ABSTRACT
Background: Older patients with cancer remain at high risk for negative outcomes from COVID-19 infection, particularly those who have multimorbidities and on immunosuppressive therapy. These patients have been excluded or underrepresented in pivotal COVID-19 vaccine clinical trials and there are ongoing concerns that they may not acquire the same level of protection from the available vaccines as the immunocompetent adults. Moreover, the level of protection wanes over time making them more susceptible to emerging COVID-19 novel variants of concern. Despite the implementation of global vaccination campaigns which have successfully reduced COVID-related hospitalisations and deaths in many parts of the world, there remains many unresolved issues and challenges to address as the pandemic ensues. With aging, concerns for age-related dysregulation and immune dysfunctions called immunosenescence may lead to potentially lower immunogenicity to vaccines. Despite receiving the primary vaccination, real-world evidence showed that both patients aged > 65 years and those with cancer have a higher risk of developing breakthrough COVID-19 infections and related complications. Subsequent booster doses are found to be effective at improving immune response, particularly against the novel variants, and the vulnerable population should be given the priority in booster campaigns. Method(s): Since the beginning of the pandemic in 2020, The International Society of Geriatric Oncology set up a COVID-19 Working Group comprised of multidisciplinary specialists by developing recommendations, advocacy, and action plans based on expert opinion and evidence related to older adults with cancer. Result(s): The table below summarises the updated recommendations from the SIOG COVID-19 Working Group. Conclusion(s): The SIOG COVID-19 Working Group supports ongoing public health interventions, continued mass immunisations, and booster campaigns targeting the most vulnerable members of the society, including older adults with cancer (Table Presented).
ABSTRACT
Background: Bladder-preserving combinedmodality therapies constitute an alternative to radical cystectomy for selected pts with MIBC. In preclinical studies, combination of radiation and dual checkpoint blockade appears to activate non-redundant immune mechanisms, potentiating antitumor activity. The purpose of the present study is to explore feasibility, toxicity and activity of this approach in MIBC. Methods: Pts with localized MIBC in clinical stages T2-4a N0 M0, ECOG 0-1, without contraindications to immunotherapy, who either wished for bladder preservation or were ineligible for cystectomy, were included in this phase II study. Treatment consisted of initial transurethral resection (TUR) of the tumor, followed by durvalumab 1,500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for 3 doses. Normofractionated external-beam RT was started 2 weeks later, at doses of 46 Gy to minor pelvis and 64-66 Gy to bladder. Pts with either residual or relapsed MIBC were offered salvage cystectomy. The primary endpoint was complete response (CR) defined as absence of MIBC at post-treatment tumor site biopsy. A 2- stage sequential design was used (CR rate P0=5, P1=0.7, α=0.10, β=0.20) requiring at least 6 CR in the first 12 pts to expand to a second cohort of 20 pts. Results: From 1/2019 to 8/2020, 32 pts were enrolled at 6 centers. Median age was 71 years (49-91). PS was 0 in 24 pts,1 in 8. 25 were males. Clinical stage was T2 in 28 pts, T3 in 3 and T4a in 1. All pts received at least two immunotherapy cycles. The median dose of RT administered was 64 Gy (60-65). CR at posttreatment biopsy was documented in 26 (81%) pts, 2 pts had residual MIBC and 4 pts were not evaluated due to rejection (1), clinical impairment (1), death from COVID 19 (1) and a suspected treatment-related death from peritonitis (1). After a median follow up of 6.1 months (2.5 - 20.1), 2 pts underwent salvage cystectomy because of MIBC and T1 relapses, respectively. The estimated 6-months rates for disease-free survival (DFS) with bladder intact, DFS and overall survival were 76% (95%CI, 61%-95%), 80% (95%CI, 66%-98%) and 93% (95%CI, 85%-100%), respectively. A total of 31 (97%) pts experienced adverse events related to RT and/or immunotherapy, with diarrhea (41%) and urinary disorders (37.5%) as the most frequent. Grade 3 or 4 adverse events related to therapy were reported in 31% pts, being the most frequent gastrointestinal toxicity (12.5%), acute kidney failure (6%) and hepatitis (6%). Conclusions: A combined-modality approach including durvalumab + tremelimumab with concurrent RT is feasible and safe, showing high efficacy in terms of response and eliciting bladder preservation in a large number of pts. Further research on this approach as an alternative to cystectomy is warranted.