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Background: We retrospectively investigated the role of (neo)adjuvant chemotherapy in patients with primary, localized angiosarcoma. Methods: We selected all patients with primary, localized angiosarcoma, who had received radical surgery between January 2005 and December 2019 at 33 European sarcoma reference centers. The primary objective was to compare the outcome of patients who received (neo)adjuvant chemotherapy versus those who did not, in terms of overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). To reduce the risk of confounding due to imbalance, a propensity-score matching(PSM) was performed. Finally, subgroups analysis was performed according to tumor site, tumor size (< 50 mm or ≥ 50 mm) and patients predicted 10-years OS according to the nomogram sarculator (two different cutoff-values were applied: ≤ 33% or > 33% and < 60% or ≥ 60%). Results: 362 patients were analyzed: 149 (41.2%; treated group) received (neo) adjuvant chemotherapy and 213 (58.6%; control group) did not. The median follow-up for the OS endpoint was 5.1 years (95% CI: 4.0–5.5). The OS-HR was 0.58 (95%CI: 0.40–0.83; p-value = 0.003) in the univariate analysis and 0.74 (95% CI: 0.38–1.43; p = 0.367) in the PSM analysis. The DFS-HR was 0.75 (95% CI: 0.57–0.98; p-value = 0.036) in the univariate analysis, and 0.91 (95% CI:0.56–1.48; p-value = 0.7) in the PSM analysis. The DMFS-HR was 0.75 (95% CI: 0.55–1.02; p-value = 0.065) in univariate analysis and 0.92 (95% CI: 0.53–1.61; p-value = 0.769) in the PSM analysis. Subgroup analysis revealed no heterogeneity of results in strata of tumor site. On the contrary, there was a trend for heterogeneity according to tumor size and patient's risk of death. For all the endpoints analyzed, patients with tumors smaller than 50 mm or at lower risk of death seem to have no benefit from chemotherapy, while patients with larger tumors or at higher risk of death at 10 years seem to derive substantial benefit. Conclusion: This large, retrospective study suggests that patients affected by > 50 mm and/or high-risk primary, localized angiosarcoma could benefit from (neo)adjuvant chemotherapy.

The epidemiological evidence on soft-tissue sarcoma (STS) mortality is inconsistent in geographic and time coverage. This study provides mortality trends for STSs in selected countries worldwide over the last 2 decades, together with predicted figures for 2025.We extracted official numbers of certified deaths coded as C47 (i.e. malignant neoplasm of peripheral nerves and autonomic nervous system) and C49 (i.e. malignant neoplasm of other connective and soft tissue) according to the 10th Revision of the International Classification of Disease and population estimates from the WHO and the Pan American Health Organization databases. We computed age-standardized (world standard population) mortality rates (ASMRs). We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2025.The pattern emerging from the number of deaths and ASMRs up to 2018 shows an increase in most countries in both sexes. Around 2015 to 2018, ASMRs differed by 2.5-fold in both sexes with the highest rates being registered in Central-Eastern Europe, North America and Australia, while the lowest ones in Latin America, Japan, and Korea. In 2025, the number of STS deaths is predicted to increase in most countries and both sexes, and unfavourable rates are predicted in Central Europe in both sexes.In addition to improvements in STSs registration, unfavourable mortality rates reported in this study reflect inadequate referral of patients with STSs to high-volume multidisciplinary centres, as well as insufficient advancements in STS prevention, diagnosis, and treatments.

BackgroundAmong sarcomas, which are rare cancers with an incidence of Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).MethodsA post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.ResultsThirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).ConclusionsTrabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

BACKGROUND. The optimal use of antiresorptive agents (bisphosphonates; denosumab) in patients with bone metastases from solid tumors is uncertain in several aspects, including the initial drug choice and the planned treatment duration, till the long-term therapy. Drug costs, logistics and facilities, patients’ preferences, renal toxicity, and expected risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), as well as other side effects, may conditionate the oncologists’ choice. MATERIAL AND METHODS. Italian oncologists from a study group on bone metastatic disease within the “Rete Oncologica Piemonte-Valle d’Aosta” (a cancer network in North-Western Italy) evaluated scientific literature and current guidelines and recommendations, to answer a PICO (Patient/population; Intervention; Comparison; Outcome) question. The question was: in patients with bone metastases from solid tumors, is treatment with antiresorptive drugs (bisphosphonates or denosumab) amenable to personalized use (for choice of drug and duration of treatment) based on the type of disease, the expected risk of side effects, and patient compliance, as an alternative to “one-fit-for-all” therapy (monthly zoledronic acid or denosumab, indefinitely), in order to: reduce the commitment to the patient and to the oncological structure; reduce economic costs; reduce the risk of medium/long-term side effects (e.g., MRONJ)? RESULTS. The study group analysed the cost of drugs; the engagement of the oncology unit; the patient commitment/compliance; the risk of side effects (renal toxicity, hypocalcaemia, MRONJ); the options of the planned initial duration of treatment; the timing of administration (monthly versus quarterly). Early antiresorptive treatment was recommended (at the diagnosis of bone metastases, after pre-therapy dental evaluation). Four types of tailored treatment options were recommended, in four main different metastatic cancer scenarios. CONCLUSION. A tailored antiresorptive treatment might reduce the number of accesses to oncological structures by the patient, the costs for the structure and for the healthcare system (both in terms of work and cost of drugs), and the risk of medium/long-term side effects (renal failure; MRONJ), potentially without reducing the expected benefits of the treatment.

Background This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients and methods mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT. Results The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72–1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55–1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively. Conclusions This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.

Trabectedin is a marine-derived anticancer drug approved for the treatment of patients with advanced soft-tissue sarcomas (STS). Here, we aimed to analyze its use in a large cohort of STS patients treated in Italy in a real-world setting. Data on STS patients treated with trabectedin in Italy were prospectively collected from January 2013 to December 2019 by the national drug regulator, the Italian Medicines Agency (AIFA). Time-to-off-treatment (TToT) was defined as the time between the initial prescription of trabectedin and the date of treatment discontinuation for any cause. The impact of the different baseline covariates, including the initial prescribed dose of trabectedin, on TToT was evaluated using an accelerated failure time (AFT) models with log-logistic distribution. In total, we analyzed data from 2633 sarcoma patients and 14 950 individual cycles of trabectedin. The median number of cycles of trabectedin received per patient was 3 (interquartile range 2-7). The labeled 1.5 mg/sqm dose was used in 27.3% of all first prescriptions. Overall, the median TToT was 93 days. In the final AFT model, the variables significantly associated to longer TToT were female gender (+13% increase in TToT); ECOG performance status 0 (+50%); histological diagnosis of leiomyosarcoma (+22%), well-differentiated/dedifferentiated liposarcoma (+72%) or myxoid liposarcoma (+61%); receiving treatment in a high-volume center (+23%). In this large real-world cohort of STS patients treated with trabectedin, our findings support the use of trabectedin in STS patients, in particular in leiomyosarcoma and liposarcoma patients, and highlight the role of treatment center volume in their management.

Background To prevent the spread of SARS-CoV-2, containment measures were implemented leading to huge healthcare changes worldwide. This study aimed to describe the impact of COVID-19 pandemic on surgical oncology healthcare in a large Italian sample. Methods A retrospective observational study included 99651 patients admitted to the hospitals of Piedmont (Northern Italy) to undergo oncological surgery, provided in ordinary hospitalization. We compared data of 2020 with 2016-2019 mean values. Data were stratified by tumor site, year, month and admission way. Chi-squared tests were used to assess differences in the percentage of admission modes between 2020 and 2016-2019. Results An overall reduction in oncological surgery (-12.3%) was observed in 2020 (n = 17923) compared to the mean of period 2016-2019 (n = 20432). A relevant decrease began in March (-11%), continued in April (-18%) and peaked in May (-26%). There was a greater reduction in surgery of breast (-19.2%), bladder (-17.5%), colorectal (-16.5%), kidney (-14.2%), prostate (-14%). Little or no difference was observed for liver (-5.2%), body of uterus (-0.54%), ovary (-0.07%), lymphoma (+4.5%). There was a marked reduction of non-emergency admissions (-13.6%), in particular for some tumor sites: colorectal (-19.4%), breast (-19.4%), bladder (-18.7%). The overall volume of surgeries following an emergency access was unchanged (-0.3%). The proportion of hospitalizations with emergency access increased (p < 0.001). Conclusions Our results highlight the burden of the reduction in cancer surgery in 2020 and the risk of delays in diagnosis and treatment for time-dependent conditions. For cancers that can be diagnosed early thanks to screening, the reduction in surgery is likely to be an indirect consequence of discontinuing screening activities. Therefore, further studies are needed to assess, as soon as data are available, the trend in 2021, and to compare our results with those reported in other European countries. Key messages • The COVID-19 pandemic caused a significant decline in cancer surgeries in 2020 in Piedmont, Italy. It is necessary to compare our results with those reported in other European countries. • These results show an increase in the proportion of oncological surgical admissions following emergency access in 2020 compared to the average for 2016-2019.

[Background] The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS., [Methods] This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%)., [Results] The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105)., [Conclusions] High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS., This was a nonfunded analysis. In the ISG-STS 1001 trial, PharmaMar provided trabectedin for the HG-MRLPS cohort. That trial was partially funded through a European Union grant (EUROSARC FP7 278472).