Inadvertently boarding a pirate ship: disease progression in a paediatric patient with relapsed metastatic Ewing sarcoma receiving treatment at a centre for alternative therapy in Mexico

10013 Background: Options for local control in patients (pts) with Ewing sarcoma (EWS) include surgery (S), radiation (R), or surgery plus radiation (S+R). The choice of local control depends on factors that also impact outcome in EWS, including tumor site, tumor size, and age. Our objective was to determine if risk of disease progression differs between local control methods, after controlling for potential confounders. Methods: We analyzed the cohort of pts with non-metastatic EWS of the bone treated on Intergroup Study-0091 (Grier et al, NEJM, 2003). Local control decisions were made on an individual basis. We excluded pts with tumors of the skull/face, progression prior to end of local control, or incomplete local control data. Disease progression was recorded from end of local control. Cumulative incidence of disease progression was determined using a competing risks approach. We constructed a Cox proportional hazards model of progression free survival incorporating local control mode and potential confounders into the model. Secondary analyses evaluated overall survival, local failure, and distant failure. Results: 329 pts met eligibility criteria for analysis. 122 pts received S, 142 received R, and 65 received S+R. The cumulative incidence of disease progression at 5 years was 22.1% (95% CI 15.1–29.9%) for S, 36.9% (29.0–44.9%) for R, and 48.1% (35.5- 59.7%) for S+R. Using R as the reference group and controlling for age, tumor size, tumor location, and chemotherapy regimen, the hazard ratio for progression was 0.66 (95% CI 0.38–1.13) for S and 1.55 (0.96–2.49) for S+R. The hazard ratio for death was 0.77 (95% CI 0.44–1.34) for S and 1.46 (0.88–2.42) for S+R. The hazard ratio for local failure was 0.38 (95% CI 0.15–0.98; p=0.04) for S and 0.77 (0.34–1.75) for S+R. The hazard ratio for distant failure was 0.78 (0.42–1.46) for S and 1.60 (0.91–2.82) for S+R. Conclusions: Observed differences in outcome between local control groups are largely due to confounding factors that affect outcome and local control choice. Risk of disease progression, distant failure, or death does not differ between pts who receive S or R. Pts who receive S have a decreased risk of local failure compared to pts who receive R. No significant financial relationships to disclose.

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Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10011 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10011-10011

Author(s):

P. Leavey ◽

L. Mascarenhas ◽

N. Marina ◽

Z. Chen ◽

M. Krailo ◽

...

Keyword(s):

Prognostic Factors ◽

Disease Progression ◽

Metastatic Disease ◽

Ewing Sarcoma ◽

Significant Risk ◽

Female Gender ◽

Initial Diagnosis ◽

Phase Iii ◽

Rank Test ◽

First Recurrence

10011 Background: The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%. Since 30–40% of patients with newly diagnosed, non-metastatic EWS develop recurrence, the Children's Oncology Group (COG) sought to evaluate prognostic factors for these patients. Data was derived from the phase III, multi-institutional study INT 0091. Methods: Between 1988 and 1994, five hundred and seventy-eight eligible patients with previously untreated EWS or PNET of bone were enrolled on INT 0091. Patients who experienced recurrence or disease progression as their first analytic event were considered. Survival was calculated from date of disease progression to death or last patient contact. Comparisons of the risk for death across groups were accomplished using the log-rank test. Survivor functions were estimated by the method of Kaplan and Meier. Results: Two hundred and sixty-two patients experienced disease progression or recurrence. The median time to first recurrence was 1.3 years (range 0–7.4 years) for all patients, 1.4 years (range 0 to 7.4 years) for patients with initially localized disease and 1 year (range 0 to 6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (p<0.0001). Twenty-one percent of patients whose disease recurred or progressed experienced first recurrence 2 or more years from initial diagnosis and had an estimated 5 year post-recurrence survival of 30%. This compares with 7% for those whose first recurrence or progression was earlier. No statistical difference was detected when patients whose disease recurred < 12 months were compared with those whose recurrence was 12–24 months from initial diagnosis. Significant risk factors for death after recurrence included metastatic disease at initial diagnosis, elevated LDH at initial diagnosis and female gender. In patients non-metastatic at initial diagnosis pelvic primary site was also a risk factor for death after recurrence. Conclusions: Patients with longer time to first recurrence represent the subset of patients most likely to survive following recurrence. All patients with recurrent Ewing sarcoma would benefit from collaborative trials to investigate new therapeutic options. No significant financial relationships to disclose.

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A phase I/II clinical trial of the reversible LSD1 inhibitor, seclidemstat, in patients with relapsed/refractory Ewing sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps11567 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS11567-TPS11567

Author(s):

Damon R. Reed ◽

Leo Mascarenhas ◽

Paul A. Meyers ◽

Sant P. Chawla ◽

Douglas James Harrison ◽

...

Keyword(s):

Gene Expression ◽

Clinical Trial ◽

Disease Progression ◽

Dose Escalation ◽

Ewing Sarcoma ◽

The United States ◽

Vehicle Group ◽

Tumor Growth Inhibition ◽

Aberrant Gene Expression ◽

Aberrant Gene

TPS11567 Background: Ewing sarcoma (ES) is a rare, aggressive bone and soft tissue cancer that predominantly afflicts adolescents and young adults. Novel therapeutic agents are needed as there are no approved targeted treatments for this disease. ES is characterized by a chromosomal translocation resulting in an EWS/ETS fusion oncoprotein, a transcription factor that results in aberrant gene expression leading to ES progression. Lysine specific demethylase 1 (LSD1) associates with EWS/ETS oncoproteins to alter gene expression and contribute to disease progression. Directly inhibiting EWS/ETS is challenging and little progress has been made, though targeting LSD1 presents a viable therapeutic strategy for ES. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is a first-in-class, orally bioavailable, small molecule with reversible and noncompetitive selective inhibition of LSD1 at low nanomolar concentrations (IC50: 25-50 nM). Seclidemstat inhibits LSD1’s scaffolding functions and enzymatic activity to help reverse aberrant gene expression. In vitro data show that treatment with seclidemstat, or seclidemstat analog, modulates EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression. In in vivo xenograft studies (e.g., SK-N-MC, A673), mice treated with seclidemstat show significant tumor growth inhibition/regression vs the control vehicle group. Methods: This phase 1/2 clinical study of seclidemstat is being conducted in relapsed or refractory ES (NCT03600649). The trial is an open-label, non-randomized dose-escalation/dose-expansion study designed to determine the maximum tolerated dose through single-patient dose escalation followed by traditional 3+3 design. The primary objective is to assess seclidemstat’s safety and tolerability while secondary objectives include pharmacokinetics, efficacy and exploratory pharmacodynamic markers. Patients must be ≥12 years old, have received at least 1 prior line of therapy including a prior camptothecin-based regimen, with a life expectancy > 4 months. All patients receive seclidemstat twice-daily (BID) as oral tablets until unacceptable toxicity or disease progression. Patients are followed for survival until the end of study. The trial is currently recruiting across 8 locations in the United States. Upon identification of the recommended phase 2 dose, that cohort will be expanded to enroll a total of 20 patients. Clinical trial information: NCT03600649 .

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Kambô-Induced Systemic Inflammatory Response: A Case Report of Acute Disease Progression of Cholangiocarcinoma

Integrative Cancer Therapies ◽

10.1177/1534735421999106 ◽

2021 ◽

Vol 20 ◽

pp. 153473542199910

Author(s):

Shira Peleg Hasson ◽

Eliya Shachar ◽

Rivka Kessner ◽

Shulim Shpigel ◽

Ido Wolf

Keyword(s):

Case Report ◽

Inflammatory Response ◽

Disease Progression ◽

Alternative Therapy ◽

Systemic Reaction ◽

Systemic Inflammatory Response ◽

Physician Education ◽

Severe Adverse Reaction ◽

Impaired Liver ◽

Complementary And Integrative Medicine

Kambô is a cleansing ritual involving the application of a toxin produced by the giant leaf frog ( Phyllomedusa bicolor). The Kambô ritual has increasingly been adopted among cancer patients in Europe. Accumulating data indicate various adverse effects. We report another severe adverse reaction to Kambô, a systemic inflammatory response syndrome mimicking disease progression in a patient with cholangiocarcinoma. We describe a systemic reaction to Kambô, manifested as tachycardia, tachypnea, impaired liver cholestatic enzymes, and enlargement of lymphadenopathy mimicking disease progression. The clinical features and onset of symptoms, the rapid reaction, and the lack of other identified causes make the diagnosis of Kambô-induced SIRS highly probable. This case report calls for future studies examining standard oncological care such as chemotherapy, radiotherapy, and immunotherapy in conjunction with alternative therapy. Additionally, greater awareness and physician education should be promoted, encouraging inquiry of oncology patients’ administration of alternative, complementary, and integrative medicine.

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CD99 polymorphisms significantly influence the probability to develop Ewing sarcoma in earlier age and patient disease progression

Oncotarget ◽

10.18632/oncotarget.12862 ◽

2016 ◽

Vol 7 (47) ◽

pp. 77958-77967 ◽

Cited By ~ 4

Author(s):

Marcella Martinelli ◽

Alessandro Parra ◽

Luca Scapoli ◽

Paola De Sanctis ◽

Valentina Chiadini ◽

...

Keyword(s):

Disease Progression ◽

Ewing Sarcoma

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Ewing sarcoma of the rib presenting with hemothorax

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492319858560 ◽

2019 ◽

Vol 27 (9) ◽

pp. 779-781

Author(s):

Ahmed Mohamed Abdel Shafi ◽

Sarah Fendius ◽

Wael Ibrahim Awad

Keyword(s):

Children And Adolescents ◽

Disease Progression ◽

Rare Disease ◽

Chest Wall ◽

Ewing Sarcoma ◽

Primitive Neuroectodermal Tumor ◽

Long Bones ◽

Rapid Disease Progression ◽

Massive Hemothorax ◽

Common Malignancy

Ewing sarcoma is a malignant primitive neuroectodermal tumor, primarily affecting the long bones in young children and adolescents. It is a rare disease but is the most common malignancy of the chest wall, accounting for 6%–16% of chest wall cancers. We report a case of Ewing sarcoma of the rib presenting with massive hemothorax in a teenage boy, with rapid disease progression.

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Maintenance therapy with oral cyclophosphamide plus celecoxib in patients with metastatic Ewing sarcoma: Results of the Italian Sarcoma Group/AIEOP EW-2 study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10517 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10517-10517

Author(s):

Nadia Puma ◽

Asaftei Dorin Sebastian ◽

Anna Paioli ◽

Gianni Bisogno ◽

Marco Rabusin ◽

...

Keyword(s):

Maintenance Therapy ◽

Disease Progression ◽

Ewing Sarcoma ◽

Maintenance Phase ◽

Metastatic Spread ◽

Hematological Toxicity ◽

High Dose ◽

Oral Cyclophosphamide ◽

Single Bone

10517 Background: The prognosis of patients with metastatic Ewing sarcoma remains poor. The primary aim of the ISG/AIEOP EW2 Study (EUDRACT# 2009-011197-15) was to evaluate the feasibility and efficacy of maintenance therapy with oral cyclophosphamide plus celecoxib. Methods: From June 1st 2009 to Nov 22nd 2019, 112 patients with metastatic Ewing sarcoma at onset entered the ISG/AIEOP EW2 study, consisting of induction chemotherapy, radiotherapy and/or surgery at the site of the primary tumor, a consolidation phase with high-dose busulphan/melphalan + autologous stem cell rescue, whole-lung irradiation (12-15Gy), and a maintenance phase of 180 days with cyclophosphamide 50 mg daily (35 mg/mq daily if age < 14 years) plus celecoxib 400 mg twice daily (250 mg/mq twice daily if age < 14 years). Exclusion criteria from the maintenance phase were disease progression, cardiac or gastro-intestinal comorbidity. For CTCAE v4.0 grade 3-4 toxicities a temporary interruption was planned. Results: Seventy-one patients were eligible and entered the maintenance phase. Median age was 16 years (range 13-41); sites of metastases were lung or single bone (n = 56) and multicentric metastatic spread (n = 15). Sixty-one patients terminated the maintenance phase, 4 patients are still on treatment, 1 patient interrupted the treatment due to auto-immune thrombocytopenia at 4 months, 5 patients were withdrawn throughout maintenance due to disease progression/relapse. The duration of maintenance therapy was 89% of the scheduled days, with a median suspension length of 12 days (range 1-44 days). Causes of temporary suspension were hematological toxicity (19 episodes), infections (12 episodes), gastrointestinal disorders (9 episodes), fluid retention/distal oedema (3 episodes), renal disorders (3 episodes). Median follow-up was 42 months. The 3-year EFS of patients who entered the maintenance phase was 0.79 ± 0.09 for lung or single bone, and 0.19 ± 0.11 for those with multicentric metastatic spread. Conclusions: This schedule of maintenance phase is feasible, despite previous intensive treatment. A longer follow-up is needed to monitor side effects and to evaluate clinical outcome of patients with lung or single bone metastases, while the outcome remains dismal for multicentric metastatic Ewing sarcoma. Clinical trial information: NCT02727387.

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