Christian P. Karger

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.

Treatment planning for heavy ion radiotherapy: clinical implementation and application.

The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI). All treatment plans are evaluated on the basis of biologically effective dose distributions. For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used. The absence of a gantry restricts the treatment plans to horizontal beams. Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields. In only a very few cases a single beam was used. For patients with very complex target volumes lateral and even distal field patching techniques were applied. Additional improvements can be achieved when the patients head is fixed in a tilted position, in order to achieve sparing of the organs at risk. In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume. The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations. The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000. Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting. Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up. The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery.

Accuracy of a commercial optical 3D surface imaging system for realignment of patients for radiotherapy of the thorax

Accurate and reproducible patient setup is a prerequisite to fractionated radiotherapy. To evaluate the applicability and technical performance of a commercial 3D surface imaging system for repositioning of breast cancer patients, measurements were performed in a rigid anthropomorphic phantom as well as in healthy volunteers. The camera system records a respiration-gated surface model of the imaged object, which may be registered to a previously recorded reference model. A transformation is provided, which may be applied to the treatment couch to correct the setup of the patient. The system showed a high stability and detected pre-defined shifts of phantoms and healthy volunteers with an accuracy of 0.40 +/- 0.26 mm and 1.02 +/- 0.51 mm, respectively (spatial deviation between pre-defined shift and suggested correction). The accuracy of the suggested rotational correction around the vertical axis was always better than 0.3 degrees in phantom measurements and 0.8 degrees in volunteers, respectively. Comparison of the suggested setup correction with that detected by a second and independently operated marker-based optical system provided consistent results. The results demonstrate that the camera system provides highly accurate setup corrections in a phantom and healthy volunteers. The most efficient use of the system for improving the setup accuracy in breast cancer patients has to be investigated in routine patient treatments.

Three-dimensional accuracy and interfractional reproducibility of patient fixation and positioning using a stereotactic head mask system.

PURPOSE Conformal radiotherapy in the head and neck region requires precise and reproducible patient setup. The definition of safety margins around the clinical target volume has to take into account uncertainties of fixation and positioning. Data are presented to quantify the involved uncertainties for the system used. METHODS AND MATERIALS Interfractional reproducibility of fixation and positioning of a target point in the brain was evaluated by biplanar films. 118 film pairs obtained at 52 fractions in 4 patients were analyzed. The setup was verified at the actual treatment table position by diagnostic X-ray units aligned to the isocenter and by a stereotactic X-ray localization technique. The stereotactic coordinates of the treated isocenter, of fiducials on the mask, and of implanted internal markers within the patient were measured to determine systematic and random errors. The data are corrected for uncertainty of the localization method. RESULTS Displacements in target point positioning were 0.35 +/- 0.41 mm, 1.22 +/- 0.25 mm, and -0.74 +/- 0.32 mm in the x, y, and z direction, respectively. The reproducibility of the fixation of the patients head within the mask was 0.48 mm (x), 0.67 mm (y), and 0.72 mm (z). Rotational uncertainties around an axis parallel to the x, y, and z axis were 0.72 degrees, 0.43 degrees, and 0.70 degrees, respectively. A simulation, based on the acquired data, yields a typical radial overall uncertainty for positioning and fixation of 1.80 +/- 0.60 mm. CONCLUSIONS The applied setup technique showed to be highly reproducible. The data suggest that for the applied technique, a safety margin between clinical and planning target volume of 1-2 mm along one axis is sufficient for a target at the base of skull.

Relation between carbon ion ranges and x-ray CT numbers.

Measurements of carbon ion ranges in various phantom materials and real bones are presented. Together with measured Hounsfield values, an empirical relation between ranges and Hounsfield units is derived, which is an important prerequisite for treatment planning in carbon ion therapy.

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients.

Purpose:To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas.Patients and Methods:Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the “Gesellschaft für Schwerionenforschung” (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction.Results:Median follow-up was 15 months (range 3–46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC°III have been observed.Conclusions:These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.Ziel:Prospektive Evaluation von Therapieergebnissen und Toxizität bei Chordomen und niedriggradigen Chondrosarkomen nach Kohlenstoffionentherapie.Patienten und Methodik:Von September 1998 bis Dezember 2001 wurden 74 Patienten mit Chordomen und Chondrosarkomen bei der Gesellschaft für Schwerionenforschung (GSI) mit Kohlenstoffionen bestrahlt. Sieben mit konventioneller Radiotherapie vorbestrahlte Patienten, die eine Rebestrahlung mit reduzierter Kohlenstoffionendosis erhielten, wurden von der Analyse ausgeschlossen. Die Analyse umfasst 67 Patienten (44 Chordome und 23 Chondrosarkome), die eine voll fraktionierte Kohlenstoffionentherapie erhielten. Die tumorkonforme Kohlenstoffionenapplikation erfolgte mittels intensitätsgesteuerten Rasterscanverfahrens mit aktiver Energievariation. Die dreidimensionale Bestrahlungsplanung beinhaltete eine Intensitätsmodulation sowie eine biologische Planoptimierung. Die mediane Dosis betrug 60 GyE im Zielvolumen und wurde an 20 aufeinander folgenden Tagen bei einer täglichen Fraktionierung von 3,0 GyE appliziert.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 15 Monate (3–46 Monate). Die aktuarische lokale Kontrollrate nach 3 Jahren lag bei 100% für Chondrosarkome und bei 87% für Chordome. Eine partielle Tumorremission wurde bei 14/44 (31%) Chordompatienten und bei 4/23 (17%) Chondrosarkompatienten beobachtet. Die aktuarische Gesamtüberlebensrate lag nach 3 Jahren bei 100% für Chondrosarkome und bei 89% für Chordome. Schwere Nebenwirkungen > CTC°III wurden nicht beobachtet.Schlussfolgerungen:Die Daten belegen die klinische Effektivität und Sicherheit der Kohlenstoffionentherapie mit einem gescannten Kohlenstoffionenstrahl bei Patienten mit Chordomen und Chondrosarkomen der Schädelbasis. Die Beobachtung von Tumorregressionen bei einer Dosis von 60 GyE weist darauf hin, dass die biologische Wirksamkeit der Kohlenstoffionen bei Chordomen und Chondrosarkomen höher sein könnte als ursprünglich angenommen.

A system for three‐dimensional dosimetric verification of treatment plans in intensity‐modulated radiotherapy with heavy ions

The introduction of dynamic intensity modulation into radiotherapy using conventional photon beams or scanning particle beams requires additional and efficient methods of dose verification. Dose measurements in dynamically generated dose distributions with a single ionization chamber require a complete application of the treatment field for each single measurement. Therefore measurements are performed by simultaneous use of multiple ionization chambers. The measurement is performed by a computer controlled system and is comprised of the following steps: (a) automated positioning of the ionization chambers, (b) measurement at these points, (c) a comparison with the calculated dose from the treatment planning system, and (d) documentation of the measurement. The ionization chambers are read out by a multichannel electrometer and are densely packed into a mounting of polymethylmetacrylate, which is attached to the arm of a three-dimensional motor-driven water phantom. The measured and planned dose values are displayed numerically as well as graphically. The mean deviation between measured and planned doses as well as their standard deviation are calculated and displayed. Through printouts complete documentation of the measurement is obtained and a quick decision can be made whether the dose distribution is acceptable for the patient. The system is now routinely used for dose verification at the heavy ion therapy project at the Gesellschaft für Schwerionenforschung in Darmstadt. Up to now 242 measurements have been performed for heavy ion treatment of 30 patients. The system allows efficient verification and documentation of carbon ion fields and is in principle also applicable to intensity-modulated photon beams.

Dosimetry for ion beam radiotherapy

Recently, ion beam radiotherapy (including protons as well as heavier ions) gained considerable interest. Although ion beam radiotherapy requires dose prescription in terms of iso-effective dose (referring to an iso-effective photon dose), absorbed dose is still required as an operative quantity to control beam delivery, to characterize the beam dosimetrically and to verify dose delivery. This paper reviews current methods and standards to determine absorbed dose to water in ion beam radiotherapy, including (i) the detectors used to measure absorbed dose, (ii) dosimetry under reference conditions and (iii) dosimetry under non-reference conditions. Due to the LET dependence of the response of films and solid-state detectors, dosimetric measurements are mostly based on ion chambers. While a primary standard for ion beam radiotherapy still remains to be established, ion chamber dosimetry under reference conditions is based on similar protocols as for photons and electrons although the involved uncertainty is larger than for photon beams. For non-reference conditions, dose measurements in tissue-equivalent materials may also be necessary. Regarding the atomic numbers of the composites of tissue-equivalent phantoms, special requirements have to be fulfilled for ion beams. Methods for calibrating the beam monitor depend on whether passive or active beam delivery techniques are used. QA measurements are comparable to conventional radiotherapy; however, dose verification is usually single field rather than treatment plan based. Dose verification for active beam delivery techniques requires the use of multi-channel dosimetry systems to check the compliance of measured and calculated dose for a representative sample of measurement points. Although methods for ion beam dosimetry have been established, there is still room for developments. This includes improvement of the dosimetric accuracy as well as development of more efficient measurement techniques.

Carbon Ion Radiotherapy for Chordomas and Low-Grade Chondrosarcomas of the Skull Base

Purpose:To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas.Patients and Methods:Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the “Gesellschaft für Schwerionenforschung” (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction.Results:Median follow-up was 15 months (range 3–46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC°III have been observed.Conclusions:These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.Ziel:Prospektive Evaluation von Therapieergebnissen und Toxizität bei Chordomen und niedriggradigen Chondrosarkomen nach Kohlenstoffionentherapie.Patienten und Methodik:Von September 1998 bis Dezember 2001 wurden 74 Patienten mit Chordomen und Chondrosarkomen bei der Gesellschaft für Schwerionenforschung (GSI) mit Kohlenstoffionen bestrahlt. Sieben mit konventioneller Radiotherapie vorbestrahlte Patienten, die eine Rebestrahlung mit reduzierter Kohlenstoffionendosis erhielten, wurden von der Analyse ausgeschlossen. Die Analyse umfasst 67 Patienten (44 Chordome und 23 Chondrosarkome), die eine voll fraktionierte Kohlenstoffionentherapie erhielten. Die tumorkonforme Kohlenstoffionenapplikation erfolgte mittels intensitätsgesteuerten Rasterscanverfahrens mit aktiver Energievariation. Die dreidimensionale Bestrahlungsplanung beinhaltete eine Intensitätsmodulation sowie eine biologische Planoptimierung. Die mediane Dosis betrug 60 GyE im Zielvolumen und wurde an 20 aufeinander folgenden Tagen bei einer täglichen Fraktionierung von 3,0 GyE appliziert.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 15 Monate (3–46 Monate). Die aktuarische lokale Kontrollrate nach 3 Jahren lag bei 100% für Chondrosarkome und bei 87% für Chordome. Eine partielle Tumorremission wurde bei 14/44 (31%) Chordompatienten und bei 4/23 (17%) Chondrosarkompatienten beobachtet. Die aktuarische Gesamtüberlebensrate lag nach 3 Jahren bei 100% für Chondrosarkome und bei 89% für Chordome. Schwere Nebenwirkungen > CTC°III wurden nicht beobachtet.Schlussfolgerungen:Die Daten belegen die klinische Effektivität und Sicherheit der Kohlenstoffionentherapie mit einem gescannten Kohlenstoffionenstrahl bei Patienten mit Chordomen und Chondrosarkomen der Schädelbasis. Die Beobachtung von Tumorregressionen bei einer Dosis von 60 GyE weist darauf hin, dass die biologische Wirksamkeit der Kohlenstoffionen bei Chordomen und Chondrosarkomen höher sein könnte als ursprünglich angenommen.

Determination of water absorbed dose in a carbon ion beam using thimble ionization chambers

The method to measure absorbed dose to water in a field of carbon ions as applied for the heavy ion therapy project at the Heavy Ion Research Laboratory in Darmstadt (GSI), Germany, is described in detail. Thimble ionization chambers with a water absorbed calibration factor are applied. The dose obtained with this method was compared with that obtained at the heavy ion therapy facility HIMAC at the National Institute of Radiological Sciences in Chiba, Japan, using the Japanese code of practice. The agreement found was better than 1%. The combined uncertainty of the determination of absorbed dose to water was estimated to amount to 5%.