The last decade has seen significant treatment advances in the management of renal cell cancer, from the availability of oral, targeted therapies to the recent introduction of immunotherapy. In this article the authors cover the risk factors for renal cancer and its different histological types, as well as the staging and management of both early and late‐stage disease.

• Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain.

Citation for published version (Harvard): Jamal-hanjani, M, Wilson, GA, Mcgranahan, N, Birkbak, NJ, Watkins, TBK, Veeriah, S, Shafi, S, Johnson, DH, Mitter, R, Rosenthal, R, Salm, M, Horswell, S, Escudero, M, Matthews, N, Rowan, A, Chambers, T, Moore, DA, Turajlic, S, Xu, H, Lee, S, Forster, MD, Ahmad, T, Hiley, CT, Abbosh, C, Falzon, M, Borg, E, Marafioti, T, Lawrence, D, Hayward, M, Kolvekar, S, Panagiotopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Shah, R, Joseph, L, Quinn, AM, Crosbie, PA, Naidu, B, Middleton, G, Langman, G, Trotter, S, Nicolson, M, Remmen, H, Kerr, K, Chetty, M, Gomersall, L, Fennell, DA, Nakas, A, Rathinam, S, Anand, G, Khan, S, Russell, P, Ezhil, V, Ismail, B, Irvin-sellers, M, Prakash, V, Lester, JF, Kornaszewska, M, Attanoos, R, Adams, H, Davies, H, Dentro, S, Taniere, P, O?sullivan, B, Lowe, HL, Hartley, JA, Iles, N, Bell, H, Ngai, Y, Shaw, JA, Herrero, J, Szallasi, Z, Schwarz, RF, Stewart, A, Quezada, SA, Le Quesne, J, Van Loo, P, Dive, C, Hackshaw, A & Swanton, C 2017, 'Tracking the Evolution of Non-Small-Cell Lung Cancer', New England Journal of Medicine, vol. 376, no. 22, pp. 2109-2121. https://doi.org/10.1056/NEJMoa1616288

Citation for published version (Harvard): Jamal-hanjani, M, Wilson, GA, Mcgranahan, N, Birkbak, NJ, Watkins, TBK, Veeriah, S, Shafi, S, Johnson, DH, Mitter, R, Rosenthal, R, Salm, M, Horswell, S, Escudero, M, Matthews, N, Rowan, A, Chambers, T, Moore, DA, Turajlic, S, Xu, H, Lee, S, Forster, MD, Ahmad, T, Hiley, CT, Abbosh, C, Falzon, M, Borg, E, Marafioti, T, Lawrence, D, Hayward, M, Kolvekar, S, Panagiotopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Shah, R, Joseph, L, Quinn, AM, Crosbie, PA, Naidu, B, Middleton, G, Langman, G, Trotter, S, Nicolson, M, Remmen, H, Kerr, K, Chetty, M, Gomersall, L, Fennell, DA, Nakas, A, Rathinam, S, Anand, G, Khan, S, Russell, P, Ezhil, V, Ismail, B, Irvin-sellers, M, Prakash, V, Lester, JF, Kornaszewska, M, Attanoos, R, Adams, H, Davies, H, Dentro, S, Taniere, P, O?sullivan, B, Lowe, HL, Hartley, JA, Iles, N, Bell, H, Ngai, Y, Shaw, JA, Herrero, J, Szallasi, Z, Schwarz, RF, Stewart, A, Quezada, SA, Le Quesne, J, Van Loo, P, Dive, C, Hackshaw, A & Swanton, C 2017, 'Tracking the Evolution of Non-Small-Cell Lung Cancer' New England Journal of Medicine, vol. 376, no. 22, pp. 2109-2121. DOI: 10.1056/NEJMoa1616288

Background Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We also review the existing literature and propose an investigation and management algorithm. Methods All patients with advanced melanoma treated with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi + nivo), managed at the Royal Marsden Hospital between September 2010 and December 2015, including patients on (published) clinical trials were included. Medical records for each patient were reviewed and information on neurotoxicity recorded. A systematic search strategy was performed to collate existing reports of neurological toxicity. Results In total, 413 immunotherapy treatment episodes in 352 patients were included, with median follow-up of 26.7 months. Ten cases of neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from grade 1 to 4, affecting both central and peripheral nervous systems. A rate of 14% was noted with ipi + nivo. Three of five patients commenced on corticosteroids responded to these. Six patients had made a full recovery at the time of reporting. A favorable radiological response was found in 7 of the 10 cases. Unusual presentations are described in detail. Conclusions Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipi + nivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.

Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immunerelated neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as< 1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We also review the existing literature and propose an investigation and management algorithm. Methods: All patients with advanced melanoma treated with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi_nivo), managed at the Royal Marsden Hospital between September 2010 and December 2015, including patients on (published) clinical trials were included. Medical records for each patient were reviewed and information on neurotoxicity recorded. A systematic search strategy was performed to collate existing reports of neurological toxicity. Results: In total, 413 immunotherapy treatment episodes in 352 patients were included, with median follow-up of 26.7 months. Ten cases of neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from grade 1 to 4, affecting both central and peripheral nervous systems. A rate of 14% was noted with ipi_nivo. Three of five patients commenced on corticosteroids responded to these. Six patients had made a full recovery at the time of reporting. A favorable radiological response was found in 7 of the 10 cases. Unusual presentations are described in detail. Conclusions: Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipinivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.

Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab.

TPS4583Background: Cytoreductive nephrectomy may be beneficial in patients with metastatic clear cell renal cell carcinoma (mccRCC). However, there are currently no standard pre-operative systemic ...

TPS9599Background: Several large-scale clinical trials of pembrolizumab have demonstrated substantial efficacy and survival benefit in metastatic melanoma (MM). However, responses are limited to a ...

Therapeutic advances in oncology have not fully translated to the treatment of metastatic disease, which remains largely incurable. Metastatic subclones can emerge both early and late in the life of the primary tumor. A better understanding of the genetic evolution of metastatic disease has the potential to reveal differences in the therapeutic vulnerabilities of primary and metastatic tumors, shed light on the temporal patterns of and routes to metastatic colonization, and provide insight into the biology of the metastatic process. Here we review recent comparative studies of primary and metastatic tumors, including data suggesting that macroevolutionary shifts (the onset of chromosomal instability) contribute to the evolution of metastatic disease. We also discuss the practical challenges associated with these studies and how they might be overcome.