and SI directions was found. This led to a significant reduction of the margins, potentially important for dose escalation studies. Conclusions Daily on-line IGRT with stereoscopic X-ray imaging allowed a consistent PTV margin reduction considering residual interfraction prostate localization error and intrafraction motion. X-ray offers the best compromise among accuracy, reliability, dose to the patient, and time investment for daily IGRT treatment of prostate.

Urinary bladder preservation for muscle-invasive bladder cancer: a survey among radiation oncologists of Lombardy, Italy

Aims and Background Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy. Methods and Study Design A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy. Results Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation. Conclusions Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.