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PICO-SM was a prospective longitudinal study investigating the psychological impact of the COVID-19 pandemic on patients with colorectal cancer treated in a large UK tertiary cancer centre. Here, we present the impact of the third wave of the pandemic (December 2021 to February 2022), when the Omicron variant became prevalent in the UK, and the complete longitudinal comparison across the entire duration of this study. Patients were invited to complete a questionnaire, including screening psychometric tools. In total, n = 312 patients were included in the final analysis. Specifically, in this Omicron-predominant wave, n = 96 patients were studied in detail: the mean age was 64 years, 64% were male, 33% reported poor well-being, 27% anxiety, 11% depressive symptoms, and 3% trauma-related symptoms. The participants who had investigations cancelled (OR 9.22, 95% CI 1.09-77.85; p = 0.041) or felt that the pandemic would affect their mental health (OR 3.82, 95% CI 1.96-7.44; p < 0.001) had an increased risk of anxiety according to a multivariate analysis. Similarly, independent predictors of poor well-being included concern that the pandemic would affect their cancer treatment (OR 4.59, 95% CI 1.03-20.56; p = 0.046) or mental health (OR 3.90, 95% CI 1.38-11.03; p = 0.010). The psychological distress experienced by patients, particularly anxiety, remained high during the third wave of the COVID-19 pandemic. These results align with our previously reported findings, emphasising the importance of continuing cancer treatment amidst an ongoing humanitarian emergency.

Background: Burnout in health care professionals (HCPs) results from exposure to psychosocial risks at work. Left unaddressed, burnout can lead to chronic health problems, increased staff turnover, reduced work hours, absenteeism, and early retirement from clinical practice, thus impacting patient care. The European Society for Medical Oncology (ESMO) Resilience Task Force (RTF) was established in December 2019 to support the well-being of oncology HCPs globally. This ESMO RTF position paper aims to provide a set of recommendations to optimise well-being and mitigate burnout in oncology, and to help individuals and institutions maintain the delivery of optimal cancer care., Design: Recommendations were developed by a diverse multinational panel of interprofessional experts based on the key findings from three previously reported ESMO RTF surveys., Results: Several recurrent work-related psychosocial risks in oncology were identified; in particular, concerns about workload and professional development. The need for flexible work patterns, continued use of virtual resources, well-being resources, and targeted support for at-risk groups were highlighted as key considerations to safeguard HCPs' health and prevent burnout. In total, 11 recommendations relating to three priority themes were developed: (i) information and training; (ii) resources; (iii) activism and advocacy., Conclusion: Optimising the well-being of oncology HCPs is essential for the provision of high-quality, sustainable care for patients globally. The ESMO RTF will continue its mission and is rolling out several initiatives and activities to support the implementation of these recommendations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% ( n = 122) male, 92% ( n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% ( n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% ( n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% ( n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% ( n = 66/213) poor well-being (WHO-5 < 50). In the subgroup ( n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences.

Type 1 conventional dendritic cells (cDC1) play a critical role in priming anticancer cytotoxic CD8 + T cells. DNGR-1 (a.k.a. CLEC9A) is a cDC1 receptor that binds to F-actin exposed on necrotic cancer and normal cells. DNGR-1 signaling enhances cross-presentation of dead-cell associated antigens, including tumor antigens. We have recently shown that secreted gelsolin (sGSN), a plasma protein, competes with DNGR-1 for binding to dead cell-exposed F-actin and dampens anticancer immunity. Here, we investigated the effects of loss of sGSN on various anticancer therapies that are thought to induce cell death and provoke an immune response to cancer. We compared WT (wildtype) with Rag1 -/- , Batf3 -/- , Clec9a gfp/gfp , sGsn -/- or sGsn -/- Clec9a gfp/gfp mice implanted with transplantable tumor cell lines, including MCA-205 fibrosarcoma, 5555 Braf V600E melanoma and B16-F10 LifeAct (LA)-ovalbumin (OVA)-mCherry melanoma. Tumor-bearing mice were treated with (1) doxorubicin (intratumoral) chemotherapy for MCA-205, (2) BRAF-inhibitor PLX4720 (oral gavage) targeted therapy for 5555 Braf V600E , and (3) X-ray radiotherapy for B16 LA-OVA-mCherry. We confirmed that efficient tumor control following each therapy requires an immunocompetent host as efficacy was markedly reduced in Rag1 -/- compared with WT mice. Notably, across all the therapeutic modalities, loss of sGSN significantly enhanced tumor control compared with treated WT controls. This was an on-target effect as mice deficient in both sGSN and DNGR-1 behaved no differently from WT mice following therapy. In sum, we find that mice deficient in sGsn display enhanced DNGR-1-dependent responsiveness to chemotherapy, targeted therapy and radiotherapy. Our findings are consistent with the notion some cancer therapies induce immunogenic cell death (ICD), which mobilizes anticancer T cells. Our results point to cDC1 and DNGR-1 as decoders of ICD and to sGSN as a negative regulator of such decoding, highlighting sGSN as a possible target in cancer treatment. Further prospective studies are warranted to identify patients who may benefit most from inhibition of sGSN function., Competing Interests: Competing interests: KHJL, EG and CReS are named as contributors/inventors on a patent application on the use of sGSN for immunotherapies. CReS owns stock options and/or is a paid consultant for Adendra Therapeutics, Bicara Therapeutics, Montis Biosciences, Bicycle Therapeutics and Sosei Heptares. CReS holds a visiting professorship at Imperial College London and honorary professorships at University College London and King’s College London., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer., Patients and Methods: Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed., Results: A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48)., Conclusion: During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer., (Copyright © 2021. Published by Elsevier Inc.)

Background: COVID-19 has had a significant impact on the well-being and job performance of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate and monitor well-being since COVID-19 in relation to work, lifestyle and support factors in oncology professionals 1 year on since the start of the pandemic., Methods: An online, anonymous survey was conducted in February/March 2021 (Survey III). Key outcome variables included risk of poor well-being or distress (expanded Well-Being Index), feeling burnout (single item from expanded Well-Being Index), and job performance since COVID-19. Longitudinal analysis of responses to the series of three surveys since COVID-19 was carried out, and responses to job demands and resources questions were interrogated. SPSS V.26.0/V.27.0 and GraphPad Prism V9.0 were used for statistical analyses., Results: Responses from 1269 participants from 104 countries were analysed in Survey III: 55% (n = 699/1269) female, 54% (n = 686/1269) >40 years, and 69% (n = 852/1230) of white ethnicity. There continues to be an increased risk of poor well-being or distress (n = 464/1169, 40%) and feeling burnout (n = 660/1169, 57%) compared with Survey I (25% and 38% respectively, P < 0.0001), despite improved job performance. Compared with the initial period of the pandemic, more participants report feeling overwhelmed with workload (45% versus 29%, P < 0.0001). There remain concerns about the negative impact of the pandemic on career development/training (43%), job security (37%). and international fellowship opportunities (76%). Alarmingly, 25% (n = 266/1086) are considering changing their future career with 38% (n = 100/266) contemplating leaving the profession., Conclusion: Oncology professionals continue to face increased job demands. There is now significant concern regarding potential attrition in the oncology workforce. National and international stakeholders must act immediately and work closely with oncology professionals to draw up future-proof recovery plans., Competing Interests: Disclosure KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen, outside the submitted work. KP’s institution received speaker fees or honoraria for consultancy/advisory roles from AstraZeneca, Eli Lilly, Gilead Sciences, Medscape, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundipharma, PharmaMar, Seagen, Teva, and Vifor Pharma; KP’s institution received research grants from MSD and Sanofi; KP received travel support from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche; all outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from medac Pharma and Ipsen Pharma; and travel grant from PharmaMar; outside the submitted work. EÉ reports speaker honoraria, travel support and advisory board: Bayer, Roche, Servier, Amgen, Pierre-Fabre, Sanofi Aventis, MSD, and Merck Serono; outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from Bristol Myers Squibb (BMS); grants, personal fees, and travel grants from Novartis; and grants from NeraCare, Sanofi, and SkylineDx; all outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boerhinger-Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI, outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly, outside the submitted work. CBW reports speaker honoraria, travel support, and participation in advisory boards: Bayer, BMS, Celgene, GlaxoSmithKline (GSK), Merck, Rafael, RedHil, Roche, Servier, Shire/Baxalta, Sirtex, and Taiho, as well as research support from Roche, outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm; outside the submitted work. CH reports being Director of a private company Hardy People Ltd, outside the submitted work. SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria for advisory boards or lectures from Amgen, AstraZeneca, Genmab, Immunogen, Mersana, MSD, Merck Serono, OncXerna, Pfizer, Roche, Shattuck Labs, Clovis, Takeda outside the submitted work. KM, KK, MOC, ET, BD, and GM have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Competing Interests: Disclosure KHJL has received speaker honorarium from Janssen, outside the submitted work and is currently funded by the Wellcome Imperial 4i Clinical Research Fellowship. BJS has received advisory board/honoraria from Roche/Genentech, AstraZeneca, Pfizer, Novartis, Bristol-Myers-Squibb, Merck, Amgen, and Loxo oncology, outside the submitted work.

Background: The COVID-19 pandemic has resulted in significant changes to professional and personal lives of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration aimed to provide contemporaneous reports on the impact of COVID-19 on the lived experiences and well-being in oncology., Methods: This online anonymous survey (July-August 2020) is the second of a series of global surveys launched during the course of the pandemic. Longitudinal key outcome measures including well-being/distress (expanded Well-being Index-9 items), burnout (1 item from expanded Well-being Index), and job performance since COVID-19 were tracked., Results: A total of 942 participants from 99 countries were included for final analysis: 58% (n = 544) from Europe, 52% (n = 485) female, 43% (n = 409) ≤40 years old, and 36% (n = 343) of non-white ethnicity. In July/August 2020, 60% (n = 525) continued to report a change in professional duties compared with the pre-COVID-19 era. The proportion of participants at risk of poor well-being (33%, n = 310) and who reported feeling burnout (49%, n = 460) had increased significantly compared with April/May 2020 (25% and 38%, respectively; P < 0.001), despite improved job performance since COVID-19 (34% versus 51%; P < 0.001). Of those who had been tested for COVID-19, 8% (n = 39/484) tested positive; 18% (n = 7/39) felt they had not been given adequate time to recover before return to work. Since the pandemic, 39% (n = 353/908) had expressed concerns that COVID-19 would have a negative impact on their career development or training and 40% (n = 366/917) felt that their job security had been compromised. More than two-thirds (n = 608/879) revealed that COVID-19 has changed their outlook on their work-personal life balance., Conclusion: The COVID-19 pandemic continues to impact the well-being of oncology professionals globally, with significantly more in distress and feeling burnout compared with the first wave. Collective efforts from both national and international communities addressing support and coping strategies will be crucial as we recover from the COVID-19 crisis. In particular, an action plan should also be devised to tackle concerns raised regarding the negative impact of COVID-19 on career development, training, and job security., Competing Interests: Disclosure KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen, outside the submitted work. KP’s institution received speaker fees or honoraria for consultancy/advisory roles from AstraZeneca, Eli Lilly, Gilead Sciences, Medscape, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundipharma, PharmaMar, Teva, Vifor Pharma; KP’s institution received a research grant from Sanofi; KP received travel support from AstraZeneca, Novartis, Pfizer, PharmaMar and Roche; all outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from Medac Pharma and Ipsen Pharma; and travel grant from PharmaMar; outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from Bristol-Myers Squibb (BMS); grants, personal fees, and travel grants from Novartis; and grants from Neracare, Sanofi, and SkylineDx; all outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boerhinger-Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI, outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly, outside the submitted work. CBW reports speaker honoraria, travel support, and advisory board: Bayer, BMS, Celgene, Roche, Servier, Shire/Baxalta, RedHil, and Taiho; speaker honoraria from Ipsen; and advisory board in GlaxoSmithKline (GSK), Sirtex, and Rafael; outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm; outside the submitted work. CH reports being Director of a private company Hardy People Ltd., outside the submitted work. SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria from Amgen, AstraZeneca, MSD, GSK, Clovis, Genmab, Merck Serono, Mersana, Pfizer, Seattle Genetics, and Tesaro; outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cross-presentation of antigens from dead tumor cells by type 1 conventional dendritic cells (cDC1s) is thought to underlie priming of anti-cancer CD8 + T cells. cDC1 express high levels of DNGR-1 (a.k.a. CLEC9A), a receptor that binds to F-actin exposed by dead cell debris and promotes cross-presentation of associated antigens. Here, we show that secreted gelsolin (sGSN), an extracellular protein, decreases DNGR-1 binding to F-actin and cross-presentation of dead cell-associated antigens by cDC1s. Mice deficient in sGsn display increased DNGR-1-dependent resistance to transplantable tumors, especially ones expressing neoantigens associated with the actin cytoskeleton, and exhibit greater responsiveness to cancer immunotherapy. In human cancers, lower levels of intratumoral sGSN transcripts, as well as presence of mutations in proteins associated with the actin cytoskeleton, are associated with signatures of anti-cancer immunity and increased patient survival. Our results reveal a natural barrier to cross-presentation of cancer antigens that dampens anti-tumor CD8 + T cell responses., Competing Interests: Declaration of interests E.G., O.S., K.H.J.L., N.S., O.G., S.Z., S.S., P.C., and C.R.S. are named as inventors on a patent application on the use of sGSN for immunotherapies. C.R.S. owns stock options and/or is a paid consultant for Bicara Therapeutics, Montis Biosciences, Oncurious NV, Bicycle Therapeutics, and Sosei Heptares. C.R.S. holds a professorship at Imperial College London and honorary professorships at University College London and King’s College London. None of these activities are related to this work., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on well-being has the potential for serious negative consequences on work, home life, and patient care. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate well-being in oncology over time since COVID-19., Methods: Two online anonymous surveys were conducted (survey I: April/May 2020; survey II: July/August 2020). Statistical analyses were performed to examine group differences, associations, and predictors of key outcomes: (i) well-being/distress [expanded Well-being Index (eWBI; 9 items)]; (ii) burnout (1 item from eWBI); (iii) job performance since COVID-19 (JP-CV; 2 items)., Results: Responses from survey I (1520 participants from 101 countries) indicate that COVID-19 is impacting oncology professionals; in particular, 25% of participants indicated being at risk of distress (poor well-being, eWBI ≥ 4), 38% reported feeling burnout, and 66% reported not being able to perform their job compared with the pre-COVID-19 period. Higher JP-CV was associated with better well-being and not feeling burnout (P < 0.01). Differences were seen in well-being and JP-CV between countries (P < 0.001) and were related to country COVID-19 crude mortality rate (P < 0.05). Consistent predictors of well-being, burnout, and JP-CV were psychological resilience and changes to work hours. In survey II, among 272 participants who completed both surveys, while JP-CV improved (38% versus 54%, P < 0.001), eWBI scores ≥4 and burnout rates were significantly higher compared with survey I (22% versus 31%, P = 0.01; and 35% versus 49%, P = 0.001, respectively), suggesting well-being and burnout have worsened over a 3-month period during the COVID-19 pandemic., Conclusion: In the first and largest global survey series, COVID-19 is impacting well-being and job performance of oncology professionals. JP-CV has improved but risk of distress and burnout has increased over time. Urgent measures to address well-being and improve resilience are essential., Competing Interests: Disclosure SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria from Amgen, AstraZeneca, MSD, GSK, Clovis, Genmab, Immunogen, Merck Serono, Mersana, Pfizer, Seattle Genetics, Roche and Tesaro outside the submitted work. KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen outside the submitted work. KP reports personal fees from Astra Zeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundi Pharma, and PharmaMar; and other fees paid to institution from Vifor Pharma, TEVA, and Sanofi outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from Medac Pharma and Ipsen Pharma; and travel grant from PharmaMar outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly outside the submitted work. CBW reports speaker honoraria, travel support, and serving on the advisory board in Bayer, BMS, Celgene, Roche, Servier, Shire/Baxalta, RedHill, and Taiho; speaker honoraria from Ipsen; and advisory board in GSK, Sirtex, and Rafael outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boehringer Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from BMS; grants, personal fees, and travel grants from Novartis; and grants from NeraCare, Sanofi, and SkylineDx outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm outside the submitted work. CH reports private company Hardy People Ltd. outside the submitted work. The remaining authors have declared no conflicts of interest., (Copyright © 2021 ESMO. Published by Elsevier Ltd.. All rights reserved.)

Objective: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions., Methods: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed ., Results: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS., Conclusions: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: COMPETING INTERESTS No competing interests in regards to this podcast. KHJL has received speaker honorarium from Janssen, outside the submitted work. FG has received speaker honorarium from AstraZeneca and Boehringer Ingelheim; grants from Takeda and Pfizer; and travel fees from Pfizer, outside the submitted work. Patient consent for publication Not required. Provenance and peer review Not commissioned; internally peer-reviewed.

Background: The prognostic significance of lymph nodes (LNs) metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours (GEP NETs) undergoing curative resection is still debatable. Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy., Aim: To evaluate the effect of lymph node (LN) status and yield on relapse-free survival (RFS) and overall survival (OS) in patients with resected GEP NETs., Methods: Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively. Grade 3 tumours (Ki67 > 20%) were excluded. Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS., Results: A total of 217 patients were included in the study. The median age was 59 years (21-97 years) and 51% ( n = 111) were male. Primary tumour sites were small bowel (42%), pancreas (25%), appendix (18%), rectum (7%), colon (3%), gastric (2%), others (2%). Median follow up times for all patients were 41 mo (95%CI: 36-51) and 71 mo (95%CI: 63-76) for RFS and OS respectively; 50 relapses and 35 deaths were reported. LNs were retrieved in 151 patients. Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients. Three or more positive LNs were detected in 62 cases. The result of univariate analysis suggested perineural invasion ( P = 0.0023), LN positivity ( P = 0.033), LN retrieval of ≥ 8 ( P = 0.047) and localisation ( P = 0.0049) have a statistically significant association with shorter RFS, but there was no effect of LN ratio on RFS: P = 0.1 or OS: P = 0.75. Tumour necrosis ( P = 0.021) and perineural invasion ( P = 0.016) were the only two variables significantly associated with worse OS. In the final multivariable analysis, localisation (pancreas HR = 27.33, P = 0.006, small bowel HR = 32.44, P = 0.005), and retrieval of ≥ 8 LNs (HR = 2.7, P = 0.036) were independent prognostic factors for worse RFS., Conclusion: An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery. Removal of ≥ 8 LNs is associated with increased risk of relapse, which could be due to high rates of LN positivity at the time of surgery. Given that localisation had a significant association with RFS, a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs., Competing Interests: Conflict-of-interest statement: The authors report no conflict of interest in this work., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs)., Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement., Methods: A retrospective study of all patients with NENs, except Grade 3 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12., Results: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n = 42) followed by lung (25%, n = 21), unknown primary (20%, n = 17), and "others" (6%, n = 5). Two-thirds (n = 57) had G1-2 neuroendocrine tumours, and 41% (n = 35) had functional tumours. Overall, 28% (n = 24) presented with synchronous BMs at first NEN diagnosis, and 55% (n = 47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n = 38), median time to development of BMs was 14.0 months. BMs were "widespread" in 61% (n = 52). Although only 22% (n = 19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n = 37). Radiotherapy and bisphosphonates were used in 34% (n = 29) and 22% (n = 19) respectively. Surgery was rarely performed (2%, n = 2). Median OS from identification of BMs was 31.0, and 18.9 months from development of BMs-related symptoms., Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients' quality of life and survival outcomes., (© 2019 S. Karger AG, Basel.)

Background: With increasing treatment options available, neuroendocrine tumor has become a chronic disease and may present later on with atypical manifestation of disease spread once resistant to treatment., Case Presentation: A 74-year-old white British woman undergoing treatment for metastatic well-differentiated neuroendocrine tumor for the past 9 years presented with a brief history of mild frontal headache, and progressive left ptosis and ocular palsy. She had no visual loss, and had neither speech nor motor deficit. At the outset, it was crucial to exclude acute or missed stroke. An urgent magnetic resonance imaging of her head revealed an unusual skull base metastasis extending into the cavernous sinus, with no peritumoral edema. Following discussion at a specialist neuro-oncology meeting and a neuroendocrine tumor multidisciplinary team meeting, she proceeded to have conventional fractionated radiotherapy followed by subsequent palliative chemotherapy., Conclusions: Intracranial metastasis is rare in patients with neuroendocrine tumor, particularly in those with well-differentiated histology; skull base metastasis is even more uncommon. Management of intracranial metastasis from a rare tumor should always be discussed in a specialist multidisciplinary meeting. Surgery or radiotherapy, including stereotactic radiosurgery, should be considered in skull base metastases. Hormonal abnormalities may occur following radiotherapy to skull base metastases and should be monitored closely in the first few months post treatment.

Background: Agreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain (every 6 months for 3 years, then annually in years 4 and 5) as well as clinical examination for high-risk resected Stages II and III cutaneous melanoma. Our aim was to assess patterns of relapse and whether imaging surveillance could be of clinical benefit., Patients and Methods: A retrospective study of patients enrolled between July 2013 and June 2015 from three UK tertiary cancer centres followed-up according to this protocol was undertaken. We evaluated time-to-recurrence (TTR), recurrence-free survival (RFS), method of detection and characteristics of recurrence, treatment received and overall survival (OS)., Results: A total of 173 patients were included. Most (79%) had treated Stages IIIB and IIIC disease. With a median follow-up of 23.3 months, 82 patients (47%) had relapsed. Median TTR was 10.1 months and median RFS was 21.2 months. The majority of recurrences (66%) were asymptomatic and detected by scheduled surveillance scan. Fifty-six (68%) patients recurred with Stage IV disease, with a median OS of 25.3 months; 26 (31.7%) patients had a locoregional recurrence, median OS not reached (P=0.016). Patients who underwent surgery at recurrence for either Stage III (27%) or IV (18%) disease did not reach their median OS. The median OS for the 33 patients (40%) who received systemic therapy was 12.9 months., Conclusion: Imaging appears to reliably detect subclinical disease and identify patients suitable for surgery, conferring favourable outcomes. The short median TTR provides rationale to intensify imaging schedule in the first year of surveillance. The poor OS of patients treated with systemic therapy probably reflects the relatively inferior treatment options during this time and requires further evaluation in the current era., Competing Interests: Competing interests: JL is supported by the NIHR Royal Marsden/Institute of Cancer Research BRC for Cancer.