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Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy., Methods: we conducted a multi-regional survey on ctDNA testing practices in lung cancer patients., Results: Median time from blood collection to plasma separation was 50 min (20-120 min), median time from plasma extraction to ctDNA analysis was 24 h (30 min-5 days) and median turnaround time was 24 h (6 h-5 days). Four hundred and seventy five patients and 654 samples were tested. One hundred and ninety-two patients were tested at diagnosis, with 16% EGFR mutation rate. Among the 283 patients tested at disease progression, 35% were T790M+. Main differences in LB results between 2017 and 2018 were the number of LBs performed for each patient at disease progression (2.88 vs. 1.2, respectively) and the percentage of T790M+ patients (61% vs. 26%).

[This corrects the article DOI: 10.18632/oncotarget.21485.].

Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification., Competing Interests: CONFLICTS OF INTEREST The authors declare they have no conflicts of interest.

Background: Oral anticancer drugs are an attractive treatment option, even if patient-focused education and specific nursing staff are needed to support home care intervention. Our aim was to assess the feasibility of a nurse monitoring program for patients taking oral chemotherapy, and to evaluate the patients' approval of the program., Methods: At the beginning of oral chemotherapy treatment, outpatients completed a specific form so that we could assess their comprehension of the information related to therapy. Nurses gave patients a diary to record drug intake and toxicity at home, and phone calls were planned to evaluate toxicity or modification of the treatment plan during the first and second cycles of therapy. Finally, patients were requested to complete a specific form to express their level of agreement with the program., Results: Eighty-one patients were included in the analysis. Nurse intervention at the beginning of therapy resulted in an increased proportion of patients having received correct information related to treatment, with a level of confidence rising to more than 90% for all items considered. One hundred ninety-one of 243 planned phone calls were made, corresponding to 78.6% of the planned activity. The diary proved a valid tool for patients and 144 of 153 diaries were completed at home (94%). Only 5 patients (6%) had unplanned hospital admission for toxicity, probably because of early intervention by nursing staff. Only 2 out of 63 patients expressed a negative opinion, while the remaining patients expressed their approval of the program., Conclusion: Our model proved practicable and accepted by patients, thus supporting the role of nurse intervention in training and monitoring patients receiving oral chemotherapy.

We present the case of a 51-year-old woman with a follicular variant of papillary thyroid carcinoma. After surgery she experienced a relapse. Chemotherapy treatment led only to disease stabilization. In August 2009, we decided to start therapy with sunitinib 50 mg daily in an intermittent schedule (4 weeks on/2 weeks off). A CT scan after 3 months of treatment showed partial remission of disease according to the RECIST criteria. The patient continued sunitinib until January 2011, when CT evidenced progression in the mediastinal lymph nodes and pleura. Genetic analyses were carried out to determine if the clinical response in our patient was correlated with the presence of RET or BRAF mutations. No RET/PTC rearrangements or BRAF-V600E mutation, which are the two most common genetic alterations detected in papillary thyroid carcinoma, were found. It can be hypothesized that the activity of sunitinib in this patient was due to its antiangiogenic properties.

Aims and Background: When there is little hope of a clinical benefit, too delayed a withdrawal from chemotherapy might be detrimental for a patient's quality of life. We evaluated appropriately timed cessation of chemotherapy in our Oncology Department after integration of a Supportive and Palliative Care Unit., Methods: We carried out a review of deceased patients in our department from January 2006 to December 2009. Activities of the Supportive and Palliative Care Unit started in late 2007. We analyzed the characteristics of patients near the end of life and chemotherapy use within 30 days of death as an aggressiveness of cure index., Results: During the considered period, 361 hospitalized patients died: 69 in 2006, 77 in 2007, 97 in 2008 and 118 in 2009; 102 never received chemotherapy. Sixty-one of the remaining 259 patients died within 30 days of the last drug administration. The percentage of patients receiving chemotherapy in their last 30 days fell from 19% in 2006 and 20% in 2007, to 16% in 2008 and 14% in 2009., Conclusions: Supportive and Palliative Care Unit integration decreased chemotherapy use in the last 30 days of life. A careful evaluation of prognostic factors of advanced cancer patients and provision of appropriate supportive and palliative cares can reduce the use of futile anticancer chemotherapy and preserve a patient's qualify of life.

This study compares two cytotoxic regimens comprising the same dose and schedule of cisplatin (CP) plus vinorelbine (VNR) or gemcitabine (GEM) administered under the same schedule to patients with advanced non-small cell lung cancers (NSCLC). From April 1998 to February 2003, 285 patients were randomised to receive either VNR 25 mg/m(2) on days 1 and 8 as an intravenous (i.v.) bolus plus CP 75 mg/m(2) on day 1 (regimen A) or GEM 1200 mg/m(2) on days 1 and 8 as an i.v. 30-min infusion plus CP 75 mg/m(2) on day 1 (regimen B). Both treatments were recycled every 21 days. If no progression had occurred after six cycles, the patients continued to receive VNR or GEM monochemotherapy weekly. Cross-over of the two single agents was considered if disease progression occurred. Objective response (OR), time to progression (TTP) and overall survival (OS) were analysed according to the intention-to-treat principle. 272 patients were ultimately eligible (137 on A and 135 on B). Their main characteristics were: male/female ratio 214/58; median age 63 (range 32-77) years; median Karnofsky Performance Status (PS) 80 (range 70-100); stage IIIB 34%, stage IV 61%, recurrent disease 5%; histology - epidermoid 29%, adenocarcinoma 53%, other NSCLC 18%. The characteristics of the patients in the two arms were well matched. The following response rates were observed in regimens A and B, respectively: complete response (CR) 0.7% and 3.7%, partial response (PR) 31.9% and 22.2% (P = 0.321). Median CR+PR duration was 8 months in both arms. Clinical benefit represented by an improvement in symptoms was evident in 25.7% and 28.1%, respectively. Median TTP was 5 months in both arms and median OS 11 months in both arms. Grade III-IV neutropenia occurred in 30.7% and 17.7% of the patients in arms A and B, respectively (P = 0.017); thrombocytopenia occurred in 0% and 9.3% (P = 0.004), respectively. No difference in the incidence of anaemia was observed. Non-haematological toxicity was generally mild: a higher incidence of grade 1-2 peripheral neurotoxicity and grade 1-2 local toxicity with regimen A and grade 1-2 liver toxicity with regimen B was reported. A pharmaco-economic comparison showed a difference between the two doublets, principally due to the different costs of VNR and GEM. Under the study conditions the combination of VNR or GEM with the same dose and schedule of CP produced similar OR, clinical benefits, TTP and OS in advanced NSCLC, and only mild toxicological differences were observed. Pharmaco-economic evaluation favoured the CP + VNR doublet.

Background: High dose Epirubicin (HD-EPI) (>90 mg/m2) and Vinorelbine (VNR) demonstrated antitumor activity as single agent (about 20%) in the treatment of advanced NSCLC. This trial compares these two agents combined with cisplatin (CP)., Patients and Methods: From August 1992 to February 1996, 228 patients with locally advanced or metastatic NSCLC were randomized to receive either EPI 120 mg/m2 as i.v. bolus plus Cisplatin (CP) 60 mg/m2 on day 1 (regimen A) or VNR 25 mg/m2 as i.v. bolus on day 1 and 8 plus CP 60 mg/m2 on day 1 (regimen B). Both treatments were recycled every 21 days up to a maximum cumulative dose of EPI of 840 mg/m2 or 12 cycles. Eligible patients were 212 and 198 patients were evaluable for objective response (95 in arm A and 103 in arm B). The main characteristics of eligible patients were: male/female 179/33; median age 61 (42-72); median Karnofsky PS 80 (70-100); stage IIIA 12%, stage IIIB 40%, stage IV 41%, recurrence 7%; histotype: epidermoid 48%, adenoca 36%, others 16%., Results: The following response rates were observed in regimens A and B, respectively; CR, 1 and 2%, PR, 32 and 25% (P = 0.4567). Median CR + PR duration was 9 and 8 months, respectively. Median survival was 10.5 and 9.6 months, respectively. Grade III-IV leucopenia occurred in 38 and 21% in arm A and arm B, respectively(P = 0.01), thrombocytopenia in 6 and 0% (P = 0.02), anemia in 8 and 7% (n.s.). Non-hematological toxicity was moderate and the only difference between the treatments was alopecia (88 vs. 33% in arm A and B, respectively). Supraventricular arrhythmia occurred in three patients on regimen A; a >15% LVEF absolute decrease was observed in 9 (22.5%) and three (14%) patients on arm A and arm B, respectively (n.s.). No congestive heart failure was observed., Conclusion: HD-EPI+CP and VNR+CP are both active combinations in advanced NSCLC with a similar response rate, response duration and survival but regimen A was significantly more toxic (myelosuppression and alopecia).