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Soft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. Treatment options remain limited in advanced STS with high rates of recurrence following resection of localised disease. Prognostication in clinical practice relies predominantly on histological grading systems as well as sarcoma nomograms. Rapid developments in gene expression profiling technologies presented opportunities for applications in sarcoma. Molecular profiling of sarcomas has improved our understanding of the cancer biology of these rare cancers and identified potential novel therapeutic targets. In particular, transcriptomic signatures could play a role in risk classification in sarcoma to aid prognostication. Unlike other solid and haematological malignancies, transcriptomic signatures have not yet reached routine clinical use in sarcomas. Herein, we evaluate early developments in gene expression profiling in sarcomas that laid the foundations for transcriptomic signature development. We discuss the development and clinical evaluation of key transcriptomic biomarker signatures in sarcomas, including Complexity INdex in SARComas (CINSARC), Genomic Grade Index, and hypoxia-associated signatures. Prospective validation of these transcriptomic signatures is required, and prospective trials are in progress to evaluate reliability for clinical application. We anticipate that integration of these gene expression signatures alongside existing prognosticators and other Omics methodologies, including proteomics and DNA methylation analysis, could improve the identification of ‘high-risk’ patients who would benefit from more aggressive or selective treatment strategies. Moving forward, the incorporation of these transcriptomic prognostication signatures in clinical practice will undoubtedly advance precision medicine in the routine clinical management of sarcoma patients.

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. 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. 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<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113–148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18–2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45–8·59]), but dose or regimen adjustments were not (0·84 [0·35–2·02]). Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients. National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

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. 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. 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. 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. National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

ObjectiveUnderrepresentation of elderly ovarian cancer patients in clinical trials has led to lack of clarity regarding optimal first-line chemotherapy in this cohort. The Elderly Women with Ovarian Cancer (EWOC)-1 trial demonstrated that 3-weekly carboplatin (3wC) resulted in worse survival and feasibility compared with standard 3-weekly carboplatin-paclitaxel (3wCP) in frail, elderly ovarian cancer patients. Our retrospective study compares feasibility, safety, and efficacy of first-line 3wCP and 3wC in a frail ovarian cancer cohort.MethodsClinical data were retrospectively analyzed for newly-diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV, ≥70-year-old epithelial ovarian cancer patients, treated by clinician choice with 3wC or 3wCP at two London cancer centers over a 2 year period. Charlson Comorbidity Index (CCI) and Eastern Cooperative Oncology Group (ECOG) performance status provided surrogate markers of frailty. Common Terminology Criteria for Adverse Events v5.0 graded toxicity.ResultsA total of 107 patients were treated with 3wC (n=30) and 3wCP (n=77). Age, performance status, and CCI were significantly different between cohorts, with 3wC patients older (84 vs 75 years, p<0.001), with more comorbidities (median CCI 4 vs 3, p<0.001) and worse performance status (47% vs 17% PS ≥2, p=0.015). Surgical outcomes differed significantly between cohorts, with 20 (67%) 3wC patients not undergoing surgery, compared with 22 (29%) 3wCP patients (p<0.001). Median follow-up was 45.8 months (IQR 38.7–56.3 months). While we observed improved progression-free (HR 0.55, 95% CI 0.33 to 0.90, p=0.017) and overall survival (HR 0.44, 95% CI 0.27 to 0.73, p=0.001, log-rank test) in a univariate cox proportional hazards comparison between 3wCP and 3wC, this was not significant on multivariate analysis. Completion of six planned chemotherapy cycles was achieved by the majority, with similar discontinuation rates between groups (13% 3wC vs 8% 3wCP, p>0.05). Overall grade ≥3 hematological toxicity rates were similar between regimens (33% 3wC vs 44% 3wCP, p=0.37) with grade ≥3 neutropenia (p=0.019) and grade ≥3 thrombocytopenia (p=0.006) more common with 3wCP and 3wC, respectively. No treatment-related deaths occurred.ConclusionOur data demonstrates that standard 3wCP is a well-tolerated, feasible first-line treatment for frail, elderly ovarian cancer patients. Improved survival with 3wCP was not significant when corrected for established clinical prognostic factors.

Sarcomas are rare cancers with a spectrum of clinical needs and outcomes. We investigated care experiences and health-related quality of life (HRQoL) in sarcoma patients during the COVID-19 pandemic. Patients with appointments during the first two months of the UK lockdown were invited to complete a survey. Questions included views on care modifications, COVID-19 worry and psychosocial impact, and EORTC-QLQ-C30 items. 350 patients completed the survey; median age 58 (16–92) years. Care modifications included telemedicine (74%) and postponement of appointments (34%), scans (34%) or treatment (10%). Most felt the quality of care was not affected (72%), however, social life (87%) and emotional wellbeing (41%) were affected. Worry about COVID-19 infection was moderately high (mean 5.8/10) and significantly related to higher cancer-related worry; associated with lower emotional functioning irrespective of treatment intent. Curative patients (44%) with low resilient coping scores had significantly higher COVID-19 worry. Patients who did not know their treatment intent (22%) had significantly higher COVID-19 worry and insomnia. In summary, care experiences were generally positive; however, cancer-related worry, low resilient coping and uncertainty about treatment intent were associated with COVID-19 worry. These patients may benefit from additional psychological support during the pandemic and beyond.

Introduction/BackgroundFrail elderly patients with ovarian cancer (OC) are often treated with 3-weekly carboplatin (3wC) rather than carboplatin-paclitaxel (CP). Elderly Women with OC (EWOC)-1 trial demonstrated that 3-weekly carboplatin-paclitaxel (3wCP) achieved better survival outcomes and was more feasible (defined as the ability to complete 6 chemotherapy cycles without disease progression, death, or premature discontinuation due to toxicity) than 3wC in patients ≥70 years old (≥70 yo) with FIGO stage III/IV OC. We compared the feasibility of treatment with 3wC or 3wCP in frail elderly OC patients.MethodologyData from two cancer centres was retrospectively analysed for newly-diagnosed stage III/IV OC patients ≥70 yo treated with 3wC or 3wCP. Frailty was scored using the Charlson-Comorbidity Index (CCI) and ECOG performance status. Toxicity was graded using CTCAE v5.0.Results107 patients received 3wC (n=31) or 3wCP (n=76, 2 receiving 3wC with weekly paclitaxel). Patients treated with 3wC rather than 3wCP were older ((median age 83 vs. 75 (p<0.001)) with more comorbidities ((median CCI 4 vs. 3 (p<0.001)). Treatment was discontinued for 4 of the 31 (13%) 3wC patients and 6 of the 76 (8%) patients who received 3wCP, with death and disease progression the most common reasons for discontinuation respectively, although the difference in discontinuation rate was not significant (p>0.05). Dose reductions occurred in 16% (5/31) of patients who received 3wC and 57% (43/76) of patients treated with 3wCP, most commonly due to haematological toxicity and peripheral neuropathy respectively.Abstract 2022-RA-1312-ESGO Figure 1Overview of toxicities leading to dose reduction and treatment discontinuation in 3wCP and 3wC cohortsConclusionIn spite of the limitations of our retrospective analysis, 3wCP appears as feasible as 3wC monotherapy for frail ≥70 yo FIGO stage III/IV OC patients, in keeping with the EWOC-1 data, and should be considered in this cohort given that it has been shown to achieve better survival outcomes. Toxicity profiles differ and dose reductions may be required in each treatment arm.

An increased mortality risk was observed in patients with cancer during the first wave of COVID-19. Here, we describe determinants of mortality in patients with solid cancer comparing the first and second waves of COVID-19. A retrospective analysis encompassing two waves of COVID-19 (March–May 2020; December 2020–February 2021) was performed. 207 patients with cancer were matched to 452 patients without cancer. Patient demographics and oncological variables such as cancer subtype, staging and anti-cancer treatment were evaluated for association with COVID-19 mortality. Overall mortality was lower in wave two compared to wave one, HR 0.41 (95% CI: 0.30–0.56). In patients with cancer, mortality was 43.6% in wave one and 15.9% in wave two. In hospitalized patients, after adjusting for age, ethnicity and co-morbidities, a history of cancer was associated with increased mortality in wave one but not wave two. In summary, the second UK wave of COVID-19 is associated with lower mortality in hospitalized patients. A history of solid cancer was not associated with increased mortality despite the dominance of the more transmissible B.1.1.7 SARS-CoV-2 variant. In both waves, metastatic disease and systemic anti-cancer treatment appeared to be independent risk factors for death within the combined cancer cohort.

Background Sarcomas are rare and heterogeneous tumours of mesenchymal origin, with over 100 histological subtypes. Paraneoplastic dermatomyositis has rarely been described in sarcoma. This is the first documented case of paraneoplastic dermatomyositis in a patient with metastatic leiomyosarcoma. Case presentation A 43-year-old female diagnosed with metastatic leiomyosarcoma of unknown primary presented with a mild rash in sun-exposed areas of her face and upper chest, with no other neuromuscular symptoms. This rash resolved with systemic treatment with doxorubicin for metastatic leiomyosarcoma. Imaging assessment confirmed overall stable disease after chemotherapy completion. She presented acutely 2 months later with new onset rash in a shawl-like distribution, periorbital oedema and proximal muscle weakness. Based on the characteristic cutaneous signs and symmetrical proximal muscle weakness, abnormal electromyography and raised skeletal muscle enzymes with a positive anti-transcription intermediary factor-1 gamma antibody result, a diagnosis of paraneoplastic dermatomyositis was made. Re-evaluation of her metastatic leiomyosarcoma revealed disease progression. Second-line chemotherapy was commenced once the dermatomyositis was controlled on steroid therapy. Systemic anti-cancer therapy was again associated with mild improvement in dermatomyositis symptoms. Discussion Paraneoplastic dermatomyositis heralded disease progression after first-line chemotherapy; however, in hindsight, subtle cutaneous features were present at sarcoma diagnosis. The temporal relationship between paraneoplastic dermatomyositis and metastatic leiomyosarcoma is key in this case, as fluctuations in dermatomyositis severity correlated with growth of metastatic disease. Understanding this relationship may provide clues for tumour progression and prompt timely initiation of anti-cancer therapy. It is important to recognise that in addition to the more common cancers associated with paraneoplastic dermatomyositis, it can also occur in rarer tumours such as leiomyosarcoma.