Excessive esophageal toxicity in patients with locally advanced non-small cell lung cancer treated with concurrent hypofractionated chemoradiotherapy and 3-weekly platinum doublet chemotherapy.

Introduction: Concurrent chemoradiation followed by immunotherapy is the standard of care for patients with stage III non-small cell lung cancer (NSCLC). Prior to the introduction of adjuvant immunotherapy, we treated patients with stage III NSCLC with concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions. We determined the toxicity of this treatment. Methods: A retrospective observational study was performed in a cohort of patients with stage III NSCLC, <70 years old, and WHO performance score 0-1. Patients were treated with concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions. All patients were staged with a PET-scan and brain MRI-scan. Toxicity was scored using the common criteria for adverse events (CTCAE v4.03). Results: Between 2012 and 2017, 41 patients were treated with mildly hypofractionated radiotherapy and platinum doublet chemotherapy. The median follow-up was 4.7 years. The median age was 57 and 58% of patients were male. The majority of patients had stage IIIB disease (68%). The median total Gross Tumor Volume (GTV) was 104 cc (range: 15-367 cc). The median lymph node GTV was 59 cc (10-341 cc). Five patients died: four due to an esophagus perforation or fistula, and one due to pulmonary bleeding. Grade ≥ 3 esophageal toxicity occurred in 16 patients. Five patients had late grade ≥ 3 esophageal toxicity (12%). The median overall survival was 19 months. Conclusion: Toxicity was unexpectedly high in patients with stage III NSCLC (WHO 0-1) after concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions.

Target volume delineation in breast conserving radiotherapy: are co-registered CT and MR images of added value?

INTRODUCTION: In breast conserving radiotherapy differences of target volume delineations between observers do occur. We evaluated whether delineations based on co-registered computed tomography (CT) and magnetic resonance (MR) imaging may result in an improved consistency between observers. We used the delineation conformity index (CI) to compare clinical target volumes of glandular breast tissue (CTV breast) and lumpectomy cavity (LC) on both imaging modalities. METHODS AND MATERIALS: Four observers delineated CTV breast and LC on co-registered CTMR images in ten breast cancer patients. CIs were determined for CT and CTMR. Furthermore, the Cavity Visualization Score (CVS) of LC was taken into account. RESULTS: The mean CI for CTV breast (CICT;CTV: 0.82 and CICT-CTMR;CTV: 0.80) and LC (CICT;LC: 0.52 and CICT-CTMR;LC: 0.48) did not differ significantly (p=0.07 and p=0.33, respectively). Taking CVS into account for the LC, with a CVS ≥ 4 the mean CI was 0.62 for both CICT;LC and CICT-CTMR;LC. CONCLUSION: The mean volume of the delineated glandular breast tissue based on CT was significantly larger compared to the volume based on CTMR. For patients with a CVS ≥ 4, the mean CIs of the LC were higher compared to CVS<4 for volumes delineated on both CT as well as CTMR images. In our study cohort no significant differences between the CIs of the CTV breast and the LC delineated on CTMR co-registered images were found compared to the CIs on CT images only. Adding MR images does not seem to improve consistency of the delineation of the CTV breast and the LC, even though the volumes were copied from CT images. Since we included only ten patients, caution should be taken with regard to the results of our study.

MRI- versus CT-based volume delineation of lumpectomy cavity in supine position in breast-conserving therapy: an exploratory study.

PURPOSE: To examine magnetic resonance imaging (MRI) and computed tomography (CT) for lumpectomy cavity (LC) volume delineation in supine radiotherapy treatment position and to assess the interobserver variability. METHODS AND MATERIALS: A total of 15 breast cancer patients underwent a planning CT and directly afterward MRI in supine radiotherapy treatment position. Then, 4 observers (2 radiation oncologists and 2 radiologists) delineated the LC on the CT and MRI scans and assessed the cavity visualization score (CVS). The CVS, LC volume, conformity index (CI), mean shift of the center of mass (COM), with the standard deviation, were quantified for both CT and MRI. RESULTS: The CVS showed that MRI and CT provide about equal optimal visibility of the LC. If the CVS was high, magnetic resonance imaging provided more detail of the interfaces of the LC seroma with the unaffected GBT. MRI also pictured in more detail the interfaces of axillary seromas (if present) with their surroundings and their relationship to the LC. Three observers delineated smaller, and one observer larger, LC volumes comparing the MRI- and CT-derived delineations. The mean ± standard deviation CI was 32% ± 25% for MRI and 52% ± 21% for CT. The mean ± standard deviation COM shift was 11 ± 10 mm (range 1-36) for MRI and 4 ± 3 mm (range 1-10) for CT. CONCLUSIONS: MRI does not add additional information to CT in cases in which the CVS is assessed as low. The conformity (CI) is lower for MRI than for CT, especially at a low CVS owing to greater COM shifts for MRI, probably caused by inadequate visibility of the surgical clips on magnetic resonance (MR) images. The COM shifts seriously dictate a decline in the CI more than the variability of the LC volumes does. In cases in which MRI provides additional information, MRI must be combined with the CT/surgical clip data.

Magnetic resonance imaging- versus computed tomography-based target volume delineation of the glandular breast tissue (clinical target volume breast) in breast-conserving therapy: an exploratory study.

PURPOSE: To examine MRI and CT for glandular breast tissue (GBT) volume delineation and to assess interobserver variability. METHODS AND MATERIALS: Fifteen breast cancer patients underwent a planning CT and MRI, consecutively, in the treatment position. Four observers (two radiation oncologists and two radiologists) delineated the GBT according to the CT and separately to the MR images. Volumes, centers of mass, maximum extensions with standard deviations (SD), and interobserver variability were quantified. Observers viewed delineation differences between MRI and CT and delineation differences among observers. RESULTS: In cranio-lateral and cranio-medial directions, GBT volumes were delineated larger using MRI when compared with those delineated with CT. Center of mass on MRI shifted a mean (SD) 17% (4%) into the cranial direction and a mean 3% (4%) into the dorsal direction when compared with that on the planning CT. Only small variations between observers were noted. The GBT volumes were approximately 4% larger on MRI (mean [SD] ratio MRI to CT GBT volumes, 1.04 [0.06]). Findings were concordant with viewed MRI and CT images and contours. Conformity indices were only slightly different; mean conformity index was 77% (3%) for MRI and 79% (4%) for CT. Delineation differences arising from personal preferences remained recognizable irrespective of the imaging modality used. CONCLUSIONS: Contoured GBT extends substantially further into the cranio-lateral and cranio-medial directions on MRI when compared with CT. Interobserver variability is comparable for both imaging modalities. Observers should be aware of existing personal delineation preferences. Institutions are recommended to review and discuss target volume delineations and to design supplementary guidelines if necessary.

Measuring the similarity of target volume delineations independent of the number of observers.

The variability of target delineations is a topic of interest in radiotherapy. The similarity of delineations is often quantified by use of a conformity index (CI) defined as the ratio of common to encompassing volume. Several forms of CI are in use, but no consensus exists on how to calculate the CI for more than two delineations. This study proposes a generalization of the CI applicable to any number of delineations. The generalization of the CI was developed, unbiased with respect to the number of delineations. Numerical values were calculated for clinical and theoretical cases, and differences with other forms of CI were considered. A simple expression could be derived, applicable to any number of delineations, and is equivalent to the known CI for two delineations. The use of this index is advised, although another frequently used index obtained from averaging the CI between all possible pairs of delineations results in minor differences. The use of the third generalization for the CI which is based upon the volume common to all delineations shows a clear dependence upon the number of delineations and is discouraged.

Dosimetric characteristics of the Leipzig surface applicators used in the high dose rate brachy radiotherapy.

The nucletron Leipzig applicator is designed for (HDR) 192Ir brachy radiotherapy of surface lesions. The dosimetric characteristics of this applicator were investigated using simulation method based on Monte Carlo N-particle (MCNP) code and phantom measurements. The simulation method was validated by comparing calculated dose rate distributions of nucletron microSelectron HDR 192Ir source against published data. Radiochromic films and metal-oxide-semiconductor field-effect transistor (MOSFET) detectors were used for phantom measurements. The double exposure technique, correcting the nonuniform film sensitivity, was applied in the film dosimetry. The linear fit of multiple readings with different irradiation times performed for each MOSFET detector measurement was used to obtain the dose rate of each measurement and to correct the source transit-time error. The film and MOSFET measurements have uncertainties of 3%-7% and 3%-5%, respectively. The dose rate distributions of the Leipzig applicator with 30 mm opening calculated by the validated MC method were verified by measurements of film and MOSFET detectors. Calculated two-dimensional planar dose rate distributions show similar patterns as the film measurement. MC calculated dose rate at a reference point defined at depth 5 mm on the applicator's central axis is 7% lower than the film and 3% higher than the MOSFET measurements. The dose rate of a Leipzig applicator with 30 mm opening at reference point is 0.241+/-3% cGy h(-1) U(-1). The MC calculated depth dose rates and profiles were tabulated for clinic use.