Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies.

A safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly demonstrated by our human tumor ex vivo assay. Temporary endocytosis inhibition results in enhanced target availability and improved efficiency of natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC), a mediator of clinical responses induced by IgG1 antibodies, demonstrated here for cetuximab, trastuzumab, and avelumab. Extensive analysis of downstream signaling pathways ruled out on-target toxicities. By overcoming the heterogeneity of drug target availability that frequently characterizes poorly responsive or resistant tumors, clinical application of reversible endocytosis inhibition may considerably improve the clinical benefit of ADCC-mediating therapeutic antibodies.

Cost-utility analysis of a telehealth psychological support intervention for people with primary brain tumor: Telehealth Making Sense of brain tumor.

OBJECTIVE: To undertake an economic evaluation of a telehealth psychological support intervention for patients with primary brain tumor (PBT). METHODS: A within-trial cost-utility analysis over 6 months was performed comparing a tailored telehealth-psychological support intervention with standard care (SC) in a randomized control trial. Data were sourced from the Telehealth Making Sense of Brain Tumor (Tele-MAST) trial survey data, project records, and administrative healthcare claims. Quality-adjusted life years (QALYs) were calculated based on the EuroQol-5D-5L. Non-parametric bootstrapping with 2000 iterations was used to determine sampling uncertainty. Multiple imputation was used for handling missing data. RESULTS: The Tele-MAST trial included 82 participants and was conducted in Queensland, Australia during 2018-2021. When all healthcare claims were included, the incremental cost savings from Tele-MAST were -AU$4,327 (95% CI: -$8637, -$18) while incremental QALY gains were small at 0.03 (95% CI: -0.02, 0.08). The likelihood of Tele-MAST being cost-effective versus SC was 87% at a willingness-to-pay threshold of AU$50,000 per QALY gain. When psychological-related healthcare costs were included only, the incremental cost per QALY gain was AU$10,685 (95% CI: dominant, $24,566) and net monetary benefits were AU$534 (95% CI: $466, $602) with a 65% likelihood of the intervention being cost-effective. CONCLUSIONS: Based on this small randomized controlled trial, the Tele-MAST intervention is a cost-effective intervention for improving the quality of life of people with PBT in Australia. Patients receiving the intervention incurred significantly lower overall healthcare costs than patients in SC. There was no significant difference in costs incurred for psychological health services.

Individuals' perceptions of health and well-being in the context of stereotactic radiosurgery for benign brain tumour: A longitudinal qualitative investigation.

BACKGROUND AND OBJECTIVES: Treatment-related outcomes after Gamma Knife Stereotactic Radiosurgery (GKSRS) for benign brain tumour are well-established; yet patient reported outcomes have been largely overlooked. This study explored individuals' perspectives of their health and well-being prior to and following GKSRS. METHOD: Twenty adults (65% female) aged 24-71 years with benign brain tumour were recruited from a major metropolitan hospital and assessed approximately one week prior to, two weeks after, and at three months following GKSRS. They completed telephone-based interviews focusing on general health, symptoms, and well-being. Interviews were transcribed and analysed using thematic analysis. RESULTS: Three major themes characterized individuals' perceptions of their health and well-being. "Understanding my Illness and Treatment" reflected individuals' efforts to make sense of their illness and symptoms to reduce ambiguity and increase sense of control. "Experiencing Gamma Knife" related to expectations of the procedure, outcomes, daily impacts, and emotional reactions. "Adjusting one's Mindset and Coping" characterised how peoples' approaches to coping with their illness were altered over time. CONCLUSIONS: Coping and adjustment is highly individualistic in the context of GKSRS. Over time, most individuals were able to make sense of their illness, adjust their mindset and utilize behavioural strategies and support systems to cope with the long-term effects.

Evaluation of the telehealth making sense of brain tumor psychological support intervention for people with primary brain tumor and their caregivers: A randomized controlled trial.

OBJECTIVE: This pragmatic randomized control trial aimed to evaluate clinical efficacy of the Making Sense of Brain Tumour program delivered via videoconferencing (Tele-MAST) for improving mental health and quality of life (QoL) relative to standard care in individuals with primary brain tumor (PBT). METHOD: Adults with PBT experiencing at least mild distress (Distress Thermometer ≥4) and caregivers were randomly allocated to the 10-session Tele-MAST program or standard care. Mental health and QoL were assessed pre-intervention, post-intervention (primary endpoint), and 6-weeks and 6-months follow-up. The primary outcome was clinician-rated depressive symptoms on the Montgomery-Asberg Depression Rating Scale. RESULTS: 82 participants with PBT (34% benign, 20% lower-grade glioma, 46% high-grade glioma) and 36 caregivers were recruited (2018-2021). Controlling for baseline functioning, Tele-MAST participants with PBT had lower depressive symptoms at post-intervention (95% CI: 10.2-14.6, vs. 15.2-19.6, p = 0.002) and 6-weeks post-intervention (95% CI: 11.5-15.8 vs. 15.6-19.9, p = 0.010) than standard care, and were almost 4 times more likely to experience clinically reduced depression (OR, 3.89; 95% CI: 1.5-9.9). Tele-MAST participants with PBT also reported significantly better global QoL, emotional QoL and lower anxiety at post-intervention and 6-weeks post-intervention than standard care. There were no significant intervention effects for caregivers. At 6-months follow-up participants with PBT who received Tele-MAST reported significantly better mental health and QoL relative to pre-intervention. CONCLUSIONS: Tele-MAST was found to be more effective for reducing depressive symptoms at post-intervention than standard care for people with PBT but not caregivers. Tailored and extended psychological support may be beneficial for people with PBT.

"Hey, I'm still here!": Maintaining, managing and rebuilding social connections after brain tumour.

It is well recognized that social networks can buffer the adverse effects of chronic illness on psychological wellbeing. However, the functional impairments associated with brain tumour often affect social participation, which may reduce people's capacity to draw upon their social capital for support. This qualitative phenomenological study aimed to understand how brain tumour influences people's ability to manage, maintain, and rebuild their social networks. Participants were 20 individuals (65% female) aged 22-69 years with diverse types of primary brain tumour (50% high grade or malignant) who were on average 35 months post-diagnosis. Two semi-structured interviews, conducted three months apart, comprised a Social Identity Mapping exercise and questions exploring changes in social groups since diagnosis. Two overarching and interrelated themes emerged: engaging and connecting and then versus now. An interplay of barriers, facilitators and strategies influenced people's ability to engage and connect with their social groups, which in turn influenced whether they experienced stability; maintenance and expansion; loss and rebuilding; or loss and shrinkage of their social networks over time. These novel findings highlight the need to develop interventions that specifically focus on enhancing individuals' abilities to maintain or rebuild their social networks.

Feasibility and acceptability of a telehealth platform for delivering the Making Sense of Brain Tumour programme: A mixed-methods pilot study.

ABSTRACTGlioma is a common type of brain tumour that is associated with neurocognitive and psychosocial impairments. This study primarily aimed to investigate the feasibility and acceptability of a videoconferencing format of the Making Sense of Brain Tumour (Tele-MAST) programme. Recruited from a multidisciplinary brain tumour clinic, participants were randomly allocated to the 10-session Tele-MAST programme or standard care, with the latter group offered Tele-MAST after re-assessment. Semi-structured interviews explored participants' experiences of receiving psychological support via the videoconferencing platform. Measures of mental health and quality of life were administered at pre-intervention and post-intervention assessments. Of the 35 patients deemed eligible for the study, 14 (40% accrual) with high grade (71%) or low grade (29%) glioma participated. They were randomized to the Tele-MAST condition (n = 8) or standard care/waitlist (n = 6). Ten individuals commenced the Tele-MAST programme, of whom eight completed ≥8 sessions. The major themes that depicted their experience of the Tele-MAST programme were ease of access and benefits of remote delivery, tailored support and immediacy, and sense of connection versus disconnection. Most participants (63%) demonstrated clinically reliable improvement at post-intervention. These preliminary findings support the feasibility and acceptability of remote delivery of psychological support and highlight the need for a larger-scale evaluation of the Tele-MAST programme.

Radiation Necrosis from Stereotactic Radiosurgery-How Do We Mitigate?

OPINION STATEMENT: Intracranial stereotactic radiosurgery (SRS) is an effective and convenient treatment for many brain conditions. Data regarding safety come mostly from retrospective single institutional studies and a small number of prospective studies. Variations in target delineation, treatment delivery, imaging follow-up protocols and dose prescription limit the interpretation of this data. There has been much clinical focus on radiation necrosis (RN) in particular, as it is being increasingly recognized on follow-up imaging. Symptomatic RN may be treated with medical therapy (such as corticosteroids and bevacizumab) with surgical resection being reserved for refractory patients. Nevertheless, RN remains a challenging condition to manage, and therefore upfront patient selection for SRS remains critical to provide complication-free control. Mitigation strategies need to be considered in situations where the baseline risk of RN is expected to be high-such as large target volume or re-irradiation. These may involve reduction in the prescribed dose or hypofractionated stereotactic radiation therapy (HSRT). Recently published guidelines and international meta-analysis report the benefit of HSRT in larger lesions, without compromising control rates. However, careful attention to planning parameters and SRS techniques still need to be adhered, even with HSRT. In cases where the risk is deemed to be high despite mitigation, a combination approach of surgery with or without post-operative radiation should be considered.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

BACKGROUND AND OBJECTIVE: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. METHODS: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/ß = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. RESULTS: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. CONCLUSION: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Extent of surrounding edema does not correlate with acute complications after radiosurgery for melanoma brain metastases.

AIM: To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM). METHODS: Patients with melanoma BM treated with SRS were included in a single center retrospective analysis. A contrast-enhanced magnetic resonance image (MRI) brain was acquired on the day of treatment and used to calculate the volume of the largest lesion (the index BM) and total volume of all BM. Their corresponding volume of surrounding edema was defined based on the fluid attenuated inversion recovery (FLAIR) sequence. After SRS, MRI was performed every 3 months for at least 2 years if the patient remained well enough to do so. Adverse neurologic events after SRS were defined using common terminology criteria for adverse events (CTCAE) version 5.0. Multivariate regression analyses assessed for associations between BM size and edema at baseline with increasing edema and neurologic adverse events within 3 months after SRS. RESULTS: Mean volume of the index BM reduced from 2.2 to 0.5 cm3 at 3 months after SRS (p = 0.03). Mean volume of edema surrounding the index BM was 6.4 cm3 at baseline, 10.2 cm3 at 3 months and 5.5 cm3 at 6 months. There were 7/43 (16%) patients that experienced an adverse neurological event within 3 months (attributable to any cause) and 4/43 (9%) were associated with an increase in BM edema. On univariate and multivariate analyses, there were no correlations between any baseline factors and volume of edema at 3 months. However, SRS dose delivered and systemic therapy use within 4 weeks of SRS both correlated with a reduction in edema surrounding the index BM. CONCLUSION: A transient increase in mean volume of edema was apparent at 3 months after SRS. However, this resolved by 6 months and did not correlate with adverse events or dexamethasone requirement. Thus, the clinical significance is uncertain.

The importance of staying connected: Mediating and moderating effects of social group memberships on psychological well-being after brain tumor.

OBJECTIVE: Functional impairments can lower psychological well-being after brain tumor. Changes in social groups and confidence in support potentially impact this relationship. This study aimed to investigate the influence of social group memberships (SGMs) on the relationship between perceived cognitive and physical impairment and psychological well-being. METHODS: Seventy adults (60% female) with primary brain tumor (46% benign; 18% low grade; 36% high grade) aged 22 to 75 years undertook a brief cognitive test (Brief Test of Adult Cognition by Telephone) then completed self-report measures of cognitive and physical impairment (Functional Assessment of Cancer Therapy), social groups (Exeter Identity Transition Scale), confidence in social support (Self-Efficacy Scale), depression (depression scale of the 21-item Depression, Anxiety and Stress Scale), anxiety (General Anxiety Disorder 7-item scale), and life satisfaction (Satisfaction With Life Scale). The mediating and moderating effects of SGMs were tested using a bootstrapping method and PROCESS macro. RESULTS: Greater perceived cognitive and physical impairments were significantly related to poorer psychological well-being. Mediation analyses indicated significant indirect effects of social group loss for depression and anxiety (P < .05), whereby the relationship between perceived functional impairment and depression and anxiety was partly accounted for by loss of SGMs. Confidence in social groups was a moderator for depression and anxiety (P < .001), such that those perceiving high levels of physical and cognitive impairments who were more confident in their social groups reported lower depression and anxiety. CONCLUSIONS: Functional impairment is in part related to higher levels of depression and anxiety through loss of social groups. However, greater confidence in social support can buffer the effects of functional impairment on psychological well-being after brain tumor. Interventions focusing on ways to maintain social participation and supportive relationships may be beneficial.

Evaluation of a telehealth psychological support intervention for people with primary brain tumour and their family members: Study protocol for a randomised controlled trial.

OBJECTIVE: There is a lack of research on interventions that address the specific psychosocial needs of people with brain tumour and their families. This paper describes the protocol for a pragmatic randomised control trial (RCT) evaluating the clinical efficacy and cost-effectiveness of the Making Sense of Brain Tumour program delivered via telehealth (Tele-MAST) relative to standard care. METHODS: The 148 adults with primary brain tumour will be randomly allocated to the 10-session Tele-MAST videoconferencing program or standard care from a cancer counselling service. The primary outcome is level of depression and secondary outcomes are quality of life, mental health and incremental cost per quality-adjusted life year. The mental health and quality of life of family members will also be assessed. Assessments will be conducted at pre-intervention, post-intervention (primary endpoint), 6-weeks post-intervention and 6-months post-intervention. The main analysis will determine whether the Tele-MAST intervention is more effective than standard care at post-intervention, and whether these effects are sustained at follow-up. CONCLUSION: Results will indicate whether the Tele-MAST program is associated with better clinical outcomes and is more cost-effective than existing cancer support services. Such outcomes will contribute to effective and accessible psychosocial care for the brain tumour population.

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study.

BACKGROUND: Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease. METHODOLOGY: An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. RESULTS: Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03). CONCLUSIONS: Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

In response to Fogarty et al. and why adjuvant whole brain radiotherapy is not recommended routinely.

The routine use of adjuvant whole brain radiotherapy (AWBRT) after surgery or stereotactic radiosurgery is now discouraged by a number of international expert panels. Three decades of randomised studies have shown that, although AWBRT improves radiological measures of intracranial disease control, the clinical benefit is unclear and it is also associated with inferior quality of life and neurocognitive function. The number of patients with melanoma in these trials was low, but data suggesting that treatment-related side effects should vary according to histology of the primary malignancy are lacking. For metastatic melanoma, the role of AWBRT to control microscopic disease in the brain is also a less relevant concern because systemic therapies with intracranial activity are now available. Whether AWBRT is useful in select patients deemed at high risk of neurologic death remains undefined.

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma.

BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy. RESULTS: Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (<10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events. CONCLUSIONS: The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

AIM: Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. MATERIALS & METHODS: Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. RESULTS & CONCLUSION: We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up.

Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns. Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3), or no agreement. Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2-5) and three within a single organ (range 2-5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up. Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.

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 group's 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.

Patterns of Recurrence in Patients with Stage IIIB/C Cutaneous Melanoma of the Head and Neck Following Surgery With and Without Adjuvant Radiation Therapy: Is Isolated Regional Recurrence Salvageable?

BACKGROUND: Understanding recurrence patterns is vital for guiding treatment. This study describes recurrence patterns for patients with stage IIIB/C head and neck melanoma (HNM) after therapeutic lymph node dissection (TLND) ± adjuvant radiation therapy (RT). We also report outcomes for salvage therapy for patients with isolated regional relapse. METHODS AND MATERIALS: A single-institution prospective database of 173 patients with American Joint Committee on Cancer (AJCC) stage IIIB/C HNM undergoing TLND between 1997 and 2012 was retrospectively reviewed. Timing and patterns of recurrence were reviewed. Univariable and multivariable analyses were undertaken using the Kaplan-Meier and Cox regression methods to determine factors predictive of recurrence. Median follow-up was 32 months. RESULTS: Adjuvant RT was administered to 66/173 (38 %) patients. Patients selected for RT had a higher AJCC stage and had more extracapsular invasion. The 5-year distant, cervical nodal and in-transit recurrence rates were 38, 10, and 13 %, respectively, following surgery alone compared with 60, 17, and 31 %, respectively, for the adjuvant RT group. The head and neck regional 5-year recurrence rate (combining in-basin nodal and in-transit) was 23 % for the entire cohort. Isolated cervical recurrence occurred in 19 patients: 17/19 underwent salvage surgery (10/17 patients received RT after salvage surgery) and 2/19 had RT alone. However, distant recurrence occurred in 12/19 salvage patients, with most occurring within 12 months, while 4/19 were disease free. CONCLUSIONS: Using a selective approach for adjuvant RT, isolated cervical recurrence after TLND is uncommon. Isolated cervical recurrence can be salvaged effectively with further local therapy; however, distant disease frequently follows.

Radiotherapy for cutaneous melanoma: current and future applications.

Cutaneous malignant melanoma remains a significant health burden worldwide despite advances in the management of locoregionally advanced and metastatic disease. Historically, the efficacy of radiation therapy (RT) has been questioned due to the perceived radioresistance of melanoma cancer cells in vitro. Nowadays, RT has limited indications for primary disease, but is used for high-risk nodal disease and in the palliative setting. This review article outlines the current role of RT for melanoma and its expanding role in oligometastatic disease scenarios as an alternative approach to surgery and highlights potential future applications to harness RT interaction with immunomodulatory targeted therapies.

The development of stereotactic body radiotherapy in the past decade: a global perspective.

In the past 10 years, there has been an exponential increase in the incorporation of stereotactic body radiotherapy, also known as stereotactic ablative radiotherapy, into the armamentarium against various types of cancer in different settings worldwide. In this article in the 10th year anniversary issue of Future Oncology, representatives from the USA, Canada, Japan, Germany, The Netherlands, Australia and Singapore will provide individual perspectives of the development of stereotactic body radiotherapy in their respective countries.