Integrating Liquid Biopsy and Radiomics to Monitor Clonal Heterogeneity of EGFR-Positive Non-Small Cell Lung Cancer

Background: EGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient’s follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment. Case presentation: In this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p <0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis. Conclusion: To our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - An observational study in 29 countries

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (V T) size was 500 ml, or 7 to 9 ml kg−1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P ˂ 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P ˂ 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high V T and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome.</p

Radioguided Surgery, a Cost-Effective Strategy for Treating Solitary Pulmonary Nodules: 20-Year Experience of a Single Center

Solitary pulmonary nodules are an increasingly common finding worldwide. When surgery is requested for a definitive diagnosis, the international guidelines agree that minimally invasive surgery should be performed. However, can be difficult to localize small, deep, or subsolid nodes during minimally invasive surgery. This large observational cohort study shows that radioguided surgery is a cost-effective strategy with a low conversion rate

Thyroid blood flow evaluation by color-flow Doppler sonography distinguishes Graves' disease from Hashimoto's thyroiditis.

Thyroid hypoechogenicity at ultrasound is a characteristic of autoimmune thyroid diseases, with an overlap of this echographic pattern in patients affected by Graves' disease or Hashimoto's thyroiditis. Aim of the present paper was to study the thyroid blood flow (TBF) by color-flow doppler (CFD) and peak systolic velocity (PSV) at the inferior thyroid artery in 37 Graves' and 45 goitrous Hashimoto's thyroiditis patients. CFD pattern was defined as normal (or type 0): TBF limited to peripheral thyroid arteries (PSV = 17.7 +/- 3 cm/sec, mean +/- SD); type I: TBF mildly increased; type II: TBF clearly increased; type III: TBF markedly increased. The CFD was in direct relationship to the PSV. Out of 18 patients with Graves' disease and untreated active hyperthyroidism CFD pattern was type III in 17 and type II in 1. The PSV was 42.1 +/- 15 cm/sec. In 17 patients euthyroid under methimazole, the CFD pattern was type 0 in 3 (17%) type I in 5 (30%), type II in 5 (30%), type III in 4 (23%). In this group of Graves' patients the PSV was 36 +/- 14 cm/sec. In two patients, hypothyroid after radioiodine treatment, the CFD pattern was type 0 in 1 and type I in 1. In the group of Hashimoto's patients TBF was in no relationship with thyroid status or treatment and was type 0 in 22 (49%), type I in 20 (44%), type II in 3 (7%), while none had type III CFD pattern. Thyroid hypoechogenicity at ultrasound was present in 32/37 (86%) Graves' and 41/45 (91%) Hashimoto's patients. All the four patients with Hashimoto's thyroiditis and normal thyroid ultrasound pattern had also a normal CFD pattern, while 4/5 patients with Graves' disease and normal echographic pattern had an increased TBF. In conclusion, a diffusely increased thyroid blood flow is pathognomonic of untreated Graves' disease and an abnormal CFD pattern identifies the majority of Graves' patients with a normal thyroid ultrasound pattern. Thus, CFD sonography may be useful in distinguishing patients with Graves' disease and Hashimoto's thyroiditis having a similar thyroid echographic pattern at ultrasound

Long-Term Results of Radiofrequency Ablation Treatment of Stage I Non-small Cell Lung Cancer: A Prospective Intention-to-Treat Study

Introduction: About one-fifth of patients with resectable non-small cell lung cancer (NSCLC) are unsuitable for surgical treatment. Radiofrequency ablation offers an alternative minimally invasive option. We report the result of an intention-to-treat study with long-term follow-up. Methods: From 2001 to 2009, we performed 80 percutaneous radiofrequency ablations of 59 stage I NSCLC in 57 inoperable patients. Two patients were treated for two separate lesions. The study group consisted of 45 males and 12 females, with mean age of 74 years (range, 40-88 years). All patients had pathological evidence of NSCLC, which was in stage IA in 44 cases and in stage IB in the other 15 cases. The mean size of the lesions was 2.6 cm (range, 1.1-5 cm). Fourteen lesions were retreated up to five times. The procedure was always performed under local anesthesia and conscious sedation. Most of the procedures were performed under computed tomography guidance, with nine under ultrasonography guidance. Results: In all cases, the procedure was technically successful. No mortality was recorded, and major morbidity consisted of four cases of pneumothorax requiring pleural drainage. At a mean follow-up of 47 months, the complete response rate was 59.3% (stage Ia 65.9%, stage Ib 40%, p = 0.01), with a mean local recurrence interval of 25.9 months. Median overall survival and cancer-specific survival were 33.4 and 41.4 months, respectively. Cancer-specific actuarial survival was 89% at 1 year, 59% at 3 years, and 40% at 5 years. Conclusions: Radiofrequency ablation treatment of early-stage NSCLC seems to be a effective minimally invasive therapy even in the long-term period, particularly for stage Ia tumors. Copyright © 2011 by the International Association for the Study of Lung Cancer

Usefulness of echo-color Doppler in differentiating parathyroid lesions from other cervical masses

The aim of our study was to clarify possible differential color Doppler US features between parathyroid lesions and other cervical masses. A total of 56 parathyroid lesions in 54 patients with primary hyperparathyroidism were preoperatively examined with color Doppler sonography. Color Doppler flow patterns were compared with those of 72 thyroid nodules and 20 cervical lymph nodes. In 38 parathyroid lesions a correlation between color Doppler patterns and size, location, and pathological findings was performed. Color Doppler sonography showed five vascular distribution patterns: pattern I, absence of flow; pattern II, focal peripheral flow ("vascular pole") with arterial Doppler spectrum; pattern III, peripheral flow; pattern IV, internal flow ("parenchymal pattern"); pattern V, peripheral and intranodular flow. Pattern I was not specific for any cervical lesion considered. Conversely, pattern IV was observed solely in parathyroid lesions, and pattern II was observed in only one nonparathyroid lesion (thyroid nodule). Mixed pattern (pattern V) was observed solely in thyroid nodules. In addition, pattern III was a characteristic finding of thyroid nodules and was observed in only one parathyroid lesion. Color Doppler patterns of the parathyroid masses did not correlate with the size of the lesion or pathological findings, but only with the location of the gland. Our study showed that color Doppler assessment of parathyroid lesions is a useful integration of gray-scale US and may be helpful in distinguishing parathyroid lesions from other cervical masse