Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival.

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.

Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.

Psoralen cream plus ultraviolet A photochemotherapy (PUVA cream): our experience.

BACKGROUND: Psoralen ultraviolet A (PUVA) bath photochemotherapy has been proved highly effective in the treatment of various dermatoses without potential side-effects of systemic therapy. Another form of topical PUVA therapy (PUVA cream) without the logistical requirements for bath tubs has recently been developed. OBJECTIVE: We sought to develop preparation and treatment standards to PUVA cream and to confirm its clinical efficacy in the treatment of various dermatoses. METHODS: In the first phase, the safety of a novel cream containing 0.002% 8-methoxypsoralen (8-MOP) was determined in six healthy volunteers. In a second phase, 40 patients with different dermatoses were treated with a minor concentration (0.001% 8-MOP), following the guidelines for topical PUVA of the British Photodermatology Group. RESULTS: Plasma levels of psoralen after the application of the novel cream containing 0.002% 8-MOP, were less than 34 ng/mL, the maximum 8-MOP concentration reported for topical PUVA. With a minor concentration (0.001% 8-MOP), important improvement or healing was found in 53.3% of the cycles, generally with a good response since the first month of treatment. Only mild side-effects were detected in 14 patients. CONCLUSIONS: Based on our data, PUVA cream photochemotherapy is well accepted by patients and may be a highly effective treatment even if previous therapy was unsuccessful. In addition, PUVA cream is easier to use than PUVA bath.

Spectrofluorometric determination of ibuprofen in pharmaceutical formulations.

The spectrofluorometric determination of ibuprofen in pharmaceutical tablets, creams and syrup is described. It involves excitation at 263 nm and emission at 288 nm. the linear range is 2-73 mg L(-1). Other drugs or excipients present in the different formulations do not interfere, except in the case of chlorzoxazone containing tablets. Due to its strong absorbance in the spectral range the chlorzoxazone does interfere, so that in this case the proposed method can't be applied.

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer.

PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Spectrofluorometric determination of piroxicam.

The spectrofluorometric determination of piroxicam [4-hydroxy-2-methyl-N-(2-pyridyl)-2II-1,2-benzothiazine-3-carboxam ide-1, 1-dioxide] in pharmaceutical tablets is described. It involves excitation at 330 nm of an acid solution (HNO3 0.5 M) of the drug, and measurement of the fluorescence intensity at 440 nm. The linear range is 0.01-1.25 micrograms ml-1.