ABSTRACT
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
ABSTRACT
Background: The efficacy of SARS-COV-2 vaccination has been demonstrated in healthy individuals. Immune responses are less well characterised in cancer patient groups, especially those receiving anticancer therapy (e.g. immune therapy, chemotherapy and targeted therapies. We aim to assess the immune response to the SARS-COV-2 vaccination in patients with solid organ cancer on different systemic anti-cancer therapies. Methods: All patients received 2 doses of COVID-19 mRNA vaccination as part of the UK National vaccination programme;with the second booster dose administered within 12 weeks of the first dose. All patients received either BNT162b2 (Pfizer/BioNTech) or ChAdOx1 S (AstraZeneca) vaccines. Sequential serum samples were collected pre-booster dose vaccination (baseline/within -30 days) and after second dose SARS-COV-2 vaccination, at 14-35 days and 36-63 days. Presence and titres of serum Anti-SARS-CoV-2 Spike protein (S) antibody titres were measured. Seroconversion is defined as a response >0.8 U/ml, and maximum response to Anti-S is defined as >250 U/ml. Responses were measured in 3 patient groups according to the type of anti-cancer therapy: chemotherapy (CHT group), immune therapy (IO group) and targeted therapies, mainly VEGF TKI (TT group). Results: Overall, 61 patients were recruited: 45.9%(28/61) in CHT group, 32.8% (20/61) in IO group and 21.3% (13/61) in the TT group. Baseline characteristics were comparable between patient groups. In response to the booster dose vaccination at 14-35 days, the number of patients who seroconverted was 79.3% (23/29), 94.7% (18/19) and 84.6% (11/13) in the CHT, IO and TT groups, respectively. At this same time point, 51.7% (15/29) in the CHT group achieved maximum anti-S titre levels (>250 U/ml), compared with 78.9% (15/19) of patients in IO group and 69.2% (9/13) of patients in TT group. All 3 groups demonstrated a significant increase in Anti-S antibodies at 14-35 days after second dose vaccine when compared to pre-booster serum levels, with the largest increase seen in the IO group with a mean Anti-S increase of 149.1 U/ml (SD±105.0, p < 0.0001) followed by the TT group mean increase 120.2 U/ml (SD ±110.8, p < 0.01) and the CHT group, mean increase 83.0 U/ml (SD ±108.4, p < 0.001). Anti-S antibody levels were sustained at 36-63 days post-booster across all groups. However only IO patients had a sustained immune response to vaccination, with median Anti-S titres level of >250 U/ml and a significant drop was seen in the CHT group (median Anti-S level 138, p < 0.05). Conclusions: Anti-S titres increase following vaccination in all 3 groups but remain most sustained in the IO group at 36-63 days post-vaccination. Chemotherapy and other targeted therapy treated patients may benefit from early COVID-19 vaccine boosters, compared to patients receiving immune therapy.
ABSTRACT
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.
ABSTRACT
Background: Invasive mechanical ventilation (IMV) was recommended over non-invasive ventilation (NIV) for acute respiratory distress syndrome. A potential role for NIV to delay or avoid IMV has emerged during the COVID-19 pandemic. Aim: We explored the role of NIV in treatment of hypoxemic respiratory failure during the COVID-19 pandemic. Methods: Data from all patients admitted with COVID-19 infection to local Respiratory Units (RU) between 10/03 and 25/04/2020 were retrospectively extracted from routine health records into a piloted database. Descriptive analyses and associations between NIV usage and outcomes are described. Results: 209 patients were included. Median age was 66 years, 65% were male, 40% were of Black, Asian or minority ethnicity. 50% were clinically assessed as potentially benefitting from critical care (CCU) admission;17% were for RU-based NIV and 33% not for non/invasive ventilation. 48 patients had RU-based NIV, of which 88% was continuous-positive pressure ventilation. Of those who received NIV and were considered for CCU, 74% required CCU admission (N=20/27). 46% patients receiving NIV in RU were proned. Overall, 73 patients died (35%). Mortality may be higher amongst patients receiving NIVthan those not (44% vs 32%, p=0.14), likely reflecting disease severity. Awake proning may be associated with lower mortality (26% vs 55%, p=0.07). 23% patients admitted to ITU died;amongst those intubated, mortality was 45%. Conclusions: Ward-based NIV, particularly in conjunction with proning, may have a role in management of respiratory failure due to COVID-19, however the majority of patients ultimately required CCU. Ward-based NIV may benefit frailer patients not for CCU admission.