Matthew Foote

Stereotactic body radiotherapy for spinal metastases: current status, with a focus on its application in the postoperative patient. A review

Stereotactic body radiotherapy (SBRT) for spinal metastases is an emerging therapeutic option aimed at delivering high biologically effective doses to metastases while sparing the adjacent normal tissues. This technique has emerged following advances in radiation delivery that include sophisticated radiation treatment planning software, body immobilization devices, and capabilities of detecting and correcting patient positional deviations with image-guided radiotherapy. There are limited clinical data specifically supporting the role of SBRT as a superior alternative to conventional radiation in the postoperative patient. The focus of this review was to examine the evidence pertaining to spine SBRT in the treatment of spinal metastases and to provide a comprehensive analysis of published patterns of failure, with emphasis on the postoperative patient.

Results of a prospective study of positron emission tomography–directed management of residual nodal abnormalities in node‐positive head and neck cancer after definitive radiotherapy with or without systemic therapy

The purpose of this study was to present our prospectively evaluated positron emission tomography (PET)‐directed policy for managing the neck in node‐positive head and neck squamous cell carcinoma (N+HNSCC) after definitive radiotherapy (RT) with or without concurrent systemic therapy.

The role of radiotherapy alone in patients with merkel cell carcinoma: reporting the Australian experience of 43 patients.

PURPOSE To review the role of radiotherapy (RTx) alone in patients with Merkel cell carcinoma (MCC). METHODS AND MATERIALS The records of 43 patients with MCC treated with RTx alone between 1993 and 2007 at the Westmead and Royal Brisbane/Mater Hospitals, Australia, were reviewed. Multivariate analysis was performed by use of Cox regression analysis. RESULTS The median age was 79 years (range, 48-91 years) in 19 women (44%) and 24 men (56%). All patients were white, and 5 (12%) had immunosuppression. A majority (56%) underwent irradiation at initial diagnosis, with the remainder (44%) treated in the relapse setting. The median duration of follow-up was 39 months. The head and neck comprised the most frequently treated site (47%). The median maximum lesion size was 30 mm (range, 5-130 mm). Relapse developed in 60% of patients, with most being out-of-field relapses. The in-field control rate was 75%. Most out-of-field relapses were to visceral organs. Relapse developed outside the irradiated field in 53% of patients. On multivariate analysis, only nodal status (negative nodes vs. nodes present) was significantly associated with relapse-free survival, with p = 0.005 (hazard ratio, 0.25; 95% confidence interval, 0.96-0.663). Overall survival at 2 and 5 years was 58% and 37%, respectively. CONCLUSIONS Patients with MCC treated with RTx have a high likelihood of obtaining in-field control. Doses of 50 to 55 Gy in 20 to 25 fractions are recommended. A minority of patients are cured, with many dying of systemic relapse. Lower dose fractionation schedules (e.g., 25 Gy in 5 fractions) may be considered in patients with a very poor performance status.

Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

PURPOSE To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). PATIENTS AND METHODS This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. RESULTS Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%) were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving >or=50 Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). CONCLUSION This study indicates a dose-response for subclinical and gross MCC. Doses of >or=50 Gy for subclinical disease and >or=55 Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.

Therapeutic gold, silver, and platinum nanoparticles

There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high-Z nature of gold dramatically increases the photoelectric cross-section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor-killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems.

Technique for stereotactic body radiotherapy for spinal metastases

Stereotactic body radiotherapy (SBRT) is an emerging technique for spinal tumours that is a natural succession to brain radiosurgery. The spine is an ideal site for SBRT due to its relative immobility and the potential clinical benefits of high dose delivery, particularly to optimise local control and avoid disease progression that can result in spinal cord compression. However, the proximity of the tumour to the spinal cord, with the potential for radiation myelopathy if the dose is delivered inaccurately or if the spinal cord dose limit is set too high, demands technical accuracy with radiation myelopathy a feared complication. Spine SBRT has been delivered with either a robotic-based linac system such as the Cyberknife, or with linac-based systems equipped with a multileaf collimator and image guidance system. Regardless of the technology, spine SBRT demands sophisticated treatment planning and delivery. This case-based technical review outlines the SBRT apparatus, planning and treatment delivery in use at the University of Toronto, Toronto, Canada.

Impact of Immobilization on Intrafraction Motion for Spine Stereotactic Body Radiotherapy Using Cone Beam Computed Tomography

PURPOSE Spine stereotactic body radiotherapy (SBRT) involves tight planning margins and steep dose gradients to the surrounding organs at risk (OAR). This study aimed to assess intrafraction motion using cone beam computed tomography (CBCT) for spine SBRT patients treated using three immobilization devices. METHODS AND MATERIALS Setup accuracy using CBCT was retrospectively analyzed for 102 treated spinal metastases in 84 patients. Thoracic and lumbar spine patients were immobilized with either an evacuated cushion (EC, n = 24) or a semirigid vacuum body fixation (BF, n = 60). For cases treated at cervical/upper thoracic (thoracic [T]1-T3) vertebrae, a thermoplastic S-frame (SF) mask (n = 18) was used. Patient setup was corrected by using bony anatomy image registration and couch translations only (no rotation corrections) with shifts confirmed on verification CBCTs. Repeat imaging was performed mid- and post-treatment. Patient translational and rotational positioning data were recorded to calculate means, standard deviations (SD), and corresponding margins ± 2 SD for residual setup errors and intrafraction motion. RESULTS A total of 355 localizations, 333 verifications, and 248 mid- and 280 post-treatment CBCTs were analyzed. Residual translations and rotations after couch corrections (verification scans) were similar for all immobilization systems, with SDs of 0.6 to 0.9 mm in any direction and 0.9° to 1.6°, respectively. Margins to encompass residual setup errors after couch corrections were within 2 mm. Including intrafraction motion, as measured on post-treatment CBCTs, SDs for total setup error in the left-right, cranial-caudal, and anterior-posterior directions were 1.3, 1.2, and 1.0 mm for EC; 0.9, 0.7, and 0.9 mm for BF; and 1.3, 0.9, and 1.1 mm for SF, respectively. The calculated margins required to encompass total setup error increased to 3 mm for EC and SF and remained within 2 mm for BF. CONCLUSION Following image guidance, residual setup errors for spine SBRT were similar across three immobilization systems. The BF device resulted in the least amount of intrafraction motion, and based on this device, we justify a 2-mm margin for the planning OAR and target volume.

Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the groups first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Merkel cell carcinoma: The prognostic implications of an occult primary in stage IIIB (nodal) disease

BACKGROUND Merkel cell carcinoma is a highly aggressive cutaneous malignancy with a high rate of lymph node and distant metastatic disease. Approximately one third of patients present with stage IIIB (nodal) disease. OBJECTIVE This cohort study was performed to analyze the outcome of patients with stage IIIB disease with or without an occult primary. METHODS The details of 91 patients with stage IIIB (nodal) Merkel cell carcinoma treated curatively between 1985 and 2010 at 3 tertiary referral hospitals in Australia were reviewed. Kaplan-Meier plots were used with the primary end point being overall survival. Secondary end points were disease-free survival and relapse-free survival. A multivariate Cox regression analysis was performed for known prognostic factors. RESULTS Of 91 patients with stage IIIB (nodal) disease, 36 (40%) had an occult primary. A total of 78 patients (86%) had surgery and 79 patients (87%) had definitive or adjuvant radiotherapy. With a median follow-up of 4.3 years, those with an occult primary did significantly better in terms of overall survival, disease-free survival, and relapse-free survival. On multivariate analysis, occult primary and patient age were the only factors predicting survival with hazard ratios of 0.30 (95% confidence interval 0.13-0.67) and 1.64 (95% confidence interval 1.13-2.38), respectively. LIMITATIONS This is a retrospective study over several decades with patients treated using various modalities. CONCLUSION This study indicates that for patients with stage IIIB (nodal) Merkel cell carcinoma, the presence of an occult primary confers a significantly better prognosis that may have implications in the future staging and treatment of patients with stage III disease.

Desmoplastic melanoma: the role of radiotherapy in improving local control

Background:  Desmoplastic melanoma (DM) is a rare subtype of cutaneous malignant melanoma reported to have a high local recurrence rate with surgical excision alone. The incidence of regional and distant metastasis is considered to be lower than traditional cutaneous melanoma, warranting more aggressive treatment of local disease. We conducted a retrospective analysis of patients with DM treated through the Princess Alexandra Hospital Melanoma Clinic to address the role of radiotherapy in the local control of this tumour.