1,721,022 research outputs found
Biomarkers of prognosis and toxicity for metastatic melanoma patients treated with ipilimumab.
Full text linkBackground
Metastatic melanoma has a dismal prognosis, as a consequence of its intrinsic aggressiveness and the lack of effective treatment options: in fact, until recently, systemic therapies were numbered. Ipilimumab is a fully humanized monoclonal anti-Cytotoxic T-Lymphocyte Antigen 4 antibody that demonstrated a significant improvement of metastatic melanoma patient survival, however toxicity may be severe and life threatening. Clinicians lack reliable prognostic factors for prognosis and toxicity and this makes treatment decisions difficult.
Methods
An observational prospective study was performed at the Veneto Institute of Oncology (IOV), the main inclusion criteria being the administration of ipilimumab 3mg/kg every 3 weeks for metastatic melanoma. A total of 140 patients were included, clinical features and circulating biomarkers were evaluated for an association with prognosis or adverse events. Out of 140 patients, 113 were evaluated for prognostic factors, and the full cohort was included in a toxicity study. A prognostic model was derived and data from 97 patients from two other Italian Institutes were used to validate this prognostic model.
Results
Baseline serum lactic dehydrogenase (LDH) concentration and neutrophil count were significantly associated with prognosis. In particular, patients with higher circulating levels of LDH and higher neutrophils before treatment had a shorter survival and increased HR of death (HR=1.36, 95% CI 1.16-1.58, P<.001 and HR=1.76, 95% CI 1.41-2.10, P<.001, respectively). Data were validated on the external cohort and the prognostic model was confirmed.
Female patients and patients with lower baseline serum levels of interleukin-6 (IL6) had a higher risk of developing severe toxicity (OR=1.5, 95% CI 1.06-2.16 and OR=2.84 for 1ng/L variation, 95% CI 1.34-6.03, respectively).
Conclusions
We demonstrated that baseline levels of neutrophils and serum LDH could help clinicians to predict the outcome of melanoma patients treated with ipilimumab and that ipilimumab may not be the best treatment in patients with higher neutrophil count and LDH. Only comparative and translational studies could define if patients with high LDH and neutrophil are refractory to immunotherapy or have a more aggressive variant of melanoma independent from the treatment. Serum baseline IL6 could help in identifying patients with a greater risk of toxicity from ipilimumab and in planning a more specific monitoring during and after the treatment, with the purpose of increasing its safety. In particular, females with low IL6 serum levels should be carefully monitored for AEs
Small datasets to develop and validate prognostic models may be a necessary evil to study rare tumours
No full textNot available
Consolidation electrochemotherapy with bleomycin in metastatic melanoma during treatment with dabrafenib.
No full textBACKGROUND:
Small molecules that inhibit V600 mutated BRAF protein, such as vemurafenib and dabrafenib, are effective in treatment of metastatic melanoma.
CASE REPORT: We here describe the clinical course of a V600E BRAF mutated metastatic melanoma patient with systemic disease, who developed tumor progression on superficial soft-tissue metastases during treatment with dabrafenib. Bleomycin electrochemotherapy during dabrafenib treatment was administered to control the soft-tissue progressing metastases and ensured sustained local control without significant toxicity.
CONCLUSIONS: The new combined approach maintained the patient quality of life and allowed for the prosecution of the target therapy, which proved to be still effective on systemic disease, up to 17 months
Treatment of cutaneous metastases of breast cancer with electrochemotherapy: what is the magnitude of clinical benefit?
No full textNot applicable
Angiosarcoma on lymphedema (Stewart-Treves Syndrome): a 12-year follow-up after isolated limb perfusion, limb Infusion, and electrochemotherapy
No full text[Electrochemotherapy: mechanism of action and clinical results in the locoregional treatment of patients with skin cancers and superficial metastases]
No full textElectrochemotherapy (ECT) has emerged among European centers as an innovative locoregional treatment for patients with unresectable skin cancers or superficial metastases from any histotype. The combined administration of a cytotoxic agent (bleomycin or cisplatin) with properly tuned electric pulses results in locally-enhanced drug delivery (reversible electroporation) into malignant cells and sustained tumor response. Reversible electroporation represents the basis of ECT and allows the potentiation of two low permeant cytotoxic agents such as bleomycin (~8000 fold) and cisplatin (~80 fold). The procedure was standardized in 2006 - thanks to a European project - and shortly after introduced in the clinical practice. In recent years, experience with ECT has accumulated mainly in melanoma and breast cancer patients with cutaneous metastases, in whom complete response rates of 20-50% and 40-75% have been reported, respectively, depending on tumor size. Currently, this therapy is being investigated in deep-seated (i.e. bone, soft tissue) metastases and visceral malignancies (i.e. locally advanced pancreatic cancer), with encouraging results
Minimally invasive treatment of peristomal metastases from gastric cancer at an ileostomy site by electrochemotherapy.
Full text linkBACKGROUND:
Peristomal metastases are rare, but potentially associated with relevant morbidity. Surgical resection, followed by stoma relocation, represent the gold standard in most patients. We describe electrochemotherapy (ECT), a minimally invasive method for locally-enhancing drug delivery by means of electric pulses, as an alternative approach.
PATIENT AND METHODS:
A 49-year-old man with advanced gastric cancer developed skin metastases around an ileostomy site. The ulcerated and oozing tumor growth impaired patient's quality of life due to continuous trouble in fitting the ostomy appliance, its poor adherence and consequent stools spillage. ECT consisted of a 20-minute course under mild general sedation. A bleomycin bolus of 15 000 IU/m(2) was followed by the percutaneous application of multiple, 1.5 ms -long electric pulses by means of a needle electrode.
RESULTS:
Post ECT course was uneventful and the patient was discharged on the same day. After one week, tumor nodules were flattened and partial tumor regression was appreciable at one-month follow-up. More importantly, peristomal skin conditions significantly improved, thus allowing for an effective application of the ostomy appliance during the following moths, until patient's death.
CONCLUSIONS:
This report suggests the feasibility of ECT as a minimally invasive approach for peristomal tumors. In selected cases, ECT, by achieving a rapid tumor control, may ensure effective ostomy management and preserve patients' quality of life
Hyperthermic isolated limb perfusion in locally advanced limb soft tissue sarcoma: A 24-year single-centre experience.
Full text linkBackground: Hyperthermic isolated limb perfusion (HILP) is a locoregional treatment aimed at avoiding amputation in patients with advanced extremity soft tissue sarcomas (STS). Over the last 25 years, HILP procedure has been implemented to maximise its therapeutic ratio. Methods: A retrospective analysis including 117 patients who underwent HILP from 1989 to 2013 was performed. Three different drug schedules were applied: 1) doxorubicin (n = 47), 2) high dose (3–4 mg) tumour necrosis factor-alpha (TNF-α) plus doxorubicin (n = 30), 3) low dose (1 mg) TNF-α plus melphalan (L-PAM) (n = 40). Tumour response was evaluated by MRI or CT and surgical specimens. Toxicity and local progression-free survival (LPFS) were also evaluated. Results: In total 92 (78.6%) patients had primary, 25 (21.4%) had recurrent and 17 (14.5%) had metastatic disease. The subjects in the three groups were homogeneous for clinical-pathological features. Pathological response was complete in 55 patients (47%), partial in 35 (29.9%), regardless of drug schedule (p = 0.501) and tumour presentation (p = 0.094). Wieberdink III–V toxicity was registered in 19.1%, 20% and 2.5% of patients, respectively (p < 0.051). Twenty-eight patients (23.9%) received adjuvant radiotherapy with no relevant toxicity. Five-year LPFS was 81.6% and 74.2% in patients with primary or recurrent disease, respectively (p = 0.652). After a median follow-up of 36.5 months, the limb sparing rate was 77.8%. Conclusions: HILP performed with different drugs was equally active, either in primary, recurrent or metastatic STS, providing effective limb sparing and durable local control. Low dose TNF-α plus L-PAM had the most favourable toxicity profile. Adjuvant radiotherapy was not associated with relevant toxicity
Electrochemotherapy in non-melanoma head and neck cancers: a retrospective analysis of the treated cases
No full textParaneoplastic cerebellar degeneration with anti-Yo antibodies associated with metastatic uveal melanoma
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