Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale

PURPOSE: we carried out a phase III randomized trial to compare vinorelbine-cisplatin regimen to gemcitabine-cisplatin regimen, and to a sequential administration of gemcitabine-ifosfamide followed by vinorelbine-cisplatin or the opposite sequence of vinorelbine-cisplatin followed by ifosfamide-gemcitabine according to the 'worst drug rule' hypothesis in patients with locally advanced unresectable stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoint was survival parameters, while secondary endpoints included analysis of response rates and toxicity. PATIENTS AND METHODS: patients were randomized to receive: (a) gemcitabine 1000 mg/m(2) on days 1, 8 and 15 plus ifosfamide 1500 mg/m(2) on days 8-12 with mesna uroprotection (GI regimen) followed by vinorelbine 25 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 (GI --> VC regimen); (b) the opposite sequence (VC --> GI); (c) vinorelbine plus cisplatin as above described (VC regimen); or (d) gemcitabine 1400 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 8 (GC regimen). All regimens were given every 4 weeks. All patients were chemotherapy naive and had a ECOG PS 0-2. RESULTS: 400 patients were enrolled into the trial. Interim analysis after inclusion of 243 patients showed that ORR were 19% in the GI --> VC arm, 32% in the inverse sequence arm (CV --> GI), 42% in the VC arm, and 30% in the GC arm. The VC arm was statistically superior over the GI --> VC arm (p = 0.0074), but not over the other regimens. Median TTP was 3.1 months in the GI --> VC arm versus 5.0 months in the VC --> GI arm (p = 0.014). For these reasons the GI --> VC and VC --> GI arm were closed since the 'worst drug rule' hypothesis was rejected. Accrual in the VC and GC arms continued up to 140 and 138 patients respectively. Final ORR were 44% for the VC regimen (4 CR), and 34% for the GC regimen (1 CR). This difference was statistically significant (p = 0.032). OS was 9.0 and 8.2 months, respectively, with no statistically significant difference. The 1-year survival rate was 24 and 20%, respectively for VC and GC regimens. As expected the incidence of phlebitis was higher in the VC arm, while thrombocytopenia, flu-like syndrome and asthenia were more frequent in the GC arm. CONCLUSIONS: the results of this trial indicate that the combination of vinorelbine and cisplatin and that of gemcitabine and cisplatin are equivalent in terms of median TTP and OS, although the vinorelbine-cisplatin regimen is associated with a higher ORR. Both regimens may be considered as reference treatments for future studies. Moreover, our data reject the 'worst drug rule' hypothesis of sequential treatments in NSCCL at least with the combination used in this study.     

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): a multicentre phase II clinical trial

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37-73) and a median ECOG performance status of 1 (range 0-2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m(2) diluted in 250 cc(3) of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m(2) on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3-7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22-52%) had a partial response for an overall response rate of 40% (95% CL 26-56%). Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3-4 neutropenia was recorded in 22% of cases, grade 1-3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.     

Quality of decision aids developed for women at average risk of breast cancer eligible for mammographic screening: Systematic review and assessment according to the International Patient Decision Aid Standards instrument

Mammographic screening contributes to a reduction in specific mortality, but it has disadvantages. Decision aids are tools designed to support people's decisions. Because these aids influence patient choice, their quality is crucial. The objective of the current study was to conduct a systematic review of decision aids developed for women eligible for mammographic screening who have an average breast cancer risk and to assess the quality of these aids. The systematic review included articles published between January 1, 1997, and August 1, 2019, in the PubMed, Embase, Cochrane, and PsycInfo databases. The studies were reviewed independently by 2 reviewers. Any study containing a decision aid for women eligible for mammographic screening with an average breast cancer risk was included. Two double-blind reviewers assessed the quality of the selected decision aids using the International Patient Decision Aid Standards instrument, version 3 (IPDASi). Twenty-three decision aids were extracted. Classification of decision aid quality using the IPDASi demonstrated large variations among the decision aids (maximum IPDASi score, 188; mean ± SD score, 132.6 ± 23.8; range, 85-172). Three decision aids had high overall scores. The 3 best-rated dimensions were disclosure (maximum score, 8; mean score, 6.8), focusing on transparency; information (maximum score, 32; mean score, 26.1), focusing on the provision of sufficient details; and probabilities (maximum score, 32; mean score 25), focusing on the presentation of probabilities. The 3 lowest-rated dimensions were decision support technology evaluation (maximum score, 8; mean score, 4.3), focusing on the effectiveness of the decision aid; development (maximum score, 24; mean score, 12.6), evaluating the development process; and plain language (maximum score, 4; mean score, 1.9), assessing appropriateness for patients with low literacy. The results of this review identified 3 high-quality decision aids for breast cancer screening.     

Covid-19 Infection in Cancer Patients: The Management in a Diagnostic Unit

BackgroundCOVID-19 infection is particularly aggressive in frail patients, as cancer patients. Therefore, the more suitable management of the oncological patient requires a multidisciplinary assessment, to identify which patients should be treated, as inpatients or outpatients, and which treatments can be procrastinated.ConclusionsThe role of radiologist is crucial, and, all cancer patients who need an imaging evaluation will need to be studied, using the most appropriate imaging tools related to the clinical question and paying a special attention to preserve public health. Guidelines are necessary in the correct organization of a radiology unit to manage patients with suspected or confirmed COVID-19 infection, and whenever possible, a satellite radiography center with dedicated equipment should be used to decrease the transmission risk.Key words: COVID-19 infection, cancer patients, diagnostic unit, management, guideline     

Thymectomy in myasthenia gravis via original video-assisted infra-mammary cosmetic incision and median sternotomy: long-term results in 180 patients

Objective: The clinical outcome of 180 non-thymomatous myasthenia gravis (MG) consecutive cases surgically treated is reported herein. The original surgical access, consisting of a video-assisted infra-mammary cosmetic incision and median sternotomy, has originally been designed and described by our group. Methods: The in-hospital patients’ charts and the outpatients’ clinic follow-up information of the 180 cases have been extensively reviewed. In addition to the strictly surgical benchmark referral, data on the rate of cure of the MG (complete stable remission – CSR; pharmacological remission – PR) as indicated by the Myasthenia Gravis Foundation of America (MGFA) have been analysed as recorded at the 12 months after surgery checkpoint. Cosmetic outcome was evaluated as well. Results: Female to male ratio was 156 (86.7%):24 (13.3%). Mean age: 29.1 ± 10.9 years. Preoperative MGFA score: stage I: 4 patients (2.2%); IIa: 57 (31.7%); IIb: 32 (17.8%); IIIa: 41 (23.3%); IIIb: 42 (23.3%); IVa: 2 (1.1%); V: 2 (1.1%). Median operative time was 110 min (70–130 min) and median postoperative hospital stay was 4 days (3–10 days). Postoperative mortality was nil and morbidity occurred in seven patients (3.8%). Final pathology was consistent with: 146 hyperplastic thymus (81.1%); 28 involuted thymus (15.6%) and 6 normal thymus (3.3%). Ectopic thymic tissue was found in 68% of the patients. Mean follow-up was 62.9 ± 34.6 months. A CSR was obtained in 55%; PR in 18.3%; improvement in 39.9%, unchanged in 3.5%, worse in 1.1% and died in 0.5%. Kaplan–Meier estimates of CSR were 34.1% and 75.8% at 5 and 10 years, respectively. The preoperative therapy was the only parameter significantly associated with Kaplan–Meier CSR rates (univariate analysis – p < 0.001). Remarkably, 171 (95%) patients judged their cosmetic results to be excellent or very good. Conclusions: Thymectomy in MG patients via video-assisted infra-mammary cosmetic incision and median sternotomy has shown to be a useful surgical approach as demonstrated by the good functional and very good aesthetic results, associated with a very low morbidity and no mortality. Patients with preoperative mono-therapy have higher CSR rates. CSRs are durable, as the CSR rate improves with extended follow-up.     

Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy

A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin. Two population-based dosing methods (population clearance method and bayesian feedback method) and one individual-based method (the so-called linearized Michaelis-Menten method) were evaluated, when applicable, for single-point and/or 2-point dose predictions of phenytoin. In single-point predictions, we found a generally low percentage of dose calculations falling inside the +/- 10% range (48.9% and 51.1% for the population clearance and the bayesian methods, respectively). In 2-point predictions, the bayesian method was 'accurate' (dose within the +/- 10% range) in approximately 54.3% or 55.0% of cases (depending on the particular method of implementation adopted). An even worse percentage of 'accurate' dose predictions (38.3%) was obtained by using the linearized Michaelis-Menten method. Our data do not confirm results from previous studies indicating a generally good performance of pharmacokinetic methods for predicting phenytoin dosage.     

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers (?n = 111) and non-carriers (?n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups (?p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.     

Positive end-expiratory pressure delays the progression of lung injury during ventilator strategies involving high airway pressure and lung overdistention

OBJECTIVE: Many studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury. DESIGN: Prospective, randomized laboratory animal investigation. SETTING: The University Laboratory of Ospedale Maggiore, Milano, IRCCS. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats. INTERVENTIONS: Three groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H(2)O) and PEEP of 3 and 6 cm H(2)O and a similar index of lung overdistension (Paw(p)/P(100) congruent with 1.1; where Paw(p) is peak airway pressure and P(100) is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained. RESULTS: Rats were ventilated with comparable high airway pressure (Paw(p) of 42.8 +/- 3.1, 43.5 +/- 2.6, and 46.2 +/- 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Paw(p)/P(100) - index of overdistension: 1.17 +/- 0.2, 1.06 +/- 0.1, and 1.19 +/- 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 +/- 14 mins and 60 +/- 17) as compared with zero end-expiratory pressure (18 +/- 3 mins, p <.001). CONCLUSION: These findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to "buy time" in the progression of lung injury.