SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. METHODS: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. DISCUSSION: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. TRIAL REGISTRATION: ClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Clinical applicability of and changes in perfusion MR imaging in brain metastases after stereotactic radiotherapy.

To assess the applicability of perfusion-weighted (PWI) magnetic resonance (MR) imaging in clinical practice, as well as to evaluate the changes in PWI in brain metastases before and after stereotactic radiotherapy (SRT), and to correlate these changes to tumor status on conventional MR imaging. Serial MR images at baseline and at least 3 and 6 months after SRT were retrospectively evaluated. Size of metastases and the relative cerebral blood volume (rCBV), assessed with subjective visual inspection in the contrast enhanced area, were evaluated at each time point. Tumor behavior of metastases was categorized into four groups based on predefined changes on MRI during follow-up, or on histologically confirmed diagnosis; progressive disease (PD), pseudoprogression (PsPD), non-progressive disease (non-PD) and progression unspecified (PU). Twenty-six patients with 42 metastases were included. Fifteen percent (26/168) of all PW images could not be evaluated due to localization near large vessels or the scalp, presence of hemorrhage artefacts, and in 31% (52/168) due to unmeasurable residual metastases. The most common pattern (52%, 13/25 metastases) showed a high rCBV at baseline and low rCBV during follow-up, occurring in metastases with non-PD (23%, 3/13), PsPD (38%, 5/13) and PU (38%, 5/13). Including only metastases with a definite outcome generally showed low rCBV in PsPD or non-PD, and high rCBV in PD. Although non-PD and PsPD may be distinguished from PD after SRT using the PW images, the large proportion of images that could not be assessed due to artefacts and size severely hampers value of PWI in predicting tumor response after SRT.

The ArcCHECK diode array for dosimetric verification of HybridArc.

The aim of this work is to evaluate dosimetric accuracy of a new treatment modality, HybridArc, in iPlan RT Dose 4.5 (BrainLAB, Feldkirchen, Germany) using a four-dimensional diode array (ArcCHECK, Sun Nuclear Corporation, Melbourne, USA). HybridArc is able to enhance dynamic conformal arcs with inversely planned elements. HybridArc plans for various sites (intracranial and extracranial) were constructed and after that these plans were recalculated for the ArcCHECK diode array with Monte Carlo (MC) and Pencil Beam (PB) dose algorithms in iPlan RT Dose. All measurements of these HybridArc plans were performed with 6 MV photon beams of a Novalis accelerator (BrainLAB, Feldkirchen, Germany) using the ArcCHECK device without and with an insert containing an ionization chamber. Comparison of the absolute dose distributions measured and calculated in iPlan RT Dose with the MC algorithm at the cylinder of the ArcCHECK diode array for HybridArc plans gives good agreement, even for the 2% dose difference and 2 mm distance-to-agreement criteria. The PB calculations significantly differ from the ArcCHECK measurements so that the MC algorithm is found to be superior to the PB algorithm in the calculation of the HybridArc plans. One of the drawbacks of the PB calculations in iPlan RT Dose is the too large arc step size of 10°. Use of a finer angular resolution may improve the PB results significantly.

Verification measurements and clinical evaluation of the iPlan RT Monte Carlo dose algorithm for 6 MV photon energy.

This study presents data for verification of the iPlan RT Monte Carlo (MC) dose algorithm (BrainLAB, Feldkirchen, Germany). MC calculations were compared with pencil beam (PB) calculations and verification measurements in phantoms with lung-equivalent material, air cavities or bone-equivalent material to mimic head and neck and thorax and in an Alderson anthropomorphic phantom. Dosimetric accuracy of MC for the micro-multileaf collimator (MLC) simulation was tested in a homogeneous phantom. All measurements were performed using an ionization chamber and Kodak EDR2 films with Novalis 6 MV photon beams. Dose distributions measured with film and calculated with MC in the homogeneous phantom are in excellent agreement for oval, C and squiggle-shaped fields and for a clinical IMRT plan. For a field with completely closed MLC, MC is much closer to the experimental result than the PB calculations. For fields larger than the dimensions of the inhomogeneities the MC calculations show excellent agreement (within 3%/1 mm) with the experimental data. MC calculations in the anthropomorphic phantom show good agreement with measurements for conformal beam plans and reasonable agreement for dynamic conformal arc and IMRT plans. For 6 head and neck and 15 lung patients a comparison of the MC plan with the PB plan was performed. Our results demonstrate that MC is able to accurately predict the dose in the presence of inhomogeneities typical for head and neck and thorax regions with reasonable calculation times (5-20 min). Lateral electron transport was well reproduced in MC calculations. We are planning to implement MC calculations for head and neck and lung cancer patients.

Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study.

OBJECTIVES: Most patients with advanced head and neck cancer receiving chemoradiotherapy need tube feeding for at least some weeks. For these periods gastrostomy tubes have advantages over nasogastric tubes. Tube feeding may start earlier and thus loss of weight may be limited if the gastrostomy tube already is in place. The objective of this study is to analyse the results of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement and early tube feeding. DESIGN: Retrospective chart review. SETTING: Multidisciplinary head and neck oncology team in a general hospital. PARTICIPANTS: Fifty consecutive patients with unresectable stage III and IV head and neck cancer treated with concurrent chemoradiotherapy. In all patients prophylactic PEG placement was performed. Tube feeding was initiated if food-intake became insufficient or loss of weight occurred. MAIN OUTCOME MEASURES: Loss of weight during treatment, complication rate, PEG duration. RESULTS: The mean loss of weight during treatment for all patients was only 2.8%. One complication of tube placement occurred: a colon perforation, treated successfully by surgery. The median duration of the PEG was 178 days. Three of the 17 patients (18%) with no evidence of disease (NED) still had a PEG at their last follow-up visit. Of the 26 patients who died of their cancer, 13 used the PEG until death. CONCLUSIONS: Loss of weight was limited after prophylactic gastrostomy placement and early tube feeding. Moreover, the complication rate was low. In 82% of the NED patients the PEG could eventually be removed.

Contrast vaginography is more accurate than the radiopaque rod for localization of the vagina.

PURPOSE: To compare the radiopaque vaginal rod method with contrast vaginography in localization of the vagina. METHODS AND MATERIALS: In 25 female patients who needed pelvic radiotherapy, both our standard localization procedure using the vaginal rod and a localization procedure using contrast vaginography were performed. As a rod can change the position of the vagina, contrast vaginography was considered to display the true anatomic position of the vagina. The corresponding rod and nonrod X-rays of each patient were compared. The distance from the true vaginal apex to the displaced vaginal apex (= the top of the rod) was measured in the sagittal plane. This distance was called the inaccuracy of the rod method. Furthermore, the size of the vaginal vault was measured using the contrast vaginography. RESULTS: The median inaccuracy of the rod method was 13 mm (range 2 to 24 mm). The maximal width of the vagina ranged from 24 to 68 mm in the frontal plane (median 39 mm) and from 3 to 22 mm in the sagittal plane (median 10 mm). CONCLUSION: The rod method is not accurate to localize the vagina. Furthermore, the rod gives no information on the actual size of the vaginal vault. Contrast vaginography is the method of choice to localize the vagina.

Measuring radiation fibrosis: the interobserver reliability of two methods of determining the degree of radiation fibrosis.

PURPOSE: To compare the interobserver reliability of the palpation method with the method of measuring tissue compliance with a tissue compliance meter (TCM) on women who underwent breast-conserving surgery and radiotherapy for breast cancer. METHODS AND MATERIALS: Thirty-eight patients and 30 controls were measured with the palpation method by two radiation oncologists and with the TCM by two physiotherapists. Measurements were taken on four locations of the breasts of all 68 women. Reliability coefficients were computed for both methods. A weighted kappa score was computed for the palpation method and this was compared with the intraclass correlation coefficient (ICC) computed for the TCM method. The conditions for direct comparison of these scores were met in this study. RESULTS: A weighted kappa of 0.65 was computed for the palpation method and an ICC of 0.91 was computed for the TCM method. These scores differ significantly from each other (p < 0.01). CONCLUSION: The interobserver reliability of the TCM method is superior to that of the palpation method. However, at locations where the TCM is not applicable, palpation is a good alternative.

The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.

PURPOSE: To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. PATIENTS: 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%). METHOD: Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated. RESULTS: On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule. CONCLUSION: The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.

The importance of vocal cord mobility in T2 laryngeal cancer.

In a retrospective study 75 patients with T2 laryngeal cancer treated from 1981 through 1985 were analysed. Of this group 71 patients had a full course of radiotherapy as primary therapy. All 71 patients were given 70 Gy/7 weeks on the primary and 50 Gy/5 weeks on the neck, 2 Gy per fraction. Various prognostic factors for local control and survival were studied. In our patient group we found vocal cord mobility to be an important prognostic factor for ultimate local control and survival. Patients with impaired cord mobility had a significantly worse ultimate local control (76%) than patients with normal cord mobility (98%) and a significantly worse corrected actuarial survival. It is concluded that impaired cord mobility means more advanced disease. Future studies will have to answer the question how to improve the local control rate in patients with impaired cord mobility, for example, by incorporating laryngectomy earlier in the treatment program of those patients who can not be cured by radiotherapy alone or by using innovative radiotherapy protocols.

Regression after 50 Gy as a selection for therapy in advanced laryngeal cancer.

Radiation alone for advanced laryngeal cancer will result in an initial local control rate of 50%. When a local recurrence is diagnosed, only 50% will be successfully salvaged by surgery. To identify patients with a high chance of local control with radiation alone in advanced laryngeal cancer, the clinical response following radiotherapy was assessed a few days after 50 Gy/5 weeks. In patients with T-stage reduction or greater than 50% tumor regression radiotherapy was continued, if not, laryngectomy was performed after 4-6 weeks. According to this protocol 30 patients (out of 50) with T3/T4 laryngeal cancer were treated. Initial local control was assessed 6 weeks after radiotherapy, the ultimate local control included successful salvage surgery. Initial local control in patients, treated with a full course of radiotherapy after T-stage reduction or greater than 50% tumor regression, was 69% for T3 and 43% for T4 while the ultimate local control rate was 85% and 71% respectively. Although the percentage of voice preservation in our study was slightly lower (40%) than data from literature with radiation alone, the ultimate local control was high and comparable with those of combined therapy (in which laryngectomy is a part). The corrected actuarial 5-year survival in all T3 and T4 patients treated with radiation alone and salvage surgery was 73% and 31% respectively and was not different compared to surgery with pre- or post-operative radiotherapy, 74% and 53% respectively. We believe that this protocol may select a favorable group of patients for high dose radiation alone in T3 and probably in T4 laryngeal cancer.