Daniel Vetterli

Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

BackgroundTo report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking.MethodsFrom 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months.ResultsAcute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001).DiscussionGI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

No Predictive Value of the Micronucleus Assay for Patients with Severe Acute Reaction of Normal Tissue After Radiotherapy

In approximately 5% of cancer patients undergoing radiotherapy, this treatment has to be interrupted because of an acute reaction of normal tissues. To test the possibility of predicting this type of reaction, the micronucleus assay was used to determine radiosensitivities of peripheral blood lymphocytes of 15 patients with severe acute reaction of normal tissue, 15 patients without this reaction and 15 healthy donors. Whole-blood cultures were irradiated with X-rays (4 Gy, 1.08 Gy/min) and treated with cytochalasin B. The micronuclei scores observed in irradiated cells were corrected for the scores in unirradiated cells. Intra-individual and interindividual variations in micronuclei scores were analysed in samples from healthy donors, and highly significant interindividual differences were found (P < 0.001). Scores of cells not irradiated in vitro were higher for cancer patients before radiotherapy than for healthy donors (P < 0.001), and those for cancer patients after radiotherapy were higher than for patients before radiotherapy (P < 0.001). Average micronuclei scores induced by in vitro irradiation were significantly higher in samples from cancer patients compared with those from healthy donors (P < 0.01). Moreover, all subgroups of cancer patients included individuals with very high levels of micronuclei after in vitro irradiation. There was, however, no relationship between the micronuclei scores and the occurrence of severe acute reactions in normal tissues.

Prädiktive Bedeutung der Reflexotalgie in der lokal radikalen Radiotherapie von Oropharynxkarzinomen

BACKGROUND Patients with carcinomas of the upper aero-digestive tract often suffer from ear pain as a tumor associated syndrome. This prospective study examines the predictive and prognostic value of this symptom. PATIENTS AND METHODS Ninety-six consecutive patients who completed a locally radiotherapy of a carcinoma of the oropharynx were prospectively evaluated and followed. Forty-nine out of 96 patients stated the symptom, either spontaneously or after questioning. The 2 groups showed no difference regarding TNM-classification, histology and total dose. Overall survival, local control and disease specific survival were calculated according to Kaplan-Meier and compared by the log-rank test. RESULTS A clinically complete remission was obtained in significantly fewer patients with reflex-otalgia as compared to patients without reflex-otalgia, 61.2% versus 89.3%, p < 0.002. Local control of patients with reflex-otalgia was significantly less with 49%, mean follow-up 564 days, in comparison to local control in patients without reflex-otalgia, mean follow-up 613 days, p = 0.01. Disease specific survival was significantly worse for patients with reflex-otalgia, p < 0.012. The probability of local control of T1/T2 tumors with reflex-otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all tumor categories combined is 74% for patients without reflex-otalgia versus 49% for patients with reflex-otalgia. CONCLUSION In our patients, reflex-otalgia is a new and statistically significant parameter for the probability of local control and disease specific survival.ZusammenfassungHintergrundVon Patienten mit ORL-Karzinomen werden Ohrenschmerzen häufig als tumorbegleitendes Symptom angegeben. Die prädiktive und prognostische Bedeutung der Reflexotalgie wird in dieser prospektiven Studie untersucht.Patienten und Methoden96 Patienten, die eine lokal radikale Radiotherapie wegen eines Oropharynxkarzinoms abschlossen, wurden prospektiv erfaßt und nachkontrolliert. 49/96 Patienten gaben das Symptom Reflexotalgie spontan oder auf Befragung an. Die beiden Patientengruppen untschieden sich nicht hinsichtlich TNM-Klassifikation, Histologie und Gesamtdosis. Das Gesamtüberleben, die lokale Kontrolle und das krankheitsspezifische Überleben wurden gemäß Kaplan-Meier berechnet und mit dem Log-rank-Test verglichen.ErgebnisseSignifikant weniger Patienten mit Reflexotalgie kamen in eine klinisch komplette Remission (61,2% versus 89,3%, p<0,002). Die lokale Kontrolle der Patienten mit Reflexotalgie lag mit 49% bei einer mittleren Nachbeobachtungszeit von 564 Tagen signifikant unter derjenigen von Patienten ohne Reflexotalgie mit 74,5%, mittlere Nachbeobachtungszeit 613 Tage, p=0,01. Das krankheitsspezifische Überleben war signifikant schlechter für Patienten mit Reflexotalgie im Vergleich zu Patienten ohne Reflexotalgie, p<0,012. Die lokale Kontrollwahrscheinlichkeit von T1/T2-Tumoren mit dem Symptom Reflexotalgie entspricht derjenigen von T3/T4-Tumoren ohne Reflexotalgie. Für alle Tumorkategorien ist die lokale Kontrolle bei Patienten ohne Reflexotalgie (74%) der lokalen Kontrolle von Patienten mit Reflexotalgie (49%) signifikant überlegen.SchlußfolgerungIn unserem Krankengut erweist sich die Reflexotalgie als neuer und statistisch signifikanter Parameter für die Wahrscheinlichkeit der lokalen Tumorkontrolle und des krankheitsspezifischen Überlebens.AbstractBackgroundPatients with carcinomas of the upper aero-digestive tract often suffer from ear pain as a tumor associated syndrome. This prospective study examines the predictive and prognostic value of this symptom.Patients and MethodsNinety-six consecutive patients who completed a locally radical radiotherapy of a carcinoma of the oropharynx were prospectively evaluated and followed. Forty-nine out of 96 patients stated the symptom, either spontaneously or after questioning. The 2 groups showed no difference regarding TNM-classification, histology and total dose. Overall survival, local control and disease specific survival were calculated according to Kaplan-Meier and compared by the log-rank test.ResultsA clinically complete remission was obtained in significantly fewer patients with reflex-otalgia as compared to patients without reflex-otalgia, 61.2% versus 89.3%, p<0.002. Local control of patients with reflex-otalgia was significantly less with 49%, mean follow-up 564 days, in comparison to local control in patients without reflex-otalgia, mean follow-up 613 days, p=0.01. Disease specific survival was significantly worse for patients with reflex-otalgia, p<0.012. The probability of local control of T1/T2 tumors with reflex-otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all tumor categories combined is 74% for patients without reflex-otalgia versus 49% for patients with reflex-otalgia.ConclusionIn our patients, reflex-otalgia is a new and statistically significant parameter for the probability of local control and disease specific survival.

Monte Carlo based beam model using a photon MLC for modulated electron radiotherapy

PURPOSE Modulated electron radiotherapy (MERT) promises sparing of organs at risk for certain tumor sites. Any implementation of MERT treatment planning requires an accurate beam model. The aim of this work is the development of a beam model which reconstructs electron fields shaped using the Millennium photon multileaf collimator (MLC) (Varian Medical Systems, Inc., Palo Alto, CA) for a Varian linear accelerator (linac). METHODS This beam model is divided into an analytical part (two photon and two electron sources) and a Monte Carlo (MC) transport through the MLC. For dose calculation purposes the beam model has been coupled with a macro MC dose calculation algorithm. The commissioning process requires a set of measurements and precalculated MC input. The beam model has been commissioned at a source to surface distance of 70 cm for a Clinac 23EX (Varian Medical Systems, Inc., Palo Alto, CA) and a TrueBeam linac (Varian Medical Systems, Inc., Palo Alto, CA). For validation purposes, measured and calculated depth dose curves and dose profiles are compared for four different MLC shaped electron fields and all available energies. Furthermore, a measured two-dimensional dose distribution for patched segments consisting of three 18 MeV segments, three 12 MeV segments, and a 9 MeV segment is compared with corresponding dose calculations. Finally, measured and calculated two-dimensional dose distributions are compared for a circular segment encompassed with a C-shaped segment. RESULTS For 15 × 34, 5 × 5, and 2 × 2 cm(2) fields differences between water phantom measurements and calculations using the beam model coupled with the macro MC dose calculation algorithm are generally within 2% of the maximal dose value or 2 mm distance to agreement (DTA) for all electron beam energies. For a more complex MLC pattern, differences between measurements and calculations are generally within 3% of the maximal dose value or 3 mm DTA for all electron beam energies. For the two-dimensional dose comparisons, the differences between calculations and measurements are generally within 2% of the maximal dose value or 2 mm DTA. CONCLUSIONS The results of the dose comparisons suggest that the developed beam model is suitable to accurately reconstruct photon MLC shaped electron beams for a Clinac 23EX and a TrueBeam linac. Hence, in future work the beam model will be utilized to investigate the possibilities of MERT using the photon MLC to shape electron beams.

Dosimetric properties of an amorphous silicon EPID for verification of modulated electron radiotherapy

PURPOSE To investigate the dosimetric properties of an electronic portal imaging device (EPID) for electron beam detection and to evaluate its potential for quality assurance (QA) of modulated electron radiotherapy (MERT). METHODS A commercially available EPID was used to detect electron beams shaped by a photon multileaf collimator (MLC) at a source-surface distance of 70 cm. The fundamental dosimetric properties such as reproducibility, dose linearity, field size response, energy response, and saturation were investigated for electron beams. A new method to acquire the flood-field for the EPID calibration was tested. For validation purpose, profiles of open fields and various MLC fields (square and irregular) were measured with a diode in water and compared to the EPID measurements. Finally, in order to use the EPID for QA of MERT delivery, a method was developed to reconstruct EPID two-dimensional (2D) dose distributions in a water-equivalent depth of 1.5 cm. Comparisons were performed with film measurement for static and dynamic monoenergy fields as well as for multienergy fields composed by several segments of different electron energies. RESULTS The advantageous EPID dosimetric properties already known for photons as reproducibility, linearity with dose, and dose rate were found to be identical for electron detection. The flood-field calibration method was proven to be effective and the EPID was capable to accurately reproduce the dose measured in water at 1.0 cm depth for 6 MeV, 1.3 cm for 9 MeV, and 1.5 cm for 12, 15, and 18 MeV. The deviations between the output factors measured with EPID and in water at these depths were within ±1.2% for all the energies with a mean deviation of 0.1%. The average gamma pass rate (criteria: 1.5%, 1.5 mm) for profile comparison between EPID and measurements in water was better than 99% for all the energies considered in this study. When comparing the reconstructed EPID 2D dose distributions at 1.5 cm depth to film measurements, the gamma pass rate (criteria: 2%, 2 mm) was better than 97% for all the tested cases. CONCLUSIONS This study demonstrates the high potential of the EPID for electron dosimetry, and in particular, confirms the possibility to use it as an efficient verification tool for MERT delivery.PURPOSE To investigate the dosimetric properties of an electronic portal imaging device (EPID) for electron beam detection and to evaluate its potential for quality assurance (QA) of modulated electron radiotherapy (MERT). METHODS A commercially available EPID was used to detect electron beams shaped by a photon multileaf collimator (MLC) at a source-surface distance of 70 cm. The fundamental dosimetric properties such as reproducibility, dose linearity, field size response, energy response, and saturation were investigated for electron beams. A new method to acquire the flood-field for the EPID calibration was tested. For validation purpose, profiles of open fields and various MLC fields (square and irregular) were measured with a diode in water and compared to the EPID measurements. Finally, in order to use the EPID for QA of MERT delivery, a method was developed to reconstruct EPID two-dimensional (2D) dose distributions in a water-equivalent depth of 1.5 cm. Comparisons were performed with film measurement for static and dynamic monoenergy fields as well as for multienergy fields composed by several segments of different electron energies. RESULTS The advantageous EPID dosimetric properties already known for photons as reproducibility, linearity with dose, and dose rate were found to be identical for electron detection. The flood-field calibration method was proven to be effective and the EPID was capable to accurately reproduce the dose measured in water at 1.0 cm depth for 6 MeV, 1.3 cm for 9 MeV, and 1.5 cm for 12, 15, and 18 MeV. The deviations between the output factors measured with EPID and in water at these depths were within ±1.2% for all the energies with a mean deviation of 0.1%. The average gamma pass rate (criteria: 1.5%, 1.5 mm) for profile comparison between EPID and measurements in water was better than 99% for all the energies considered in this study. When comparing the reconstructed EPID 2D dose distributions at 1.5 cm depth to film measurements, the gamma pass rate (criteria: 2%, 2 mm) was better than 97% for all the tested cases. CONCLUSIONS This study demonstrates the high potential of the EPID for electron dosimetry, and in particular, confirms the possibility to use it as an efficient verification tool for MERT delivery.