Liquid biopsies in lung cancer: The new ambrosia of researchers

In the last decades the approach to cancer patient management has been deeply revolutionized. We are moving from a "one-fits-all" strategy to the "personalized medicine" based on the molecular characterization of the tumor. In this new era it is becoming more and more clear that the monitoring of the disease is fundamental for the success of the treatment, thus there is the need of new biomarker discovery. More precisely in the last years the scientific community has started to use the term "liquid biopsy". A liquid biopsy is a liquid biomarker that can be easily isolated from many body fluids (blood, saliva, urine, ascites, pleural effusion, etc.) and, as well as a tissue biopsy, a representative of the tissue from which it is spread. In this review we will focus our attention on circulating tumor cells, circulating tumor DNA, exosomes and secretomes with the aim to underlie their usefulness and potential application in a clinical setting for lung cancer patient management

Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice

Exosomes are nano-sized vesicles of endolysosomal origin, released by several cytotypes in physiological and pathological conditions. Tumor derived exosomes, interacting with other cells of the tumor microenvironment, modulate tumor progression, angiogenic switch, metastasis, and immune escape. Recently, extracellular vesicles were proposed as excellent biomarkers for disease monitoring and prognosis in cancer patients. Non-small cell lung cancer (NSCLC) has a poor 5-year survival rate due to the delay in the detection of the disease. The majority of patients are diagnosed in an advanced disease stage. Exosomes might be promising beneficial tools as biomarker candidates in the scenario of NSCLC, since they contain both, proteins and miRNAs. The clinical case reported in this manuscript is a proof of concept revealing that NSCLC exosomes and sorted miRNAs might constitute, in a near future, novel biomarkers. This review summarizes the role of exosomes in NSCLC, focusing on the importance of exosomal microRNAs in lung cancer diagnosis and prognosi

A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m2, paclitaxel 85 mg/m2, and topotecan 2.25 mg/m2weekly, with G-CSF (5 μg/kg days 3–5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65–92%] ORR. At a 13-month (range, 4–26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches. © 2001 Cancer Research Campaign http://www.bjcancer.co

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention

<p>Abstract</p> <p>Background</p> <p>There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.</p> <p>Methods</p> <p>Medical charts of all patients in the Segal Cancer Centre aged 65 and over were screened and evaluated for inclusion. Several strategies to facilitate recruitment and retention were implemented. Reasons for exclusion, refusal and loss to follow-up were recorded. Descriptive statistics were used to report the reasons for refusal and loss to follow-up. A non-response analysis using chi-square tests and t-tests was conducted to compare respondents to those who refused to participate and to compare those who completed the study to those who were lost to follow-up. A feedback form with open-ended questions was administered following the last interview to obtain patient's opinions on the length of the interviews and conduct of this pilot study.</p> <p>Results</p> <p>3060 medical charts were screened and 156 eligible patients were identified. Of these 112 patients participated for a response rate of 72%. Reasons for refusal were: feeling too anxious (40%), not interested (25%), no time (12.5%), too sick (5%) or too healthy (5%) or other reasons (5%). Ninety-one patients participated in the six-month follow-up (retention 81.3%), seven patients refused follow-up (6.2%) and fourteen patients died (12.5%) during the course of the study. The median time to conduct the baseline interview was 45 minutes and 57% of baseline interviews were conducted at home. Most patients enjoyed participation and only five felt that the interviews were too long.</p> <p>Conclusion</p> <p>It was feasible to recruit newly-diagnosed cancer patients prior to treatment although it required considerable time and effort. Once patients were included, the retention rate was high despite the fact that most were undergoing active cancer treatment.</p

Myelotoxicity from cytostatic treatment, an important risk factor in the management of neoplasias in the elderly

Myelotoxicity is the most common complication of cancer chemotherapy. A brief review of hematopoiesis is necessary to understand the mechanisms of myelotoxicity and the treatment strategies that may minimize this complication in elderly patients. From this review of hematopoiesis and age, we may draw three conclusions: aging is associated with a progressive reduction in hematopoietic reserve; by itself, the decline in hematopoietic reserve does not produce abnormalities of the circulating blood, these may occur as a consequence of hematopoietic stress; hematopoietic growth factors are effective in promoting granulopoiesis and erythropoiesis in older individuals. Alternative strategies include reduction of chemotherapy doses, the use of prophylactic oral antibiotics and antifungal agents for the prevention of neutropenic infections, and blood transfusions for the management of anemia

Metronomic therapy irinotecan (IRI) capecitabine (CAP) plus bevacizumab (BEV) in treatment of advanced colorectal cancer (ACRC) in very elderly people.

Background: ACRC is one of most common neoplastic disease in very old pts. The administration of oral fluoropyrimidine (capecitabine-CAP) in a standard schedule of 1,200 mg/sqm twice a day for 14 d shows similar effects to 5-FU continuous infusion (C.I.). Furthermore, CAP- IRI showed super -additive antitumor activity. Recently many study show the safety and efficacy of a "flat dose" administration of CAP particularly in the treatment of elderly people with cancer. Also, the efficacy of BEV is well demonstrated in CRC pts. Aim of the study is to evaluate impact of bevacizumab (BEV) in combination with IRI and XEL in ACRC very old patients. Methods: 42 (20 f-22 m) elderly patients with advanced colorectal cancer (median age: 77; range: 73-91) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. All Patients were included into groups I, according to Balducci's classification of frailty. Primary endpoint: clinical response rates (RR) according to RECIST criteria and toxicity profile using NCI-CTC v2.0. Secondary endpoints: PFS, OS and QoL score measured through EORTC QLQ-C30 questionnaires. All patients were evaluated for common treatment-related adverse events with regard to haematological and liver toxicity, nausea and vomiting, stomatitis, diarrhea, hand/foot syndrome and sensory neuropathy, according to the ECOG Common Toxicity Criteria. Results: Patients were treated with IRI (180 mg/mq) + BEV (7.5 mg/Kg) on day 1q21, and XEL (fixed dose of 1,000 mg bid) assumed orally continuously for a maximum of 12 cycles. Medium value of cycles delivered was 9.7. Tumor response rates observed were 37.1% (CR+PR). Clinical benefit, including stable disease, was 77.8%. No grade 4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 22 months with a 12 months survival probability of 77.8%. Conclusions: In elderly ACRC BEV plus IRI every 3 weeks with CAP continuously show a good toxicity and effectiveness profile and seem to be a valid terapeutical opportunity also for ACRC very old patients