Evaluating AI-generated CBCT-based synthetic CT images for target delineation in palliative treatments of pelvic bone metastasis at conventional C-arm linacs.

PURPOSE: One-table treatments with treatment imaging, preparation and delivery occurring at one treatment couch, could increase patients' comfort and throughput for palliative treatments. On regular C-arm linacs, however, cone-beam CT (CBCT) imaging quality is currently insufficient. Therefore, our goal was to assess the suitability of AI-generated CBCT based synthetic CT (sCT) images for target delineation and treatment planning for palliative radiotherapy. MATERIALS AND METHODS: CBCTs and planning CT-scans of 22 female patients with pelvic bone metastasis were included. For each CBCT, a corresponding sCT image was generated by a deep learning model in ADMIRE 3.38.0. Radiation oncologists delineated 23 target volumes (TV) on the sCTs (TVsCT) and scored their delineation confidence. The delineations were transferred to planning CTs and manually adjusted if needed to yield gold standard target volumes (TVclin). TVsCT were geometrically compared to TVclin using Dice coefficient (DC) and Hausdorff Distance (HD). The dosimetric impact of TVsCT inaccuracies was evaluated for VMAT plans with different PTV margins. RESULTS: Radiation oncologists scored the sCT quality as sufficient for 13/23 TVsCT (median: DC = 0.9, HD = 11 mm) and insufficient for 10/23 TVsCT (median: DC = 0.7, HD = 34 mm). For the sufficient category, remaining inaccuracies could be compensated by +1 to +4 mm additional margin to achieve coverage of V95% > 95% and V95% > 98%, respectively in 12/13 TVsCT. CONCLUSION: The evaluated sCT quality allowed for accurate delineation for most targets. sCTs with insufficient quality could be identified accurately upfront. A moderate PTV margin expansion could address remaining delineation inaccuracies. Therefore, these findings support further exploration of CBCT based one-table treatments on C-arm linacs.

Brain Metastases: Patient-Reported Outcome and Quality of Life after Whole-Brain Radiotherapy.

Purpose: The aim of this prospective cohort study was to determine the outcome and quality of life (QoL) for patients with brain metastases treated with whole-brain radiotherapy (WBRT). Materials and Methods: WBRT was given to 162 patients. Treatment outcome was reported through telephone consultation at four and eight weeks after the last fraction of the treatment. Treatment outcome was scored as a benefit when patients reported positively on the question whether radiotherapy of the whole brain did relieve their complaints. Patients who scored the treatment as beneficial were categorized as responders. The European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C15-PAL was scored at day 0 and eight weeks after the last fraction of WBRT. Results: Patients who were alive after 2 months and reported benefit from treatment had a median survival of 8.1 months compared with 2.9 months for patients who reported no benefit. Forty-three patients died within two months (27%). Median overall survival was 3.5 months. Improvement of neurological symptoms was the most commonly reported benefit of the treatment. The responders had significantly better sleep (p = 0.032) and were less tense (p = 0.014). The nonresponders were also less tense (p = 0.042), but had less appetite (p = 0.023), felt weaker (p = 0.011), and experienced more fatigue (p = 0.001). Conclusions: WBRT is effective in a selected group of patients. Forty-nine percent of the patients surviving two months reported benefit from the treatment, resulting in a significantly increased survival rate for this group. However, 27% of patients died within two months. QoL increased in responders, but decreased in nonresponders.

Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.

PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.

Pain flare, complexity and analgesia in bone oligometastases treated with stereotactic body radiation therapy.

The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS ≥ 2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n = 18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n = 23), pain control was obtained in 62% of patients at 1 year; median time to pain progression after SBRT was 29 months (CI95% 6-52 months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30 months, p = 0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies.

Effectiveness and toxicity of conventional radiotherapy treatment for painful spinal metastases: a detailed course of side effects after opposing fields versus a single posterior field technique.

BACKGROUND: Conventional radiotherapy for painful spinal metastases can be delivered with a single posterior-anterior (PA) or two opposed anterior-posterior (APPA) fields. We studied the effectiveness and toxicity of both techniques and studied whether treatment technique was predictive for abdominal and skin toxicity. PATIENTS AND METHODS: Within the Dutch Bone Metastasis Study, 343 patients received 8 Gray in a single fraction or 24 Gray in six fractions for painful spinal metastases. Treatment technique was not randomized. At baseline and weekly during follow-up, patients reported pain and other physical complaints. Any complaint increasing within 4 weeks after treatment was noted as a side effect. Pain response was calculated according to international standards, taking into account changes in pain score and medication. Repeated measurement analyses and multivariate logistic analyses were performed. RESULTS: Patients were mainly treated on the thoracic (34%) and lumbar (53%) spine and 73% received a PA field. Pain response was similar between both techniques (74%). In patients treated at the thoraco-lumbar and lumbar spine, with multiple fractions, significantly more abdominal complaints were noticed. In multivariate analysis, radiotherapy technique did not predict for side effects. CONCLUSION: Conventional radiotherapy of painful spinal metastases provides limited toxicity. Radiotherapy technique is not an independent predictor of abdominal and skin toxicity of irradiation.

A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities.

UNLABELLED: Accumulating evidence suggests significant synergism combining radiotherapy (RT) with angiogenesis targeted therapies. This multicenter prospective phase I clinical trial established the safety profile and recommended dose for further studies of pazopanib concurrent with preoperative RT in patients with extremity soft tissue sarcomas (ESTS) in curative setting. METHODS: Patients with deep seated intermediate and high grade sarcomas, ≥ 5 cm, received once daily pazopanib (dose-escalation cohorts 400 mg, 600 mg and 800 mg) for 6 weeks and 50 Gy preoperative RT starting Day 8. Surgery was performed 5-7 weeks later. Toxicity was scored according to CTC criteria 4.0. Dose limiting toxicities (DLT) were divided into two separate sets; DLT-I being toxicities occurring during the 6-week chemoradiotherapy period within the radiation portals until day of surgery (designated as DLT-I) and those occurring perioperatively until Day 21 after surgery (DLT-II). RESULTS: A total of 12 patients were enrolled, 11 were evaluable (3 females and 8 males, median age 58 years, range 24-78 years, median tumor size 9 cm, range 5-15 cm). Ten underwent surgery. No increased toxicity inside the radiation fields was seen, but two of 10 patients (one each in the 400 mg and 600 mg cohorts) showed delayed wound healing after surgery. None of the patients showed significant volume reductions after RT. Evaluation of the resection specimen showed pathological (near) complete responses (≥ 95% necrosis rate) in four of 10 cases. Unexpectedly, grade 3 + hepatotoxicity led to premature pazopanib interruption in three of 11 (27%) of cases. CONCLUSION: Apart from hepatotoxicity, neoadjuvant pazopanib 800 mg daily in combination with 50 Gy seems tolerable; the regimen appears to demonstrate promising activity in ESTS and is the recommended dose for further studies.

Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix-uterus shape and position.

BACKGROUND AND PURPOSE: To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. METHODS AND MATERIALS: For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. RESULTS: The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. CONCLUSION: For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy.

Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: proof of principle.

PURPOSE: To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy. MATERIALS AND METHODS: Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner. RESULTS: Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm±10.8 with a residual of only 2.2 mm±1.7. For the marker-CoM, the 8.4 mm±5.3 mean positioning error was predicted with a residual of 0.9 mm±0.7. After 40Gy, the mean ToU displacement was 26.8 mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5mm±11.2 for systematic errors in SI-direction). CONCLUSIONS: Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.

Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimensional ultrasound bladder scanner.

BACKGROUND AND PURPOSE: For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements. METHODS AND MATERIALS: For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations. RESULTS: Measured US and CT bladder volumes were strongly correlated (R = 0.97, slope 1.1 +/- 0.1). The population mean bladder volume at planning of 378 +/- 209 ml (1 SD) reduced to 109 +/- 88 ml (1 SD) in week 6, a reduction by 71% (average reduction 46 ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168 ml (1 SD) (range 70-266 ml). Rotation around the LR axis was significantly correlated with bladder volume changes. CONCLUSIONS: Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation.

Cardiac metastases.

We report a case of esophageal cancer with symptomatic metastases to the heart; the patient was treated with short-course radiotherapy with good symptomatic relief. We reviewed the current literature regarding the epidemiology, clinical presentation, diagnostic tools, treatment modalities, and the prognosis of cardiac metastases. In this report we summarize the most recent autopsy studies (published between 1975 and 2007), in which we found an autopsy incidence of cardiac metastases of 2.3% among the general population, while the incidence among autopsies of cancer patients was 7.1%. Therefore, we share the opinion with others that there has been an increase in the incidence of cardiac metastases among cancer patients diagnosed after 1970, in comparison with the reported incidences in older series before 1970 (7.1% vs 3.8%; Kruskal-Wallis rank test; P = 0.039). Special attention was given to the role of radiotherapy in the management of cardiac metastases.