Leiomyosarcoma as a Second Metachronous Malignant Neoplasm Following Colon Adenocarcinoma. A Case Report and Review of the Literature

Long-term cancer survivors are at increased risk for the development of second primary malignancies. This is usually associated with common genetic and etiologic factors and the treatment modality used for the primary cancer. In this paper we describe the case of a patient who developed a leiomyosarcoma in his left arm 5 years after he had a colon adenocarcinoma resected. Both primary tumours were treated successfully with surgical resection alone. The literature regarding second primary neoplasms, specifically focused on sarcomas, is briefly reviewed

Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m2/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m^{2}/14 days) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care

Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection?

<p>Abstract</p> <p>Background</p> <p>Patient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is 'life expectancy > 3 months', however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict.</p> <p>Methods</p> <p>We analyzed 233 patients who were enrolled in PIT at Princess Margaret Hospital. We assessed the relationship between 17 clinical characteristics and 90DM using univariate and multivariate logistic regression analyses to create a risk score (PMHI). We also applied the Royal Marsden Hospital risk score (RMI), which consists of 3 markers (albumin < 35g/L, > 2 metastatic sites, LDH > ULN).</p> <p>Results</p> <p>Median age was 57 years (range 21-88). The 90DM rate was 14%; median OS was 320 days. Predictors of 90DM were albumin < 35g/L (OR = 8.2, p = 0.01), > 2 metastatic sites (OR = 2.6, p = 0.02), and ECOG > 0 (OR = 6.3, p = 0.001); all 3 factors constitute the PMHI. To predict 90DM, the PMHI performed better than the RMI (AUC = 0.78 vs 0.69). To predict OS, the RMI performed slightly better (RMI ≥ 2, HR = 2.2, p = 0.002 vs PMHI ≥ 2, HR = 1.6, p = 0.05).</p> <p>Conclusions</p> <p>To predict 90DM, the PMHI is helpful. To predict OS, risk models should include ECOG > 0, > 2 metastatic sites, and LDH > ULN. Prospective validation of the PMHI is warranted.</p

Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma The European Organisation for Research and Treatment of Cancer – Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group (FSG) study

BACKGROUND: We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy. METHODS: The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients). RESULTS: The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR) = 3.83 if PS = 1, OR = 12.00 if PS >= 2), presence of liver metastasis (OR = 2.37) and rare site metastasis (OR = 2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS >= 2). In both models, PS was the most powerful PF for 90-day mortality. CONCLUSION: Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities. British Journal of Cancer (2011) 104, 1544-1550. doi: 10.1038/bjc.2011.136 www.bjcancer.com Published online 19 April 2011 (C) 2011 Cancer Research U

Randomised phase 2 study comparing the efficacy and safety of the oral tyrosine kinase inhibitor nintedanib with single agent ifosfamide in patients with advanced, inoperable, metastatic soft tissue sarcoma after failure of first-line chemotherapy: EORTC-1506-STBSG "ANITA"

Purpose: EORTC-1506-STBSG was a prospective, multicentric, randomised, open-label phase 2 trial to assess the efficacy and safety of second-line nintedanib versus ifosfamide in patients with advanced, inoperable metastatic soft tissue sarcoma (STS). The primary end-point was progression-free survival.Patients/methods: Patients with a variety of STS subtypes were randomised 1:1 to nintedanib (200 mg b.i.d. p.o. until disease progression) or ifosfamide (3 g/m(2) i.v. days 1-3, every 21 days for <= 6 cycles). A Korn design was applied aiming to detect an improvement in median progression-free survival (mPFS) from 3 to 4.5 months (HR = 0.667). An interim look was incorporated to stop the trial for futility if <19 of the first 36 patients treated with nintedanib were progression-free at week 12.Results: At the interim analysis, among the first 36 eligible and evaluable patients randomised for nintedanib, only 13 (36%) were progression-free at week 12. The trial was closed for further accrual as per protocol. In total, 80 patients were randomised (40 per treatment group). The mPFS was 2.5 months (95% CI: 1.5-3.4) for nintedanib and 4.4 months (95% CI: 2.9-6.7) on ifosfamide (adjusted HR = 1.56 [80% CI: 1.14-2.13], p = 0.070). The median overall survival was 13.7 months (95% CI: 9.4-23.4) on nintedanib and 24.1 months (95% CI: 10.9-NE) on ifosfamide (adjusted HR = 1.65 [95%CI:0.89-3.06], p = 0.111). The clinical benefit rate for nintedanib and ifosfamide was 50% versus 62.5% (p = 0.368), respectively. Common treatment-related adverse events (all grades) were diarrhoea (35.9% of patients), fatigue (25.6%) and nausea (20.5%) for nintedanib; and fatigue (52.6%), nausea (44.7%) and vomiting, anorexia and alopecia (28.9% each) for ifosfamide.Conclusion: The trial was stopped for futility. The activity of nintedanib did not warrant further exploration in non-selected, advanced STSs. (C) 2021 The Authors. Published by Elsevier Ltd.Experimentele farmacotherapi