Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: a case report and review of the literature.

BACKGROUND: Hypercalcemia is the most common oncologic metabolic emergency but very rarely observed in patients with gastrointestinal stromal tumour, which is a rare mesenchymal malignancy of the gastrointestinal tract. We describe a case of hypercalcemia caused by elevated levels of activated vitamin D in a patient with gastrointestinal tumour. Prior to this case report, only one paper has reported an association between hypercalcemia, gastrointestinal stromal tumours and elevated levels of vitamin D. CASE PRESENTATION: An otherwise healthy 70-year-old Caucasian woman, previously treated for duodenal gastrointestinal stromal tumour, was diagnosed with liver metastasis, and relapse of gastrointestinal stromal tumour was confirmed by biopsy. At presentation, the patient suffered from severe symptoms of hypercalcemia. The most common causes of hypercalcemia, hyperparathyrodism, parathyroid hormone-related peptide secretion from tumour cells, and metastatic bone disease, were all dismissed as the etiology. Analysis of vitamin D subtypes revealed normal levels of both 25-OH Vitamin D2 and 25-OH Vitamin D3, whereas the level of activated vitamin D, 1,25 OH Vitamin D3, also referred to as calcitriol, was elevated. CONCLUSION: The fact that plasma calcitriol decreased after initiation of oncological treatment and the finding that hypercalcemia did not recur during treatment support the conclusion that elevated calcitriol was a consequence of the gastrointestinal stromal tumour. We suggest that gastrointestinal stromal tumours should be added to the list of causes of humoral hypercalcemia in malignancy, and propose that gastrointestinal stromal tumour tissue may have high activity of the specific enzyme 1α-hydroxylase, which can lead to increased levels of calcitriol and secondarily hypercalcemia.

The Prognostic Value of Plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) in Patients with Gastrointestinal Stromal Tumor.

BACKGROUND: This study investigates the prognostic value of plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) concentrations in patients with Gastrointestinal Stromal Tumor (GIST). METHODS: Patients with GIST were included (n = 157) from the two Danish sarcoma centers, independent of disease- and treatment status. The patients were divided into three subgroups; 1: patients with localized disease who underwent radical surgery; 2: patients with local, locally advanced, or metastatic disease; and 3: patients without measurable disease who had undergone radical surgery. Sensitive electrochemiluminescence immune-assays were used to determine PD-1 and PD-L1 concentration in plasma samples. The primary endpoint was the PFS. RESULTS: No patients progressed in group 1 (n = 15), 34 progressed in group 2 (n = 122), and three progressed in group 3 (n = 20). Significantly higher plasma concentrations of PD-1 (p = 0.0023) and PD-L1 (0.012) were found in patients in group 2 compared to PD-1/PD-L1 levels in postoperative plasma samples from patient group 1. Patients with active GIST having a plasma concentration of PD-L1 above the cutoff (225 pg/mL) had a significantly poorer prognosis compared to patients with plasma PD-L1 concentration below the cutoff. CONCLUSIONS: Plasma PD-L1 shows potential as a prognostic biomarker in patients with GIST and should be further evaluated.

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/m(2) and 50 mg/m(2) Dox, cohort 2: Bel 600 mg/m(2) and 75 mg/m(2) Dox, cohort 3: Bel 800 mg/m(2) and 75 mg/m(2) Dox, and cohort 4: Bel 1000 mg/m(2) and 75 mg/m(2) 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/m(2)/d and Dox 75 mg/m(2). 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.

Health-related quality of life in long-term survivors of testicular cancer.

PURPOSE: A growing number of patients with testicular cancer (TC) become long-term survivors. As a consequence, quality-of-life (QOL) issues become increasingly important. The objective of this study was to investigate QOL among Danish TC survivors. METHODS: A long-term follow-up assessment of all patients with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000 was conducted. A total of 401 survivors (response rate, 66%) completed questionnaires concerning QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), depression (Beck Depression Inventory-II), fatigue (Multidimensional Fatigue Inventory-20), and health-related issues such as neurotoxic symptoms and Raynaud-like phenomena. On the basis of their treatment, participants were categorized as having received surveillance, radiotherapy, or chemotherapy. RESULTS: QOL among patients with TC was equal to that of men from the general population. Although patients who received chemotherapy reported higher levels of peripheral sensory neuropathy, ototoxicity, and Raynaud-like phenomena, treatment strategies were generally unrelated to QOL and depressive symptoms. CONCLUSION: Overall, the patients in this study reported high levels of QOL. The results suggest that patients treated for TC should be informed about the anticipated good post-therapeutic QOL and the low risk of psychosocial and physical long-term effects.