As diverse therapeutic options are now available for advanced melanoma patients, predictive markers that may assist treatment decision are needed. A model based on baseline serum lactate ...dehydrogenase (LDH), peripheral blood relative lymphocyte counts (RLC) and eosinophil counts (REC) and pattern of distant metastasis, has been recently proposed for pembrolizumab-treated patients. Here, we applied this model to advanced melanoma patients receiving chemotherapy (
116) or anti-CTLA-4 therapy (
128). Visceral involvement, LDH and RLC were associated with prognosis regardless of treatment. Instead, when compared to chemotherapy-treated patients with REC < 1.5%, those with REC ≥ 1.5% had improved overall survival when receiving anti-CTLA-4 Hazard Ratio (HR) = 0.56 (0.4-0.93) but not chemotherapy HR = 1.13, (0.74-1.74), and the treatment-by-REC interaction was significant for both overall (
= 0.04) and progression free survival (
= 0.009). These results indicate baseline REC ≥ 1.5% as a candidate predictive biomarker for benefit from anti-CTLA-4. Further studies are needed to confirm these findings in patients receiving immune-modulating agents.
ABSTRACT
Electroporation uses pulsed, high‐intensity electric fields to temporarily increase cell membrane permeability by creation of pores, through which small molecules, such as chemotherapeutic ...agents, can diffuse inside cells before they reseal. The combination of electroporation with the administration of otherwise low‐permeant cytotoxic drugs is known as electrochemotherapy (ECT). The two most commonly used drugs are bleomycin and cisplatin. ECT has already been proven to be effective in diverse tumor histotypes, including melanoma and basal and squamous cell carcinoma, Kaposi sarcoma, and breast cancer, also in those cases nonresponding to classical chemotherapies or other loco‐regional treatment modalities, with a good safety profile. ECT can be proposed as loco‐regional therapy for disseminated cutaneous and subcutaneous tumor lesions as alternative treatment modality to conventional therapies or as palliative care, in order to improve patients' quality of life.
The combined treatment of dacarbazine with an antiangiogenic drug such as bevacizumab may potentiate the therapeutic effects of dacarbazine in metastatic melanoma (MM). Preliminary antitumour ...activity of dacarbazine plus bevacizumab is evaluated, together with the toxicity and safety profile, in MM patients. This prospective, open-label, phase II study included patients with previously untreated MM or unresectable melanoma. Patients received dacarbazine and bevacizumab until progressive disease or unacceptable toxicity. The primary efficacy variable was the overall response rate. The secondary efficacy parameters included duration of response, duration of stable disease, time to progression/progression-free survival, time to treatment failure and overall survival. The safety analysis included recordings of adverse events and exposure to study treatment. The intention-to-treat population included 37 patients (24 men and 13 women, mean age 54.2±13.1 years). Overall response rate was 18.9% (seven patients achieved a response) and clinical benefit was 48.6%. In patients who achieved a response, the median duration of response was 16.9 months and the median duration of stable disease was 12.5 months. The median time to progression/progression-free survival and time to treatment failure were 5.5 and 3.1 months, respectively. The median overall survival was 11.4 months. Almost all patients (94.6%) experienced at least one adverse event; however, no new area of toxicity of bevacizumab emerged. The dacarbazine/bevacizumab combination provides benefits compared with dacarbazine monotherapy in historical controls, with an acceptable safety profile. This combination appears to be a valid option in specific subgroups of patients, namely, those triple negative (BRAF, C-KIT and NRAS wild type) or with a BRAF mutation who have already received, or are not eligible for, immunomodulating or targeted agents.
We have investigated the role of high-resolution ultrasound (US) in the analysis of sentinel node(s) in melanoma patients in pre-operative staging and follow-up. One hundred and six lymph node basins ...in 88 melanoma patients undergoing sentinel node biopsy (SNB) were examined: 25 (23.6%) were US positive for metastases and 81 (76.4%) were negative. Subsequent histological analysis of the 81 negative lymph nodes confirmed the absence of metastases in 80 cases (98.8%), whereas, in the 25 US-positive lymph nodes, metastases were found in 16 cases (64%). The follow-up of all patients submitted to SNB in our unit included a US investigation of operated and contralateral nodal basins every 4 months for the first 3 years and then every 6 months. Of a total of 300 patients, four (1.6%) were found to have locoregional nodal disease during follow-up. In three of these four patients, US was crucial in indicating the presence of nodal metastases, which would have gone undetected on physical examination. The result of this study (negative predictive value of 98.7%) introduces the possibility of selecting patients who may avoid an SNB procedure based on the results of pre-operative US examination.
This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue ...sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment.
Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was <5 cm in 20 cases and >5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy.
With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%.
PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.
The aim of this study was to determine whether excision biopsy and primary closure of primary cutaneous melanoma modifies lymphatic drainage and accuracy of sentinel node biopsy. Thirty patients with ...31 cutaneous melanomas were prospectively enrolled to undergo lymphoscintigraphy (LS) before and after excision biopsy. Tc-human serum albumin nanocolloid was first injected intradermally around the primary tumor and subsequently, after excision biopsy, adjacent to the scar. Sentinel nodes were identified by preoperative LS and the gamma-probe. Patent Blue V dye was injected intraoperatively before sentinel node biopsy. Intraoperative sentinel node identification was 100%. In 23 of 31 cases, both LSs were concordant in terms of nodal basins visualized. Two patients had a basin downstaged and six patients had a basin upstaged by the second LS. Only 50% of LS hot nodes stained blue (42 of 84). In 24 of 31 cases, the sentinel node was negative for metastases. Seven patients underwent complete lymph node dissection because of sentinel node positivity. Only one patient had metastases also to a non-sentinel node. After a median follow-up of 30 months lymph node metastases have not been observed in the eight discordant cases. This study shows that sentinel node identification and biopsy after lymphatic mapping is accurate after excision biopsy of primary cutaneous melanoma. Excision biopsy may, however, modify lymphatic drainage and a narrow excision margin should be performed if melanoma is suspected.
Environmental estrogen-like compounds（i.e. xenoestrogens） are a variety of pollutants,ranging from synthetic to natural occurring molecules, that are found in surface and waste waters over a wide ...range of concentrations. In aquatic environment, the overall estrogenic activity is often due to the presence of a mixture of chemicals and their degraded products which can induce synergistic effects. Current strategies for monitoring estrogen-like chemicals are based on the use of a battery of in vivo and in vitro ecotoxicological tests. In this regard, the aim of the present work was to carry out a bio-monitoring study for testing estrogenicity of the Chienti river（Marche Region, Italy） by using both an E-screen and a vitellogenin（Vtg） induction assay in juvenile goldfish. Three sites were used for analysis,localized at the mouth（sampling point 1）, in the middle（sampling point 2） and at the origin（sampling point 3） of Chienti river. For most of the water samples（i.e. samples collected at sampling points 2 and 3）, clear estrogenic activity was detected in the E-screen assay suggesting different proliferation activities in function of the collecting site. In contrast, the Vtg ELISA demonstrated that water samples collected from each sampling point were estrogenic. Overall, we showed for the first time that the estrogenic activities in water samples from the Chienti river were significant in both in vivo and in vitro; we also observed a different sensitivity between bioassays.
We report a case of primary cutaneous cryptococcosis in an HIV-negative patient, who presented with painless, ulcerated lesions involving the right forearm (fingers and elbow), which developed over ...45 days. On the basis of the clinical appearance, serological and cultural examinations were performed to confirm the diagnosis; the histological evaluation of a skin biopsy showed an acute inflammatory infiltrate containing several PAS + Cryptococci. Subsequently, the patient was treated with fluconazole (400 mg/day for 10 days, then a maintenance therapy of 200 mg/day); after one month, the cutaneous lesions were remarkably improved, but, although a series of further laboratory and clinical examinations was scheduled, the patient repeatedly refused any other re-evaluation, and he was lost from follow-up.
PDF
