Patients' survival after free flap reconstructive surgery of head and neck squamous cell carcinoma : a retrospective multicentre study

Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the Head & Neck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival

Evaluation of the presence of 2-LTR HIV-1 unintegrated DNA as a simple molecular predictor of disease progression.

In a preliminary cross-sectional analysis of 109 human immunodeficiency virus type 1 (HIV-1)-infected subjects the presence of 2-long terminal repeat (LTR) unintegrated circular HIV-1 DNA in peripheral blood mononuclear cells (PBMC) was found to be associated with both symptomatic infection (P = 0.0037) and low CD4 counts (P = 0.0004). To investigate the prognostic significance of the presence of 2-LTR HIV-1 DNA, a subset of 23 2-LTR-negative and 25 2-LTR-positive asymptomatic individuals were followed up for 12-24 months. The two groups did not differ in terms of baseline CD4 counts, zidovudine (ZDV) therapy, and duration of HIV-1 infection. Longitudinal analysis of CD4 values did not indicate a significantly different CD4 outcome between the two groups. However, when only ZDV-treated subjects were considered, a significant (P = 0.042) decrease in CD4 counts was found at month 24 with respect to baseline in 2-LTR-positive (n = 12) but not in 2-LTR-negative (n = 11) patients. Moreover, when > 40% CD4 loss from baseline and/or development of CDC stage B or C symptoms were considered as indicators of disease progression, there was a significantly higher number of events in the whole 2-LTR-positive group than in the whole 2-LTR-negative group (P = 0.0197 at month 12, P = 0.0299 at month 18, P = 0.0373 at month 24). Thus, the presence of 2-LTR HIV-1 DNA in PBMC merits further investigation as a simple, qualitative, molecular predictor of disease progression and decreased response to antiretroviral therapy

EFFICACY AND SAFETY PROFILE OF DASATINIB IN A SUBSET OF VERY ELDERLY PATIENS WITH CHRONIC MYELOID LEUKEMIA (CML) RESISTANT/INTOLERANT TO IMATINIB

Dasatinib is a second generation TK inhibitor active in CML resistant and/or intolerant to imatinib. Data on efficacy and safety profile in “very elderly”patients (age >75 yrs) are scanty. We studied 28 patients with CP-CML treated with dasatinib when aged >75 yrs at 16 Centers. Median age at diagnosis was 72.3 yrs (IR 62.8-83.9). Male/female ratio was 1.33 (M=16, F=12); Sokal risk was calculated in 20/28 cases (low risk n=4, intermediate n=12, high n=4). Twenty-four patients (85.7%) received a treatment before imatinib. Imatinib starting dose was 400 mg/day in 21 cases (75%) and median period of therapy was of 36.6 months (IR 2.8- 71.3). Cause of imatinib failure was primary resistance in 15 patients (53.6%), secondary resistance in 11 (39.3%) and intolerance in 2 (7.1%). Median age at dasatinib start was 79.3 years (IR 75.0-76.5), with a median time from diagnosis of 76.4 months (IR 4.7 - 173.9). Eleven patients (39.3%) have received a second-line treatment after imatinib stop. Baseline BCR/ABL mutational status was evaluated in 11 cases: 4 displayed no mutation; 3 cases had M244V; M315T, E494G, V299L were present in 1 case each; 1 case presented M351T and F317L. Twenty-three patients had at least one co-morbidity, and median number of concomitant medicaments was 3.5 (IR 1-11). Dasatinib was started at 140 mg/day in 12/28 cases (42.8%), 100 mg in 8 (28.6%), ≥50 mg in 8 (28.6%). After a median treatment period of 18.1 months (IR 0.9-39.8 ), grade 3-4 toxicity was evaluated: 5/28 patients (17.8%) showed hematological toxicity (140 mg n=2; 100 mg n=1; 50 mg n=2); 11 (39.3%) extra-hematological toxicity (140 mg n=6, 100 mg n=2, 50 mg n=3). Seven patients (25%) presented serosal effusions (SE): WHO grade 1-2 in 5 cases (17.8%; 4 cases 140 mg, 2 cases 50 mg); grade 3-4 in 2 (7.1%) (1 case 140 mg, 1 case 50 mg). Sixteen patients (57.1%) underwent dose reduction: of the patients treated with 140 mg (n=12), 11 had a dose reduction vs. 5 reductions in the 16 cases receiving ≤100 mg (P=0.005). Nine patients discontinued dasatinib for ≤6 weeks, while 7 (25%) permanently discontinued therapy: 3 (10.7%) due to drug-related toxicity (n=1 with 100 mg and gastrointestinal toxicity; n=2 with 50 mg and SE, grade 2 and grade 3 respectively), 4 (14.3%) for emergency of a T315I mutation, after a median of 11 months of treatment. Response to treatment was assessable in 24/28 patients (85.7%): 14 (53.8%) had a cytogenetic response (CCyR in 9 cases, PCyR in 3 and minCyR in 2); of these, 5 attained also a molecular response. Nine patients (57.5%) reached at least a complete hematological remission. One case (4.1%) was resistant. The mean Overall Survival and Event Free Survival of the whole cohort were 24.2 and 14.3 months respectively. The present analysis shows that dasatinib may have a major role in the treatment of very elderly patients resistant/intolerant to imatinib; moreover dasatinib 100 mg showed great efficacy and a favorable safety profile in pretreated patients