The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma.
Thirty patients were entered onto the ...study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles.
The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities.
Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
Doxorubicin is one of the most largely prescribed antitumor drug for the treatment of breast, liver and colon cancers as well as leukemia, but the cardiotoxicity of this anthracycline derivative ...limits its clinical use. Although doxorubicin is toxic to both cancer and cardiac cells, there are evidences suggesting that the mechanism of cell death is different for the two cell types. To investigate further this issue, we have compared the proapoptotic effects of doxorubicin and the functionally related anthracenedione compound mitoxantrone, which is also used in the clinic for the treatment of cancer. After evaluating the toxicity of the two drugs to mammary adenocarcinoma MTLn3 cells and H9C2 cardiomyocytes, we dissected the drug-induced apoptotic machinery by measuring the effects on the cell cycle progression, DNA condensation and fragmentation, production of endogenous peroxides and caspase activation. Both doxorubicin and mitoxantrone are potent inducers of apoptosis in H9C2 cardiomyocytes and MTLn3 breast cancer cells, but there are significant differences between the two cell types in terms of kinetics and order of the events. In particular, flow cytometry measurements of drug-induced changes in mitochondrial transmembrane potential and mitochondrial mass with different fluorescent probes suggested that the two drugs induced a progressive increase in mitochondrial mass in the cancer cells but not in the cardiac cells. The hypothesis was validated by means of electron microscopy, which revealed a significant increase in the number of mitochondria in drug-treated MTLn3 but not in H9C2 cells. The mitochondrial proliferation precedes the nuclear apoptosis in doxorubicin-treated MTLn3 cells. The changes in the architecture and number of mitochondria are linked to the drug-induced perturbation of the cell cycle progression and apoptosis. The proliferation of mitochondria could explain the higher toxicity of doxorubicin to cancer cells compared to cardiac cells and this suggests novel therapeutic opportunities to better control the cardiotoxicity of anthracyclines.
Summary Few studies reported both functional and sensitive long-term evaluations after tongue reconstruction. The aim of this study was to assess functional outcomes and sensitive recovery after ...tongue reconstruction with fasciocutaneous free flap (FCFF) or musculocutaneous pedicled flap (MCPF) without nerve anastomosis. We enrolled 30 patients having no recurrence from a consecutive series of 79 tongue reconstructions as part of a cancer treatment. All patients were submitted to functional and sensitive tests. The functional study included intelligibility, tongue motility, food, and swallowing scores. Flap sensibility was evaluated too. Male-to-female sex ratio was 6.5 with a mean age of 52 years old. The lesions were mainly advanced (T3–T4 73%). Mobile tongue and base of tongue resection was carried out in 43% of cases, and resection was limited to the oral tongue for 53%. Twenty-one FCFF and nine MCPF were performed. The mean follow-up was 2 years and 11 months. Swallowing (slightly impaired 63%), food (normal 40%), and intelligibility (excellent 77%) assessments were satisfactory. Spontaneous sensory recovery was regularly observed (mean response 62%). The two groups FCFF and MCPF were similar regarding population and tumors characteristics. Functional results were higher in case of FCFF (food score p = 0.05; intelligibility p = 0.04). No difference was observed on sensitive recovery. This study emphasizes good functional results either for swallowing or intelligibility, with higher scores for the FCFF, strengthening the opinion that FCFF is the best choice for tongue reconstruction whenever possible.
Objectives: Squamous cell carcinoma (SCC) in young people is rare and the literature is confusing. This study was carried out to assess the demographics, clinical features, and treatment outcome in a ...cohort of patients aged 35 years or less with SCC of the oral tongue (SCCOT). Patients and methods: This was a multicenter retrospective study. Fifty-two patients treated between 1990 and 2000 were identified. Descriptive statistics were analyzed to assess demographic and tumor variables. Results: The WHO performance status was excellent for all patients. Thirty-seven were classified as T1-T2 and 38 were N0. All of them except one were treated with curative intent. Treatment failures were observed in 25 patients (48%). Four patients could be successfully salvaged after SCCOT recurrence or progression. The disease-free survival (DFS) was 52% at 5 years. The 5-year overall survival (OS) rate was 64%. Factors that affected the OS were invasion of the floor (p=0.009), cross over of the midline (p=0.02), positive lymph nodes (p=0.02), and the lack of disease control (p=0.0001). Conclusion: Prognosis was very poor as soon as a local failure developed. Up-front treatment should be optimized to control this rare disease. We propose producing and reporting recommendations via a concerted oncologic physician referral network.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Santos Harbor Area (SHA) in Sao Paulo Coastline (Brazil) is the most important marine cargo transfer terminal in the Southern Hemisphere. A long term relative tidal level variability assessment shows ...a consistent response to relative sea level rise. A wave data base Wave Watch III was compared with a long term wave data-base generated by the ERA40-ECMWF (2003), both local validated. The current bed level of SHA Outer Channel is -15.00 m (Chart Datum or, in abbreviation, CD), maintained by dredging. According to the cargo throughput forecast, in 2025, the Access Channel will have to be deepened to level of -17.00 m. The feasibility of that choice is discussed from a technical, economical and conceptual navigation point of view in that context. A data set found from a scale model of the whole area of Santos Bay, Estuary and nearby beaches, showed the impact of maritime climate changes upon the coastal area. In the previous researches developed by the authors, it was demonstrated that the wave climate, the tides and tidal currents affect harbor and coastal structures maintenance, beaches stability, tidal inlet, sediment transport, saline intrusion and wetlands. Considering the increasing of the sea hazards and the high values of the infrastructures in that coastline, it is necessary to mitigate the risks. Hence, based on the results obtained by the authors, are highlighted guidelines strategies suggested for Access Channels dimensions, wharves free-board, jetties dimensions, dredging rates, rigid and flexible littoral defenses and land protection against flooding (including wetlands).
The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with ...superficial esophageal cancer.
From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications.
Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%).
This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.
The aims of our retrospective study were to study first the causes of 245 febrile episodes in cancer patients and then the value of procalcitonin (PCT) and C-reactive protein (CRP) in differentiating ...infections from paraneoplastic fever.
The causes of fever were studied in 245 consecutive cases observed between January and December 2002, and PCT and CRP diagnostic value in 155 cases (114 infections and 41 paraneoplastic fever).
The two main causes of fever were infection (121 cases) and paraneoplastic fever (43 cases); 77 infections were microbiologically documented. Cocci gram positive caused 41 out of 77 documented infections. Paraneoplastic fever was more frequent in metastatic disease ( p=6.10(-6)). CRP and PCT serum levels at admission did not differ significantly in the infection group and paraneoplastic fever group (respectively p=0.39 and p=0.14 with Mann-Whitney test). The PCT and CRP levels had poor prognostic value in infection (respectively 0.04 and 0.0003 with Mann-Whitney test).
Causes of fever are very numerous in cancer patients (more than 75 different causes in this study). Bacterial infection is the most frequent cause. PCT and CRP failed to discriminate infection, but both had pejorative prognostic value in infected patients.
There is no standard treatment for progressive epithelioid hemangioendothelioma (EHE). To investigate the significant vascularization of EHE, the activity/toxicity of sorafenib in patients with ...progressive EHE was explored.
In this multicenter, 1-stage, phase 2 trial of sorafenib (800 mg daily), the primary endpoint, which was chosen by default, was the 9-month progression-free rate. All patients had documented progressive disease at the time of study entry.
Fifteen patients were enrolled between June 2009 and February 2011. The median age was 57 years (range, 31-76 years), and the ratio of men to women was 9:6. The performance status was zero in 10 patients and 1 in 5 patients. Twelve patients had metastases, mainly in the lung (12 patients), liver (5 patients), and bone (3 patients). Five patients had received prior chemotherapy (doxorubicin in 5 patients and taxane in 3 patients). The median sorafenib treatment duration was 124 days (range, from 27 to >271 days). Seven patients required dose reductions or transient treatment discontinuation. The 9-month progression-free rate was 30.7% (4 of 13 patients). The 2-month, 4-month, and 6-month progression-free rate was 84.6% (11 of 13 patients), 46.4% (6 of 13 patients), and 38.4% (5 of 13 patients), respectively. Two partial responses were observed that lasted 2 months and 9 months.
Further clinical trials exploring sorafenib as treatment of progressive EHE are needed.
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