Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

Ultrarapid high-dose course of prophylactic cranial irradiation in small-cell lung cancer: evaluation of late neurologic morbidity in 16 long-term survivors.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Radiation therapy in the elderly with head and neck cancer.

Head and neck cancer is quite common in the elderly, its most common origin being the larynx, oropharynx and oral cavity. In patients aged 70 and over, assessment of comorbidity and performance status is very important in order to establish the most suitable therapeutic approach, if feasible. Often radiation therapy is the only choice because the patient general condition may entail an excessively high risk for surgery. In the literature there are scarce studies focusing on radiation therapy and its complications, and only retrospective data are available: for this reason the Italian "Geriatric Radiation Oncology Group" (GROG) has planned a prospective study in order to collect the different results achieved in head and neck cancer treated in the same period with radiation therapy, or surgery or both.

Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients (P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

[Neoplasms of the gallbladder and the extrahepatic bile ducts: radio-chemotherapeutic combined treatment. Results in 18 treated cases]. / Neoplasie della colecisti e delle vie biliari extraepatiche: trattamento integrato radio-chemioterapico. Risultati in 18 casi trattati.

According to current literature, the main cause of death in patients with gallbladder (GB) and extrahepatic biliary ducts (EHBD) neoplasms is related to local and locoregional tumor spread rather than to distant metastases. Surgery, even when radical, is followed by a high number of relapses. That is why postoperative radiation therapy (RT) is usually combined with surgery. Alone, however, RT is not effective enough to markedly improve loco-regional control, considering that the adjacent organs would be damaged by higher doses. Referring to experimental studies published in the 1960s and relative to the biological effect of ionizing radiation with 5-Fluorouracil (5-FU) in slowing the pace of tumor growth, the Department of Radiotherapy, together with the Department of Medical Oncology in Padua General Hospital, began administering a combined surgical-chemo-radiotherapeutic protocol in January 1982, to January 1989. The protocol included 5-FU administration both 3 days before and during RT, after a surgical intervention as radical as possible. Eighteen patients were given this treatment. By the end of December 1989, 7 patients were alive--6 of them disease-free with a 26-month mean survival. Eleven patients died--7 due to local/loco-regional relapse, 1 from a distant metastasis, 1 from gastric hemorrhage, with no disease, and 2 from unknown causes. Overall mean survival in the two groups was 16 months. The combined treatment proved to be tolerable and feasible, even though severe complications were observed in 2 patients, 1 case of toxic death (gastric hemorrhage) and another with complete duodenal stenosis which required further surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Dosimetry of the bladder and the rectum: comparison between the measured and calculated dose (author's transl)]. / Dosimetria della vescica e del retto: confronto fra le dosi misurate e le dosi calcolate.

The authors examine 62 cases of curietherapy in the deep vagina on 21 cases of utero-vaginal applications and make a comparison between two dosimetric methods used to measure the dose to the rectum and to the bladder: the direct measure by the Siemens Gammameter dosimeter and the Chassagne-Horiot method. Very large differences were found between the doses evaluated by the two methods. The values with the direct measure were often found to be higher than the calculated ones. When the measurements were done by different doctors, the result was almost the same.