Is Lobectomy Actually Worse Than Segmentectomy for All Stage I Non-Small Cell Lung Cancer?

INTRODUCTION: The recent results of the JCOG 0802 and CALGB 140503 studies suggest that segmentectomy should be considered instead of lobectomy for patients with peripheral <2 cm node-negative non-small cell lung cancer (NSCLC). This study aimed to test this hypothesis in a retrospective analysis of a larger dataset of patients with stage I NSCLC recorded in the Surveillance, Epidemiology, and End Results database. METHODS: Patients with all stage I NSCLC (≤4 cm in size) who underwent either segmentectomy or lobectomy from 2000 to 2017 were analyzed. The primary endpoints were overall survival and lung cancer-specific survival, while the secondary endpoints were the 30-day and 90-day mortality. RESULTS: Overall, 32,673 patients treated by lobectomy and 2166 patients treated by segmentectomy were included in the initial data collection. After 1:1 propensity score matching (PSM), 2016 patients in each group were enrolled in the final analysis with well-balanced baseline characteristics. After PSM, there was no difference between segmentectomy and lobectomy for all stage IA NSCLC (≤3 cm in size) in both overall survival and lung cancer-specific survival (hazard ratio: 0.87 [0.74-1.02], P value: 0.09 and hazard ratio: 0.81 [0.4-1.03], P value: 0.09, respectively). Furthermore, lobectomy had higher 30-day mortality than segmentectomy: 1.1% versus 2.1%, P value: 0.01. However, this difference was not significant for 90-day mortality, even after PSM (3.9% versus 3.0%, P value: 0.17). CONCLUSIONS: We found no evidence to support the use of lobectomy rather than segmentectomy in stage IA NSCLC in terms of either overall or lung cancer-specific long-term survival. The choice of lobectomy may also be detrimental to early postoperative recovery.

The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios.

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.

Lung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle aspiration for solid noncalcified, subsolid and mixed pulmonary nodules.

PURPOSE: The aim of this study was to analyse factors predicting the diagnostic accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with particular attention to those responsible for false negative results with a view to suggesting a method for their correction. MATERIALS AND METHODS: From January 2007 to March 2010, we retrospectively reviewed the CT images of 198 patients of both sexes (124 males and 74 females; mean age, 70 years; range age, 44-90) used for the guidance of TTFNA of pulmonary nodules. Aspects considered were: lesion size and density, distance from the pleura, and lesion site. Multiplanar reformatted images (MPR) were retrospectively obtained in the sagittal and axial oblique planes relative to needle orientation. RESULTS: The overall diagnostic accuracy of TTFNA CT-guided biopsy was 86% for nodules between 0.7 and 3 cm, 83.3% for those between 0.7 and 1.5 cm, and 92% for those between 2 and 3 cm. Accuracy was 95.1% for solid pulmonary nodules, 84.6% for mixed nodules, and 66.6% for subsolid nodules. The diagnostic accuracy of CT-guided TTFNA in relation to the distance between the nodule and the pleural plane was 95.6% for lesions adhering to the pleura and 83.5% for central ones. The diagnostic accuracy was 84.2% for the pulmonary upper lobe nodules, 85.3% for the lower lobe and 90.9% for those in the lingula and middle lobe. In 75% of false negative and inadequate/insufficient cases the needle was found to lie outside the lesion, after reconstruction of the needle path by MPR. CONCLUSIONS: The positive predictive factors of CT-guided TTFNA are related to the nodule size, density and distance from the pleural plane. The most common negative predictive factor of CT-guided TTFNA is the wrong position of the needle tip, as observed in the sagittal and axial oblique sections of the MPR reconstructions. The diagnostic accuracy of CT-guided TTFNA can therefore be improved by using the MPR technique to plan the needle path during the FNA procedure.

Cardiac autonomic and cortisol stress responses to real operations in surgeons: relationship with individual psychobiological characteristics and experience.

BACKGROUND: Surgeons are exposed to high levels of intraoperative stress, which could compromise their psychological well-being in the long term. This study aimed at exploring the effects of real operations on the activity of stress response systems (i.e., cardiac autonomic function and hypothalamic-pituitary-adrenal axis) during and in the aftermath of surgery, and the moderating role of individual psychobiological characteristics and different levels of experience (senior vs expert surgeons). METHODS: Heart rate, heart rate variability, and salivary cortisol measures (as indexes of cardiac autonomic and hypothalamic-pituitary-adrenal axis activity, respectively) were assessed during real operations and in the perioperative period in a sample of surgeons (n = 16). Surgeons' psychometric characteristics were collected using questionnaires. RESULTS: Real operations triggered both cardiac autonomic and cortisol stress responses which were independent from surgeons' level of experience. Intraoperative stress responses did not affect cardiac autonomic activity during the following night but were associated with a blunted cortisol awakening response. Moreover, senior surgeons reported higher levels of negative affectivity and depressive symptoms than expert surgeons prior to the surgery. Lastly, the magnitude of heart rate responses to surgery positively correlated with scores on negative affectivity, depression, perceived stress, and trait anxiety scales. CONCLUSION: This exploratory study allows to put forward the hypotheses that in surgeons cardiac autonomic and cortisol stress responses to real operations (i) may be associated with specific individual psychological characteristics regardless of the level of experience, (ii) and may have a longer lasting impact on hypothalamic-pituitary-adrenal axis function with potential implications for surgeons' physical and psychological well-being.

Relationship Between the Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) and Lung Adenocarcinoma Patterns: New Possible Insights.

INTRODUCTION: This study aimed to evaluate a potential relationship between the diffusing capacity of the lung for carbon monoxide (DLCO) and the aggressiveness of lung adenocarcinoma (ADC). METHODS: Patients who underwent radical surgery for lung ADC between 2001 and 2018 were retrospectively reviewed. DLCO values were dichotomized into DLCOlow (<80% of predicted) and DLCOnormal (≥80%). Relationships between DLCO and ADC histopathological features, clinical features, as well as with overall survival (OS), were evaluated. RESULTS: Four-hundred and sixty patients were enrolled, of which 193 (42%) were included in the DLCOlow group. DLCOlow was associated with smoking status, low FEV1, micropapillary and solid ADC, tumour grade 3, high tumour lymphoid infiltrate and presence of tumour desmoplasia. In addition, DLCO values were higher in low-grade ADC and progressively decreased in intermediate and high-grade ADC (p=0.024). After adjusting for clinical variables, at multivariable logistic regression analysis, DLCOlow still showed a significant correlation with high lymphoid infiltrate (p=0.017), presence of desmoplasia (p=0.065), tumour grade 3 (p=0.062), micropapillary and solid ADC subtypes (p=0.008). To exclude the association between non-smokers and well-differentiated ADC, the relationship between DLCO and histopathological ADC patterns was confirmed in the subset of 377 former and current smokers (p=0.021). At univariate analysis, gender, DLCO, FEV1, ADC histotype, tumour grade, stage, pleural invasion, tumour necrosis, tumour desmoplasia, lymphatic and blood invasion were significantly related with OS. At multivariate analysis, only gender (p<0.001), tumour stage (p<0.001) and DLCO (p=0.050) were significantly related with the OS. CONCLUSIONS: We found a relationship between DLCO and ADC patterns as well as with tumour grade, tumour lymphoid infiltrate and desmoplasia, suggesting that lung damage may be associated with tumour aggressiveness.

Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.

The Overweight Paradox: Impact of Body Mass Index on Patients Undergoing VATS Lobectomy or Segmentectomy.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E. = 1.57) in overweight patients, and 33.12 minutes (S.E. = 10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P = 0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.

Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines.

BACKGROUND: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. RESULTS: In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. CONCLUSION: Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

Evaluation of a pilot surgical adverse event detection system for Italian hospitals.

OBJECTIVE: To devise an adverse event (AE) detection system and assess its validity and utility. DESIGN: Observational, retrospective study. SETTING: Six public hospitals in Northern Italy including a Teaching Hospital. PARTICIPANTS: Eligible cases were all patients with at least one admission to a surgical ward, over a 3-month period. INTERVENTIONS: Computerized screening of administrative data and review of flagged charts by an independent panel. MAIN OUTCOME MEASURES: Number of records needed to identify an AE using this detection system. RESULTS: Out of the 3310 eligible cases, 436 (13%) were extracted by computerized screening. In addition, out of the 2874 unflagged cases, 77 randomly extracted records (3%) were added to the sample, to measure unidentified cases. Nursing staff judged 108 of 504 (21%) charts positive for one or more criteria; surgeons confirmed the occurrence of AEs in 80 of 108 (74%) of these. Compared with random chart review, the number of cases needed to detect an AE, with the computerized screening suggested by this study, was reduced by two-thirds, although sensitivity was low (41%). CONCLUSIONS: This approach has the potential to allow the timely identification of AEs, enabling to quickly devise interventions. This detection system could be of true benefit for hospitals that intend assessing their AEs.

Prognostic role of standard uptake value according to pathologic features of lung adenocarcinoma.

OBJECTIVE: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. METHODS: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. RESULTS: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern (p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort (p = 0.002) and in low- and intermediate-grade predominant pattern groups (p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. CONCLUSIONS: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

Transcervical video-assisted thymectomy: preliminary results of a modified surgical approach.

PURPOSE: A number of surgical approaches have been reported for thymectomy, including transsternal, transcervical, a combination of complete transsternal and transcervical, and various video-assisted thoracoscopic surgery techniques. A modified video-assisted transcervical approach to thymectomy is here described. METHODS: A video-assisted total thymectomy was performed through a 30-mm cervical incision. No hyperextension of the patient's neck or sternal retractor was used. The surgical instruments utilized for the resection were the ones created for the minimally invasive video-assisted thyroidectomy. RESULTS: Five patients have been operated on so far. The encapsulated gland was removed without any difficulties. No complications occurred. No pain relief was administered after the first 24 h. The patients were discharged within the first two postoperative days. An improvement in clinical symptoms was registered in all patients. CONCLUSIONS: An advantage of this minimally invasive video-assisted transcervical approach to thymectomy is that the entire operation can be performed without neck hyperextension or permanent sternum elevation. Moreover, the surgical instruments created for minimally invasive video-assisted thyroidectomy enabled us to be very precise and to complete the resection without any postoperative morbidity.

Hydrogen Sulfide Inhibits TMPRSS2 in Human Airway Epithelial Cells: Implications for SARS-CoV-2 Infection.

The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, requiring angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) to enter target cells. Therefore, these surface proteins are considered potential druggable targets. Hydrogen sulfide (H2S) is a gasotransmitter produced by several cell types and is also part of natural compounds, such as sulfurous waters that are often inhaled as low-intensity therapy and prevention in different respiratory conditions. H2S is a potent biological mediator, with anti-oxidant, anti-inflammatory, and, as more recently shown, also anti-viral activities. Considering that respiratory epithelial cells can be directly exposed to H2S by inhalation, here we tested the in vitro effects of H2S-donors on TMPRSS2 and ACE2 expression in human upper and lower airway epithelial cells. We showed that H2S significantly reduces the expression of TMPRSS2 without modifying ACE2 expression both in respiratory cell lines and primary human upper and lower airway epithelial cells. Results suggest that inhalational exposure of respiratory epithelial cells to natural H2S sources may hinder SARS-CoV-2 entry into airway epithelial cells and, consequently, potentially prevent the virus from spreading into the lower respiratory tract and the lung.

Multiple primary malignancies involving lung cancer: a single-center experience.

OBJECTIVE: Currently, unlike earlier years, patients affected by multiple primary malignancies (MPM) are significantly increased, thus representing a clinical-pathologic category worthy of attention. Their clinical features and prognosis still need to be studied thoroughly, and this is the aim of our study. METHODS: Patients with MPM involving lung cancer admitted in our center between January 2006 and December 2016 were considered. Parametric and nonparametric testing was used for statistical comparisons. Univariate and multivariate analysis was used to evaluate the variables associated with a prognostic value. RESULTS: MPM incidence was 19.8%. Among the 222 patients with MPM enrolled, 204 (91.8%) had two malignancies, while 18 (8.2%) had three malignancies, 38 (17.1%) were synchronous, 41 (18.5%) had lung cancer first (LCF) and 181 (81.5%) had other cancer first (OCF). A significant difference between the time of first cancer diagnosis to the second cancer diagnosis in the LCF vs OCF group was found (median 32 vs 51 months; p-value: 0.038). The most frequent anatomical sites of malignancies preceding or following lung cancer were prostate, colorectal, bladder, and larynx. Multivariate analysis revealed that sex, histologic pattern, and time and order of occurrence were independent factors for overall survival, with male sex, squamous cell lung carcinoma, synchronous and LCF MPM significantly associated with poorer overall survival. CONCLUSIONS: Prostate, colorectal, bladder, and larynx were the most frequent anatomical sites of malignancies preceding or following lung cancer. Male sex, squamous cell lung carcinoma, synchronous and LCF MPM might be associated with poorer prognosis.

Prognostic value of [18F]FDG PET/CT parameters in surgically resected primary lung adenocarcinoma: a single-center experience.

OBJECTIVE: To evaluate the prognostic role of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) measured by FDG-positron emission tomography (PET)/computed tomography (CT) in patients with primary lung adenocarcinoma undergoing surgical resection. METHODS: All consecutive patients undergoing curative surgery for primary lung adenocarcinoma at the Thoracic Surgery Unit of the University Hospital of Parma between January 2009 and December 2014 were retrospectively analyzed. The cutoff point of each continuous PET parameter was determined through receiver operating characteristic curve and Youden index, using overall survival (OS) as the classification status. Univariate and multivariate Cox proportional hazards models were applied to evaluate the association between OS and potential prognostic variables, including SUVmax, MTV, and TLG. RESULTS: A total of 193 patients were considered eligible for this study. The mean 5-year OS rate was 70.5 ± 3.5%. Acinar and lepidic patterns were more frequently associated with absent or low (<2.5) SUVmax values [18F]FDG uptake. At univariate analysis, male sex, advanced stage, micropapillary and solid pattern, lymphatic, blood vessels and pleural invasion, high SUVmax, MTV, and TLG were significantly associated with poorer OS. Multivariate analyses revealed that only sex, stage, and TLG were independent factors for OS, with male sex, stage 3+4, and high TLG value (p = 0.041) significantly associated with poorer OS. CONCLUSIONS: In this study, [18F]FDG PET/CT parameters SUVmax, MTV, and TLG were prognostic factors in patients with surgically resected lung adenocarcinoma, able to predict OS and helping to further stratify these patients into prognostic subsets. Elevated TLG was also an independent predictor for shorter OS.

Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer.

OBJECTIVES: Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC. METHODS: High-speed scanning of whole slide images was performed on immunohistochemically stained tissue sections from 97 NSCLC patients to assess the number and ratio of CD3+, CD8+ and PD-1+ T-lymphocytes. TIL distribution was computed considering the intratumoural (proximal or distal) and peripheral (invasive margin) localization as well as their location within the fibrotic tissue (immune excluded). The tumour proliferative index was assessed by Ki67 labelling. The impact of TILs number and distribution on clinical-pathological characteristics and outcomes were statistically analysed. RESULTS: High density and percentage of proximal CD8+ TILs and low PD-1-to-CD8 ratio had a positive impact on disease-free-survival (P = 0.03) and overall survival (P = 0.003). An inverse correlation was observed between the abundance of intratumoural CD8+ TILs carrying PD-1 inhibitory receptor and cancer cell proliferation. Cases with high compared to low fraction of immune excluded CD8+ TILs had significantly reduced 5-year overall survival (n events: 22 vs 12; P = 0.04) and disease-free survival (n events: 24 vs 16; P = 0.03) rates while the amount of CD3+ and CD8+ TILs located at the invasive margin had a favourable effect on the clinical course. CONCLUSIONS: Mapping TIL subpopulations may implement the definition of prognostic parameters in surgically resected NSCLC.