Sten Myrehaug

Cardiac morbidity following modern treatment for Hodgkin lymphoma : Supra-additive cardiotoxicity of doxorubicin and radiation therapy

Age- and sex-specific estimates of the rate of cardiac morbidity among Hodgkin lymphoma (HL) patients treated with doxorubicin-based chemotherapy and radiation therapy (RT) are scarce. We evaluated the risk of hospital admission for cardiac disease in 615 HL patients, adjusting for age, sex, treatment, cardiac risk factors and competing causes of death. Compared with the general population, the risk of cardiac morbidity was highest among patients treated with both doxorubicin and mediastinal RT (HR = 2.77, p < 0.0001). Mediastinal RT without chemotherapy also significantly increased the risk (HR = 1.82, p = 0.038). For females and males treated with doxorubicin plus mediastinal RT at age 40, the estimated 15-year incidence rate of cardiac hospitalisation were 7.3% and 16.5%, respectively, rates 5–15% higher than expected. These results suggest that the risk of clinically important cardiac toxicity following HL treatment that includes both doxorubicin and mediastinal RT may be greater than that reported in prior studies of patients treated with RT alone.

A Treatment Planning and Acute Toxicity Comparison of Two Pelvic Nodal Volume Delineation Techniques and Delivery Comparison of Intensity-Modulated Radiotherapy Versus Volumetric Modulated Arc Therapy for Hypofractionated High-Risk Prostate Cancer Radiotherapy

PURPOSE To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. RESULTS RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. CONCLUSION The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.

Stereotactic body radiotherapy for pancreatic cancer: recent progress and future directions.

ABSTRACT Despite advances in surgical, medical, and radiation therapy for pancreatic cancer, the prognosis remains poor. At this time, the only chance for long-term survival is surgical resection. More challenging is the optimal management of unresectable locally advanced pancreatic cancer, which has historically been treated with concurrent chemoradiation or chemotherapy alone. However, the survival and local control benefit of conventional radiotherapy in addition to chemotherapy was unclear. More recently, stereotactic body radiotherapy (SBRT) is emerging as a viable approach to maximizing local tumor control with a tolerable side effect profile. SBRT achieves sharp dose fall-off facilitating safe delivery of highly focused radiation to the tumor over 1-5 days. Although the optimal regimen of pancreas SBRT has not yet been established, its short treatment course limits the delay of additional. Future directions involve prospective study of pancreas SBRT and exploration of biomarkers and imaging technology in order to adopt a personalized management paradigm.

High-dose-rate prostate brachytherapy in a patient with bilateral hip prostheses planned using megavoltage computed tomography images acquired with a helical tomotherapy unit

PURPOSE The presence of hip prostheses results in significant image artifacts making delineation of anatomy for planning difficult with traditional kilovoltage CT images. This report presents the use of megavoltage computed tomography (MVCT) imaging acquired with a helical tomotherapy unit to plan a high-dose-rate (HDR) prostate brachytherapy treatment for a patient with bilateral hip prostheses. METHODS AND MATERIALS A 77-year-old man presented with a localized clinical Stage T3a, Gleason 7 prostate cancer. Past history was also significant for bilateral hip prostheses. Staging workup included a negative bone scan and CT of abdomen and pelvis. The pelvic CT exhibited significant streak artifacts obscuring the prostate. HDR monotherapy with adjuvant androgen deprivation therapy was proposed. On the day of the implant and after catheter insertion, MVCT imaging of the pelvic area of the patient was obtained using a commercial helical tomotherapy unit. The MVCT images were transferred to Nucletron PLATO (v14.3.2) for planning with optimization of catheter dwell positions and times. RESULTS MVCT images acquired with the helical tomotherapy unit allow good visualization of bony anatomy and of the hip prosthesis. No reconstruction streak artifacts are visible in the images as seen in the diagnostic kilovoltage CT images. Sufficient soft tissue contrast exists to allow delineation of the bladder and rectum. The absence of streak artifacts provides good quantification of Hounsfield number in the region surrounding the hip prosthesis and allows for good dose quantification. CONCLUSIONS MVCT images obtained using the commercial helical tomotherapy unit have been shown to provide good soft tissue contrast and no streak artifacts when planning a patient for prostate HDR brachytherapy having bilateral prosthetic hip replacements. The rectum and bladder can be clearly seen in the MVCT images and contoured independently. Prostate delineation is assumed from the position of the brachytherapy catheters.

Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of Caution:

Study Design: A broad narrative review. Objectives: The objective of this article is to provide a technical review of spine stereotactic body radiotherapy (SBRT) planning and delivery, indications for treatment, outcomes, complications, and the challenges of response assessment. The surgical approach to spinal metastases is discussed with an overview of emerging minimally invasive techniques. Methods: A comprehensive review of the literature was conducted on the techniques, outcomes, and developments in SBRT and surgery for spinal metastases. Results: The optimal management of patients with spinal metastases is complex and requires multidisciplinary assessment from an oncologic team that is familiar with the shifting paradigm as a consequence of evolving techniques in surgery and stereotactic radiation, as well as new developments in systemic agents. The Spinal Instability Neoplastic Score and the epidural spinal cord compression (Bilsky) grading system are useful tools that facilitate communication among oncologic team members and can direct management by providing a baseline assessment of risks prior to therapy. The combined multimodality approach with “separation surgery” followed by postoperative spine SBRT achieves thecal sac decompression, improves tumor control, and avoids complications that may be associated with more extensive surgery. Conclusion: Spine SBRT is a highly effective treatment that is capable of delivering ablative doses to the target while sparing the critical organs-at-risk, chiefly the critical neural tissues, within a short and manageable schedule. At the same time, surgery occupies an important role in select patients, particularly with the expanding availability and expertise in minimally invasive techniques. With rapid adoption of spine SBRT in centers outside of the academic setting, it is imperative for the practicing oncologist to understand the relevance and application of these evolving concepts.

Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era

Vertebral bodies remain one of the most common sites of metastases. In cases where surgical intervention is not indicated or appropriate, conventional external radiation therapy (cEBRT) has been the standard treatment modality. Unfortunately, cEBRT is typically limited, with low complete response and poor local control rates. Disappointing results with re-irradiation using cEBRT highlight the need for innovative salvage therapeutic strategies, such as stereotactic body radiotherapy. A detailed description of this complex treatment strategy is outlined, as is a systematic review of current literature. Although data are limited to single institution series, re-irradiation has consistently been found to be effective with respect to local control (1 year rates range from 66 to 90%) and pain response. Importantly, the treatment is shown to be safe, with the crude rate of radiation myelopathy <1% and a rate of vertebral compression fracture of 12%. As further research and technologic advances continue to refine therapy, stereotactic body radiotherapy is now a recommended option for the treatment of previously irradiated vertebral body metastases.

Vertebral Compression Fracture After Spine Stereotactic Body Radiation Therapy: A Review of the Pathophysiology and Risk Factors

BACKGROUND Vertebral compression fracture (VCF) is a challenging and not infrequent complication observed following spine stereotactic body radiation therapy (SBRT). OBJECTIVE To summarize the data from the multiple studies that have been published, addressing the risk and predictive factors for VCF post-SBRT. METHODS A systematic literature review was conducted. Studies were selected if they specifically addressed risk factors for post-SBRT VCF in their analyses. RESULTS A total of 11 studies were identified, reporting both the risk of VCF post-SBRT and an analysis of risk factors based on univariate and multivariate analysis. A total of 2911 spinal segments were treated with a crude VCF rate of 13.9%. The most frequently identified risk factors on multivariate analysis were: lytic disease (hazard ratio [HR] range, 2.76-12.2), baseline VCF prior to SBRT (HR range, 1.69-9.25), higher dose per fraction SBRT (HR range, 5.03-6.82), spinal deformity (HR range, 2.99-11.1), older age (HR range, 2.15-5.67), and more than 40% to 50% of vertebral body involved by tumor (HR range, 3.9-4.46). In the 9 studies that specifically reported on the use of post-SBRT surgical procedures, 37% of VCF had undergone an intervention (range, 11%-60%). CONCLUSION VCF is an important adverse effect following SBRT. Risk factors have been identified to guide the selection of high-risk patients. Evidence-based algorithms with respect to patient selection and intervention are needed.

Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference

PURPOSE Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI). METHODS AND MATERIALS Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dices similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached. RESULTS Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI. CONCLUSIONS Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

The radiobiological impact of motion tracking of liver, pancreas and kidney SBRT tumors in a MR-linac

The purpose of this work is to evaluate and quantify the potential radiobiological advantages of tumor tracking using the MR-linac for three disease sites: liver, pancreas and kidney. From each disease site, three patients were selected and 4DCT data sets were used. We applied two planning methods using the Monaco treatment planning system (Elekta AB,Stockholm,Sweden): (1) the conventional ITV method using a 6MV Agility beam and (2) a simulated tracking method using MLC GTV tracking with a 7MV MR-linac beam model incorporating a 1.5 T transverse magnetic field. A 5 mm isotropic PTV margin was added to the ITV or the GTV, and 95% of the PTV volume received 100% of the prescription dose. To evaluate the potential radiobiological advantages of tumor tracking, the normal tissue complication probabilities (NTCPs) were calculated for each organ at risk (OAR) using the Layman Kutcher Burman (LKB) model. The average reduction in the target volume, due to tracking, was 31.1%, 26.3% and 26.9% for liver, pancreas and kidney patients, respectively. For each OAR, the % differences in NTCP between the two methods were calculated. The mean 2 Gy equivalent OAR dose for all patients was less than 29.1 Gy, below which the NTCP for most OARs was not sensitive to equivalent uniform dose (EUD). As a result, a NTCP benefit, due to tracking, was observed in 26% of the data. For all three disease sites, the maximum NTCP improvements were for the normal kidney, the bowels, and the duodenum, with reductions in associated toxicities of 79% (radiation nephropathy), 69% (stricture/fistula) and 25% (ulceration), respectively. This study demonstrates the potential benefit of using a MR-linac tracking system to reduce NTCPs. The normal kidney, the bowels and the duodenum showed the largest NTCP improvements. This, in part, is due to the rapid changes in NTCP for small EUD changes.

Population description and clinical response assessment for spinal metastases: part 2 of the SPIne Response Assessment in Neuro-Oncology (SPINO) group report

Background Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group. Methods The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches. Results Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity. Conclusions Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).