Einar Dale

Inter fraction variations in rectum and bladder volumes and dose distributions during high dose rate brachytherapy treatment of the uterine cervix investigated by repetitive CT-examinations

PURPOSE To evaluate variation of dose to organs at risk for patients receiving fractionated high dose rate gynaecological brachytherapy by using CT-based 3D treatment planning and dose-volume histograms (DVH). MATERIALS AND METHODS Fourteen patients with cancer of the uterine cervix underwent three to six CT examinations (mean 4.9) during their course of high-dose-rate brachytherapy using radiographically compatible applicators. The rectal and bladder walls were delineated and DVHs were calculated. RESULTS Inter fraction variation of the bladder volume (CV(mean)=44.1%) was significantly larger than the inter fraction variation of the mean dose (CV(mean)=19.9%, P=0.005) and the maximum dose (CV(mean)=17.5%, P=0.003) of the bladder wall. The same trend was seen for rectum, although the figures were not significantly different. Performing CT examinations at four of seven brachytherapy fractions reduced the uncertainty to 4 and 7% for the bladder and rectal doses, respectively. A linear regression analysis showed a significant, negative relationship between time after treatment start and the whole bladder volume (P=0.018), whereas no correlation was found for the rectum. For both rectum and bladder a linear regression analysis revealed a significant, negative relationship between the whole volume and median dose (P<0.05). CONCLUSION Preferably a CT examination should be provided at every fraction. However, this is logistically unfeasible in most institutions. To obtain reliable DVHs the patients will in the future undergo 3-4 CT examinations during the course of brachytherapy at our institution. Since this study showed an association between large bladder volumes and dose reductions, the patients will be treated with a standardized bladder volume.

Modeling normal tissue complication probability from repetitive computed tomography scans during fractionated high-dose-rate brachytherapy and external beam radiotherapy of the uterine cervix

PURPOSE To calculate the normal tissue complication probability (NTCP) of late radiation effects on the rectum and bladder from repetitive CT scans during fractionated high-dose-rate brachytherapy (HDRB) and external beam radiotherapy (EBRT) of the uterine cervix and compare the NTCP with the clinical frequency of late effects. METHODS AND MATERIALS Fourteen patients with cancer of the uterine cervix (Stage IIb-IVa) underwent 3-6 (mean, 4.9) CT scans in treatment position during their course of HDRB using a ring applicator with an Iridium stepping source. The rectal and bladder walls were delineated on the treatment-planning system, such that a constant wall volume independent of organ filling was achieved. Dose-volume histograms (DVH) of the rectal and bladder walls were acquired. A method of summing multiple DVHs accounting for variable dose per fraction were applied to the DVHs of HDRB and EBRT together with the Lyman-Kutcher NTCP model fitted to clinical dose-volume tolerance data from recent studies. RESULTS The D(mean) of the DVH from EBRT was close to the D(max) for both the rectum and bladder, confirming that the DVH from EBRT corresponded with homogeneous whole-organ irradiation. The NTCP of the rectum was 19.7% (13.5%, 25. 9%) (mean and 95% confidence interval), whereas the clinical frequency of late rectal sequelae (Grade 3-4, RTOG/EORTC) was 13% based on material from 200 patients. For the bladder the NTCP was 61. 9% (46.8%, 76.9%) as compared to the clinical frequency of Grade 3-4 late effects of 14%. If only 1 CT scan from HDRB was assumed available, the relative uncertainty (standard deviation or SD) of the NTCP value for an arbitrary patient was 20-30%, whereas 4 CT scans provided an uncertainty of 12-13%. CONCLUSION The NTCP for the rectum was almost consistent with the clinical frequency of late effects, whereas the NTCP for bladder was too high. To obtain reliable (SD of 12-13%) NTCP values, 3-4 CT scans are needed during 5-7 fractions of HDRB treatments.

Specification of the dose to organs at risk in external beam radiotherapy

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the Dmax value for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the Dmedian or Dmean of the DVH may be applied. Our calculations reveal that Dmean is the parameter of choice when Dmedian is quite small, but when the two parameters approach each other. Dmedian will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither Dmax, Dmedian nor Dmean may predict the actual NTCP.

Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps

ABSTRACT Background. Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented. Material and methods. DPBN tumor dose prescription maps were generated from 18F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD). Results. Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered. Conclusions. The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

MODELING VOLUME EFFECTS OF EXPERIMENTAL BRACHYTHERAPY IN THE RAT RECTUM: UNCOVERING THE LIMITATIONS OF A RADIOBIOLOGIC CONCEPT

PURPOSE To analyze the significance of volume effects in experimental brachytherapy, based on modeling normal tissue complication probability. METHODS AND MATERIALS Experimental brachytherapy in the rat rectum was based on an eight-step 2.5-mm step size source configuration for 192Ir, afterloaded into an unshielded polystyrene applicator. Volume effects were studied using a half-circumferential lead-shielded applicator and a shorter (two-step) source configuration. The main end point was rectal stenosis. RESULTS Rectal stenosis was always caused by a radiation ulcer. With the shielded configuration, single-dose ED50 (50% incidence of rectal stenosis) increased from 23 Gy to 36.5 Gy. Single-dose ED50 for the short configuration was 77.9 Gy. The data showed a reasonable fit to a three-parameter version of the biophysical model described by Jackson et al. (1995). This model assumes that organs consist of a large number of radiobiologically independent subunits and that radiation causes a complication if the fraction of the organ damaged is greater than its functional reserve. The fraction of the organ damaged is calculated summing over fractions of the organ damaged at each dose level. The calculated mean functional reserve (nu50) of the rat rectum, assuming a cumulative functional reserve distribution in the group of experimental rats, was 0.53. CONCLUSIONS The volume effect observed within small brachytherapy volumes agreed well with clinical experience of large tolerance doses in contact X-ray therapy. However, the nu50 value was comparable to the high functional reserve value reported for liver. Experimental volume effects probably reflect repair processes originating in the areas adjacent to small radiation fields of brachytherapy more than the radiobiologic characteristics of the cells in the irradiated volume.

CT Density in Lung Cancer Patients After Radiotherapy Sensitized by Metoclopramide

Purpose:To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide.Patients and Methods:Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction.Results:Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V40Gy) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01).Conclusion:There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V40Gy) seemed to protect against fibrosis development.ZusammenfassungZiel:Computertomographische (CT) Messung der Strahlenreaktion in Lungengewebe nach Strahlentherapie in Kombination mit Metoclopramid.Patienten und Methodik:Patienten mit nichtkleinzelligem Bronchialkarzinom (Tumorstadium IIIA und IIIB), die in eine randomisierte, multizentrische Phase-III-Studie zur Untersuchung des strahlensensitivierenden Effekts von Metoclopramid eingeschlossen waren, wurden mittels wiederholter posttherapeutischer CTs untersucht. Verlaufskontrolldaten bis 100 Tage nach Beendigung der Strahlentherapie einer Untergruppe von 16 Patienten, die mit einer Gesamtdosis von 60 Gy, appliziert in Tagesdosen von 1,82 Gy, behandelt wurden, standen für die Analyse zur Verfügung.Ergebnisse:Hohe Strahlendosen auf Teilvolumina resultierten in höherer CT-Dichte im bestrahlten Lungengewebe (p < 0,001). Im Gegensatz dazu korrelierte das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) negativ mit der Zunahme der CTDichte im bestrahlten Lungengewebe (p = 0,003). Bei Patienten, die in den Therapiarm mit Metoclopramid randomisiert wurden, war eine weniger ausgeprägte Zunahme der CT-Dichte im bestrahlten Lungengewebe zu verzeichnen (p = 0,01).Schlussfolgerung:Es fand sich ein Zusammenhang zwischen der Zunahme der gemessenen CT-Dichte im bestrahlten Lungengewebe, der applizierten Strahlendosis und der Zeit nach Bestrahlung. Metoclopramid und das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) scheinen einen protektiven Effekt auf die Entwicklung einer Lungenfibrose zu haben.

CT Density in Lung Cancer Patients After Radiotherapy Sensitized by Metoclopramide : A Subgroup Analysis of a Randomized Trial

Purpose:To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide.Patients and Methods:Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction.Results:Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V40Gy) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01).Conclusion:There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V40Gy) seemed to protect against fibrosis development.ZusammenfassungZiel:Computertomographische (CT) Messung der Strahlenreaktion in Lungengewebe nach Strahlentherapie in Kombination mit Metoclopramid.Patienten und Methodik:Patienten mit nichtkleinzelligem Bronchialkarzinom (Tumorstadium IIIA und IIIB), die in eine randomisierte, multizentrische Phase-III-Studie zur Untersuchung des strahlensensitivierenden Effekts von Metoclopramid eingeschlossen waren, wurden mittels wiederholter posttherapeutischer CTs untersucht. Verlaufskontrolldaten bis 100 Tage nach Beendigung der Strahlentherapie einer Untergruppe von 16 Patienten, die mit einer Gesamtdosis von 60 Gy, appliziert in Tagesdosen von 1,82 Gy, behandelt wurden, standen für die Analyse zur Verfügung.Ergebnisse:Hohe Strahlendosen auf Teilvolumina resultierten in höherer CT-Dichte im bestrahlten Lungengewebe (p < 0,001). Im Gegensatz dazu korrelierte das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) negativ mit der Zunahme der CTDichte im bestrahlten Lungengewebe (p = 0,003). Bei Patienten, die in den Therapiarm mit Metoclopramid randomisiert wurden, war eine weniger ausgeprägte Zunahme der CT-Dichte im bestrahlten Lungengewebe zu verzeichnen (p = 0,01).Schlussfolgerung:Es fand sich ein Zusammenhang zwischen der Zunahme der gemessenen CT-Dichte im bestrahlten Lungengewebe, der applizierten Strahlendosis und der Zeit nach Bestrahlung. Metoclopramid und das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) scheinen einen protektiven Effekt auf die Entwicklung einer Lungenfibrose zu haben.

CT Density in Lung Cancer Patients After Radiotherapy Sensitized by Metoclopramide@@@CT-Dichte von Patienten mit Bronchialkarzinom nach Strahlentherapie in Kombination mit strahlensensitivierender Metoclopramidbehandlung. Subgruppenanalyse einer randomisierten Studie: A Subgroup Analysis of a Randomized Trial

Purpose:To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide.Patients and Methods:Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction.Results:Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V40Gy) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01).Conclusion:There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V40Gy) seemed to protect against fibrosis development.ZusammenfassungZiel:Computertomographische (CT) Messung der Strahlenreaktion in Lungengewebe nach Strahlentherapie in Kombination mit Metoclopramid.Patienten und Methodik:Patienten mit nichtkleinzelligem Bronchialkarzinom (Tumorstadium IIIA und IIIB), die in eine randomisierte, multizentrische Phase-III-Studie zur Untersuchung des strahlensensitivierenden Effekts von Metoclopramid eingeschlossen waren, wurden mittels wiederholter posttherapeutischer CTs untersucht. Verlaufskontrolldaten bis 100 Tage nach Beendigung der Strahlentherapie einer Untergruppe von 16 Patienten, die mit einer Gesamtdosis von 60 Gy, appliziert in Tagesdosen von 1,82 Gy, behandelt wurden, standen für die Analyse zur Verfügung.Ergebnisse:Hohe Strahlendosen auf Teilvolumina resultierten in höherer CT-Dichte im bestrahlten Lungengewebe (p < 0,001). Im Gegensatz dazu korrelierte das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) negativ mit der Zunahme der CTDichte im bestrahlten Lungengewebe (p = 0,003). Bei Patienten, die in den Therapiarm mit Metoclopramid randomisiert wurden, war eine weniger ausgeprägte Zunahme der CT-Dichte im bestrahlten Lungengewebe zu verzeichnen (p = 0,01).Schlussfolgerung:Es fand sich ein Zusammenhang zwischen der Zunahme der gemessenen CT-Dichte im bestrahlten Lungengewebe, der applizierten Strahlendosis und der Zeit nach Bestrahlung. Metoclopramid und das mit signifikanter Dosis bestrahlte Lungenvolumen (V40Gy) scheinen einen protektiven Effekt auf die Entwicklung einer Lungenfibrose zu haben.