Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study (NCT04858568) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

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Intracranial germ cell tumours (icGCTs) are uncommon tumours occurring in children and young adults. They are usually segregated into germinomas and non-germinomatous tumours (NGGCTs) in most classifications. Germinomas are highly curable tumours with multimodality treatment, but NGGCTs are associated with poorer survival outcomes. There are some differences in the approach to the management of icGCTs globally. Current research generally focuses on reducing treatment intensity, particularly the dose and volume of radiotherapy, in order to minimise the risks of late sequelae while maintaining high cure rates in icGCTs.

SUMMARYSARS-CoV-2 vaccination protects against COVID-19. Antibodies and antigen-specific T-cell responses against the spike domain can be used to measure vaccine immune response. Individuals with lymphoma have defects in humoral and cellular immunity that may compromise vaccine response. In this prospective observational study of 457 participants with lymphoma, 52% of participants vaccinated on treatment had undetectable anti-spike IgG antibodies compared to 9% who were not on treatment. Marked impairment was observed in those receiving anti- CD20 antibody within 12 months where 60% had undetectable antibodies compared to 11% on chemotherapy, which persisted despite three vaccine doses. Overall, 63% had positive T-cell responses irrespective of treatment. Individuals with indolent B-cell lymphoma have impaired antibody and cellular responses that were independent of treatment. The significant reduction and heterogeneity in immune responses in these individuals emphasise the urgent need for immune response monitoring and alternative prophylactic strategies to protect against COVID- 19.

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Abstract.Background: The use of conventionally fractionated intensity modulated radiotherapy (IMRT) in the management of oligometastatic renal cell carcinoma (RCC) is currently poorly characterised in the literature. Objective: To evaluate the safety and effectiveness of IMRT for intraabdominal and retroperitoneal RCC oligometastases. Methods: Retrospective analysis of 14 patients with oligometastatic RCC treated with IMRT with the aim of inducing longterm control. Indications for radiotherapy included bleeding abdominal mass (5 patients), solitary renal bed recurrence (5 patients) and isolated, asymptomatic pancreatic mass (4 patients). The prescribed radiotherapy dose was 50 Gray in 20 to 25 fractions. Patients were followed up long-term using regular cross-sectional imaging and clinical review to assess local and distant disease control and treatment related toxicity. Results: At median follow up of 33.5 (6-68) months, 12 patients remain alive (86%), of whom 11 (92%) have no evidence of local recurrence. Six patients (43%) developed further metastatic disease, of whom 4 (67%) received systemic treatment. Median duration of local control was 33.5 months, and 1-and 3-year overall survival (OS) was 92.9% and 85.7% respectively. No treatment-related toxicities ≥ grade 3 and no long-term sequelae were observed. Conclusions: IMRT to intra-abdominal and retroperitoneal metastasis in oligo-metastatic RCC can be delivered safely, provide durable responses and excellent longer-term survival if given to a sufficiently high dose over a conventionally fractionated course. Our study is the first to date with long-term follow up to evaluate the role of IMRT in such cases and has important implications for treatment of oligometastatic RCC.

439 Background: Anal cancer, a tumour induced by the human papilloma virus (HPV) is highly responsive to chemoradiation. Smoking appears to be an important cofactor in its development, possibly through immunomodulatory mechanism and has been reported to have a negative effect on prognosis. Objective is to evaluate the relation between smoking and the outcome in patients receiving radical chemoradiotherapy (50.4 Gy/ 28f with concomitant 5FU/Mitomycin) for squamous carcinoma of the anus. Methods: 109 patients treated with radical intent from January 2009- Feb 2013 were retrospectively analysed. Details of staging, smoking history, HIV status, response to treatment, follow up time and recording of persistent or recurrence were collected. High risk disease (HR) was defined as any T3/T4 disease or TxN2+, standard risk (SR) as T1/2 N0-1. Results: 68 females and 41 males with an age range 38-83 (median 61).Data about smoking status was available in 74 patients: 28 smokers, 8 ex-smokers, and 38 non-smokers. 54/109 (49%) had high risk disease (HR), and the distribution was balanced across the groups. 4 patients were HIV positive. Median follow up time was 23 months. Complete clinical response was achieved in 101/109 (93%), 1 patient died (cause unknown), and 7 had persistent disease. Of these 6 were smokers (2 SR, 3HR, 1 HR and HIV+) 1 was a non-smoker (1 HR). 9 patients developed recurrent disease: 5 smokers (2 SR, 3 HR), 1 ex-smoker (HR), 3 unknown (2HR, 1SR). 11/16 patients who had a local failure were persistent smokers. Using ordinal logistic regression, smoking increases the risk of recurrence with an Odds ratio of 17.4 (p=0.008). Conclusions: This retrospective series suggest that smoking is associated with a higher risk of local recurrence following chemoradiotherapy. One of the hypothesis is that tissue hypoxia may impact on the oxygen dependent effect of chemoradiation. Patients should be encouraged to stop smoking and smoking may need to be considered as a factor defining a higher risk category which may benefit from dose escalation.

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