Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United ...Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU.
We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19–specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models.
Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio HR, 1.64 95% confidence interval {CI}, 1.36–1.99) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 95% CI, 1.33–1.88). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti–COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti–COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts.
UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti–SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted.
•Coronavirus disease 2019 (COVID-19) mortality in the United Kingdom (UK) has exceeded that of all other European countries.•Outcomes of UK patients with cancer and COVID-19 may compare unfavourably with European countries.•This is the first study to report detrimental outcomes for UK patients with cancer.•UK patients are older, have more comorbidities and are less likely to have received COVID-19 therapy.•Considering our results, rapid vaccination against severe acute respiratory syndrome coronavirus 2 should be recommended.
Introduction:
The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive ...chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma.
Methods:
Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study.
Results:
The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively.
In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity.
Conclusions:
In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.
Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.
...Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.
2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p < 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).
This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.
•Immunogenicity of SARS-CoV-2 vaccines in patients with cancer has been investigated.•There is a need for evidence of SARS-CoV-2 vaccines’ efficacy from large populations.•In this analysis, vaccinated patients experienced improved COVID-19 outcomes.•SARS-CoV-2 vaccines are effective in reducing severe COVID-19 in patients with cancer.
COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We ...aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2.
OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)–delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974.
At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24–68) from COVID-19 diagnosis, were included (964 50·7% of 1902 patients with sex data were female and 938 49·3% were male). Overall, 317 (16·6%; 95% CI 14·8–18·5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the pre-vaccination phase (191 19·1%; 95% CI 16·4–22·0 of 1000 patients). The prevalence was similar in the alpha–delta phase (110 16·8%; 13·8–20·3 of 653 patients, p=0·24), but significantly lower in the omicron phase (16 6·2%; 3·5–10·2 of 256 patients, p<0·0001). In the alpha–delta phase, 84 (18·3%; 95% CI 14·6–22·7) of 458 unvaccinated patients and three (9·4%; 1·9–27·3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten 7·4%; 95% CI 3·5–13·5 of 136 boosted patients, 18 9·8%; 5·8–15·5 of 183 patients who had two vaccine doses vs 277 18·5%; 16·5–20·9 of 1489 unvaccinated patients, p=0·0001), respiratory sequelae (six 4·4%; 1·6–9·6, 11 6·0%; 3·0–10·7 vs 148 9·9%; 8·4–11·6, p=0·030), and prolonged fatigue (three 2·2%; 0·1–6·4, ten 5·4%; 2·6–10·0 vs 115 7·7%; 6·3–9·3, p=0·037).
Unvaccinated patients with cancer remain highly vulnerable to COVID-19 sequelae irrespective of viral strain. This study confirms the role of previous SARS-CoV-2 immunisation as an effective measure to protect patients from COVID-19 sequelae, disruption of therapy, and ensuing mortality.
UK National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of ...URCS patients.
URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.
In total, 148 patients were identified 88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70). One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).
This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.
•Undifferentiated small round cell sarcomas (URCS) represent a therapeutic challenge.•Pathological, clinical and molecular data of these ultra-rare sarcomas are provided.•CIC-rearranged tumours have poor survival compared to BCOR:CCNB3/unclassified URCS.•Translational research and RNA-seq findings are discussed.
Background
According to retrospective osteosarcoma series, ABCB1/P‐glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk‐adapted treatment strategy using ...mifamurtide in Pgp+ patients was performed.
Methods
This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high‐grade osteosarcoma stratified according to Pgp expression. All patients received high‐dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders GRs) or with high‐dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders PRs). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event‐free survival (EFS). A postamendment analysis was performed.
Results
In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow‐up was 51 months. For Pgp+ patients, 5‐year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval CI, 62.2%‐76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5‐year EFS rate was 66.4% (90% CI, 55.6%‐75.1%).
Conclusions
This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
The expression of ABCB1/P‐glycoprotein (Pgp) at diagnosis has been used to stratify patients with high‐grade osteosarcoma. Adjuvant mifamurtide, combined with high‐dose ifosfamide for a poor response to induction chemotherapy, can improve event‐free survival in Pgp+ patients.
Background
Rhabdomyosarcoma (RMS), the most frequent soft‐tissue sarcoma in childhood, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Adolescents ...and young adults (AYA) with RMS form a subgroup of patients whose survival lacks behind that of children while diagnosed with histologically similar tumors.
Procedures
A 67‐gene prognostic signature related to chromosome integrity, mitotic control, and genome complexity in sarcomas (CINSARC) is considered a powerful tool for identifying tumors with a highly metastatic potential. With this study, we investigated the prognostic value of CINSARC signature on a cohort of 48 pediatric (PEDs) and AYAs‐RMS.
Results
CINSARC resulted not significantly correlated with age, suggesting other determinants to be responsible for that difference in survival. It remained a significant prognostic variable in both the groups of PEDs and AYAs. Also, genomic grade index signature was tested on the same cohort and showed very similar results with CINSARC.
Conclusions
Our study showed that CINSARC correlated with outcome in RMS patients and may be potentially considered a tool to predict outcome, and so stratify RMS patients.
A significant proportion of patients with cancer who recover from Coronavirus Disease 2019 (COVID-19) may experience COVID-19 sequelae in the early post-infection phase, which negatively affect their ...continuity of care and oncological outcome. The long-term prevalence and clinical impact of the post-COVID-19 syndrome in patients with cancer are largely unknown.
In this study, we describe the time course of COVID-19 sequelae in patients with non-advanced cancers enrolled in the OnCovid registry.
Overall, 186 patients were included, with a median observation period of 9.9 months (95%CI:8,8–11.3) post-COVID-19 resolution. After a median interval of 2.3 months post-COVID-19 (interquartile range: 1.4–3.7), 31 patients (16.6%) reported ≥1 sequelae, including respiratory complications (14, 7.6%), fatigue (13, 7.1%), neuro-cognitive sequelae (7, 3.8%). The vast majority of the patients were not vaccinated prior to COVID-19. COVID-19-related sequelae persisted in 9.8% and 8% of patients 6 and 12 months after COVID-19 resolution. Persistence of sequelae at first oncological follow-up was associated with history of complicated COVID-19 (45.2% vs 24.8%, p = 0.0223), irrespective of oncological features at COVID-19 diagnosis.
This study confirms for the first time that, in a largely unvaccinated population, post-COVID-19 syndrome can affect a significant proportion of patients with non-advanced cancer who recovered from the acute illness. COVID-19 sequelae may persist up to 12 months in some patients, highlighting the need for dedicated prevention and supportive strategies.
•Patients with cancer may experience ‘long-COVID’.•We evaluated long-term sequelae from COVID-19 across OnCovid registry participants.•A significant proportion of patients may experience long-term COVID-19 sequelae.
The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy ...from the EUROpean Bone Over 40 Sarcoma Study.
The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models.
Fifty-seven patients with DDCS (localised, 34 60%; metastatic, 23 40%) aged 42–65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22–25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles.
Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
•This is the first prospective study conducted on patients with dedifferentiated chondrosarcoma.•Addition of chemotherapy to surgery was feasible.•Chemotherapy gave favourable survival compared with previous retrospective studies.•Almost half of the patients in complete surgical remission were alive.
This article outlines some of the highlights of the fourth ESMO Conference on Sarcoma and GIST, a broad-based international multidisciplinary educational meeting that focused on recent advances made ...in molecular biology and genetics, and the state-of-the art diagnosis and treatment of soft tissue sarcoma and gastrointestinal stromal tumors.
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