J. Bernard Davis

Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): A feasibility study

PURPOSE To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. METHODS AND MATERIALS Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. RESULTS Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced > or =25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm(3) to 9.2 cm(3) associated with a reduction of the standard deviation from 38.3 cm(3) to 13.3 cm(3) (p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. CONCLUSION Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.

The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I–III breast cancer

PURPOSE To present the results of the dummy run of the European Organization for Research and Treatment of Cancer (EORTC) trial investigating the role of adjuvant internal mammary and medial supraclavicular (IM-MS) irradiation in Stage I--III breast cancer. METHODS AND MATERIALS All participating institutions were asked to produce a treatment plan without (Arm 1) and with (Arm 2) simultaneous IM-MS irradiation of 1 patient after mastectomy and of 1 patient after lumpectomy. Thirty-two dummy runs have been evaluated for compliance to protocol guidelines, with respect to treatment technique and dose prescription. RESULTS A number of more or less important deviations in treatment setup and prescription have been found. The dose in the IM-MS region deviated significantly from the prescribed dose in 10% of the cases for Arm 1, and in 21% for Arm 2. Assuming a true 5% 10-year survival benefit from optimal IM-MS irradiation, an increase of only 3.8% will be found due to this suboptimal dose distribution. CONCLUSION In the dummy run, a number of potential systematic protocol deviations that might lead to false-negative results were detected. By providing recommendations to the participating institutions, we expect to improve the interinstitutional consistency and to promote a high quality irradiation in all institutions participating in the trial.

A comparison of dose distributions of proton and photon beams in stereotactic conformal radiotherapy of brain lesions

PURPOSE Micromultileaf collimators (mMLC) have recently been introduced to conform photon beams in stereotactic irradiation of brain lesions. Proton beams and stereotactic conformal radiotherapy (SCRT) can be used to tailor the dose to nonspherical targets, as most tumors of the brain are irregularly shaped. Comparative planning of brain lesions using either proton or stereotactically guided photon beams was done to assess the institutions clinically available modality for three-dimensional conformal radiotherapy. METHODS AND MATERIALS For the photon treatment, multiple stereotactically guided uniform intensity beams from a linear accelerator were used, each conformed to a projection of the planning target volume (PTV) by a mMLC. Proton beams were delivered from an isocentrically mounted gantry, using the spot-scanning technique and energy modulation. Seven patients were scanned in a stereotactic frame; target volumes and organs at risk (OAR) were delineated with the help of MR images. Four different lesions were selected: (1) concave, (2) ellipsoid isolated, (3) superficial and close to an organ at risk, and (4) irregular complex. Dose distributions in the PTV and critical structures were calculated using three-dimensional treatment-planning systems, followed by both a quantitative (by dose--volume histogram and conformity index) and qualitative (visual inspection) assessment of the plans. RESULTS A high degree of conformation was achieved with a mMLC and stereotactic uniform intensity beams with comparable conformity indices to protons for 5 out of 7 plans, especially for superficial or spherical lesions. In the cases studied, the conformity index was better for protons than for photons for complex or concave lesions, or when the PTV was in the neighborhood of critical structures. CONCLUSION The results for the cases studied, show that for simple geometries or for superficial lesions, there is no advantage in using protons. However, for complex PTV shapes, or when the PTV is in the vicinity of critical structures, protons seem to be potentially better than the fixed-field photon technique.

Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base

PURPOSE This study evaluates a possible advantage of intensity-modulated stereotactic radiotherapy (IMSRT) over stereotactic conformal radiotherapy (SCRT) in the treatment of lesions in the base of the skull. METHODS AND MATERIALS Ten patients (7 with a skull base meningioma) planned for routine SCRT were replanned for IMSRT. The criteria for comparison were the same for both methods: optimal dose to the planning target volume (PTV) and optimal sparing of the organs at risk (OAR). For SCRT, sparing of OAR was achieved by conformal avoidance using 5-6 fields. The IMSRT inverse planning process used optimized OAR sparing through user-defined dose constraints. Dose to the PTV and OAR were assessed by dose-volume histograms, maximum dose, 2 conformity indices, and volumes of relevant isodoses. RESULTS The conformity index is consistently higher for IMSRT, the largest improvement being for the multifocal and irregular cases. Volumes of the 90% and 80% isodoses were smaller for IMSRT, whereas the volume of the 30% isodose was larger for IMSRT in 6 cases. The maximum dose was consistently higher for IMSRT (mean values 102% and 108% for SCRT and IMSRT, respectively). Sparing of OAR was better with IMSRT, especially for those OARs situated in or near a concave PTV. CONCLUSIONS In terms of PTV coverage, there is an advantage in using IMSRT for all target shapes, but especially for irregular and concave targets. The dose to OAR is lower with IMSRT, although the volume of normal tissue receiving a low dose can be larger than for SCRT.

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: Dummy run and individual case review

INTRODUCTION EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

BackgroundImpact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma.Patients and methodsForty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6–49 months) for the PET/CT-IMRT group and twenty eight months (range, 1–168 months) for the controls.ResultsPET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005).ConclusionPET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings.

Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas

PURPOSE To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. MATERIALS AND METHODS Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) < or =4 cm in maximum diameter, with a good performance status (WHO > or =2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. RESULTS All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). CONCLUSION A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial.

The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network

PurposeA multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours.Patients and methodsOne hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed.ResultsThe combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis.ConclusionPostoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients.

Quality Assurance in the EORTC Randomized Trial 22922/10925 Investigating the Role of Irradiation of the Internal Mammary and Medial Supraclavicular Lymph Node Chain Works

Background and Purpose:A quality assurance (QA) program in conjunction with the EORTC trial investigating the role of adjuvant internal mammary and medial supraclavicular irradiation in stage I–III breast cancer is presented. The results of a dummy run procedure and of an individual case review are compared to each other. The effects of recommendations based on QA procedures on the protocol compliance are evaluated.Material and Methods:Prior to protocol activation all participating institutes were asked to produce treatment plans according to the guidelines of the protocol based on manual outlines of an average patient. Thereafter, they were asked to provide data on each of their first six randomized patients.Results:The dummy run provided a lot of information on specific treatment techniques. In the individual case review, additional patient- and tumor-related data were collected, showing the use of anatomic information for treatment planning. A comparison between both procedures revealed that the individual case reports concurred more accurately with protocol guidelines than the dummy run.Conclusion:It was observed that the number of systematic protocol deviations was substantially decreased in trial patients compared to the dummy run case. Therefore, it is concluded that this extensive QA program had a positive effect on the consistency of all institutes participating in the trial.Hintergrund und Ziel:Ein Qualitätssicherungsprogramm der EORTC-Studie, welche die Rolle der Bestrahlung der Mammaria-interna- und der supraklavikulären Lymphknoten beim Mammakarzinom des Stadiums I–III untersucht, wird vorgestellt. Die Ergebnisse eines Testverfahrens (DR [„dummy run“]) und eines individuellen Fallberichts (ICR [„individual case review“]) werden miteinander verglichen. Basierend auf der Auswertung des DR wird der Einfluss der Empfehlungen auf die Befolgung der Protokollrichtlinien beurteilt.Material und Methodik:Vor Studienbeginn wurden alle teilnehmenden Institute gebeten, Behandlungspläne entsprechend den Protokollrichtlinien zu erstellen. Als Planungsdaten dienten von Hand angefertigte Konturzeichnungen einer durchschnittlichen Patientin. Für den ICR wurden die Daten der ersten sechs randomisierten Patientinnen dieser Institute ausgewertet. Für 19 Institute konnten die Daten des DR sowie des ICR von der Qualitätssicherungsgruppe ausgewertet werden.Ergebnisse:Bereits der DR lieferte zahlreiche Informationen über die spezifischen Behandlungstechniken. Beim ICR wurden zusätzliche patienten- und tumorbezogene Daten evaluiert, die die Verwendung anatomischer Informationen zur Bestrahlungsplanung belegten. Der Vergleich beider Verfahren ergab, dass der ICR den Protokollrichtlinien näher kamen als der DR.Schlussfolgerung:Die Zahl der systematischen Protokollabweichungen war bei den Studienpatienten deutlich geringer als beim initialen DR. Das lässt den Schluss zu, dass dieses umfassende Qualitätssicherungsprogramm einen positiven Einfluss auf die Einheitlichkeit der Therapie der an dieser Studie teilnehmenden Institute hatte.

Target motion variability and on-line positioning accuracy during external-beam radiation therapy of prostate cancer with an endorectal balloon device.

Purpose:To prospectively define the setup error and the interfraction prostate localization accuracy of the planning target volume (PTV) in the presence of an endorectal balloon (ERB) device.Patients and Methods:Weekly portal images (PIs) of 15 patients undergoing external-beam radiotherapy were analyzed. Displacements of the isocenter and the center of the ERB were measured. The setup and target motion variability were assessed with regard to the position variability of the ERB.Results:The setup error was random and target motion variability was largest in the craniocaudal direction. The mean displacement of the isocenter was 2.1 mm (± 1.2 mm SD [standard deviation]), 2.4 mm (± 2.2 mm SD), and 3.8 mm (± 4.0 mm SD) in the left-right, craniocaudal, and anteroposterior directions, respectively (p = 0.1). The mean displacement of the ERB was 2.0 mm (± 1.4 mm SD), 4.1 mm (± 2.0 mm SD), and 3.8 mm (± 3.3 mm SD; p = 0.03). Setup margin and internal margin contributed equally to the PTV margin. Cumulative placement insecurity of the field and the ERB together was 4.0 mm (± 2.1 mm SD) laterally, 6.4 mm (± 2.5 mm SD) craniocaudally, and 7.7 mm (± 7.0 mm SD) anteroposteriorly. The 95% CIs (confidence intervals) were 2.9–5.2 mm, 5.1–7.8 mm, and 3.8–11.5 mm. In 35% of cases, the estimation of the dorsal margin exceeded 1 cm.Conclusion:Margin estimate dorsally may exceed 1 cm and on-line position verification with an ERB cannot be recommended for dose escalation > 70 Gy.Ziel:Analyse des Positionierungsfehlers und der Lokalisationsgenauigkeit der Prostata zwischen den Bestrahlungen unter der Verwendung eines endorektalen Ballons (ERB) zwecks Positionierungshilfe.Patienten und Methodik:Die sequentiellen Einstellungsaufnahmen von 15 Patienten, die in kurativer Absicht eine externe Radiotherapie erhielten, wurden analysiert. Die Positionierungsvariabilität des ERB wurde unter Berücksichtigung der Lagevariabilität des Set-up und des Zielvolumens gemessen.Ergebnisse:Der Einstellungsfehler (systemischer Fehler) zeigte keine Prädispositionen in x-, y- oder z-Richtung. Die Bewegungsvariabilität in kraniokaudaler Richtung war am größten. Die Lagevariabilität des Feldzentrums betrug 2,1 mm (± 1,2 mm), 2,4 mm (± 2,2 mm) und 3,8 mm (± 4,0 mm) in seitlicher, kraniokaudaler und anteroposteriorer Richtung (p = 0,1). Der ERB zeigte eine Lagevariabilität von 2 mm (± 1,4 mm), 4,1 mm (± 2,0 mm) und 3,8 mm (± 3,3 mm) seitlich, kraniokaudal und anteroposterior (p = 0,03). Die Positionsvariabilität des Feldzentrums in Bezug auf die Lokalisation des ERB war vernachlässigbar. Zur kumulativen Zielunsicherheit trugen der systemische und der spezifische Fehler gleichermaßen bei. Die durchschnittliche Lageunsicherheit des Feldes und des Ballons gemeinsam betrug 4,0 mm (± 2,1 mm) lateral, 6,4 mm (± 2,5 mm) kraniokaudal und 7,7 mm (± 7,0 mm) anteroposterior. Die 95%-Konfidenzintervalle betrugen 2.9–5.2 mm, 5.1–7.8 mm, und 3.8–11.5 mm. Der geschätzte Sicherheitsabstand in dorsaler Richtung lag in 35% der Fälle bei > 1 cm.Schlussfolgerung:Um einen Sicherheitsrand von < 1 cm gegen dorsal zu erzielen, reicht ein ERB allein nicht aus. Für Therapien mit Dosen > 70 Gy empfehlen sich zusätzliche Positionierungs- und Positionsverifikationssysteme, um den dorsalen Sicherheitsabstand klein halten zu können.