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Background: There is no standard of care for both rare sarcomas. Regarding, the important vascularization of EHE and SFT, we explored the activity/toxicity of So in pts with these ...sarcomas. Methods: We conducted a multicenter one-step phase II trial of So (800 mg/d). The primary endpoint was the 9-months progression-free rate (9-PFR). According to EORTC criteria, So is considered as promising drug if 6-PFR≥14%. All pts have had documented progressive disease at entry. Results: 20 pts (15 EHE & 5 SFT) were enrolled from June 2009 to February 2011 in the 8 participating institutions. 12 men and 8 women. Median age was 57. The most common primaries were superficial trunk (8 cases) and liver (4 cases). PS were 0 in 10 cases, 1 in 7 cases and 2 in 3 cases. 16 pts had metastasic disease , especially in lung (15), liver (6) and bone (4). Eight pts received prior chemotherapy (Doxorubicin : n= 8 cases and taxane : n =3). The median So treatment duration was 124 days. 9 pts experienced grade-3 toxicities; the most frequent grade-3 toxic events were hand foot syndrome (5 pts), myalgia (1), stomatitis (1), anorexia (1), diarrhea (1) and arterial hypertension (1).Because of this toxicity, treatment discontinuation was necessary in 6 cases and dose reduction was necessary in 5 pts. The 9-PFR was 6/18 (33.3% 11.5-55.1). The 2, 4 and 6 PFR were 15/18 (83.3%), 8/18 (44.4%) and 7/18 (38.8) respectively We observed 2 partial responses lasting 2 and 9 months in 2 pts with EHE. Analysis of the predictive value of circulating pre-angiogenetic biomarkers is ongoing. Conclusions: According to the STBSG-EORTC criteria (3-PFR≥40% & 6-PFR≥14%), So is a promising drug for EHE and SFT pts. Further trials is needed, especially a discontinuation randomized trial.
In 1937, Ernest Hemingway and Langston Hughes spent a brief period of time together in Madrid, Spain during the Spanish Civil War. Hughes reports on this interaction, but Hemingway never wrote about ...it. In this thesis, I use a cultural geographical lens to provide an explanation for this interaction and for Hemingway's silencing of Hughes. Through an exploration of vernacular landscapes, I argue that Hemingway performed a persona that appeased an American hegemonic public and that Hemingway was able to subvert his persona and hegemonic ideals when travelling abroad. This subversion, I believe, allowed for his interaction with Hughes, but his persona restricted his ability to write about Hughes to an American audience. In the first chapter, I demonstrate how Hemingway's persona developed in an American vernacular landscape focused on the strenuous life. I discuss the significance of mobility for the construction and maintenance of Hemingway's persona and literature in the second chapter. The third and final chapter serves as an exploration of Europe as a space that Hemingway perceived differently than America, which allowed for his ability to subvert American ideals when abroad.
Regarding the frequency of muscular complains with the use of tyrosine kinase inhibitors (TKIs), we hypothesize that creatine kinase (CK) elevation may be more frequent than usually reported. We ...conducted a prospective study on patients treated with TKIs for solid tumors, to assess the incidence of CK increase on treatment. Most of the patients (105/155) had a gastrointestinal stromal tumor. Treatments were carried out with the following drugs: imatinib (87 cases); sunitinib (21 cases); HER antagonists (14 cases), other TKIs (15 cases); and imatinib-based combinations (2 cases). Myalgias were found in 50/155 patients (32 %). Fifty-four patients (35 %; 95 %CI, 27–42 %) had elevated CK. According to NCI-CTC grading, there was 49/54 (31 %) grade 1 and 5/54 (3 %) grade 2 (2.5 to 5 times ULN). CK elevation was more frequent with imatinib than with other TKIs (39 cases, 45 % vs. 14 cases, 21 %, respectively; chi-squared test:
P
= 0.003), and CK was more likely to be abnormal in patients treated with any TKI for more than 6 months. We found increased CK in about one-third of patients under TKIs for solid tumors, including 3 % of patients with CK as high as 2.5–5 times ULN.
To evaluate the therapeutic results obtained with (192)Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma.
Between December 1979 and January 1998, 279 patients with T2N0 ...mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. (192)Ir brachytherapy was performed according to the "Paris system" with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h).
Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meier method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus).
Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.
A new molecule 4 (GGH-DAE)2DHQ associating the 1,4,5,8-tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide ...Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose.
Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with ...hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002–January 2004). Hypercalcemia was defined by calcemia level above 2.55mmol/l. Univariate analysis for prognosis was performed with Mann–Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18–86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2–553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2–553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07–6.82), age inferior to 50 (OR=2.67 CI 95% 1.23–5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8–11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73–17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99–13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02–10.52), male gender (OR=38.22 CI 95% 12.2–89), calcemia level superior to 2.7mmol/l (OR=3.08 CI 95% 1.42–6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01–4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.
