Integrating new oral selective oestrogen receptor degraders in the breast cancer treatment.

PURPOSE OF REVIEW: Oral SERDs are under extensive development to overcome fulvestrant main limitations, including intramuscular-only formulation and poor performance in early-stage hormone receptor-positive (HR+)/HER2-negative breast cancer. This review summarizes the most relevant evidence published so far and envisions the potential integration of oral SERDs in the therapeutic algorithm of HR+/HER2-negative metastatic breast cancer (MBC). RECENT FINDINGS: Amcenestrant and giredestrant, two of the most promising oral SERDs, recently failed to show a significant improvement in progression-free survival (PFS) in pivotal trials. Conversely, elacestrant demonstrated significant PFS superiority over standard-of-care endocrine therapy (aromatase inhibitors or fulvestrant) in MBC. Additionally, it did not show unusual side effects observed with other oral SERDs, like bradycardia, hematotoxicity and vision impairment, and proved to be effective also in case of ESR1 -mutant endocrine-resistant breast cancer. Combination trials of oral SERDs with target agents, such as CDK4/6-inhibitors, are ongoing. Finally, some window-of-opportunity trials showed promising on-target activity in early-stage for this drug class. SUMMARY: Promising results from early-phase trials are not translating into sufficient clinical benefit in pivotal trials of main oral SERDs in monotherapy, except for elacestrant. Whether oral SERDs might become the backbone for combination strategies in MBC or the preferred (neo)adjuvant endocrine agents is under evaluation.

Nonsyndromic craniosynostosis: novel coding variants.

BACKGROUND: Craniosynostosis (CS), the premature fusion of one or more neurocranial sutures, is associated with approximately 200 syndromes; however, about 65-85% of patients present with no additional major birth defects. METHODS: We conducted targeted next-generation sequencing of 60 known syndromic and other candidate genes in patients with sagittal nonsyndromic CS (sNCS, n = 40) and coronal nonsyndromic CS (cNCS, n = 19). RESULTS: We identified 18 previously published and 5 novel pathogenic variants, including three de novo variants. Novel variants included a paternally inherited c.2209C>G:p.(Leu737Val) variant in BBS9 of a patient with cNCS. Common variants in BBS9, a gene required for ciliogenesis during cranial suture development, have been associated with sNCS risk in a previous genome-wide association study. We also identified c.313G>T:p.(Glu105*) variant in EFNB1 and c.435G>C:p.(Lys145Asn) variant in TWIST1, both in patients with cNCS. Mutations in EFNB1 and TWIST1 have been linked to craniofrontonasal and Saethre-Chotzen syndrome, respectively; both present with coronal CS. CONCLUSIONS: We provide additional evidence that variants in genes implicated in syndromic CS play a role in isolated CS, supporting their inclusion in genetic panels for screening patients with NCS. We also identified a novel BBS9 variant that further shows the potential involvement of BBS9 in the pathogenesis of CS.

The Spanish version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for fibromyalgia: reliability and validity assessment.

OBJECTIVES: To investigate the reliability and validity of the Spanish version of the 2010 American College of Rheumatology (ACR) Preliminary Diagnostic Criteria for Fibromyalgia (FM) in patients with chronic pain. METHODS: The 2010 ACR Preliminary Diagnostic Criteria for FM were adapted to a Spanish version following the guidelines of the Rheumatology Spanish Society Study Group of FM. Based on the 1990 ACR classi cation criteria for FM, patients with chronic pain were initially divided into two groups: a FM group and another group of non-FM individuals. Patients from the FM group were evaluated by tender points (TP) examination, Fibromyalgia Impact Questionnaire (FIQ), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS). The non-FM (control) group included patients with rheumatoid arthritis (RA) and osteoarthritis (OA). They were evaluated by WPI and SSS. RESULTS: We included 1,169 patients divided into two groups: FM group (n=803; 777 women and 26 men) and non-FM group (n= 366; 147 patients with RA, and 219 with OA). The median value of TP and FIQ in the FM group was 16 and 74 respectively. The preliminary 2010 ACR criteria were met by 665 (82.8%) FM patients and by 112 (30.6%) patients from the non-FM group (p<0.0001). Statistically signi cant differences in the number of TP (p<0.03), FIQ (p<0.0001), WPI (p<0.0001) and SSS (p<0.0001) were observed when FM patients fulfilling the 2010 ACR criteria were compared with the remaining FM patients who did not fulfill these criteria. Sensitivity of the Spanish version of the 2010 ACR criteria was 85.6% (95%CI: 83.1-88.1), speci city 73.2% (95%CI: 68.4-78), positive predictive value 87.7% (95%CI: 85.3-90.1) and negative predictive value 69.4% (95%CI: 64.5-74.2). CONCLUSIONS: Our results indicate that the 2010 ACR Preliminary Diagnostic Criteria for FM may be useful to establish a diagnosis of FM in Spanish individuals with chronic pain.

[Choroid plexus tumours in childhood: Experience in Sant Joan de Déu hospital]. / Tumores de plexo coroideo en la infancia: experiencia en el hospital Sant Joan de Déu.

Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor.

Low-grade gliomas in children: single institutional experience in 198 cases.

INTRODUCTION: In pediatric population (0-18 years), low-grade gliomas (PLGG) are the most frequent brain tumors and majority are amenable for surgical removal. PATIENTS AND METHODS: A retrospective review of 198 children diagnosed with PLGG between 1980 and 2010 at HSJD was carried out. Several variables were studied to find prognostic factors related to the outcomes (progression-free survival (PFS) and overall survival (OS)). RESULTS: Median age at onset was 88.8 months (3.1 to 214.5 months, SD 53). Surgery was performed in 175 patients (88.4%), achieving gross total resection (GTR) in 77 (44%), subtotal resection (STR) in 87 (49.7%), and 11 (6.3%) biopsies. Pathological review classified 84 tumors as WHO grade I (48%) and 89 as grade II (50.8%). Adjuvant therapy (AT) was given to 75 patients (37.9%), radiotherapy in 24 (12.1%), chemotherapy in 33 (16.7%), and combined in 18 (9.1%). Sixteen patients (8.1%) died, 89 (43.4%) are alive with no evidence of disease, and 93 (47%) alive with disease, median follow-up 65.2 months. Outcome is significantly correlated with age (p = 0001, worse OS for patients younger than 12 months) and extent of tumor resection (p < 0001). OS for GTR/STR/biopsy was >200, 154.3, and 101.9 months, respectively. Patients treated with AT presented worse OS/PFS (p < 0.001) than those not treated. Histology was non significantly related to outcomes. CONCLUSION: In our series of PLGG, the best prognostic markers are tumor location (cerebellar) and the extent of tumor resection (GTR). Infants and patients who require adjuvant therapy because of tumor progression or recurrence have worse outcome.

Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life.

INTRODUCTION: Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. METHODS: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients' medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. RESULTS: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. CONCLUSIONS: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life.

[Epidemiology and classification of arachnoid cysts in children]. / Epidemiología y clasificación de los quistes aracnoideos en niños.

The prevalence of arachnoid cysts in children is 1-3%. They are more frequent in boys. They can be located intracranially or in the spine. Intracranial cysts are classified as supratentorial, infratentorial, and supra-infratentorial (tentorial notch). Supratentorial are divided into middle cranial fossa, convexity, inter-hemisferic, sellar region, and intraventricular. Infratentorial are classified into supracerebellar, infracerebellar, hemispheric, clivus, and cerebellopontine angle. Finally spinal arachnoid cysts are classified taking into account whether they are extra- or intradural, and nerve root involvement.

Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes.

BACKGROUND: fibroblast growth factor receptor (FGFR) -related craniosynostosis syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain FGFR mutations are associated with more than one clinical syndrome. These syndromes share coronal craniosynostosis and characteristic facial skeletal features, although Apert syndrome (AS) is characterized by a more dysmorphic facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes. METHODS: Here we perform a detailed three-dimensional evaluation of facial skeletal shape in a retrospective sample of cases clinically and/or genetically diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial dysmorphology, precisely identify specific facial features pertaining to these four syndromes, and further elucidate what knowledge of the causative FGFR mutation brings to our understanding of these syndromes. RESULTS: Our results confirm a strong correspondence between genotype and facial phenotype for AS and MS with severity of facial dysmorphology diminishing from Apert FGFR2(S252W) to Apert FGFR2(P253R) to MS. We show that AS facial shape variation is increased relative to CS, although CS has been shown to be caused by numerous distinct mutations within FGFRs and reduced dosage in ERF. CONCLUSION: Our quantitative analysis of facial phenotypes demonstrate subtle variation within and among craniosynostosis syndromes that might, with further research, provide information about the impact of the mutation on facial skeletal and nonskeletal development. We suggest that precise studies of the phenotypic consequences of genetic mutations at many levels of analysis should accompany next-generation genetic research and that these approaches should proceed cooperatively.

Comparative biological activity of palbociclib and ribociclib in hormone receptor-positive breast cancer.

This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated ß-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated ß-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.

Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.

BACKGROUND: The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT. METHODS: We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples. RESULTS: The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS. CONCLUSIONS: HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.

A 14-gene B-cell immune signature in early-stage triple-negative breast cancer (TNBC): a pooled analysis of seven studies.

BACKGROUND: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. METHODS: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging (IGG-Clin) were assessed for event-free survival (EFS) and overall survival (OS) in each cohort. Random effects model was used to derive pooled effect sizes. Association of IGG with pathological complete response (pCR) was assessed in CALGB-40603 and BrighTNess. Immune significance of IGG was estimated through CIBERSORTx and EcoTyper. FINDINGS: IGG was associated with improved EFS (pooled HR = 0.77, [95% CI = 0.70-0.85], I2 = 18%) and OS (pooled HR = 0.79, [0.73-0.85], I2 = 0%) across cohorts, and was predictive of pCR in CALGB-40603 (OR 1.25, [1.10-1.50]) and BrighTNess (OR 1.57 [1.25-1.98]). IGG-Clin was predictive of recurrence (pooled HR = 2.11, [1.75-2.55], I2 = 0%) and death (pooled HR = 1.99, 95% [0.84-4.73], I2 = 79%) across cohorts. IGG was associated with adaptive immune response at CIBERSORTx and EcoTyper analysis. INTERPRETATION: IGG is linked to improved prognosis and pCR in early-stage TNBC. The integration of IGG alongside tumor and nodal staging holds promise as an approach to identify patients benefitting from intensified or de-intensified treatments. FUNDING: This study received funding from: Associació Beca Marta Santamaria, European Union's Horizon 2020 research and innovation and Marie Sklodowska-Curie Actions programs, Fundación FERO, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundación Contigo, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.

Pituitary dysfunction after traumatic brain injury in children: is there a need for ongoing endocrine assessment?

BACKGROUND: Hypopituitarism has been widely described in adults after traumatic brain injury (TBI); however, the available data in paediatric populations are scarce. Here, we report the results of a prospective, long-term study in children, adolescents and young adults. STUDY GROUP: Thirty-seven children (age, 2 months to 19·9 years) of 51 eligible patients were followed for 1 year. Clinical and baseline endocrine variables were assessed in all 3 and 12 months after TBI; children ≥ 6 years underwent two stimulation tests (glucagon stimulation and megatest). RESULTS: In the group ≥6 years, 11 of 23 patients (47·8%) had a subnormal GH peak 3 months after TBI that persisted in 8 of 23 patients (34%) after 1 year. The GH response showed no correlation with injury severity (GCS, Marshall classification). Growth velocity was normal in all patients, except for one. Body mass index (BMI) SDS increased significantly in the group with low GH response. A suboptimal cortisol was observed in 10 of 23 subjects, which normalized in all but three, 1 year thereafter. All patients but one showed a pubertal response to GnRH testing. No clinical or hormonal abnormalities were detectable in children <6 years. CONCLUSION: Our results recommend to prospectively follow children after TBI: firstly, because the impairment of pituitary function cannot be predicted, and secondly, to avoid the potential consequences of pituitary dysfunction. Prospective clinical trials are needed before recommending a systematic screening after TBI and/or GH therapy either in postpubertal children or in prepubertal children who grow normally.

Brain stem tumors in children and adolescents: single institutional experience.

PURPOSE: Pediatric brain stem tumors (BsT) are a heterogeneous group of diseases. Our aim was to analyze our experience to find out prognostic factors. METHOD: A retrospective study with BsT patients was performed. Imaging characteristics, extension of surgery, pathology, and adjuvant therapy were analyzed and correlated with overall survival (OS) and progression-free survival (PFS) as outcome measures. RESULT: Since 1980 to 2010, we analyzed 65 BsT patients, 41 of them girls (63%), median age of 8 years (range 13.9 months to 17.6 years). Twenty-two patients (33.8%) had diffuse intrinsic pontine gliomas (DIPG) and 43 (66.2%) presented with focal BsT. Histology was available in 42 patients; the most frequent is low-grade glioma in 24/42 patients (57%). DIPG's histology (obtained usually at necropsy) confirmed five high-grade gliomas. After median follow-up of 49.3 months (0.5-175 months), 20/22 DIPG patients have died (90.9%), while 27/43 with focal tumors were alive (62.8%). Variables related to outcome were histology (better for low-grade glioma (LGG) OS p < 0.001), surgery (better if operated OS p < 0.001), and adjuvant therapy (worse if given, PFS p = 0.001, OS p = 0.024). The outcome for DIPG was dismal, median OS/EFS of 14.2/9.4 months, significantly worse than focal BsT (p = 0.000), while OS/EFS was 122.8/87.2 months for focal intrinsic, 88.2/47.1 months for exophytic, and 124.4/54 months for cervico-medullary tumors: no differences were found among them, except the histology (OS p < 0.001 for low-grade vs high-grade tumors). CONCLUSION: BsT in children comprised two different groups: diffuse (DIPG) and focal gliomas. The DIPGs continue having a dismal prognosis, needing new approaches, while focal tumors including LGG have better prognosis.

Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis.

BACKGROUND: In hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2 (HER2)-enriched (HER2-E), basal-like (BL) intrinsic subtypes and a normal-like group. This classification has an established prognostic value in early-stage HoR+ BC. Here, we carried out a trial-level meta-analysis to determine the prognostic ability of subtypes in metastatic BC (MBC). MATERIALS AND METHODS: We systematically reviewed all the available prospective phase II/III trials in HoR+ MBC where subtype was assessed. The primary endpoint was progression-free survival (PFS)/time to progression (TTP) of the LumA subtype compared to non-LumA. Secondary endpoints were PFS/TTP of each individual subtype, according to treatment, menopausal and HER2 status and overall survival (OS). The random-effect model was applied, and heterogeneity assessed through Cochran's Q and I2. Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769). RESULTS: Seven studies were included (2536 patients). Non-LumA represented 55.2% and was associated with worse PFS/TTP than LumA [hazard ratio (HR) 1.77, P < 0.001, I2 = 61%], independently of clinical HER2 status [Psubgroup difference (Psub) = 0.16], systemic treatment (Psub = 0.96) and menopausal status (Psub = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I2 = 65%), with significantly different outcomes for LumB (PFS/TTP HR 1.46; OS HR 1.41), HER2-E (PFS/TTP HR 2.39; OS HR 2.08) and BL (PFS/TTP HR 2.67; OS HR 3.26), separately (PFS/TTP Psub = 0.01; OS Psub = 0.005). Sensitivity analyses supported the main result. No publication bias was observed. CONCLUSIONS: In HoR+ MBC, non-LumA disease is associated with poorer PFS/TTP and OS than LumA, independently of HER2, treatment and menopausal status. Future trials in HoR+ MBC should consider this clinically relevant biological classification.

[Occult anterior sacral meningocele]. / Meningocele sacro anterior oculto.

BACKGROUND: The anterior sacral meningocele is a rare form of spinal dysraphism located in the presacral extraperitoneal space. It is generally asymptomatic and appears as a small pelvic mass. CASE DESCRIPTION: We present a case of a 10 year-old male that develops a bacteria meningitis because of a pararectal abscess that is connected with an anterior sacral meningocele. We successfully treated it using a posterior approach. CONCLUSION: The aim of the surgery is to repair the dural defect and to obliterate the communication between the thecal sac and the herniation defect. The posterior approach is the simplest and most effective surgical technique because the lower risk of neurological injury than the anterior approach.

Doege-Potter syndrome in a facial solitary fibrous tumor: Diagnose and clinical management discussion.

Doege-Potter syndrome is a rare hypoglycemic paraneoplastic disorder. This case describes that severe and symptomatic hypoglycemia can occasionally be due to a rare malignant neoplasm, and the differential diagnosis of malignancy should not be overlooked in this setting.

Specialist palliative and end-of-life care for patients with cancer and SARS-CoV-2 infection: a European perspective.

BACKGROUND: Specialist palliative care team (SPCT) involvement has been shown to improve symptom control and end-of-life care for patients with cancer, but little is known as to how these have been impacted by the COVID-19 pandemic. Here, we report SPCT involvement during the first wave of the pandemic and compare outcomes for patients with cancer who received and did not receive SPCT input from multiple European cancer centres. METHODS: From the OnCovid repository (N = 1318), we analysed cancer patients aged ⩾18 diagnosed with COVID-19 between 26 February and 22 June 2020 who had complete specialist palliative care team data (SPCT+ referred; SPCT- not referred). RESULTS: Of 555 eligible patients, 317 were male (57.1%), with a median age of 70 years (IQR 20). At COVID-19 diagnosis, 44.7% were on anti-cancer therapy and 53.3% had ⩾1 co-morbidity. Two hundred and six patients received SPCT input for symptom control (80.1%), psychological support (54.4%) and/or advance care planning (51%). SPCT+ patients had more 'Do not attempt cardio-pulmonary resuscitation' orders completed prior to (12.6% versus 3.7%) and during admission (50% versus 22.1%, p < 0.001), with more SPCT+ patients deemed suitable for treatment escalation (50% versus 22.1%, p < 0.001). SPCT involvement was associated with higher discharge rates from hospital for end-of-life care (9.7% versus 0%, p < 0.001). End-of-life anticipatory prescribing was higher in SPCT+ patients, with opioids (96.3% versus 47.1%) and benzodiazepines (82.9% versus 41.2%) being used frequently for symptom control. CONCLUSION: SPCT referral facilitated symptom control, emergency care and discharge planning, as well as high rates of referral for psychological support than previously reported. Our study highlighted the critical need of SPCTs for patients with cancer during the pandemic and should inform service planning for this population.

Presenting Features and Early Mortality from SARS-CoV-2 Infection in Cancer Patients during the Initial Stage of the COVID-19 Pandemic in Europe.

We describe the outcomes in cancer patients during the initial outbreak of the COVID-19 in Europe from the retrospective, multi-center observational OnCovid study. We identified 204 cancer patients from eight centers in the United Kingdom, Italy, and Spain aged > 18 (mean = 69) and diagnosed with COVID-19 between February 26th and April 1st, 2020. A total of 127 (62%) were male, 184 (91%) had a diagnosis of solid malignancy, and 103 (51%) had non-metastatic disease. A total of 161 (79%) had > 1 co-morbidity. A total of 141 (69%) patients had > 1 COVID-19 complication. A total of 36 (19%) were escalated to high-dependency or intensive care. A total of 59 (29%) died, 53 (26%) were discharged, and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged > 65 (36% versus 16%), in those with > 2 co-morbidities (40% versus 18%) and developing > 1 complication from COVID-19 (38% versus 4%, p = 0.004). Multi-variable analyses confirmed age > 65 and > 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy, or anticancer therapy. During the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age predicted for adverse disease course in cancer patients. The ongoing OnCovid study will allow us to compare risks and outcomes in cancer patients between the initial and later stages of the COVID-19 pandemic.

Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients.

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.