Palmar-Plantar Erythrodysesthesia Associated with Chemotherapy and Its Treatment

Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome, is a relatively common dermatologic toxic reaction associated with cytotoxic chemotherapy that can limit the use of such drugs. Definitive prevention and treatment strategies for PPE have not yet been established. We present a patient with recurrent ovarian cancer developing severe hand-foot syndrome after treatment with pegylated liposomal doxorubicin. A review of the relevant literature concerning pathophysiology, preventive measures and management of PPE is given. Electronic search was conducted using the Medline database for English-language records. The search terms used were ‘palmar-plantar erythrodysesthesia’, ‘hand-foot syndrome’, ‘pegylated liposomal doxorubicin’ and ‘acral erythema’

Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin

Serum Natrium Determines Outcome of Treatment of Advanced GIST with Imatinib: A Retrospective Study of 80 Patients from a Single Institution

Treatment with tyrosine kinase inhibitors (TKIs) has drastically improved overall survival (OS) of patients with advanced GIST. The aim of this study is to evaluate the results of treatment with different TKIs on advanced GIST and identify prognostic factors for OS. The medical records of all patients treated at the Department of Oncology, Aarhus University Hospital were retrospectively reviewed. Between 2001 and 2009, 80 patients with advanced GIST were treated with imatinib as first-line therapy. The median OS was 44 months (95% CI 31–56), and the 5-year OS was 40%. Since 2005, 32 patients were treated with sunitinib as 2nd-line therapy. The median time to progression was 9 months (95% CI: 3–13 months), and the 3-year OS was 30%. The data illustrate that data from large multicenter studies are reproducible in a single sarcoma centre. This retrospective study pointed to low serum sodium at the start of imatinib as a possible prognostic factor affecting OS

Use of Healthcare Services Two Years before Diagnosis in Danish Sarcoma Patients, 2000-2013

Background. Sarcoma is a rare type of cancer with nonspecific symptoms and uncertain aetiology. Thus, timely diagnosis of sarcomas is a clinical challenge. The aim of this study was to investigate the use of healthcare services 24 months preceding a sarcoma diagnosis compared to a matched cohort. Materials and Methods. The study was a retrospective, population-based, matched cohort registry-study. Patients with sarcoma in Denmark in 2000–2013 were identified in the Danish Sarcoma Registry (n = 2167) and matched 1 : 10 on gender, age, and listed general practice. Using a binomial regression model, incidence rate ratios were calculated for face-to-face contacts in general practice, inpatient and outpatient visits, surgery, paraclinical examinations, and diagnostic imaging. Analyses were stratified for sarcoma subtypes, grade, stage, gender, and presence of comorbidity. Results. The sarcoma patients had significantly increased incidence rate ratios in use of healthcare services compared to the matched cohort a year before their diagnoses. An increase in consultation rates was seen 11 months before diagnosis for inpatient visits, 9 months before diagnosis in general practice and outpatient visits, 8 months before diagnosis for paraclinical examinations, and 4 and 3 months before diagnosis for diagnostic imaging and surgery, respectively. There were no clinical significant differences in length of increased consultation rates between sarcoma type, stage, and grade. Sarcoma patients with comorbidity had persistently higher consultation rates compared to patients without comorbidity. Conclusions. The use of healthcare services among sarcoma patients increased several months before diagnosis in all healthcare sectors. The results reveal a diagnostic time window and a potential to refer, diagnose, and treat sarcoma patients in a timelier manner

A Retrospective Clinicopathological Study of 37 Patients With Chordoma: A Danish National Series

Purpose. There are, in general, few published series on chordoma. It is a rare disease and further data are still needed

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

AbstractOBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model. RESULTS: A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality. CONCLUSION: Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set

A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas

Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate (RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1–5 and on day 5 with Dox. The dose escalation schedule was as follows: cohort 1: Bel 600 mg/m2 and 50 mg/m2 Dox, cohort 2: Bel 600 mg/m2 and 75 mg/m2 Dox, cohort 3: Bel 800 mg/m2 and 75 mg/m2 Dox, and cohort 4: Bel 1000 mg/m2 and 75 mg/m2 Dox. Results. 41 patients were included (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT, grade 3 rash/hand and foot syndrome. MTD was Bel 1000 mg/m2/d and Dox 75 mg/m2. Four responses were seen: 2 PR in phase I, RR of 8%; in phase II, 1 PR/1 CR, RR of 13%, and 9 patients (56%) with SD. Conclusion. The combination was well tolerated. Response rate was moderate but median time to progression was 6.0 months (95% CI, 1.6–9.7 months) which is superior to some reports of single-agent Dox

TEDDI : radiotherapy delivery in deep inspiration for pediatric patients - a NOPHO feasibility study

Background: Radiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is a simple technique, in which changes in patient anatomy can significantly reduce the irradiation of the organs at risk (OARs) surrounding the treatment target. DIBH is routinely used in the treatment of some adult patients to diminish the risk of late effects; however, no formalized studies have addressed the potential benefit of DIBH in children. Methods/Design: TEDDI is a multicenter, non-randomized, feasibility study. The study investigates the dosimetric benefit of RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also, the study aims to establish the compliance to DIBH and to determine the accuracy and reproducibility in a pediatric setting. Pediatric patients (aged 5-17 years) with a tumor in the mediastinum or upper abdomen with the possible need of RT will be included in the study. Written informed consent is obligatory. Prior to any treatment, patients will undergo a DIBH training session followed by a diagnostic PET/CT-or CT-staging scan in both DIBH and FB. If the patient proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and two separate treatment plans will be calculated. The superior treatment plan, i.e. equal target coverage and lowest overall dose to the OARs, will be chosen for treatment. Patient comfort will be assessed daily by questionnaires and by adherence to the respiratory management procedure. Discussion: RT in DIBH is expected to diminish irradiation of the OARs surrounding the treatment target and thereby reduce the risk of late effects in childhood cancer survivors.Peer reviewe