HALT - Targeted Therapy with or without Dose-Intensified Radiotherapy in Oligo-Progressive Disease in Oncogene Addicted Lung Tumours

Introduction: Following initial response to TKI, advanced NSCLC patients with actionable mutations ultimately develop treatment resistance. In a proportion of patients (15-40%), initial, limited progression (≤5 lesions) is observed, termed oligoprogressive disease (OPD). SBRT offers hypofractionated, targeted radiotherapy treatment hypothesised to prolong clinical benefit from TKI prior to widespread disease development. With limited evidence to date, and poor clinical/biological selection criteria, the potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address. Methods: HALT is a randomised, multi-centre, phase II/III international trial with seamless transition to phase III incorporated. Eligible patients (stage IV NSCLC, actionable mutation, TKI response prior to OPD) are randomised 2:1 to SBRT/continued TKI or continued TKI alone. Eligibility is confirmed by a virtual MDT (vMDT) comprising trial clinicians and radiologists (confirmation of OPD, SBRT suitability). Follow-up assessments are aligned with routine care at 3-monthly intervals until change in systemic therapy is clinically indicated, with imaging and toxicity assessment at each visit. Results: Recruitment commenced November 2017 with 25 centres (17 UK;8 non-UK) open to date. Following the COVID-19 pandemic, recruitment is recovering with 129 registered and 74 randomised patients. Over the last 4 years, little evidence has emerged to confirm any potential benefit of SBRT in this patient group and the impact on patient toxicity remains unknown. Therefore, with persisting questions around clinical equipoise, HALT remains highly relevant. With an 18-month extension and a recent amendment to the HALT inclusion criteria (≤5 OPD lesions, ≤7cm and OPD assessments by PET-avidity), the target of 110 randomised patients remains achievable. Conclusions: As the first randomised trial assessing SBRT benefit in this mutation-positive NSCLC patient population, HALT will provide valuable treatment efficacy and safety information, informing subsequent trial design and contribute to the development of international guidelines for the identification and clinical management of oligoprogression in mutation positive lung cancer. Keywords: Stereotactic body radiotherapy, NSCLC, Phase II

Stereotactic MRI-guided radiation therapy for localized prostate cancer (SMILE): a prospective, multicentric phase-II-trial.

BACKGROUND: Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. METHODS: The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. DISCUSSION: With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

171 HALT: targeted therapy with or without dose-intensified radiotherapy in oligo-progressive disease in oncogene addicted lung tumours

Background: Following initial response to TKI, advanced NSCLC patients with actionable mutations ultimately develop treatment resistance. In a proportion of patients (15-40%), initial, limited progression (<3 lesions) is observed, termed oligoprogressive disease (OPD). SBRT offers hypofractionated, targeted radiotherapy treatment hypothesised to prolong clinical benefit from TKI prior to widespread disease development. The potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address, particularly during the current pandemic, where reducing clinic visits is particularly advantageous. Method: HALT is a randomised, multi-centre, phase II/III international trial with seamless transition to phase III incorporated. Eligible patients (stage IV NSCLC, actionable mutation, TKI response prior to OPD) are randomised 2:1 to SBRT/continued TKI or continued TKI alone. Eligibility is confirmed by a virtual MDT comprising trial clinicians and radiologists (OPD, SBRT suitability). Follow-up assessments aligned with routine care at 3-monthly intervals until change in systemic therapy is clinically indicated, imaging and toxicity assessment at each visit. Current status: Recruitment commenced November 2017;27 centres (16 UK;11 non-UK) open to date (09/03/2021), 94 patients registered and 50 randomised. Because of the COVID-19 pandemic, recruitment was temporarily paused on 20/03/2020 and restarted in accordance with national guidelines on 16/06/2020. Of 94 patients registered, vMDT review performed for 74 patients (18 screen fails prior to vMDT);50 randomised, 22 confirmed ineligible via vMDT (inc. >3 lesions, lesion >5cm, intracranial disease identified). Conclusion: The vMDT remains an important, novel aspect of the trial, ensuring robust patient selection ahead of randomisation. As the first randomised trial assessing SBRT benefit in this patient population, HALT will provide valuable treatment efficacy and safety information, informing subsequent trial design and contribute to the development of international guidelines for the identification and clinical management of oligoprogression in mutation positive lung cancer. Disclosure: No significant relationships.

Prospective assessment of employees stress during the COVID-19 pandemic

Purpose or Objective: The COVID-19 pandemic has required rapid and repetitive adjustment of radiotherapy practice, hospital and department organization and hygienic measures. This has been in parallel with significant changes in everyone’s private life. In the Department of Radiation Oncology, University Zurich, all employees were invited to participate in weekly assessments of their stress levels, aiming to rapidly and precisely implement anti-stress measures. Materials and Methods: Starting from March 31st 2020, weekly anonymized surveys were distributed to all employees (n=134) of the Department of Radiation Oncology, University of Zurich. Survey Monkey was used, and distribution was performed via email. The survey asked about the profession (clinician, medical physics and dosimetry, RTT, nurse, administration and research) and whether work in the last week was performed in hospital with or without patient contact or in home office. Global stress level during the last week was assessed on a 10-point scale. Additionally, stress was assessed in the sub-categories: concerns about own health;concerns about health of family & friends;concerns about patients` health. Results: Between March 31st 2020 and February 17th 2021, a total of 47 surveys resulted in 1733 responses, 37 responses on average (range 26 and 54). Response rate was 28% on average and did not change over time, overall and in each profession. Averaged over all responses, the global stress level varied substantially between professions, ranging between 2.8 for administration and 6.8 for RTTs. The global stress level was highest for in-hospital work with patient contact with an average of 4.7, whereas stress was similar for in-hospital work without patient contact and home-office with 3.5 and 3.8, respectively. Concerns about health were highest about family & friends with 4.0 on average compared to concerns about the own health and of the patients with average values of 3.1 and 3.5, respectively. Changes of global stress level over the 47 weeks were strongly associated with development of the pandemic (figure). Averaged over all employees, the global stress level stated with 4.8 on average in March 2020 and dropped continuously in the spring and summer months until the second COVID-19 wave started in September 2020 with two peaks in November and December with 5.5 and 5.7 on average, respectively. Interventions against high stress levels were performed for all professions and especially the RTT subgroup with highest stress levels (workshops;meditation room;detailed information about hospital-specific infection rates;information about hospital wide possibilities for coping mechanisms, effectiveness of PPE;team meetings).