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Background The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe. Methods In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing. Findings As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47.4%] were women and 1822 [52.6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58.5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31.0%) during the alpha-delta phase, and 365 (10.5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33.3%) of 339 were fully vaccinated and 165 (48.7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16.6%) of 915 were fully vaccinated and 21 (2.3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0.32 [95% CI 0.19-0.61) and 28 days (0.34 [0.16-0.79]), complications due to COVID-19 (0.26 [0.17-0.46]), and hospitalisation due to COVID-19 (0.17 [0.09-0.32]), and had less requirements for COVID-19-specific therapy (0.22 [0.15-0.34]) and oxygen therapy (0.24 [0.14-0.43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase. Interpretation Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19. Copyright (C) 2022. Published by Elsevier Ltd. All rights reserved.

The SARS-Cov-2 pandemic significantly impacted on oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncological features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. In a multi-center study of 890 cancer patients with confirmed Covid-19 we demonstrated a worsening gradient of mortality from breast cancer to haematological malignancies and showed that male gender, older age, and number of co-morbidities identifies a subset of patients with significantly worse mortality rates from Covid-19. Provision of chemotherapy, targeted therapy and immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and support further research into emerging anti-Covid-19 therapeutics in SARS-Cov-2 infected cancer patients.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflamació; Mediadors d'inflamació Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflamación; Mediadores de la inflamación Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inflammation; Inflammation mediators Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p

Metastatic hepatic rupture; Non-small cell lung carcinoma; Tyrosine kinase inhibitor Ruptura hepática metastásica; Carcinoma de pulmón de células no pequeñas; Inhibidor de la tirosina quinasa Ruptura hepàtica metastàtica; Carcinoma de pulmó de cèl·lules no petites; Inhibidor de la tirosina quinasa Hepatic rupture is a rare complication of solid tumor malignancies, notably in lung adenocarcinomas, and carries an extremely poor overall prognosis. Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma predict benefit with tyrosine kinase inhibitors (TKIs). This case report describes a female patient who presented with a metastatic hepatic rupture and was subsequently diagnosed with EGFR-mutated lung adenocarcinoma. The tumor had an impressive response to TKI inhibitor treatment, reversing her extremely poor, short-term prognosis. We believe this unique case sheds light on the treatment management of hepatic ruptures and supports the high response rate seen with TKIs in EGFR-mutated lung cancers, regardless of the patient’s performance status.

Simple Summary Given that most patients with MSS mCRC do not respond to immunotherapy agents or do not have durable clinical responses, there is an unmet clinical need to obtain predictors of response to immunotherapy and rational immunotherapy-based combination therapies for this entity. In this review, we present the efforts that have been made to date in the clinical setting to develop immunotherapy-based combinations for MSS mCRC and the rationale that lies behind each strategy. Abstract In recent years, deepening knowledge of the complex interactions between the immune system and cancer cells has led to the advent of effective immunotherapies that have revolutionized the therapeutic paradigm of several cancer types. However, colorectal cancer (CRC) is one of the tumor types in which immunotherapy has proven less effective. While there is solid clinical evidence for the therapeutic role of immune checkpoint inhibitors in mismatch repair-deficient (dMMR) and in highly microsatellite instable (MSI-H) metastatic CRC (mCRC), blockade of CTLA-4 or PD-L1/PD-1 as monotherapy has not conferred any major clinical benefit to patients with MMR-proficient (pMMR) or microsatellite stable (MSS) mCRC, reflecting 95% of the CRC population. There thus remains a high unmet medical need for the development of novel immunotherapy approaches for the vast majority of patients with pMMR or MSS/MSI-low (MSI-L) mCRC. Defining the molecular mechanisms for immunogenicity in mCRC and mediating immune resistance in MSS mCRC is needed to develop predictive biomarkers and effective therapeutic combination strategies. Here we review available clinical data from combinatorial therapeutic approaches using immunotherapy-based strategies for MSS mCRC.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p

Agressive pituitary tumors; Capecitabine; Temozolomide Tumores hipofisarios agresivos; Capecitabina; Temozolomida Tumors hipofisaris agressius; Capecitabina; Temozolomida Nelson’s syndrome is considered a severe side effect that can occur after a total bilateral adrenalectomy in patients with Cushing’s disease. It usually presents with clinical manifestations of an enlarging pituitary tumor including visual and cranial nerve alterations, and if not treated, can cause death through local brain compression or invasion. The first therapeutic option is surgery but in extreme cases of inaccessible or resistant aggressive pituitary tumors; the off-label use of chemotherapy with capecitabine and temozolomide can be considered. However, the use of this treatment is controversial due to adverse events, lack of complete response, and inability to predict results. We present the case of a 48-year-old man diagnosed with Nelson’s syndrome with prolonged partial response and significant clinical benefit to treatment with capecitabine and temozolomide.

Metàstasis hepàtiques; Degeneració hepatocerebral; Tumors neuroendocrins Metástasis hepáticas; Degeneración hepatocerebral; Tumores neuroendocrinos Hepatic metastases; Hepatocerebral degeneration; Neuroendocrine tumors BACKGROUND Metastatic small bowel low-grade neuroendocrine tumors (NETs) have a good prognosis. Surgery is the only curative treatment; however, this may induce advanced liver disease, particularly in long-term survivor patients. Acquired hepatocerebral degeneration or Parkinsonism in cirrhosis is characterized by rapidly progressive extrapyramidal symptoms in patients with advanced liver disease. CASE SUMMARY A 70-year-old man presented to the emergency department with diminished consciousness and disorientation, and was diagnosed with hepatic encephalopathy. The patient was diagnosed in 1993 with a metastatic small bowel NET, for which he twice underwent hepatic surgery, with metastatic resection in 1993 and a right hepatectomy in 2002 to remove two hepatic metastases. In 2003, the patient started first-line chemotherapy and in 2004 started the first of three consecutive biological treatments, followed by radio-molecular therapy, achieving stable disease for 14 years. Disease progression was identified and he underwent an endoscopic retrograde cholangiopancreatography. However, in 2019 advanced liver disease was identified. We diagnosed the development of acquired hepatocerebral degeneration, an unusual long-term side effect after multiple hepatic procedures. CONCLUSION The importance of regular and ongoing surveillance in long-term NET survivors who undergo hepatic procedures should be integrated into the therapeutic management plan, as some of these negative outcomes could be prevented.

Alfa-fetoproteïna; Carcinoma hepatocel·lular; Trombe tumoral Alfafetoproteína; Carcinoma hepatocelular; Trombo tumoral Alpha-fetoprotein; Hepatocellular carcinoma; Tumor thrombus BACKGROUND Hepatocellular carcinoma (HCC) is the most important primary malignant liver disease. A large proportion of patients with advanced HCC have macrovascular invasion. HCC tends to infiltrate vascular structures, particularly the portal vein and its branches, and more rarely, the hepatic veins. The intravascular tumor thrombus can affect the inferior vena cava (IVC) or even the right atrium (RA), the latter having a poor prognosis. CASE SUMMARY HCC is one of the most aggressive malignant tumors. Tumor thrombus (TT) formation in advanced HCC stages is common and usually involves the hepatic or portal veins. Herein, we report a 69-year-old woman who presented with dyspnea to the emergency department. A ventilation/perfusion lung scan was performed, ruling out pulmonary embolism. Hepatopulmonary syndrome and portopulmonary hypertension were discarded with contrasted echocardiography, but a mass in the RA was detected and confirmed by cardiac magnetic resonance imaging. Abdominal computed tomography showed a liver mass with a dynamic enhancement pattern compatible with HCC and an intraluminal IVC mass extending from the hepatic vein into the RA. HCC with TT expansion to IVC and RA is rare and indicates poor prognosis. CONCLUSION HCC with TT expansion to IVC and RA is rare and indicates poor prognosis. There is no consensus about anticoagulation or other interventions in these patients. Gomez-Puerto D, Mirallas O, Vidal-González J, Vargas V. Hepatocellular carcinoma with tumor thrombus extends to the right atrium and portal vein: A case report. World J Hepatol 2020; 12(11): 1128-1135 [PMID: 33312435 DOI: 10.4254/wjh.v12.i11.1128]

Higher risk of death from COVID-19 among patients with cancer was correlated with male sex, greater age, presence of multiple comorbidities, advanced-stage disease, and active disease; there was no association between risk and anticancer treatment., The SARS-CoV-2 pandemic significantly affected oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncologic features to severity and mortality from COVID-19 and little guidance as to the role of anticancer and anti–COVID-19 therapy in this population. In a multicenter study of 890 patients with cancer with confirmed COVID-19, we demonstrated a worsening gradient of mortality from breast cancer to hematologic malignancies and showed that male gender, older age, and number of comorbidities identify a subset of patients with significantly worse mortality rates from COVID-19. Provision of chemotherapy, targeted therapy, or immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk stratification of patients and supports further research into emerging anti–COVID-19 therapeutics in SARS-CoV-2–infected patients with cancer. Significance: In this observational study of 890 patients with cancer diagnosed with SARS-CoV-2, mortality was 33.6% and predicted by male gender, age ≥65, and comorbidity burden. Delivery of cancer therapy was not detrimental to severity or mortality from COVID-19. These patients should be the focus of shielding efforts during the SARS-CoV-2 pandemic. This article is highlighted in the In This Issue feature, p. 1426