Proton radiation therapy patient selection and impacts of COVID-19: A scoping review.

This scoping review aimed to determine whether the COVID-19 pandemic influenced any modifications to patient selection methods or prioritisation and services provided by proton therapy (PT) centres. This review was conducted based on the PRISMA methodology and Joanna Briggs Institute scoping review guidelines. A literature search was performed in Medline, Embase, Web of Science and Scopus, as well as grey literature. Keywords such as "COVID-19" and "Proton Therapy" were used. Articles published from 1 January 2020 in English were included. In total, 138 studies were identified of which 11 articles met the inclusion criteria. A scoping review design was chosen to capture the full extent of information published relating to the aim. Six of 11 articles included statements regarding treatment of COVID-19 patients. Three publications recommended deferred or alternative treatment, two indicated to treat urgent/emergency patients and one reported continuous treatment for infectious patients. Recurring impacts on PT provision included more frequent use of unconventional therapies, reduced referrals, delayed treatment starts and CT simulation, change in treatment target volumes and staffing limitations due to pandemic restrictions. Consequently, telehealth consults, remote work, reduction in patient visitors, screening procedures and rigorous cleaning protocols were recommended. Few publications detailed changes to patient selection or workflow methods during the pandemic. Further research is needed to obtain more detailed information regarding current global patient selection methods in PT, collecting this data could aid in future planning for PT in Australia.

Shared Decision Making in Oncology and Its Implementation in Cervical Cancer Management in the Philippines: A Narrative Review.

PURPOSE: Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology. METHODS: We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines. RESULTS: Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research. CONCLUSION: Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.

'Is the technology essential or emerging?' Ways to keep radiation therapy curriculum agile amid rapidly advancing technology.

Advancing technology in radiation therapy can significantly influence clinical practice and improvement of patient outcomes. In the process, innovations in technology require that changes to clinical practice are adopted within education settings. This commentary aims to describe the uptake of new technology and ways that academics provide an up-to-date curriculum when today's innovation is tomorrow's contemporary practice.

Modelling the influence of radiosensitivity on development of second primary cancer in out-of-field organs following proton therapy for paediatric cranial cancer.

OBJECTIVE: Radiobiological modelling the risks of second primary cancer (SPC) after proton therapy (PT) for childhood cranial cancer remains largely unknown. Organ-specific dose-response risk factors such as radiosensitivity require exploration. This study compared the influence of radiosensitivity data (slope of ßEAR) on children's lifetime attributable risks (LAR) of SPC development in out-of-field organs following cranial scattering and scanning PT. METHODS: Out-of-field radiosensitivity parameter estimates for organs (α/ß and ßEAR) were sourced from literature. Physical distances for 13 out-of-field organs were measured and input into Schneider's SPC model. Sensitivity analyses were performed as a function of radiosensitivity (α/ß of 1-10 Gy) and initial slope (ßEAR) from Japanese/UK data to estimate the influence on the risk of radiation-induced SPC following scattering and scanning PT. RESULTS: Models showed similar LAR of SPC estimates for age and sex-matched paediatric phantoms, however, for breast there was a significant increase using Japanese ßEAR data. For most organs, scattering PT demonstrated a larger risk of LAR for SPC which increased with α/ß. CONCLUSION: Breast tissue exhibited the highest susceptibility in calculated LAR risk, demonstrating the importance for accurate data input when estimating LAR of SPC. ADVANCES IN KNOWLEDGE: The findings of this study demonstrated younger female patients undergoing cranial proton therapy have a higher risk of developing second primary cancer of the breast tissue. Long-term multicenter registries are important to improve predictive radiobiological modelling studies of side effects.

A scoping review of patient selection methods for proton therapy.

The aim was to explore various national and international clinical decision-making tools and dose comparison methods used for selecting cancer patients for proton versus X-ray radiation therapy. To address this aim, a literature search using defined scoping review methods was performed in Medline and Embase databases as well as grey literature. Articles published between 1 January 2015 and 4 August 2020 and those that clearly stated methods of proton versus X-ray therapy patient selection and those published in English were eligible for inclusion. In total, 321 studies were identified of which 49 articles met the study's inclusion criteria representing 13 countries. Six different clinical decision-making tools and 14 dose comparison methods were identified, demonstrating variability within countries and internationally. Proton therapy was indicated for all paediatric patients except those with lymphoma and re-irradiation where individualised model-based selection was required. The most commonly reported patient selection tools included the Normal Tissue Complication Probability model, followed by cost-effectiveness modelling and dosimetry comparison. Model-based selection methods were most commonly applied for head and neck clinical indications in adult cohorts (48% of studies). While no 'Gold Standard' currently exists for proton therapy patient selection with variations evidenced globally, some of the patient selection methods identified in this review can be used to inform future practice in Australia. As literature was not identified from all countries where proton therapy centres are available, further research is needed to evaluate patient selection methods in these jurisdictions for a comprehensive overview.

Normal tissue complication probability modeling to guide individual treatment planning in pediatric cranial proton and photon radiotherapy.

PURPOSE: Proton therapy (PT) is broadly accepted as the gold standard of care for pediatric patients with cranial cancer. The superior dose distribution of PT compared to photon radiotherapy reduces normal tissue complication probability (NTCP) for organs at risk. As NTCPs for pediatric organs are not well understood, clinics generally base radiation response on adult data. However, there is evidence that radiation response strongly depends on the age and even sex of a patient. Furthermore, questions surround the influence of individual intrinsic radiosensitivity (α/ß ratio) on pediatric NTCP. While the clinical pediatric NTCP data is scarce, radiobiological modeling and sensitivity analyses can be used to investigate the NTCP trends and its dependence on individual modeling parameters. The purpose of this study was to perform sensitivity analyses of NTCP models to ascertain the dependence of radiosensitivity, sex, and age of a child and predict cranial side-effects following intensity-modulated proton therapy (IMPT) and intensity-modulated radiotherapy (IMRT). METHODS: Previously, six sex-matched pediatric cranial datasets (5, 9, and 13 years old) were planned in Varian Eclipse treatment planning system (13.7). Up to 108 scanning beam IMPT plans and 108 IMRT plans were retrospectively optimized for a range of simulated target volumes and locations. In this work, dose-volume histograms were extracted and imported into BioSuite Software for radiobiological modeling. Relative-Seriality and Lyman-Kutcher-Burman models were used to calculate NTCP values for toxicity endpoints, where TD50, (based on reported adult clinical data) was varied to simulate sex dependence of NTCP. Plausible parameter ranges, based on published literature for adults, were used in modeling. In addition to sensitivity analyses, a 20% difference in TD50 was used to represent the radiosensitivity between the sexes (with females considered more radiosensitive) for ease of data comparison as a function of parameters such as α/ß ratio. RESULTS: IMPT plans resulted in lower NTCP compared to IMRT across all models (p < 0.0001). For medulloblastoma treatment, the risk of brainstem necrosis (> 10%) and cochlea tinnitus (> 20%) among females could potentially be underestimated considering a lower TD50 value for females. Sensitivity analyses show that the difference in NTCP between sexes was significant (p < 0.0001). Similarly, both brainstem necrosis and cochlea tinnitus NTCP varied significantly (p < 0.0001) across tested α/ß as a function of TD50 values (assumption being that TD50 values are 20% lower in females). If the true α/ß of these pediatric tissues is higher than expected (α/ß âˆ¼ 3), the risk of tinnitus for IMRT can significantly increase (p < 0.0001). CONCLUSION: Due to the scarcity of pediatric NTCP data available, sensitivity analyses were performed using plausible ranges based on published adult data. In the clinical scenario where, if female pediatric patients were 20% more radiosensitive (lower TD50 value), they could be up to twice as likely to experience side-effects of brainstem necrosis and cochlea tinnitus compared to males, highlighting the need for considering the sex in NTCP models. Based on our sensitivity analyses, age and sex of a pediatric patient could significantly affect the resultant NTCP from cranial radiotherapy, especially at higher α/ß values.

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review.

Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT.

Lifetime attributable risk of radiation induced second primary cancer from scattering and scanning proton therapy - A model for out-of-field organs of paediatric patients with cranial cancer.

BACKGROUND AND PURPOSE: Proton therapy (PT) can reduce side effects for paediatric cranial malignancies. Despite the high number of paediatric patients treated with PT, radiation induced risk factors for second primary cancer (SPC) in out-of-field organs are unknown. This study estimated lifetime attributable risk (LAR) of SPC as a function of age and sex for out-of-field organs following passive scattering and scanning beam PT in paediatric brain tumours. MATERIALS AND METHODS: Measured neutron dose equivalent spectra for scattered and scanning PT were sourced from literature. The physical distance of 12 measured organs from paediatric CT dataset-based phantoms (5, 9 and 13 years-of-age) were applied to Schneider et al.'s analytical model using MATLAB (R2020B) to calculate the organ-specific LAR of SPC. RESULTS: Scanning beam PT demonstrated smaller LAR (per 10,000 person years) of SPC compared to scattering. This was prominent for more radiosensitive organs, including the lung (320 vs 50), breast (1000 vs 150) and thyroid (350 vs 75), but not for all (i.e., rectum and reproductive organs were <10). For most organs, LAR was highest for 5-year-old females (i.e., breast LAR was 1,000 higher than for 13-year-olds), however, outliers existed for distal organs (i.e., stomach and lung). CONCLUSION: There was large variation in LAR estimates of out-of-field organs based on measured neutron dose equivalents. Younger female cranial paediatric patients were found at higher risk compared to males, especially for passive scattering PT. Not all organs had improved LAR using scanning beam PT for younger age groups.

Innovative strategies implemented by universities to support medical radiation science students during the COVID-19 pandemic.

The global COVID-19 pandemic has impacted all facets of life. In medical radiation science (MRS) education, the effects on continuity of learning were felt by educators, students and clinical supervisors both nationally and internationally. The focus of this commentary is on the common elements that impacted MRS students, specifically related to cancelled clinical placements and the interruption to their academic progress at university. An outline is provided of some innovative strategies implemented by universities and clinical departments to support students' academic progress, continuity of clinical experiences, their transition from students to practitioners and overall strategies to support student wellbeing. The recent published literature illustrates novel responses to shared challenges faced, and an opportunity to learn from collective experiences.

Normal tissue tolerance amongst paediatric brain tumour patients- current evidence in proton radiotherapy.

BACKGROUND: Proton radiotherapy (PT) is used increasingly for paediatric brain cancer patients. However, as demonstrated here, the knowledge on normal tissue dose constraints, to minimize side-effects, for this cohort is limited. METHODS: A search strategy was systematically conducted on MEDLINE® database. 65 papers were evaluated ranging from 2013 to 2021. RESULTS: Large variations in normal tissue tolerance and toxicity reporting across PT studies makes estimation of normal tissue dose constraints difficult, with the potential for significant late effects to go unmeasured. Mean dose delivered to the pituitary gland varies from 20 to 30 Gy across literature. Similarly, the hypothalamic dose delivery ranges from 20 to 54.6 Gy for paediatric patients. CONCLUSION: There is a significant lack of radiobiological data for paediatric brain cancer patients undergoing proton therapy, often using data from x-ray radiotherapy and adult populations. The way forward is through standardisation of reporting in order to validate relevant dose constraints.

Impact of Breast Size on Dosimetric Indices in Proton Versus X-ray Radiotherapy for Breast Cancer.

Deep inspiration breath hold (DIBH) radiotherapy is a technique used to manage early stage left-sided breast cancer. This study compared dosimetric indices of patient-specific X-ray versus proton therapy DIBH plans to explore differences in target coverage, radiation doses to organs at risk, and the impact of breast size. Radiotherapy plans of sixteen breast cancer patients previously treated with DIBH radiotherapy were re-planned with hybrid inverse-planned intensity modulated X-ray radiotherapy (h-IMRT) and intensity modulated proton therapy (IMPT). The total prescribed dose was 40.05 Gy in 15 fractions for all cases. Comparisons between the clinical, h-IMRT, and IMPT evaluated doses to target volumes, organs at risk, and correlations between doses and breast size. Although no differences were observed in target volume coverage between techniques, the h-IMRT and IMPT were able to produce more even dose distributions and IMPT delivered significantly less dose to all organs at risk than both X-ray techniques. A moderate negative correlation was observed between breast size and dose to the target in X-ray techniques, but not IMPT. Both h-IMRT and IMPT produced plans with more homogeneous dose distribution than forward-planned IMRT and IMPT achieved significantly lower doses to organs at risk compared to X-ray techniques.

Effect of patient size on image quality in radiotherapy kV planar verification imaging: a phantom study.

INTRODUCTION: This study aimed to determine a maximal pelvic separation and waist circumference in pelvic patients to guide radiation therapists in acquiring kilovoltage (kV) planar images of acceptable quality for treatment verification. METHODS: A pelvic anthropomorphic phantom modified with different bolus thicknesses was imaged at various default kV exposure settings. Radiation therapists rated image quality and acceptance/rejection of these images for treatment verification. RESULTS: Sixteen radiation therapists participated in the study. Image quality was inversely proportional to phantom size. AP and lateral kV images were acceptable for treatment verification up to a waist circumference of 143 cm. CONCLUSIONS: Exposure settings for kV image verification of large patients should be individualised to avoid unnecessary patient radiation dose through repeated imaging.

Clinical Limitations of Photon, Proton and Carbon Ion Therapy for Pancreatic Cancer.

INTRODUCTION: Despite improvements in radiation therapy, chemotherapy and surgical procedures over the last 30 years, pancreatic cancer 5-year survival rate remains at 9%. Reduced stroma permeability and heterogeneous blood supply to the tumour prevent chemoradiation from making a meaningful impact on overall survival. Hypoxia-activated prodrugs are the latest strategy to reintroduce oxygenation to radioresistant cells harbouring in pancreatic cancer. This paper reviews the current status of photon and particle radiation therapy for pancreatic cancer in combination with systemic therapies and hypoxia activators. METHODS: The current effectiveness of management of pancreatic cancer was systematically evaluated from MEDLINE® database search in April 2019. RESULTS: Limited published data suggest pancreatic cancer patients undergoing carbon ion therapy and proton therapy achieve a comparable median survival time (25.1 months and 25.6 months, respectively) and 1-year overall survival rate (84% and 77.8%). Inconsistencies in methodology, recording parameters and protocols have prevented the safety and technical aspects of particle therapy to be fully defined yet. CONCLUSION: There is an increasing requirement to tackle unmet clinical demands of pancreatic cancer, particularly the lack of synergistic therapies in the advancing space of radiation oncology.

Variation in radiotherapy patterns of care in the radical treatment of South Australian men with non-metastatic prostate cancer between 2005-2015.

BACKGROUND AND PURPOSE: To investigate associations between socio-demographic characteristics and radiotherapy patterns of care in non-metastatic prostate cancer [nmPCa] in South Australia [SA] between 2005-2015 and document practice patterns over time. MATERIALS AND METHODS: Men with nmPCa receiving primary curative radiotherapy were identified from SA Prostate Cancer Clinical Outcomes Collaborative database. Adjuvant, salvage and palliative therapies were excluded. Associations between socio-demographic factors (age, residence, socio-economic status, diagnostic period) and radiotherapy mode (external beam radiotherapy [EBRT] vs. brachytherapy [BT]) and technique (low-dose-rate vs. high-dose-rate brachytherapy) were investigated using multivariable logistic regression with separate models for clinical risk categories. RESULTS: Of the 1874 men who underwent primary RT, 80% received EBRT and 20% BT. For low and intermediate risk disease, likelihood of receiving EBRT was higher among older men (ORlow = 3.08; 95% CI 1.82-5.22 and ORintermediate = 3.48; 2.28-5.31 for 65-74 yrs vs. <65 yrs) and lower among regional/remote compared with metropolitan residents (ORlow = 0.34; 0.17-0.67 and ORintermediate = 0.57; 0.34-0.94). For intermediate and high risk disease, more recent diagnosis was associated with decreased likelihood of EBRT (ORintermediate = 0.22; 95% CI 0.15-0.33 and ORhigh = 0.50; 0.29-0.88, respectively). Among men receiving BT, low-dose-rate BT use decreased over time for low (OR = 0.19; 0.04-0.89) and intermediate risk disease (OR = 0.32; 0.12-0.84). Dose escalation and intensity modulation for EBRT increased after 2010. CONCLUSION: Over the last decade substantial changes in RT for nmPCa were observed. Older age and more remote residence may be barriers to accessing specific types of RT. Further research to understand how these factors affect access is warranted to improve service provision.

Influence of Target Location, Size, and Patient Age on Normal Tissue Sparing- Proton and Photon Therapy in Paediatric Brain Tumour Patient-Specific Approach.

BACKGROUND: Proton radiotherapy produces superior dose distributions compared to photon radiotherapy, reducing side effects. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Our aim was to compare intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) radiation doses for select paediatric intracranial tumours. METHODS: IMPT and IMRT dose distributions for gender-matched paediatric cranial CT-datasets (ages 5, 9 and 13 years) were retrospectively calculated to simulate irradiation of supratentorial (ependymoma) and infratentorial (medulloblastoma) target volumes diameters (1-3 cm) and position (central and 1-2 cm shifts). RESULTS: Clinical dosimetric objectives were achieved for all 216 treatment plans. Whilst infratentorial IMPT plans achieved greater maximum dose sparing to optic structures (4.8-12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Mean dose difference for optic chiasm was associated with medulloblastoma target position (p < 0.0197). Supratentorial IMPT plans demonstrated greater dose reduction for the youngest patients (pituitary gland p < 0.001). CONCLUSIONS: Normal tissue sparing was achieved regardless of patient age for infratentorial tumours. However, for supratentorial tumours, there was a dosimetric advantage of IMPT across 9 vs. 13-year-old patients.

How do radiation oncology health professionals inform breast cancer patients about the medical and technical aspects of their treatment?

BACKGROUND AND PURPOSE: Radiation therapy patients need information to make treatment decisions, understand treatment and manage side effects. The purpose of this study was to (1) Identify information about radiation therapy routinely provided to breast cancer patients; (2) Determine which health professionals provide information; (3) Examine whether information is routinely provided at the same time points; and (4) Determine whether health professionals and patients place similar importance on specific information. MATERIALS AND METHODS: Health professionals in radiation therapy departments in Australia and New Zealand completed self-administered questionnaires. Results were analysed and compared to patient responses from a previous study. RESULTS: Forty-one of 52 departments participated in this survey. Information provision was inconsistent between departments in terms of how and when information was given. Although the types of information provided to patients appeared to align with patients' needs, health professionals and patients placed different levels of importance on specific information. CONCLUSIONS: A wide range of information are provided to patients. However, the priority given to different information needs and the focus of information provision may not be optimal from the perspectives of patients. Further research needs to be conducted to determine patients' information needs and to develop specific information resources tailored to meet these needs.

Are further studies needed to justify the use of proton therapy for paediatric cancers of the central nervous system? A review of current evidence.

Clinical implementation of proton therapy demonstrated its potential to overcome some limitations of the more traditional, photon-based radiotherapy, due to physical and radiobiological advantages of protons. However, questions concerning the long-term effects of protons on paediatric patients need outcome analysis of the reported literature in order to be answered. The current paper has analysed the available clinical trials and comparative studies (protons vs photons) for paediatric cancers of the central nervous system (CNS) analysing the reported outcomes and follow-up times in order to evaluate the safety of proton therapy for this patient group. Based on the literature analysis, proton therapy for treatment of paediatric cancers of the CNS was found to provide survival and tumour control outcomes comparable, and frequently superior, to photon therapy. Furthermore, the use of protons was shown to decrease the incidence of severe acute and late toxicities, including reduced severity of endocrine, neurological, IQ and QoL deficits. Most commonly, the reported median follow-up time was up to 5 years. Only a few studies reported promising, longer follow-up results. Considering that these patients are likely to survive many of the malignancies reported on, the incidence of long term sequellae impacting growth, development and quality of life into adulthood, should be viewed longitudinally for completeness. The evidence surrounding proton therapy in paediatric tumour management supports its effectiveness and potential benefits in reducing the incidence of late-onset toxicities and second malignancies. For stronger evidence, it is highly desired for future studies to improve current reporting by (1) highlighting the paediatric patient cohort's outcome (in mixed patient groups), (2) reporting the follow-up time, (3) clearly indicating the toxicity criteria used in their evaluation, and (4) identifying the risk group. With this suggested clarity of future reporting, meaningful data to support treatment choice may then be available.

Current status of proton therapy outcome for paediatric cancers of the central nervous system - Analysis of the published literature.

INTRODUCTION: The most common solid tumours that develop in children are cancers of the central nervous system. Due to the increased rate of survival over the past decades, greater focus has been placed on the minimisation of long term side effects. In childhood cancer survivors, over 60% report one or more radiation-related late toxicities while half of these adverse events are graded as life-threatening or severe. Proton therapy enables high conformity with the planning target volume and a reduction in dose to areas beyond the target. Owing to the unique nature of dose delivery with proton therapy a reduction of low doses to normal tissues is achievable, and is believed to allow for a decrease in long-term treatment-related side effects. This paper aims to review the published literature around the effectiveness of proton therapy for the treatment of paediatric cancers of the central nervous system, with a focus on treatment outcomes and treatment-related toxicities. METHODS: A search strategy utilising the Medline database was created with the intent of including all articles reporting on proton therapy, paediatric cancers, CNS tumours and treatment outcomes. The final search strategy included the following limitations: limited to humans, English, published from 2000 onwards. The final article count total was 74. RESULTS AND CONCLUSIONS: Proton therapy for the treatment of paediatric cancers of the central nervous system was found to provide survival and tumour control outcomes comparable to photon therapy. Reduced incidence of severe acute and late toxicities was also reported with the use of proton therapy. This includes reduced severity of endocrine, neurological, IQ and QoL deficits. Currently, extensive follow-up of proton patient populations still needs to be made to determine incidences of late-onset toxicities and secondary malignancies. Current evidence surrounding proton therapy use in paediatric patients supports its effectiveness and potential benefits in reducing the incidence of severe toxicities in later life.

Do SABR-related toxicities for lung cancer depend on treatment delivery?

Stereotactic ablative radiation therapy for lung cancer is an advanced technique where tumours are ablated with hypofractionated radiation doses, with a high degree of accuracy. The aim of this paper is to review the available literature and to discuss the SABR-induced toxicities for lung malignancies as a function of radiation delivery technique. A Medline search was conducted to identify the appropriate literature to fulfil the aim of this review and data from all applicable papers were collated and analysed. The most common techniques of SABR delivery employ linear accelerators, CyberKnife robotic radiosurgery system, TomoTherapy and the Novalis beam surgery system. Linear accelerator-based treatments give rise to a variety of toxicities that are strongly dependent on both patient-related factors and planning/dosimetry-related factors. The limited number of studies using CyberKnife reported low grade toxicities. Grade three toxicities mainly include fatigue and chest pain, usually in less than 10% of patients. All treatment techniques presented show efficiency in SABR delivery with various toxicities which, at this stage, cannot render one technique better than the other. For more conclusive results, well-designed phase three randomised clinical trials are required with better patient selection criteria, including dose and fractionation, treatment machine and technique, along with the consistent selection of a common toxicity grading criterion.

Treatment-Related Adverse Effects in Lung Cancer Patients after Stereotactic Ablative Radiation Therapy.

INTRODUCTION: Lung cancer is a disease which, despite the advancements in treatment, still has a very poor 5-year survival rate. Stereotactic ablative radiation therapy (SABR) is a highly advanced, sophisticated, and safe treatment which allows patients with early stage lung cancer to be treated effectively without invasive procedures and with excellent clinical outcomes. Avoiding surgery minimises morbidity and recovery time, bettering patients' quality of life. Furthermore, SABR allows patients unsuitable for surgery to still undergo curative treatment. METHODS: We aimed to review SABR-related normal tissue toxicities reported in the literature. While many studies assess safety, clinical efficacy, and disease control of SABR for lung cancer, the number of comprehensive reviews that analyse SABR-related side-effects is scarce. This integrative review summarises the toxicities reported in literature based on published clinical trials and tumour location (central or peripheral tumours) for available SABR techniques. Given that the majority of the clinical studies did not report on the statistical significance (e.g., p-values and confidence intervals) of the toxicities experienced by patients, statistical analyses cannot be performed. As a result, adverse events are compiled from clinical reports; however, due to various techniques and nonstandard toxicity reports, no meta-analysis is possible at the current stage of reported data. RESULTS: When comparing lobectomy and SABR in phase III trials, surgery resulted in increased procedure-related morbidity. In phase II trials, very few studies showed high grade toxicities/fatalities as a result of SABR for lung cancer. Gross target volume size was a significant predictor of toxicity. An ipsilateral mean lung dose larger than 9 Gy was significantly associated with radiation pneumonitis. CONCLUSIONS: Based on the studies reviewed SABR is a safe treatment technique for lung cancer; however, further well-designed phase III randomised clinical trials are required to produce timely conclusive results and to enable their comparison and statistical analysis.