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Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02–6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28–16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82–45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30–49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p

Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44–87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34–4.86), p = 0.00] and melanoma [HR 2.42 (1.20–4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63–2.80), p = 0.44]. The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes. We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS). We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60–0.84) and HR: 0.66 (95% CI 0.55–0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57–0.79) and HR: 0.60 (95% CI 0.50–0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend

Soft tissue sarcomas (STS) have a high risk of relapse in spite of the use of (neo)adjuvant chemotherapy. In this context, looking for new prognostic biomarkers is an interesting field of research. Our aim is to analyze the prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and other serum markers in patients with STS who received chemotherapy with curative intent. This is a retrospective observational study. We included all patients with STS (primary tumor, local recurrence or resected metastatic disease) treated with high-dose ifosfamide and epirubicin with curative intent from January 2007 to December 2018. The pretreatment NLR and other serum markers were calculated, selecting the median as the cut-off value for the survival and multivariate analysis. Seventy-nine patients were included. Median NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were 2.83, 174.05 and 3.25, respectively. Median progression-free survival (PFS) was significantly longer in patients with low NLR [not reached (NR) vs 21, 92 months, P

Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies. pre-print 485 KB

Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). We provide the management and prognosis of cSCC in RDEB patients at a Spanish reference center. We retrospectively included patients with RDEB attended in La Paz University Hospital from November 1988 to October 2018. Fourteen patients developed at least one cSCC. Tumors were predominantly well differentiated. Nearly half of the tumors have recurred. Median time to first recurrence was 23.4 months (95% CI: 17.2–29.5). Five patients have developed distant metastases. Median overall survival (mOS) was 136.5 months since the diagnosis of the first cSCC (95% CI: 30.6–242.3). When distant metastases occurred, mOS was 6.78 months (95% CI: 1.94–11.61). cSCC is a life-threatening complication of RDEB patients. Although tumors are usually well differentiated, they tend to relapse. This is the first Spanish report of cSCC arising in RDEB patients.

© 2021 by the authors., The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer., This work was supported by PI18/00473 (ISCIII, Ministry of Economy and Competitiveness and co-funded with FEDER funds) and PI17CIII/00045 research project from AES-ISCIII.

Purpose. Cutaneous squamous cell carcinoma (CSCC) is a frequent complication in patients with recessive dystrophic epidermolysis bullosa (RDEB). Immunotherapy is a novel treatment approach for CSCC, however there is little experience in patients with RDEB. Methods. We included all the patients with a molecular-confirmed diagnosis of RDEB and advanced CSCC treated with systemic therapy between November 1988 and January 2021. Results. Five patients were treated with immunotherapy (n = 2), other systemic therapies (n = 2), or both (n = 1). The tolerability of immunotherapy was overall acceptable with no treatment-related serious adverse events. Radiological tumor response observed in one patient. The other patients were treated with a combination of chemotherapy and targeted therapy (EGFR inhibitors), with mixed tumor response. Median OS was 3 months (range, 1 to 11). Conclusions: Patients with RDEB and advanced CSCC benefit from immunotherapy and do not experience unexpected toxicity.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC's microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization. Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy. Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.

Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment.We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score.We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p 0.001).TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.

Background: Patients with cancer are at increased risk of severe COVID-19, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 in cancer patients predicting severe disease and build a decision-support online tool; COVID-19 Risk in Oncology Evaluation Tool (CORONET). Methods: Patients with active cancer (stage I-IV) and laboratory confirmed COVID-19 presenting to hospitals worldwide were included. Discharge (within 24hrs), admission (≥24hrs inpatient), oxygen requirement (O2) and death were combined in a 0-3 point severity scale. Association of features with outcome were investigated using Lasso regression and Random Forest (RF) combined with SHapley Additive exPlanations (SHAP). RF was further validated in 4 cohorts, split by geography. The CORONET model was then examined in the entire cohort to build an online CORONET decision-support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Findings: The dataset comprised 920 patients; median age 70 (range 5-99), 56% males, 44% females, 81% solid vs. 19% haematological cancers. In derivation, RF demonstrated superior performance over Lasso with lower mean squared error (0.801 vs. 0.807) and was selected for development. During validation, RF achieved mean AUROC 0.77, 0.80 and 0.75 for prediction of admission, O 2 and death, respectively. Using the entire cohort, CORONET cut-offs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died. SHAP explanations revealed National-Early-Warning-Score-2, C-reactive protein and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. Interpretation: CORONET, a decision-support tool validated in healthcare systems worldwide can aid admission decisions and predict COVID-19 severity in patients with cancer. Funding Information: R. Lee and T. Robinson and J. Weaver are supported by the National Institute for Health Research as Clinical Lecturers. T. Bhogal is supported by the National Institute for Health Research as an academic clinical fellow. U. Khan is an MRC Clinical Training Fellow based at the University of Liverpool supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (Award Ref. MR/N025989/1). The Liverpool Experimental Cancer Medicine Centre for providing infrastructure support (Grant Reference: C18616/A25153) and The Clatterbridge Cancer charity (North West Cancer Research). C. Dive is funded by CRUK Core funding to Manchester Institute (C5757/A27412) and is supported by the CRUK Manchester Centre Award (C5759/A25254), and by the NIHR Manchester Biomedical Research Centre. C. Zhou is funded by the CRUK Manchester Centre Award (C5759/A25254), J. Stevenson and P. Fitzpatrick are funded by the CRUK Accelerator Award (29374). This research was funded in part, by the Wellcome Trust [205228/Z/16/Z]. LT is also supported by the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. LT is based at University of Liverpool. MS is supported by a grant from the Ministry of Science and Higher Education of the Russian Federation for the state support for the creation and development of World Class Research Centers "Digital biodesign and personalized healthcare” N.075-15-2020-926. Declaration of Interests: R Lee research funding (institution) BMS and speaker fees Astrazeneca. A. Croitoru Consulting or Advisory Role: Lilly, Merck, Roche, Bayer, Novartis, Ipsen, Research Funding me and my hospital: Gilead Sciences, Pfizer, Canfite, NanoCarrier, Bristol-Myers Squibb, Merck, Amgen, Servier, Five Prime Therapeutics, Travel Accommodations: Pfizer, Genekor, and oz, Merck, Pfizer, Servier, Roche. O. Michielin reports personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Amgen, personal fees from NeraCare GmbH, outside the submitted work. E. Romano institutional research grants from Amgen, Astra Zeneca, Bristol-Myers Squibb. G. Pentheroudakis advisory board for Amgen, Astra Zeneca, Bristol-Myers Squibb, Lilly, Merck, MSD, Roche, Abbvie, institutional research grants from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Debbio, Enorasis, Genekor, Ipsen, Janssen, Lilly, Merck, MSD, Pfizer, Roche, Sanofi, Servier. Solange Peters reports consultation/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody, talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda, receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. M Rowe honoraria from Astellas Pharma, speaker fees MSD and Servier. C. Wilson consultancy and speaker fees Pfizer, Amgen, Novartis, A Armstrong conference fee Merck, spouse shares in Astrazeneca. T Robinson financial support to attend educational workshops from Amgen and Daiichi-Sankyo. C Dive, outside of this scope of work, has received research funding from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, Clearbridge Biomedics, Angle PLC, Menarini Diagnostics, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Thermofisher. C Dive is on advisory boards for, and has received consultancy fees/honoraria from, AstraZeneca, Biocartis and Merck KGaA. No other authors have nothing to declare. Ethics Approval Statement: Approval (reference 20/WA/0269) was granted from the UK Research Ethics Committee for the study. Information regarding governance/regulatory approvals for each international cohort are available in the Supp. Methods.

Neurofibromatosis type 1 (NF1) is a genetic disorder that carries a higher risk of tumor development. Plexiform neurofibromas (PNs) are present in 50% of NF1 and cause significant morbidity when surgery is not feasible. Systemic therapies had not succeeded to reduce PN tumor volume until 2016 when the first trial with an MAPK/extracellular-signal-regulated kinase (MEK) inhibitor was published. We performed a systematic research on novel targeted therapies for patients with NF1 and PNs in PubMed, EMBASE, and conference abstracts with the last update in February 2021. Since 2016, seven trials have reported positive results with MEK inhibitors and other molecular targeted therapies (cabozantinib). Selumetinib has shown an overall response rate of 68% in children with NF1 and symptomatic inoperable PNs, and was associated with pain improvement and a manageable adverse events profile. This led to Food and Drug Administration (FDA) approval of selumetinib in May 2020. Recently, cabozantinib and mirdametinib have also proven their efficacy in adult population. Other MEK inhibitors such as trametinib and binimetinib have also communicated promising preliminary results. Ongoing trials in different populations and with intermittent dosing strategies are underway., Highlights • PNs are a major cause of morbidity in NF1. • Promising efficacy results with MEK inhibitors and cabozantinib have been reported. • MEK inhibitors are associated with a manageable toxicity profile. • Selumetinib is now FDA approved for the treatment of PNs.

Background COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared pandemic in March 2020. We know that patients with cancer represent a high risk population. Lung cancer have an already damage lung that may affect the evolution and outcomes of these patients.1–3 The aim of this study is to report the characteristics and outcomes of patients with lung cancer receiving immunotherapy and SARS-CoV-2 infection. Methods We retrospectively collected sociodemographic and clinical data from patients with lung cancer and COVID-19 diagnosis who were admitted to La Paz University Hospital (Madrid, Spain) from March 1 to May 7, 2020. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Hazard ratios and corresponding 95% confidence intervals were estimated with the use of Cox proportional-hazards regression models. Results A total of 29 patients were included. Baseline characteristics are depicted in table 1. Non-small-cell lung cancer (NSCLC) was reported in 93% of the patients and 69% were at advanced stage at the time of COVID-19 diagnosis. Eighty-two percent of the patients were admitted to the hospital and 75% received experimental therapy for COVID-19, including hydroxychloroquine (HCQ) (N=9), HCQ plus azithromycin (N=11) or lopinavir/ritonavir (N=2). A total of 12 patients developed acute distress respiratory syndrome (ADRS) at a median time of 7 days from COVID-19 diagnosis. ADRS was managed with steroids in 75% of the patients. Thirteen (44.8%) deaths were reported, 11 of them were considered to be COVID-19 related. Death occurred at a median time of 8 days. In the univariate analysis, diabetes mellitus, respiratory failure at the time of admission, presence of multilobar infiltrates and SDRA were associated with death.Twenty-two patients were on systemic treatment, of whom 10 patients were receiving immunotherapy alone (N=7) or in combination with chemotherapy (N=3) at the time of COVID-19 diagnosis. No significant association with the development of ADRS (P=0.38) or death (P=0.41) was found between patients on immunotherapy versus other systemic therapies. Overall survival was not reached in the immunotherapy group vs 14 days in patients on other systemic therapies (P=0.25), see figure 1. Conclusions We found that patients with lung cancer represent an extremely vulnerable population, with a poor prognosis after COVID-19 diagnosis. Treatment with immunotherapy may also be considered a risk factor. Emphasis on prevention and treatment based on evidence-based medicine is crucial in our daily practice. Acknowledgements This work has not been supported by public grants or financial support. No sources of funding were used to assist in the preparation of this manuscript Ethics Approval The study was approved by Hospital Universitario La Paz Institution’s Ethics Board, approval number PI-4147 References Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–513. doi:10.1016/S0140-6736(20)30211-7 Giannakoulis VG, Papoutsi E, Siempos II. Effect of Cancer on Clinical Outcomes of Patients With COVID-19: a meta-analysis of patient data. JCO Glob Oncol 2020;6:799–808. doi:10.1200/GO.20.00225 Lee LYW, Cazier JB, Starkey T, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 2020;395(10241):1919–1926. doi:10.1016/S0140-6736(20)31173-9

The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes.We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS).We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS.bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.

Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility.We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain).We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44].The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

The development of high-throughput technologies such as next-generation sequencing for DNA sequencing together with the decrease in their cost has led to the progressive introduction of genomic profiling in our daily practice in oncology. Nowadays, genomic profiling is part of genetic counseling, cancer diagnosis, molecular characterization, and as a biomarker of prognosis and response to treatment. Furthermore, germline or somatic genomic characterization of the tumor may provide new treatment opportunities for patients with cancer. In this review, we will summarize the clinical applications and limitations of genomic profiling in oncology clinical practice, focusing on next-generation sequencing.

Simple Summary Glycoprotein 100 (Gp-100) is a protein highly expressed in melanoma tissue that has recently been effectively targeted by tebentafusp, a first-in-class bispecific protein of the immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs) family. Recently, a randomized phase III trial reported an overall survival benefit for tebentafusp in patients with untreated metastatic uveal melanoma. Abstract Uveal melanoma is a rare neoplasm with poor prognosis in the metastatic setting. Unlike cutaneous melanoma, treatment with kinase inhibitors or immune checkpoint inhibitors is not effective. Glycoprotein 100 (Gp-100) is a protein highly expressed in melanocytes and melanoma that has recently been effectively targeted by tebentafusp, a first-in-class bispecific protein of the immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs) family. Tebentafusp targets tumor cells that express a peptide of Gp-100 presented by HLA*A0201, creating an immune synapse that kills targeted tumor cells. Recently, a randomized phase III trial reported an overall survival benefit for tebentafusp in patients with untreated metastatic uveal melanoma. The aim of this comprehensive review is to summarize evidence of Gp-100 as a therapeutic target in melanoma, and the preclinical and clinical development of tebentafusp as a novel therapeutic strategy for patients with uveal melanoma.

Background: At the height of the first wave of the SARS-COV-2 pandemic, ESMO mobilized to accelerate research for the understanding of COVID-19 in cancer patients (pts). ESMO CoCARE is an international collaborative registry-based, cohort study, gathering real-world data and information from healthcare professionals about the natural history, treatment and outcomes of COVID-19 in cancer pts. Methods: ESMO CoCARE captures information on pts with any solid or hematologic malignancy (including cancer survivors free of disease for ≥5 years) presenting with a COVID-19 diagnosis in any of the participating centers. Data collected since 06/2020 include demographics, cancer characteristics and status, co-morbidities, COVID-19 clinical features, course, management and outcome. Factors influencing COVID-19 severity (hospitalization +/- ICU support needed) and recovery are investigated using multivariable logistic regression with backward elimination method. The study is ongoing. Results: The current analysis includes 1551 registered pts (19 countries;87% pts from 23 European centers, 7% and 6% pts from 5 Northern African and 7 Asian centers), with COVID-19 diagnosis as of 11/03/2021. Median age was 64 years, with the majority female (52%), cancer stage III/IV (58%), and on active cancer treatment (60%). 65% had severe COVID-19 requiring hospitalization, with 11% receiving intensive care. In multivariable analysis, in addition to demographics (male gender, older age, other ethnicity than Caucasian, lower BMI), co-morbidities and symptomatic COVID-19, severe disease was associated to higher ECOG PS (Odds Ratio (OR)2 vs 0=5.9, OR1 vs 0=2.1), hematological malignancies (OR hemvs solid =2.0), and active/progressive cancer status (OR progressivevs no evidence of disease =1.6). 98% of pts with mild disease recovered, as opposed to only 70% of those with severe disease. Cancer stage was an additional prognostic factor for recovery (ORI/II vs IV =3.4). Conclusions: Demographic characteristics, type and status of cancer, and symptomatology of COVID-19 increase the probability of severe disease, while advanced cancer stage is also associated with the risk of death. Legal entity responsible for the study: Institut Curie, Paris, France. Funding: ESMO - European Society for Medical Oncology. Disclosure: E. Romano: Financial Interests, Institutional, Funding, Investigator-initiated trial: AstraZeneca;Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Merck;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Pierre Fabre. R. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Funding: BMS. A. Croitoru: Financial Interests, Personal, Advisory Role: Ipsen;Financial Interests, Personal, Advisory Role: Astellas;Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb;Financial Interests, Personal and Institutional, Funding: Merck;Financial Interests, Personal and Institutional, Funding: Astellas;Financial Interests, Personal and Institutional, Funding: Servier;Financial Interests, Personal and Institutional, Funding: Five Prime Therapeutics;Financial Interests, Personal and Institutional, Funding: Amgen;Financial Interests, Personal, Other, Travel funding: Merck;Financial Interests, Personal, Other, travel funding: Servier;Financial Interests, Personal, Other, travel funding: Roche. S. Susnjar: Financial Interests, Personal, Other, Honoraria and/or advisory fees: Roche;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Pfizer;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Novartis;Financial Interests, Personal, Other, Honoraria and/or advisory fees: AstraZeneca;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Amicus. M. Rossi: Financial Interests, Personal, Other, travel and personal fees: Novartis;Financial terests, Personal, Other, travel and personal fees: Ipsen. O.A. Michielin: Financial Interests, Personal, Other, personal fees: Bristol-Myers Squibb;Financial Interests, Personal, Other, personal fees: MSD;Financial Interests, Personal, Other, personal fees: Novartis;Financial Interests, Personal, Other, personal fees: Roche;Financial Interests, Personal, Other, personal fees: Amgen;Financial Interests, Personal, Other, personal fees: NeraCare GmbH. G. Pentheroudakis: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Merck;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Institutional, Principal Investigator: AbbVie;Financial Interests, Institutional, Research Grant: Amgen;Financial Interests, Institutional, Principal Investigator, Coordinating PI: Amgen;Financial Interests, Institutional, Research Grant: AstraZeneca;Financial Interests, Institutional, Principal Investigator: AstraZeneca;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Funding: Boehringer Ingelheim;Financial Interests, Institutional, Funding: Bristol Myers Squibb;Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb;Financial Interests, Institutional, Principal Investigator: Debbiopharm;Financial Interests, Institutional, Funding: Enorasis;Financial Interests, Institutional, Funding: Genekor;Financial Interests, Institutional, Funding: Ipsen;Financial Interests, Institutional, Principal Investigator: Ipsen;Financial Interests, Institutional, Funding: Janssen;Financial Interests, Institutional, Principal Investigator: Lilly;Financial Interests, Institutional, Funding: Merck;Financial Interests, Institutional, Principal Investigator: Merck;Financial Interests, Institutional, Funding: MSD;Financial Interests, Institutional, Principal Investigator: MSD;Financial Interests, Institutional, Funding: Pfizer;Financial Interests, Institutional, Principal Investigator: Roche;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Institutional, Funding: Sanofi;Financial Interests, Institutional, Principal Investigator, Coodinating Pi: Servier;Financial Interests, Institutional, Funding: Servier. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody. Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. All other authors have declared no conflicts of interest.

Capectiabine is an oral antineoplastic drug used in multiple malignancies. Proton pump inhibitors (PPI) have been proven to interact with other oral antineoplastic agents. In this systematic review we will summarize the clinical evidence on the efficacy of capecitabine when used concomitantly with PPI. We performed a systematic literature search on the main databases up to November 2019. Nine studies met our inclusion criteria: 8 retrospective studies and 1 phase II clinical trial. Patients with colorectal, breast and gastroesophageal were represented. Four out of the 9 studies reported a shorter efficacy outcome in uni- or multivariate analysis when capecitabine was taken concomitantly with PPI than alone. Up to date, the clinical evidence reported on the use of capecitabine concomitantly with PPI is scarce and shows conflicting results. While awaiting further data, avoiding misuse of PPI in cancer patients taking capecitabine is recommended.

[Introduction]: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3–0.9% of the appendectomies, 35–58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis., [Materials and methods]: We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer., [Results]: Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively., [Conclusion]: Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series., We acknowledge ISCIII, FIS, FEDER and Cátedra UAM-ROCHE de Medicina de Innovación for funding our current research through the PI18/00473 and CIBERONIC. Gemma Domínguez and Nuria Rodriguez have received research grants from Roche Farma SA.

Lung cancer in young patients is an uncommon and understudied entity that harbors distinctive epidemiological, clinic-demographic, and genomic features. We carried out a systematic review of genomic profiling in young patients with lung cancer from 2010 to 2020 in the main electronic databases and selected 23 manuscripts. Lung cancer in young patients occurs more frequently in women with adenocarcinoma histology and at more advanced stages. Some studies report higher oncogenic genomic alteration in this population, with higher anaplastic lymphoma kinase rearrangements, a distinct profile of epidermal growth factor receptor mutations, and other novel genomic alterations. Although still uncommon, the implementation of next-generation sequencing (NGS) has shed some light on germline genomic alterations associated with lung cancer in young patients. Although outcomes when compared with the older population are conflicting, the overall prognosis is still poor in this subset of patients and efforts to find targetable genomic alterations should be made to improve survival., Highlights • Lung cancer in adolescents and young adults (AYA) has specific features that may unveil a unique genomic background. • AYA harbor a higher percent of oncogenic genomic alterations, gene fusions, and a different profile of gene alterations. • Comprehensive genomic profiling is strongly recommended to offer the best treatment available. • In driver-negative non-small-cell lung cancer by DNA-based NGS assay, RNA-based NGS should be considered.

The treatment of patients with BRAFv600 mutant melanomas progressing to BRAF inhibitors (BRAFi) and immunotherapy remains challenging. Preclinical studies and a small phase 2 trials have recently suggested that rechallenging with BRAFi may have a roll in these patients. The aim of this systematic review was to summarise the current evidence on the efficacy of BRAF inhibition therapy rechallenge after progression to BRAFi in metastatic BRAFv600 melanoma patients. We performed a systematic literature search in MEDLINE, Embase and the Cochrane Library CENTRAL up to November 2018. The target was restricted to patients with unresectable and/or metastatic BRAF V600 mutant melanoma that had previously progressed on BRAFi, were off-treatment for a period of time and then retreated with a BRAF inhibition strategy. We included prospective trials, observational studies and case reports. The primary outcomes were overall response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and median overall survival since the start of the treatment. Up to November 2018, nine reports met our inclusion criteria: five case reports, three observational studies and a phase 2 trial. No comparative studies have been reported. In total, 188 patients met the inclusion criteria for this review. Efficacy results of the observational reports and the clinical trial are presented. ORR varied between 28 and 43% and DCR between 57 and 72%. Duration of response was reported in 1 retrospective study and was of 14 months. PFS varied between 4.9 and 5 months and OS was not reported in all studies. Although no comparative studies have been conducted, rechallenging with BRAF inhibition therapy seems a plausible treatment option. Randomized trials are needed to confirm these results.

del poster presentado: ESMO 21st World Congress on Gastrointestinal Cancer, 03–06 July 2019, Barcelona, Spain.

Background Cancer and cancer therapy, such as chemotherapy and vascular endothelial growth factor targeted therapies, have been associated with an increased incidence of vascular thromboembolic events (VTEs): deep venous thrombosis (DVT), pulmonary embolus (PE), arterial thromboembolism (ATE), cerebrovascular accident (CVA), and myocardial infarction. However, the incidence of VTEs in patients on immunotherapy has not been well characterized. The purpose of this study was to assess the incidence of VTEs in cancer patients receiving immunotherapy in our institution. Methods We conducted a single institution retrospective cohort study, which included all cancer patients treated with anti PD-1/PD-L1 or anti CTLA-4 therapy from June 2013 to April 2019. Data regarding clinical characteristics, incidence of VTEs and survival were collected. Results We selected 229 patients treated with immunotherapy, of whom the majority (n = 146, 63.8%) were males with a median age of 64 years (range 19 to 86 years). Lung cancer was the most frequent tumor treated with immunotherapy (n = 110, 48.0%) followed by melanoma (n = 54, 23.6%) and renal cell carcinoma (RCC) (n = 27, 11.8%). Pembrolizumab was the most commonly used single drug immunotherapy (n = 92, 40.2%) and nivolumab plus ipilimumab was the most common multidrug regimen (n = 17, 7.4%). VTEs occurred in 18 of 229 patients (7.9%). 6 patients had DVT, 7 patients had PE, 3 patients had DVT plus PE, 1 patient had ATE and 1 patient had CVA. 13 of 18 VTEs (72.2%) were symptomatic. VTEs occurred in 12 of 110 patients with lung cancer (10.9%), 5 of 54 patients with melanoma (9.2%) and 1 of 27 patients with RCC (3.7%). In the multivariable analysis, symptomatic VTEs in patients treated with immunotherapy were associated with worse OS (3.6 vs 19.1 months for symptomatic VTEs occurrence vs no occurrence respectively), with statistically significant differences (HR = 2.4 (95%IC: 1.2-4.8) p value: 0.01). Conclusions The incidence of VTEs in cancer patients receiving immunotherapy in our sample appears to be consistent with the incidence previously reported. Symptomatic VTEs in cancer patients were associated with worsened survival. Further and prospective studies are needed to derive definitive conclusions. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.