COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

Percutaneous cryoablation for desmoid fibromatosis: initial experience at a UK centre.

AIM: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy. MATERIALS AND METHODS: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated. RESULTS: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones. CONCLUSION: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours.

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK.

INTRODUCTION: Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive. AIMS AND METHODS: We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database. RESULTS: 226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2-81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF. CONCLUSIONS: CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.

Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres.

OBJECTIVES: We conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site. SETTING: We have reviewed the outcomes of one of the largest data sets of consecutive patients with EPSCC identified from two major cancer centres. PARTICIPANTS: Consecutive patients with a histopathological diagnosis of EPSCC from the two institutions were retrospectively identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were evaluated including stage at presentation, treatments given, sites of relapse, time to distant relapse, progression-free survival and overall survival (OS). RESULTS: From a total 159 patients, 114 received first-line chemotherapy, 80.5% being platinum-based. Response rate was 48%. Commonest primary sites were genitourinary and gynaecological. 44% of patients presented with metastatic disease. 55.9% relapsed with liver the commonest site, whereas only 2.5% developed brain metastases. Median OS was 13.4 months for all patients, 7.6 months and 19.5 months for those with metastatic and non-metastatic disease, respectively. Gynaecological and head and neck patients had significantly better OS compared to gastrointestinal patients. CONCLUSIONS: EPSCCs demonstrate high response rates to chemotherapy and high rates of distant metastases. Primary sites may influence prognosis, and survival is optimal with a radical strategy. Brain metastases are rare and we therefore do not recommend prophylactic cranial irradiation.

Mitomycin C and UFT/leucovorin as salvage treatment in patients with advanced colorectal cancer.

PURPOSE: The purpose of this study was to determine the efficacy and toxicity of uracil/tegafur (UFT) plus oral leucovorin (LV) and mitomycin C as salvage chemotherapy for heavily pretreated patients with metastatic colorectal cancer. METHODS: A total of 44 patients were treated with i.v. mitomycin C (6 mg/m(2) on day 1) and oral UFT (350 mg/m(2)) plus LV (90 mg), both divided in 3 daily doses from day 1 to day 14 every 3 weeks. All patients had failed prior first-line and second- line treatment with oxaliplatin, bevacizumab, irinotecan, cetuximab and 5-fluorouracil (5-FU). Forty -three patients were evaluable for the response. RESULTS: The overall response rate (intent-to-treat) was 9.3% and disease stabilization was achieved in 25.7% of the patients. Median time to progression (TTP) was 5 months (range 2-13) and median overall survival (OS) 7.5 months (range 4-16). Fatigue and myelosuppression were the most frequent side effects. The most common nonhematological toxicities consisted of mild and reversible nausea and diarrhea. Severe symptoms were only occasionally seen. CONCLUSION: These data show that the combination of mitomycin C/UFT/LV provides an acceptable and safe therapeutic option in extensively pretreated metastatic colorectal cancer.

Breast cancer in association with thyroid disorders.

PURPOSE: The relationship between breast cancer and thyroid diseases is controversial. Conflicting results have been reported in the literature. The incidence of autoimmune and non-autoimmune thyroid diseases were investigated in patients with breast cancer who had received prior therapy as compared with age-matched control individuals without breast or thyroid disease. PATIENTS AND METHODS: Clinical and ultrasound evaluation of the thyroid gland, and determination of serum thyroid hormones and autoantibody levels were performed in 143 breast cancer patients and 128 healthy control individuals. Patients were classified into subgroups according to estrogen receptor (ER) and progesterone receptor (PR) status and type of oncological treatment. RESULTS: The mean values for serum antibodies against thyroid peroxidase (anti-TPO) were 9 IU/ml and 25 IU/ml for antithyroglobulin antibodies (anti-TGB) in breast cancer patients, and 9.5 IU/ml and 23.5 IU/ml, respectively, in the control group (p>0.05. The difference between breast cancer patients and the control group in the incidence of autoimmune and non-autoimmune thyroid diseases was not statistically significant. No significant differences between the groups according to both menopausal status and ER status were seen (p= 0.67). Also, no significant influence of hormonal therapy with tamoxifen and chemotherapy on serum levels of thyroid stimulating hormone (TSH), free thyroxin (fT4), TPO and TGB autoantibodies was proved. CONCLUSION: This study demonstrated a similar incidence of thyroid enlargement and the same frequency of thyroid disturbances in patients with breast cancer and controls. No relationship was found among ER and PR status, and the presence of serum thyroid autoantibodies. Although we have been unable to demonstrate any impact of breast cancer therapy on thyroid function tests, more prolonged studies with larger number of patients may be required to demonstrate significant trends.

Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer.

UNLABELLED: Capecitabine, an oral 5-fluorouracil (5-FU) prodrug, is increasingly replacing intravenous i.v. 5-FU/leucovorin in colorectal cancer treatment. THE AIM of this study was to evaluate efficacy and safety of the combination chemotherapy of irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal adenocarcinoma. PATIENTS AND METHODS: Forty patients received first-line chemotherapy with capecitabine (1.000 mg/m2 twice daily) on days 1-14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Baseline characteristics: 24 men, 16 women; median age 64.5 years. Most common metastatic sites were the liver (55%), lymph nodes (45%), lung (22.5%) and bones (17.5%). RESULTS: There were 12 partial responses (30%), 11 cases of stable disease (27.5%), and 17 cases of disease progression (42.5%). The median survival was 16 months (range, 6-26 months) and median progression-free survival was 7 months (range, 3-14 months). Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. CONCLUSION: XELIRI is a well-tolerated regimen, with an activity comparable to, but more convenient than, irinotecan-5-FU i.v. combinations in patients with previously untreated advanced colorectal cancer.