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Submitted by Paula Luz (pluz@ualg.pt) on 2022-01-03T16:39:42Z No. of bitstreams: 1 PICTuRE Real-world treatment pathways in stage III non-small cell lung cancer in Portugal.pdf: 98947 bytes, checksum: 90769cb7fae3ac3d8a98755f5be93bf8 (MD5) Approved for entry into archive by Filipa Custódio (fccustodio@ualg.pt) on 2022-01-10T14:33:49Z (GMT) No. of bitstreams: 1 PICTuRE Real-world treatment pathways in stage III non-small cell lung cancer in Portugal.pdf: 98947 bytes, checksum: 90769cb7fae3ac3d8a98755f5be93bf8 (MD5) Made available in DSpace on 2022-01-10T14:33:49Z (GMT). No. of bitstreams: 1 PICTuRE Real-world treatment pathways in stage III non-small cell lung cancer in Portugal.pdf: 98947 bytes, checksum: 90769cb7fae3ac3d8a98755f5be93bf8 (MD5) Previous issue date: 2021-12 AstraZeneca Portugal info:eu-repo/semantics/publishedVersion

Acute limb ischemia (ALI) is a serious medical emergency leading to high rate of complications, being not only limb- but even life-threatening, often despite early successful revascularization.1 Improvements in surgical techniques and perioperative patient care may have reduced the incidence of major complications in ALI patients over the years, but the results of trials published recently seem to document a persistent high risk, with reported 30-day amputation rate of 5% to 12%, mortality risk at 10% to 38%, combined incidence of amputation and death of 25% to 37.5%, at 1- to 6-month follow-up.2–7 Concomitant underlying diseases, the metabolic derangement that seems as a result of the acute insult, and a possible reperfusion injury following revascularization may account for this severe prognosis.8 Only anticoagulation, fasciotomy (when indicated), and perioperative supportive treatment are established strategies in ALI patients.1,8,9 Possible benefit from cardiovascular active therapies has recently been suggested in patients undergoing peripheral revascularization or noncardiac major surgical intervention.10,11 Moreover, several categories of compounds, potentially acting on pathobiological mechanisms of ischemia-reperfusion syndrome, have been tested in experimental models, but none of them has as yet been proven effective in clinical studies in patients with ALI.12–18 Because of their pharmacologic profile, prostanoids represent a potentially interesting category as adjuvant treatment of ALI patients.19 Several ischemia-reperfusion studies described the use of prostaglandins for reduction of postischemic tissue injuries, and even recently both PGE1 and PGI2 appeared as potent inhibitors of reflow-paradox in a preclinical model of reperfusion injury.20 Iloprost is a widely studied synthetic analogue of prostacyclin, with a 10-fold higher half-life than the native compound, and indicated in the treatment of severe chronic limb ischemia.1,21–23 Results from pilot studies and case reports also described the positive effects of iloprost in the management of acute ischemia secondary to various causes, particularly after accidental intra-arterial administration of drugs or toxic agents.24–26 Several preclinical studies have assessed the effects of iloprost in experimental ischemia-reperfusion injury and documented the actions of the compound on different pathophysiologic mechanisms potentially relevant for damage following ALI.27–32 A diagram indicating where iloprost can interfere in the mechanisms, leading from ischemia and reperfusion, to the development of no-reflow and reflow-paradox, is reported in Figure 1. 33 FIGURE 1. Pathobiological mechanisms leading from ischemia-reperfusion, to “no-reflow”/“reflow-paradox.” Points where iloprost can act are indicated (from de Donato et al33). Some years ago, we performed a placebo-controlled, double-blind pilot study in 30 patients with ALI undergoing Fogarty's thromboembolectomy. Encouraging results were obtained with the use of intraoperative and postoperative iloprost (lower incidence of major clinical events, more evident metabolic improvement by means of transcutaneous tensiometry).34 In this paper, we report the results of ILoprost in Acute Ischemia of Lower Limbs (ILAILL) study, a larger, multicenter trial including patients undergoing all types of surgical revascularization, who received iloprost or placebo administration during intervention and therefore for 4 to 7 days, and were observed for a 3-month postoperative period.

Objectives To evaluate the effects of iloprost, in addition to surgery, on the outcome of acute lower limb ischemia (ALLI). Design Post-hoc analysis of a randomized, double-blind, placebo-controlled study. Methods In the context of the ILAILL (ILoprost in Acute Ischemia of Lower Limbs) study, 192 elderly patients (>70 years old) undergoing surgery for ALLI were assigned to receive perioperative iloprost (intra-arterial, intra-operative bolus of 3000ng, plus intravenous infusion of 0.5–2.0ng/kg/min for six hours/day for 4–7 days following surgery), or placebo (iloprost: n =100; placebo: n =92). Patients were followed-up for three-months following surgical revascularization. Results The combined incidence of death and amputation (primary study end-point) was significantly reduced in patients treated with iloprost (16.0% vs 27.2% in the placebo group; hazard ratio 1.99, 95% confidence interval 1.05–3.75, p =0.03). A statistically significant lower mortality (6.0%) was reported in patients receiving iloprost, compared to controls (15.2%) (hazard ratio 2.93, 1.11–7.71, p =0.03). The overall incidence of death and major cardiovascular events was lower in patients receiving iloprost compared to those assigned placebo (24.0% and 35.9%, respectively), at the limits of statistical significance (relative risk 1.64, 0.97–2.79, p =0.06). Conclusions These results confirm the poor outcome in elderly patients with ALLI. Based on a subgroup analysis iloprost, as an adjuvant to surgery, appears to reduce the combined end-point of death and amputation.

Lung cancer is the most common form of cancer death in the world. Five-year survival is about 15%, without any change to this picture envisaged. It is the 3rd most prevalent type of cancer in Portugal and the primary cause of cancer death. 85% of lung cancer cases are attributable to smoking. One study performed in Portugal for 3 years (2000/2002) by the Lung Oncology Work Committee of the Portuguese Society of Pulmonology in 22 Hospitals showed that of a total of 4396 patients with lung cancer, 81.8% were male and 18.2% were female, with a mean age of 64.49 +/- 11.28 years. About 70% of patients were smokers or former smokers, with 50.3% of patients presenting with performance status (Zubrod) 1. Histologically, 37.5% were adenocarcinoma, followed by squamous carcinoma in 30.5% of cases, and small cell lung cancer in 12.5%; neuroendocrine carcinoma presented in 1.4% of cases; non small cell lung cancer in 10.5%; mixed carcinoma in 0.7%; large cell carcinoma in 2.3%; and others/not specified in 4.6% of cases. Staging (known in 4097 patients), showed 113 patients in stage IA (2.8%)and 250 patients in stage IB (6.1%); only 0.8% in stage IIA and 4.5% in stage IIB; 9.1% in stage IIIA and 29.9% in stage IIIB; 46.9% were already in stage IV by the time of diagnosis. The first therapeutic option was known in 3855 patients. Surgery was performed in 8.2% and 21.8% of cases were treated with combined therapies (surgery and chemotherapy or radiotherapy, or combination of chemotherapy and radiotherapy); chemotherapy alone was first choice in 43.7% of patients and in 20.3% only best support therapy was chosen.

Objective: The durability of carotid endarterectomy (CEA) may be affected by carotid restenosis. The data from randomized trials show that the highest incidence of restenosis after CEA occurs from 12 to 18 months after surgery. The optimal CEA technique to reduce perioperative complications and restenosis rates is still undefined. This study examines the long-term clinical outcome and incidence of recurrent stenosis in patients who undergo eversion CEA. Previously published perioperative results of this study did not show statistically significant differences in study endpoints between the eversion and standard techniques. Methods: From October 1994 to March 1997, 1353 patients with surgical indications for carotid stenosis were randomly assigned to undergo eversion (n = 678) or standard CEA (n = 675; primary closure, 419; patch, 256). Withdrawal from the assigned treatment occurred in 1.6% of the patients (in 13 assigned to eversion CEA, and in nine assigned to standard CEA). The clinical and duplex scan follow-up examination was 99% complete, and the mean follow-up interval was 33 months (range, 12 to 55 months). The primary outcomes were perioperative and late major stroke and death, carotid restenosis (stenosis ≥ 50% of the lumen diameter detected at duplex scanning), and carotid occlusion. The primary evaluation of study outcomes was conducted on the basis of an intention-to-treat analysis. Results: Restenosis was found at duplex scanning in 56 patients (19 in the eversion group, and 37 in the standard group). Within the standard group, the restenosis rates were 7.9% in the primary closure population and 1.5% in the patched population. Of the patients with restenosis, 36% underwent cerebral angiography that confirmed restenosis in all cases. The cumulative restenosis risk at 4 years was significantly lower in the group that underwent treatment with eversion CEA as compared with the standard group (3.6% vs 9.2%; P = .01), with an absolute risk reduction of 5.6% and a relative risk reduction of 62%. Eighteen patients would have had to undergo treatment with eversion CEA to prevent one restenosis during the 4-year period. The incidence rate of ipsilateral stroke was 3.3% in the eversion population and 2.2% in the standard group. There were no significant differences in the cumulative risks of ipsilateral stroke (3.9% for eversion, and 2.2% for standard; P = .2) and death (13.1% for eversion, and 12.7% for standard; P = .7)) in the two groups. Of the 18 variables that were examined for their influence on restenosis, eversion CEA (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.6; P = .0004) and patch CEA (hazard ratio, 0.2; 95% confidence interval, 0.07 to 0.6; P = .002) were negative independent predictors of restenosis with multivariate Cox proportional hazards regression analysis. Conclusion: The EVEREST (EVERsion carotid Endarterectomy versus Standard Trial) showed that eversion CEA is safe, effective, and durable. No statistically significant differences were found in late outcome between the eversion and standard techniques at the available follow-up examination. (J Vasc Surg 2000;31:19-30.)

Purpose: The EVEREST Trial was designed to determine whether the surgical technique influences the durability and complications of carotid endarterectomy (CEA). The current report focuses on the study design and preliminary results. Methods: EVEREST is a randomized multicenter trial. A total of 1353 patients with carotid stenosis requiring surgical treatment were randomly assigned to received standard (n = 675) or eversion (n = 678) CEA. Primary end points included carotid occlusion, major stroke, death, and restenosis rate. Results: The rate of perioperative major stroke and death (1.3 for each study group) and the incidence of early carotid occlusion (0.6% for eversion vs 0.4% for standard) were similar. No significant differences were found between eversion and standard CEA with respect to incidence of perioperative transient ischemic accident, minor stroke, cranial nerve injuries, neck hematoma, myocardial infarction, or surgical defects as detected with intraoperative quality controls. Clamping time was significantly shorter for eversion CEA compared with patch standard procedures (31.7 ± 15.9 vs 34.5 ± 14.4 minutes, p = 0.02). A shunt was inserted in 11% of patients undergoing eversion CEAs and in 16% of patients undergoing standard procedures. Overall 30-day events occurred in 13.3% of the eversion group and in 11.4% of the standard group ( p = 0.3). At a mean follow-up of 14.9 months (range, 1 to 38 months), 16 (2.4%) restenoses occurred in the eversion group and 28 (4.1%) occurred in the standard group (odds ratio, 0.56; 95% confidence interval, 0.3 to 1.1; p = 0.08). Conclusion: The preliminary results of the EVEREST Trial suggest that eversion CEA is a safe and rapid procedure with low major complication rates. No significant differences in restenosis rates were observed between eversion and standard CEA at the available follow-up. Longer-term results are necessary to assess whether the eversion technique influences the durability of CEA. (J Vasc Surg 1998;27:595-605.)