[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The advent of targeted kinase-inhibitors has revolutionised treatment strategies and clinical outcomes for patients with advanced GIST. In the majority of countries, sunitinib is the only approved second-line treatment option for advanced GIST patients, who are resistant or intolerant to imatinib. However, sunitinib is associated with various adverse events, which often result in a reduction of the dosage, and interruption or suspension of therapy. Effective therapy management is essential to obtain the maximum clinical benefit, and includes adequate side effect management as well as optimization of dosing and treatment duration. In the current study, examples of maximization of treatment with sunitinib are presented, describing three clinical cases in which therapy with sunitinib was continued via the adoption of alternative reduced schedules or an additional loco-regional treatment, in order to manage toxicities or overcome progressive disease.
[Show abstract][Hide abstract] ABSTRACT: Epithelioid hemangioendothelioma (EH) is a rare tumor arising from the vascular endothelial cells of soft tissue or visceral organs. The most common visceral site is the liver, where it is often involved in a multifocal manner known as hepatic EH (HEH). Surgical resection with curative intent represents the gold standard therapy. When surgery is not feasible, or in cases of metastatic disease, no standard medical treatment is currently indicated. In small series, drugs with anti-angiogenic activity (such as bevacizumab, sorafenib, thalidomide, and lenalidomide) have been proposed with promising results. We describe a 73-year-old man with multifocal non-resectable HEH treated with lenalidomide. Disease status was evaluated by abdominal ultrasound and magnetic resonance every four months. The patient was treated for a total of 39 mo with prolonged disease stabilization and, at the time of writing, is still under treatment with a good tolerance profile. During a short period of treatment discontinuation, the disease showed slight progression that immediately resolved after the reintroduction of lenalidomide. Lenalidomide may represent a valid treatment option for HEH due to its anti-angiogenic and antineoplastic activities. This preliminary result merits further study in a large series.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The peritoneum is one of the most common sites of distant gastrointestinal stromal tumor (GIST) metastases. In particular, GIST arising from the small intestine with resected minimal synchronous macroscopic peritoneal carcinomatosis or with primary tumor rupture has a higher risk of developing peritoneal recurrence. Current clinical practice does not envisage second-look surgery in GIST patients at high risk of developing peritoneal recurrence, and no literature data are available.
Presentation of case:
We describe a 45-year-old woman who underwent emergency surgical resection of jejunal GIST presenting with spontaneous tumor rupture, synchronous ovarian and minimal macroscopic peritoneal involvement, and subsequent second-look surgery after 13 months of imatinib treatment.
Second-look surgery confirmed a 2.6cm lesion close to the mesenteric border of the fourth jejunal loop, and 11 peritoneal lesions with a macroscopic necrotic aspect related to treatment response. After conversion to an open procedure, a segmental jejunal resection was performed with removal of all peritoneal lesions and macroscopic radical cytoreduction.
Second-look surgery in selected GIST patients may be performed after at least 12 months of medical treatment with tyrosine-kinase inhibitors to identify those patients with limited peritoneal disease not disclosed by instrumental imaging who could undergo radical cytoreduction of peritoneal lesions.
International Journal of Surgery Case Reports 09/2012; 4(1):7-10. DOI:10.1016/j.ijscr.2012.07.019
[Show abstract][Hide abstract] ABSTRACT: A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib.
Case Reports in Oncology 09/2012; 5(3):651-6. DOI:10.1159/000345946
[Show abstract][Hide abstract] ABSTRACT: Large-scale studies have demonstrated that continuative treatment in advanced and adjuvant settings results in a gain-of-survival. However, the discontinuation, and the duration of treatment in disease-free patients who have undergone radical surgical resection of metastases from gastrointestinal stromal tumours (GISTs) have yet to be evaluated. We retrospectively reviewed 40 patients with advanced and recurrent GIST, included in our GIST database, focusing on patients (5 males and 2 females; median age 56 years) who continued medical treatment following radical surgical resection of metastatic lesions. Seven out of 40 patients underwent surgery and continued medical treatment following radical surgical resection of metastatic lesions. The duration of adjuvant therapy was 3, 12, 16, 24, 35, 37 and 52 months, respectively, with a median of 26 months. No patients discontinued therapy and all were disease-free at the final CT-scan evaluation. Considering that the discontinuation of imatinib in responding patients with advanced GIST (even in complete remission) results in a rapid high risk of progression, and a short adjuvant therapy results in a shorter disease-free and overall survival in high-risk GIST patients, it is also likely that treatment should not be discontinued in this setting. However, large-scale studies are required to better assess the optimal duration of treatment, particularly after 5 years, by focusing on the identification of predictive factors for the selection of patients who may benefit from a prolonged or lifelong imatinib treatment.
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GISTs) are known to be poorly responsive to conventional chemotherapy and historically considered resistant to radiotherapy. In the past the mainstay of GIST treatment was surgery, but the introduction of tyrosine kinase inhibitors (TKIs) imatinib and sunitinib marked the beginning of a new era in the treatment of GIST patients. To date, radiotherapy for GIST has not been administered in clinical practice except for limited palliative settings and there are no clear data on the administration of radiotherapy, alone or in combination with TKIs, with a purely cytoreductive intent. We describe the clinical case of a 48-year-old woman with metastatic GIST treated with external radiotherapy in a critical supraclavicular tumor localization progressively increasing in size with several symptoms and not responsive to systemic TKI therapies. We obtained an initial shrinkage of the mass and subsequent stabilization with an immediate and clear clinical benefit. Although the historical medical literature considered GISTs resistant to radiation therapy, our clinical case suggests this treatment may be appropriate in selected patients.
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib) are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age), and one man (62 years of age). Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.
[Show abstract][Hide abstract] ABSTRACT: In practice, relapses of gastrointestinal stromal tumours after long time of surgical resection occur. However, few published data are available for duration, intensity and imaging sources of follow-up in radically excised patients with localized disease. Therefore, every single institution chooses the surveillance schedule according to its experience. The aim of this study was to describe the late recurrences of disease 5 years after the primary tumour's excision in a series of patients with recurrent GIST from our institution. We retrospectively reviewed 42 patients with "recurrent" GIST, collected since 2001. Ten patients were always followed at our institution, and 32 patients came to our attention at the time of recurrence. The analysed series were divided into two groups: patients who developed recurrence before 5 years and patients who developed recurrence 5 years after the primary tumour's excision. Among 42 patients, 36 patients developed the recurrence within 5 years of the primary tumour excision, whereas 6 patients developed the recurrence 5 years after primary tumour excision diagnosed during follow-up or casually for other reasons. All patients had distant recurrence, involving liver and peritoneum, whereas no local relapse was observed. These patients were heterogeneous in primary tumour site, risk classification and molecular analysis. Duration of the follow-up for radically excised patients with GIST remains still unsettled; however, the integration of every clinical, pathological and molecular parameter is essential to optimize the duration and intensity of the follow-up for each single patient.
Medical Oncology 03/2011; 29(1):144-50. DOI:10.1007/s12032-010-9806-7 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the efficacy and the toxicity of thalidomide-dexamethasone (Thal-Dex) as induction therapy before autologous peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed multiple myeloma (MM) with renal insufficiency. The study included 31 patients with a baseline creatinine clearance value <or=50 mL/min, 7 of whom required chronic hemodialysis. Patients received 4 months of Thal-Dex, followed by PBSC collection and subsequent transplantation. After induction, a partial response (PR) or greater was obtained in 23 patients (74%), including 8 (26%) who achieved a very good PR. Renal function improved more frequently in patients achieving a PR or greater (82%, vs 37% in patients achieving less than a PR; P = .04). Twenty-six patients underwent PBSC mobilization; in 17 of these patients (65%), >4 x 10(6) CD34(+) cells/kg were collected. Double autologous transplantation was performed in 15 patients, and a single autologous transplantation was performed in 7 patients. After a median of 32 months of follow-up, median event-free survival was 30 months, and median survival was not determined. According to our data, Thal-Dex is effective and safe in patients with newly diagnosed MM and renal insufficiency. Given the relationship between recovery of renal function and response to induction treatment, more intensive Thal + bortezomib regimens could be explored to rescue higher numbers of patients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(8):1115-21. DOI:10.1016/j.bbmt.2010.02.020 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T(4;14) chromosomal abnormality is one of the most adverse prognostic factors predicting for poor outcome in multiple myeloma (MM) patients. It has been recently suggested that bone disease, as evaluated by spinal magnetic resonance imaging (MRI), is relatively infrequent in these patients. In the present study, we aimed at further testing this hypothesis by analyzing the extent of whole bone involvement in patients showing t(4;14) chromosomal translocation as compared with negative patients. For this purpose, 53 consecutive newly diagnosed MM patients (35M, 18F, median age = 55 yr) underwent evaluation of total skeletal X-ray, whole spine MRI, and at the same time, quantification of markers of bone resorption (urinary N-terminal telopeptide, pyridinoline, deoxypyridinoline, serum crosslaps), and bone formation (bone alkaline phosphatase and osteocalcin) was performed. The presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), was detected in 11 patients (20.7%), whose clinical characteristics were similar to those observed in t(4;14) negative patients. The type of marrow involvement at spinal MRI (diffuse vs. focal vs. negative) was the same in both groups of patients, even though overt vertebral fractures were more frequently found in t(4;14) positive cases (82% vs. 43%, P = 0.05); in line with this finding, skeletal lesions were more common in t(4;14) positive patients (mean skeletal score = 8.54 +/- 1.36 SE, as compared with 3.42 +/- 0.57 SE in t(4;14) negative cases, P = 0.000). These data were confirmed by the evaluation of serum crosslaps, that were significantly increased in patients with t(4;14) abnormality as compared with negative individuals (10,400 pmol/L +/- 2160 SE vs. 5640 pmol/L +/- 859 SE P = 0.02) Our results indicate that, at variance to what has been previously reported, bone resorption is more prominent in t(4;14) positive patients.
European Journal Of Haematology 02/2008; 80(1):31-6. DOI:10.1111/j.1600-0609.2007.00974.x · 2.07 Impact Factor