Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry.

Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population.

Methods: We described COVID-19 morbidity and mortality among patients with STS across 'Omicron' (15 December 2021-31 January 2022), 'Pre-vaccination' (27 February 2020-30 November 2020), and 'Alpha-Delta' phase (01 December 2020-14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders.

Previous immune checkpoint inhibitor therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry.

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19.

Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs.

Outcomes of Patients Treated With RCHOP With a PET-Adapted Approach for Consolidative Radiotherapy: A Retrospective Single-Center Study at the Royal Marsden Hospital.

Background: Treatment with CHOP-based chemotherapy with consolidative radiotherapy (CRT) for primary mediastinal B cell lymphoma (PMBCL) has been the standard approach in the pre-rituximab era. Overtreatment with CRT for patients who may have already been cured by primary immunochemotherapy in the rituximab era is a significant concern due to the long-term toxicity associated with radiotherapy. Positron emission tomography (PET) may help to identify patients who may not benefit from further CRT.

Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.

FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively.

Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours.

Background: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers.

Methods: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]).

Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.

Background And Aims: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy.

Approach And Results: High-throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability.

The A.L.A.N. score identifies prognostic classes in advanced biliary cancer patients receiving first-line chemotherapy.

Background: Chemotherapy is the mainstay treatment for advanced biliary cancer (ABC). Best supportive care and clinical trials are currently alternative options. The identification of a prognostic score that can be widely applied to daily practice has the potential to better inform clinical management of ABC patients.

Pseudoprogression on treatment with immune-checkpoint inhibitors in patients with gastrointestinal malignancies: Case series and short literature review.

Gastrointestinal cancers are very common cancers with colorectal being the fourth most common type, gastric the sixth, and esophageal the tenth. Although recent advances have been made in management including incorporation of antiangiogenic, anti-EGFR, and anti-HER2 directed therapies, overall their prognosis remains poor. Anti-PD-1 therapy with nivolumab and pembrolizumab are licensed for advanced chemorefractory gastroesophageal cancer and many other checkpoint inhibitor therapies are being assessed alone and in combination in these diseases.

Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience.

Background: Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities.

Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010.

Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.

Background: We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time.

EGFR-mutated lung cancer in Li-Fraumeni syndrome.

This is a revised case report of a 52 year old Caucasian female with Li-Fraumeni syndrome with a rare TP53 mutation, who was treated for breast cancer and later developed epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer.

Change in platelet levels during radiotherapy with concurrent and adjuvant temozolomide for the treatment of glioblastoma: a novel prognostic factor for survival.

Background: Radiotherapy plus concomitant and adjuvant temozolomide (RCAT) is now standard treatment for grade IV glioblastoma (GBM). We report the results from our 7 years experience of using RCAT, and the potential role of a change in platelet count as a prognostic factor.

Methods: We identified all patients with biopsy-proven GBM who received RCAT at the Royal Free Hospital between 2002 and 2009.