Piloting a new cross-sector model of care to support parents with cancer: feasibility and acceptability of the Parent Support Worker role.

PURPOSE: A new Parent Support Worker (PSW) service was piloted in three Australian hospitals. This study assesses the feasibility and acceptability (including preliminary effectiveness) of the service in supporting cancer patients with children. METHODS: A multi-site, mixed-methods study collected quantitative and qualitative data on the effectiveness of the service (pre post-test, n = 36), qualitative and quantitative data on acceptability of the service (survey, n = 43), and qualitative data on acceptability (semi-structured interviews, n = 13). Feasibility was assessed through rates of service uptake amongst referred parents. RESULTS: Of 1133 parents referred, 810 (71%) accepted to receive the service, suggesting high interest in PSW support. Interviewees likewise reported that the service was accessible and facilitated further referrals, indicating good feasibility. Surveys completed three months after accessing PSW support showed high acceptability and satisfaction. Additionally, there was preliminary evidence of service impacts: parents' distress, parenting concerns, parenting efficacy, and stress about situations of concern improved significantly from pre- to post-service (all p < 0.005). Interviewees further described how their emotional coping and confidence to support and communicate with their children had improved through contact with the service. CONCLUSION: The PSW service, integrated into a novel cross-sector model of care, showed to be feasible and acceptable to parent patients and their partners and improved psychological and parenting outcomes. The study suggests refinements to the service and the need for future larger studies to explore the effectiveness of the service in improving parents' outcomes. This study complements previous evidence on the implementation of the PSW service in hospitals.

Cancer awareness in Australian adolescents.

BACKGROUND: Over one-third of cancer cases are attributable to modifiable risk factors. Because health-related behaviors are often established at adolescence, it is important that adolescents understand the risks and lifestyle decisions that may reduce their chances of developing cancer. This study aims to identify the levels of cancer awareness of adolescents in Australia. METHODS: Paper questionnaires were used to collect information about baseline levels of cancer awareness. These questionnaires included socio-demographic questions and the Cancer Awareness Measure (CAM) with slight modifications to ensure their suitability for the Australian adolescent population. Students aged 11 to 19 years were recruited from 13 Australian high schools between 2016 and 2019. RESULTS: A total of 766 adolescents (58% female, mean age = 14.5 years) completed the questionnaires. Adolescents' cancer awareness was low. Adolescents who knew someone with cancer recognized significantly more cancer risk factors and cancer warning signs than those who did not know someone with cancer (t (756) = 2.35, p = .019; t (747) = 5.57, p = .001). Those from high Index of Community Socio-Educational Advantage (ICSEA) schools significantly recognized more cancer risk factors than those from low ICSEA schools (t (764) = 2.42, p = .016). Females recognized significantly more warning signs than males (t (583) = 3.11, p = .002) and students from senior high school grades recognized more warning signs than those from junior grades (t (754) = 2.24, p = .02). Most adolescents (78%) were aware of skin cancer as one of the most common cancers in Australia, however half or less were aware of other common cancers. Although most adolescents would seek medical help in the presence of possible cancer symptoms as soon as possible, approximately 20% of them would not see a doctor promptly. Emotional barriers were the most common reasons to delay seeing a doctor (56%), for example "being worried about hearing bad news" (27%). CONCLUSIONS: Australian adolescents show poor awareness of cancer risk factors and cancer warning signs. A number of demographic and experience factors were found to be related to lower cancer awareness. Education is essential to raise cancer awareness, promote healthy lifestyles from adolescence and avoid a preventable cancer diagnosis.

Cancer patients as parents: implementation of a cross sector service for families with adolescent and young adult children.

BACKGROUND: Cancer patients who are parents show concerns about their ability to parent following diagnosis, and their adolescent and young adult (AYA) children have a need for improved cancer communication within the family. However, psychosocial support for families affected by parental cancer is not routinely available. This study explores the implementation of the Parent Support Worker (PSW) role, as part of a new cross sector model of care to support parent patients, their partners, and AYA children. METHODS: Two PSWs, social workers and healthcare staff (n = 26) from three hospitals participated in audio-recorded, semi-structured interviews about implementation of the PSW role. Template Analysis and Normalization Process Theory were used to analyze the interviews. Data on PSW service activity and referrals of AYA to support from a community organization were analyzed using descriptive statistics. RESULTS: Eleven themes categorized into enablers and barriers of implementation were identified. Regarding acceptability of the role, three enablers (social workers' understanding of the PSW role increasing, easy and prompt access of staff and parent patients to PSWs, satisfaction with the PSW role) and one barrier (communication related confusion and frustration about the PSW role) were identified. Additionally, three enablers (the PSW role fills gaps in parenting-focused support and continuity of care, the PSW role alleviates social workers' workload, negotiation helped to define responsibilities) and one barrier (fear of social work roles to be overtaken by PSWs) for appropriateness of the role were found. Finally, two enablers of feasibility of the role (PSWs and social workers co-managing the work, higher confidence from hospital staff to talk about children in the family) and one barrier (lack of systematic identification and referral processes) were identified. Across hospitals, the number of referrals of AYA children to the community organization increased between 2.7 and 12 times nine months post-introduction of the service. CONCLUSIONS: Established in response to identified gaps in oncology care for parents with cancer, their partners and AYA children, a novel cross-sector model of care was acceptable, appropriate, and feasible. Barriers and enablers to implementation identified in this study need to be considered when designing and implementing similar services.

Influence of innate immune activation on endocrine and metabolic pathways in infancy.

Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use, and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.

Accessing support before or after a parent dies from cancer and young people's current wellbeing.

PURPOSE: To examine differences in distress and unmet needs between bereaved adolescent and young adult (AYA) offspring who accessed support before and after being bereaved by parental cancer, and to explore aspects of their cancer experience that influenced their help-seeking. METHODS: Phase 1: Surveys completed by AYAs (11-26 years) bereaved by parental cancer were subjected to analysis of covariance examining differences in distress and unmet needs between those who accessed support before (n = 159) and after (n = 212) parental bereavement. Phase 2: Semi-structured interviews explored the cancer experiences of bereaved offspring (n = 8) and factors that influenced their decision to seek support. RESULTS: Phase 1: There were no significant group differences in distress and unmet needs; however, older and female AYAs reported higher levels of distress and unmet needs. Interestingly, individuals who accessed support pre-bereavement were older on average (M = 17.35 years, SD = 3.26) than those who accessed support post-bereavement (M = 15.73 years, SD = 3.26). Phase 2: Three themes emerged centred on socio-emotional developmental changes during and after the cancer trajectory. These related to: participants' meaning-making and changes in understanding of the cancer experience, changing relationships and desires to fit in, and understanding of their own emotional needs. CONCLUSIONS: While no differences were found in unmet needs and distress between those who sought support pre- or post-bereavement, those seeking support pre-bereavement were older on average. Social and emotional development impacts how bereaved offspring access psychosocial support. Awareness of these issues can assist in improving support by ensuring services are age appropriate and families are sufficiently supported.

Levels of unmet needs and distress amongst adolescents and young adults (AYAs) impacted by familial cancer.

OBJECTIVE: To describe levels of, and relationships between, distress and psychosocial unmet needs in adolescents and young adults (AYAs) with a family member with cancer. METHODS: Adolescents and young adults (12-24 years old) with a living sibling or parent with cancer participated. Participants completed demographics, the Kessler 10 (K10) distress scale and the Sibling or Offspring Cancer Needs Instruments. Descriptive statistics were obtained for all measures, item-level frequencies were examined to identify common unmet needs, and relationships between distress and unmet needs were explored. RESULTS: Average sibling (N = 106) and offspring (N = 256) distress levels were in the high range (K10total = 22-30), with 29.6% and 31.6% in the very high range (K10total = 31-50), respectively. Siblings had mean = 19.7 unmet needs (range 0-45), 66% had ≥10 unmet needs, and 44% of the 45 needs were unmet on average. Offspring had mean = 22.4 unmet needs (range 0-47), 77% had ≥10 unmet needs, and 48% of the 47 needs were unmet on average. Strong positive correlations were found between K10 distress and the number of sibling/offspring unmet needs (r = 0.599 and r = 0.522, respectively, P = .00). CONCLUSIONS: Australian AYA siblings and offspring impacted by familial cancer experience high levels and numbers of unmet needs and substantial distress. Strong associations were found between increased distress and more unmet needs. Distress levels were comparable to AYAs seeking treatment for mental health issues. Insights into the type and number of needs experienced by AYA siblings and offspring will facilitate development and delivery of targeted, age-appropriate interventions, and resources for these vulnerable and underserved young people.

Correlates of unmet needs and psychological distress in adolescent and young adults who have a parent diagnosed with cancer.

OBJECTIVE: Young people who have a parent with cancer experience elevated levels of psychological distress and unmet needs. In this study, we examined the associations between demographics, cancer variables and family functioning and levels of distress and unmet needs amongst young people who have a parent diagnosed with cancer. METHODS: Young people aged 12-24 years with a parent with cancer (n = 255) completed the Offspring Cancer Needs Instrument (unmet needs), the Kessler-10 (distress) and the Family Relationship Index (family functioning), along with measures of demographics and cancer variables (such as age, sex and time since cancer diagnosis). Variables associated with distress and unmet needs (including unmet need domains) were assessed using multiple linear regression. RESULTS: Being female and older, having more unmet cancer needs and poorer family functioning were associated with increased distress. Having a father with cancer, a shorter time since diagnosis and poor family functioning were associated with increased unmet needs. Family conflict and expressiveness were particularly important components of family functioning. Having a parent relapse with cancer was also associated with unmet needs in the domains of practical assistance, 'time out' and support from other young people who have been through something similar. CONCLUSIONS: Delineating factors associated with increased distress and unmet needs assist in identifying at-risk young people allowing improved assessment and tailoring of support to improve the psychosocial outcomes of young people impacted by parental cancer.

Predictors of unmet needs and psychological distress in adolescent and young adult siblings of people diagnosed with cancer.

PURPOSE: Predictors of psychological distress and unmet needs amongst adolescents and young adults (AYAs) who have a brother or sister diagnosed with cancer were examined. METHODS: There were 106 AYAs (12-24 years old) who completed questionnaires covering demographics, psychological distress (Kessler 10), unmet needs (Sibling Cancer Needs Instrument) and family relationships (Family Relationship Index; Adult Sibling Relationship Questionnaire; Sibling Perception Questionnaire (SPQ)). Three models were analysed (demographic variables, cancer-specific variables and family functioning variables) using multiple linear regression to determine the role of the variables in predicting psychological distress and unmet needs. RESULTS: Unmet needs were higher for AYA siblings when treatment was current or a relapse had occurred. Higher scores on the SPQ-Interpersonal subscale indicating a perceived decrease in the quality of relationships with parents and others were associated with higher levels of distress and unmet needs. The age and gender of the AYA sibling, whether it was their brother or sister who was diagnosed with cancer, the age difference between them, the number of parents living with the AYA sibling, parental birth country, time since diagnosis, Family Relationship Index, Adult Sibling Relationship Questionnaire and the SPQ-Communication subscale did not significantly impact outcome variables. CONCLUSIONS: These results highlight the variables that can assist in identifying AYA siblings of cancer patients who are at risk and have a greater need for psychosocial assistance. Variables that may be associated with increased distress and unmet needs are reported to assist with future research. The results are also useful in informing the development of targeted psychosocial support for AYA siblings of cancer patients.

The ß2 -adrenoceptor agonist terbutaline recovers rat pharyngeal dilator muscle force decline during severe hypoxia.

RATIONALE: Obstructive sleep apnoea syndrome (OSAS) is a debilitating condition characterized by recurrent occlusions of the pharyngeal airway during sleep accompanied by arterial hypoxaemia. Upper airway muscle dysfunction is implicated in the pathophysiology of OSAS. Pharmacological agents that improve muscle contractile and endurance properties may have therapeutic value. AIM: We tested the hypothesis that the ß(2) -adrenoceptor agonist terbutaline improves rat sternohyoid muscle performance especially during hypoxic stress. METHODS: Isometric contractile and endurance properties were examined ex vivo in Krebs solution at 35°C. Muscles were incubated in tissue baths under hyperoxic (95% O(2) /5% CO(2)) conditions in the absence (control) or presence of the ß(2) -adrenoceptor agonist terbutaline (1 µM). In additional experiments under hypoxic (95% N(2) /5% CO(2)) conditions, the effects of terbutaline were examined in the presence of the ß-adrenoceptor antagonist propranolol (1 µM). RESULTS: Hypoxia significantly impaired sternohyoid force production. Terbutaline completely recovered hypoxic depression of force, an effect that was blocked by co-application with propranolol. CONCLUSION: The ß(2) -adrenoceptor agonist terbutaline completely recovers hypoxic depression of upper airway muscle force. ß(2) -adrenoceptor agonists warrant investigation in animal models of OSAS reporting upper airway and diaphragm muscle dysfunction.

PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease.

Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with the onset of PLAN in childhood, and our report highlights the diagnostic challenges associated with this atypical PLAN subtype. In this series, the neuroradiological relevance of classical PLAN features as well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were identified in all patients. PLAN should be considered not only in patients presenting with a classic INAD phenotype but also in older patients presenting later in childhood with non-specific progressive neurological features including social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric symptoms and extrapyramidal motor features.

Psychometric evaluation of the Sibling Cancer Needs Instrument (SCNI): an instrument to assess the psychosocial unmet needs of young people who are siblings of cancer patients.

PURPOSE: The current study sought to establish the psychometric properties of the revised Sibling Cancer Needs Instrument (SCNI) when completed by young people who have a brother or sister with cancer. METHODS: The participants were 106 young people aged between 12 and 24 who had a living brother or sister diagnosed with any type or stage of cancer in the last 5 years. They were recruited from multiple settings. The initial step in determining the dimensional structure of the questionnaire was exploratory factor analysis and further assessment followed using Rasch analysis. Construct validity and test-retest reliability (n = 17) were also assessed. RESULTS: The final SCNI has 45 items and seven domains: information; practical assistance; "time out" and recreation; feelings; support (friends and other young people); understanding from my family; and sibling relationship. There was a reasonable spread of responses across the scale for every item. Rasch analysis results suggested that overall, respondents used the scale consistently. Support for construct validity was provided by the correlations between psychological distress and the SCNI domains. The internal consistency was good to excellent; Cronbach's alphas ranged from 0.78 to 0.94. The test-retest reliability of the overall measure is 0.88. CONCLUSIONS: The SCNI is the first measure of psychosocial unmet needs which has been developed for young people who have a brother or sister with cancer. The sound psychometric properties allow the instrument to be used with confidence. The measure will provide a substantial clinical benefit in highlighting the unmet needs of this population to assist with the prioritisation of targeted supportive care services and evaluating the impact of interventions targeted at siblings.

Bladder tumour focused adaptive radiotherapy: Clinical outcomes of a phase I dose escalation study.

PURPOSE/OBJECTIVES: We determine the maximum tolerated tumour focused dose (MTD) for the radical treatment of muscle invasive bladder cancer (MIBC) enabled by image guided adaptive radiotherapy (IGART) and long-term clinical outcomes. MATERIALS/METHODS: Fifty-nine patients with T2-T4aN0M0 unifocal urothelial MIBC suitable for daily radical radiotherapy were recruited prospectively to an ethics approved protocol (XX). The uninvolved bladder (PTVbladder) was planned to 52Gy in 32 fractions (f). The bladder tumour (PTVtumour) was planned to an assigned dose level of 68, 70, 72, or 74Gy. If organ at risk (OAR) dose constraints were violated, then PTVtumour was planned to 64Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using CTCAE v3.0; late toxicity was evaluated using RTOG criteria. The MTD was predefined as the highest dose level with estimated probability of ≤ 15% ≥G3 late toxicity and observed rate <50% acute G3 and <10% acute G4 toxicity. RESULTS: Twenty-six patients were assigned to 68Gy, of whom 6 were planned to 64Gy; 29 patients were assigned to 70Gy of whom 1 was planned to 68Gy, 2 patients were assigned and planned to 72Gy; no patients were assigned to 74Gy. Three patients did not complete treatment as planned, of whom only 1 patient stopped treatment because dose limiting toxicity occurred. The MTD was 70Gy. Acute genitourinary (GU) and gastrointestinal (GI) G3 acute toxicity was seen in 19% and 7% patients respectively. No grade 4 GU or GI toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% patients respectively. The 5-year overall survival was 58% (95% CI 44-71%). The bladder preservation rate was 89% (95% CI, 88 to 96%) with 6 patients not retaining native bladder function. CONCLUSION: Bladder tumour focused dose escalation to 70Gy using IGART is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomised control trial (XXXXX).

Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R.

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.

Remission of diabetes in patients with long-standing type 2 diabetes following placement of adjustable gastric band: a retrospective case control study.

Rates of remission in obese patients with long-standing type 2 diabetes (>2 years), following an adjustable gastric band are unclear. We conducted a retrospective case-control study of patients (n = 89) matched for age and body mass index with non-surgical controls. Cases had a longer duration of diabetes (99 ± 53 and 80 ± 59 months, p < 0.05) and a lower HbA1c than controls (7.9 ± 1.6 vs. 8.5 ± 1.9%, p < 0.05). At follow-up (median 105 weeks) cases had lost 16.8 ± 13.5 kg and controls 1.7 ± 8.9 kg (p < 0.001) and HbA1c decreased by 0.6-0.8% (p < 0.001 for time) with no difference between cases and controls. Diabetes resolution, defined by HbA1c less than 6.5% and taking no medications, occurred in 14 (16%) cases and 2 controls. This is in contrast to published outcomes of resolution of type 2 diabetes after bariatric surgery. We conclude that there is a clear need for randomized studies of the effect of gastric banding in patients with long-standing type 2 diabetes.

Psychometric evaluation of the Offspring Cancer Needs Instrument (OCNI): an instrument to assess the psychosocial unmet needs of young people who have a parent with cancer.

PURPOSE: The current study sought to establish the psychometric properties of the revised Offspring Cancer Needs Instrument (OCNI) when completed by a large sample of young people impacted by parental cancer recruited from multiple settings. METHODS: The psychometric properties were evaluated with 256 young people aged between 12 and 24 who had a parent or primary caregiver diagnosed with any type or stage of cancer within the last 5 years and who was still living. Exploratory factor analysis was conducted as an initial step in determining the dimensional structure of the questionnaire, and further assessment followed using Rasch analysis. Construct validity and test-retest reliability (n = 35) were also assessed. RESULTS: The final OCNI has 47 items and 7 domains: information, family issues, practical assistance, time out, feelings, support (friends) and support (other young people). There was a reasonable spread of responses across the scale for every item, and Rasch analysis results suggested that overall, respondents used the scale consistently. The retest correlation for the overall measure was 0.73. Support for construct validity was provided by the correlations between psychological distress and the OCNI domains. The internal consistency was excellent; the lowest domain Cronbach alpha is 0.89. CONCLUSIONS: The OCNI is the first measure of psychosocial unmet needs which has been developed specifically for young people who have a parent with cancer. It has sound psychometric properties and will provide substantial clinical benefit in identifying the unmet needs of this population to assist with the provision of targeted supportive care services.

Patterns of Failure After Stereotactic Body Radiotherapy to Sacral Metastases.

AIMS: Stereotactic body radiotherapy (SBRT) is increasingly used to treat sacral metastases. We analysed our centre's local relapse rates and patterns of failure after sacral SBRT and assessed whether using the consensus contouring recommendation (CCR) may have prevented local relapse. MATERIALS AND METHODS: We conducted a single-centre retrospective review of patients treated with sacral SBRT between February 2012 and December 2021. The cumulative incidence of local relapse, patterns of failure and overall survival were determined. Two investigators reviewed planning computed tomography scans and imaging at relapse to determine if local relapse was potentially preventable with a larger CCR-derived radiotherapy field. RESULTS: In total, 34 patients received sacral SBRT, with doses ranging from 24 to 40 Gy over three to five fractions. The most frequently used schedule was 30 Gy in three fractions. Common primaries treated included prostate (n = 16), breast (n = 6), lung (n = 3) and renal (n = 3) cancers. The median follow-up was 20 months (interquartile range 13-55 months). The cumulative incidence of local relapse (4/34) was 2.9% (95% confidence interval 0.2-13.2), 6.3% (95% confidence interval 1.1-18.5) and 16.8% (95% confidence interval 4.7-35.4) at 6 months, 1 year and 2 years, respectively. The patterns of failure were local-only (1/34), local and distant (3/34) and distant relapse (10/34). The overall survival was 96.7% (95% confidence interval 90.5-100) and 90.6% (95% confidence interval 78.6-100) at 1 and 2 years, respectively. For prostate/breast primaries, the cumulative incidence of local relapse was 4.5% (95% confidence interval 0.3-19.4), 4.5% (95% confidence interval 0.3-19.4) and 12.5% (95% confidence interval 1.7-34.8) at 6 months, 1 and 2 years, respectively. Twenty-nine cases (85.3%) deviated from the CCR. Sacral relapse was potentially preventable if the CCR was used in one patient (2.9% of the whole cohort and 25% of the relapsed cohort). DISCUSSION: We have shown excellent local control rates with sacral SBRT, which was largely planned with a margin expansion approach.

The Management of Oligometastases in Non-small Cell Lung Cancer - is Stereotactic Ablative Radiotherapy now Standard of Care?

Oligometastatic non-small cell lung cancer encompasses a number of distinct clinical scenarios with a pattern of limited tumour burden on imaging. Delivering local ablative therapy to individual metastatic lesions may assist in disease modification and contribute to improved outcomes. We review the published randomised clinical trials that support the implementation of stereotactic ablative radiotherapy as a standard of care in certain oligometastatic non-small cell lung cancer clinical scenarios, and highlight the current knowledge gaps and areas of ongoing research.

A Comparison of Isotoxic Dose-escalated Radiotherapy in Lung Cancer with Moderate Deep Inspiration Breath Hold, Mid-ventilation and Internal Target Volume Techniques.

AIMS: With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach. MATERIALS AND METHODS: Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques. RESULTS: The mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V21 Gy) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques. CONCLUSION: mDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome.

Assessing Bladder Radiotherapy Response With Quantitative Diffusion-Weighted Magnetic Resonance Imaging Analysis.

AIMS: Radiotherapy with radiosensitisation offers opportunity for cure with organ preservation in muscle-invasive bladder cancer (MIBC). Treatment response assessment and follow-up are reliant on regular endoscopic evaluation of the retained bladder. In this study we aim to determine the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) analysis to assess bladder radiotherapy response. MATERIALS AND METHODS: Patients with T2-T4aN0-3M0 MIBC suitable for radical radiotherapy were recruited prospectively to an ethics approved protocol. Following transurethral resection of the bladder tumour and prior to any treatment, magnetic resonance imaging including DWI was performed on a 1.5T system using b values of 0, 100, 150, 250, 500, 750 s/mm2. DWI was repeated 3 months after completing radiotherapy. Cystoscopy and tumour site biopsy were undertaken following this. The response was dichotomised into response (0.9, P < 0.01). ΔADCall mean of 0.16 × 10-3 mm2/s and ΔADCb100 mean 0.12 × 10-3 mm2/s predicted radiotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 92.9%/100.0%/100.0%/75.0% and 89.3%/100.0%/100.0%/66.7%, respectively. CONCLUSIONS: Quantitative DWI analysis can successfully provide non-invasive assessment of bladder radiotherapy response. Multicentre validation is required before prospective testing to inform MIBC radiotherapy follow-up schedules and decision making.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.