Cristina Garibaldi

Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer.

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

Transabdominal Ultrasonography, Computed Tomography and Electronic Portal Imaging for 3-Dimensional Conformal Radiotherapy for Prostate Cancer

Purpose:To evaluate the feasibility and accuracy of daily B-mode acquisition and targeting ultrasound-based prostate localization (BAT™) and to compare it with computed tomography (CT) and electronic portal imaging (EPI) in 3-dimensional conformal radiotherapy (3-D CRT) for prostate cancer.Patients and Methods:Ten patients were treated with 3-D CRT (72 Gy/30 fractions, 2.4 Gy/fraction, equivalent to 80 Gy/40 fractions, for α/β ratio of 1.5 Gy) and daily BAT-based prostate localization. For the first 5 fractions, CT and EPI were also performed in order to compare organ-motion and set-up error, respectively.Results:287 BAT-, 50 CT- and 46 EPI-alignments were performed. The average BAT-determined misalignments in latero-lateral, antero-posterior and cranio-caudal directions were –0.9 mm ± 3.3 mm, 1.0 mm ± 4.0 mm and –0.9 mm ± 3.8 mm, respectively. The differences between BAT- and CT-determined organ-motion in latero-lateral, antero-posterior and cranio-caudal directions were 2.7 mm ± 1.9 mm, 3.9 ± 2.8 mm and 3.4 ± 3.0 mm, respectively. Weak correlation was found between BAT- and CT-determined misalignments in antero-posterior direction, while no correlation was observed in latero-lateral and cranio-caudal directions. The correlation was more significant when only data of good image-quality patients were analyzed (8 patients).Conclusion:BAT ensures the relative positions of target are the same during treatment and in treatment plan, however, the reliability of alignment is patient-dependent. The average BAT-determined misalignments were small, confirming the prevalence of random errors in 3-D CRT. Further study is warranted in order to establish the clinical value of BAT.Ziel:Ziel dieser Studie ist es, die Möglichkeit und Genauigkeit der täglichen B-mode-Akquisition und zielgerichteten ultraschallbasierten Prostatapositionierung (BAT™) einzuschätzen und sie mit der Computertomographie (CT) und dem elektronischen Portal-Imaging (EPI) bei der 3D-konformalen Strahlentherapie (3D-CRT) des Prostatakrebses zu vergleichen.Patienten und Methodik:10 Patienten wurden mit 3D-CRT (72 Gy/30 Fraktionen, 2,4 Gy/Fraktion, äquivalent zu 80 Gy/40 Fraktionen, α/β-Verhältnis von 1,5 Gy ) und täglicher BAT behandelt. Für die ersten 5 Fraktionen wurden auch CT und EPI durchgeführt, um jeweils die Bewegung der Organe und die Set-up-Fehler zu vergleichen.Ergebnisse:287 BAT-, 50 CT- und 46 EPI-Positionierungen wurden durchgeführt. Der durchschnittliche BAT-Positionierungsfehler war jeweils –0,9 mm ± 3,3 mm, 1,0 mm ± 4,0 mm und –0,9 mm ± 3,8 mm in den latero-lateralen, anterior-posterioren und kraniokaudalen Richtungen. Die Unterschiede zwischen der BAT- und CT-Technik bei der Bestimmung der Organbewegung in den latero-lateralen, anterior-posterioren und kraniokaudalen Richtungen waren jeweils 2,7 mm ± 1,9 mm, 3,9 ± 2,8 mm und 3,4 ± 3,0 mm. Eine sehr geringe Korrelation zwischen BAT- und CT-Positionierungsungenauigkeit wurde nur für die anterior-posteriore Richtung gefunden (R = 0,29, p = 0,04). Die Korrelation war leicht besser, wenn nur die Patienten mit guter Bildqualität analysiert wurden (8 Patienten).Schlussfolgerung:BAT garantiert, dass die relative Position des Ziels dieselbe während der Behandlung und in dem Behandlungsplan ist, obwohl die Genauigkeit der Positionierung patientenabhängig ist. Die durchschnittlichen, mit BAT bestimmten, Positionierungsfehler waren klein und bestätigen, dass der statistische Fehler in 3D-CRT vorwiegend ist. Weitere Studien sind erforderlich, um den klinischen Wert von BAT festzustellen.

The updated ESTRO core curricula 2011 for clinicians, medical physicists and RTTs in radiotherapy/radiation oncology

INTRODUCTION In 2007 ESTRO proposed a revision and harmonisation of the core curricula for radiation oncologists, medical physicists and RTTs to encourage harmonised education programmes for the professional disciplines, to facilitate mobility between EU member states, to reflect the rapid development of the professions and to secure the best evidence-based education across Europe. MATERIAL AND METHODS Working parties for each core curriculum were established and included a broad representation with geographic spread and different experience with education from the ESTRO Educational Committee, local representatives appointed by the National Societies and support from ESTRO staff. RESULTS The revised curricula have been presented for the ESTRO community and endorsement is ongoing. All three curricula have been changed to competency based education and training, teaching methodology and assessment and include the recent introduction of the new dose planning and delivery techniques and the integration of drugs and radiation. The curricula can be downloaded at http://www.estro-education.org/europeantraining/Pages/EuropeanCurricula.aspx. CONCLUSION The main objective of the ESTRO core curricula is to update and harmonise training of the radiation oncologists, medical physicists and RTTs in Europe. It is recommended that the authorities in charge of the respective training programmes throughout Europe harmonise their own curricula according to the common framework.

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.

Three-dimensional conformal or stereotactic reirradiation of recurrent, metastatic or new primary tumors. Analysis of 108 patients.

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Three-Dimensional Conformal or Stereotactic Reirradiation of Recurrent, Metastatic or New Primary Tumors

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

PURPOSE To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. METHODS AND MATERIALS Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. RESULTS Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed (p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. CONCLUSIONS Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

Linac-based stereotactic body radiotherapy for oligometastatic patients with single abdominal lymph node recurrent cancer

Objectives:To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. Methods:Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. Results:Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. Conclusions:SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.

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.