Lung carcinoids (LCs) are staged using the non-small-cell lung cancer tumour/node/metastasis staging system; the possibility of an LC-specific staging system is still being debated. The goal of our study was to construct a composite prognostic score for LC.From January 2002 to December 2014, data from 293 patients who underwent surgical treatment for LC in 7 research institutes were retrospectively analysed. A panel of established prognostic factors in addition to lymph node metastasis patterns (single/multiple N1-N2 station, skip metastasis, lobe specific), numbers of lymph nodes resected and the ratio between the numbers of metastatic lymph nodes and the numbers of lymph nodes resected (node ratio) were correlated to overall survival (OS) and disease-free survival (DFS). The log-hazard ratio (HR), obtained from the Cox model, was used to derive weighting factors for a continuous prognostic index, designed to identify differential outcome risks. The score was dichotomized according to maximally selected log-rank statistics.Pathological analysis showed typical carcinoids in 223 (76.1%) and atypical carcinoids in 70 (23.9%) patients; the tumour/node/metastasis pattern was stage I in 72.4%, stage II in 18.1%, stage III in 9.5% and stage IV in 0.03% cases. The median numbers of lymph nodes resected was 12 (range 0-53); hilar and mediastinal node metastases were identified in 14% and 6.8% of cases, respectively. Overall, the 5-year OS and 5-year DFS rates were 90.6% and 76.7%, respectively. At multivariable analysis, sex, age, pathological T stage and node ratio were significantly related to a better OS; age, histological type, pathological T stage and node ratio were related to DFS. These factors were used to generate the prognostic score, which showed statistically significant differences between the high-risk and low-risk groups: 5-year OS = 96.6% if score <3.1 vs 63.5% if score ≥3.1 [P < 0.0001; HR 17.56, 95% confidence interval (CI) 5.45-56.53]; 5-year DFS 92.3% if score <1.5 vs 52.5% if score ≥ 1.5 (P < 0.0001; HR 7.95, 95% CI 3.48-18.16).The proposed prognostic scores seem to be effective in predicting outcomes for patients with LCs.

Mediastinal lymph node

T-stage

10.1093/icvts/ivaa114

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Citations (11)

eReply. Patient features versus surgeon experience: the clash of the titans

Interactive Cardiovascular and Thoracic Surgery (2015)

Giovanni Leuzzi Gabriele Alessandrini Daniele Forcella Francesco Facciolo

10.1093/icvts/ivv042

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Robotic Lobectomy without Complete Fissure for Non-Small Cell Lung Cancer: Technical Aspects and Perioperative Outcomes of the Tunnel Technique

Current Oncology (2023)

Filippo Tommaso Gallina Daniele Forcella Enrico Melis Francesco Facciolo

Even though the use of the "fissure-last" technique in mini-invasive lobectomy with the fissureless condition is well accepted, in terms of perioperative outcomes, controversies still surround the hilar lymph node dissection. In this article, we reported a description of the robotic "tunnel technique" approach in the right upper lobectomy in the absence of a defined fissure. We then compared the short terms outcomes of 30 consecutive cases treated using this technique, with 30 patients treated using the "fissure last" VATS approach in the same institution, before the start of the robotic surgery program.

Fissure

10.3390/curroncol30060441

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Citations (2)

Prognostic role of serum p53 antibodies in lung cancer

BMC Cancer (2015)

Manlio Mattioni Silvia Soddu Andrea Prodosmo Paolo Visca Salvatore Conti

Mutations in the TP53 (Tumour Protein 53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in cancer patients. Our aim was to evaluate the presence and prognostic role of these antibodies in lung cancer patients and to investigate whether they were related to p53 expression or TP53 mutations in tumour tissues.A total of 201 lung cancer patients were evaluated for p53 antibodies by ELISA (Enzyme-Linked Immunosorbent Assay) and control was obtained from 54 patients with non-malignant disorders; p53 expression was evaluated in 131 of the lung cancer patients by immunohistochemistry and TP53 mutations were then investigated in 53 tumours positively staining for p53 and in 12 tumours without p53 overexpression, whose DNA was available for direct sequencing.Our results show that 20.4% of cancer patients have positive levels of p53 antibodies, while none of the controls resulted positive. High levels of p53 expression are detected in 57.3% of cases and a significant correlation between serum p53 antibodies and high levels of p53 expression in the corresponding tumours is observed. In non-small cell lung cancer, p53 antibodies are significantly associated with poorly differentiated tumours; furthermore, high levels of p53 expression significantly correlated with squamous cell carcinoma and tumours with highest grade. Survival time of non-small cell lung cancer patients low/negative for serum p53 antibodies was significantly longer compared to patients with positive levels (p = 0.049); in particular, patients with squamous cell carcinoma, but not adenocarcinoma, low/negative for these antibodies show a significant better survival compared to serum-positive patients (p = 0.044).In our study, detection of serum p53 antibodies in non-small cell lung cancer patients has been shown to be useful in identifying subsets of patients with poor prognosis. A significant correlation between the presence of serum p53 antibodies in lung cancer patients and p53 overexpression in the corresponding tumours was also observed. We did not find a significant correlation between levels of serum p53 antibodies and TP53 mutations in the corresponding tumours.

Surgical oncology

10.1186/s12885-015-1174-4

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Citations (41)

Prognostic Model for Resected Squamous Cell Lung Cancer: External Multicenter Validation and Propensity Score Analysis exploring the Impact of Adjuvant and Neoadjuvant Treatment

Journal of Thoracic Oncology (2017)

Sara Pilotto Isabella Sperduti Giovanni Leuzzi Marco Chiappetta Felice Mucilli

Nomogram

Grading (engineering)

Adjuvant Therapy

10.1016/j.jtho.2017.12.003

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Citations (13)

Sequential chemotherapy in nonsmall‐cell lung cancer

Cancer (2007)

Anna Ceribelli Maria Simona Pino Alain Gelibter Michèle Milella Fabiana Letizia Cecere

Abstract BACKGROUND. Improving results in nonsmall‐cell lung cancer (NSCLC) will require the development of new drugs and strategies to combine available agents. On the basis of data indicating the activity of docetaxel as second‐line therapy, a Phase II study was conducted to evaluate the efficacy and toxicity of the sequential combination of chemotherapy consisting of cisplatin (P) and gemcitabine (G) followed by docetaxel (DOC) in patients with advanced NSCLC. METHODS. Patients with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC, performance status (PS) of 0–1, and normal organ function were eligible. Therapy consisted of P at 75 mg/m 2 on Day 1 and G 1200 mg/m 2 on Days 1 and 8 every 3 weeks for 3 cycles followed, in nonprogressive patients, by DOC 30 mg/m 2 every week for 6 consecutive weeks every 8 weeks for 2 cycles. RESULTS. Fifty‐two eligible patients were enrolled (M/F, 39/13; stage IIIB/IV, 8/44; PS 0, 73%, PS 1, 27%; median age, 58 years; range, 36–73). The overall response rate was 36.5% (95% confidence interval [CI]: 23–49). The median overall survival was 11 months (95% CI: 9–13); the median progression‐free survival was 6 months (95% CI: 5–7); and the 1‐ and 2‐year survivals were 48% and 25%, respectively. One‐ and 2‐year progression‐free survivals were 12% and 8%, respectively. Both phases of the treatment protocol were well tolerated. CONCLUSIONS. P/G followed by weekly DOC is well tolerated and active as first‐line therapy for NSCLC patients and provides a feasible chemotherapeutic option in this clinical setting. Cancer 2007 © 2007 American Cancer Society.

Performance status

Progression-free survival

10.1002/cncr.22480

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Celecoxib combined with fixed dose-rate gemcitabine (FDR-Gem)/CDDP as induction chemotherapy for stage III non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology (2005)

Michèle Milella A. Ceribelli Alain Gelibter Paola Malaguti Barbara Di Cocco

7324 Background: Induction chemotherapy with platinum-containing doublets followed by definitive loco-regional treatment is currently considered the treatment of choice for pts with stage III NSCLC. Based on evidence produced by our group that FDR-Gem results in a longer PFS when combined with CDDP in the metastatic setting (Ceribelli et al., Cancer 2003) and on recent studies suggesting that the addition of selective COX-2 inhibitors to CBDCA/Paclitaxel combinations may improve results in the neoadjuvant setting (Altorki et al., JCO 2003), we have elected to investigate the activity of Celecoxib combined with FDR-Gem/DDP as induction treatment for locally advanced NSCLC pts. Methods: Treatment consisted of continuous Celecoxib (400 mg b.i.d.) combined with FDR-Gem (1200 mg/m2 infused at 10 mg/m2/min on days 1 and 8) and CDDP (80 mg/m2 on day 1) given q3 wks for three cycles. Upon restaging, non-progressive pts underwent surgery and/or definitive RT, as evaluated by a multidisciplinary team. Results: 19 pts (median age 59 yrs, range 43–68; M/F 14/5; IIIA/IIIB: 13/6; PS 0/1: 17/2) have been accrued to date and are evaluable for response and toxicity. Three pts (16%) achieved a cCR, 7 (37%) a PR, 7 (37%) had SD, and 2 (10%) progressed on therapy. Nine pts underwent radical surgery, of whom 2 showed a pCR with no evidence of viable tumor cells in the resected specimen; 5 pts underwent RT with curative intent, 1 of whom became resectable and underwent radical surgery after RT. Toxicity was manageable with G3 neutropenia and anemia in 6/19 and 5/19 pts, respectively, and only 1 pt experiencing G3 vomiting. Treatment delays/25% dose reductions were necessary in 14/114 and 9/114 administrations, respectively. One pt discontinued Celecoxib due to G2 erosive duodenitis. With a median follow-up of 42 wks (range 13–74), 9 pts are alive and free from progression. Conclusions: Celecoxib combined with FDR-Gem/CDDP shows promising activity in locally advanced NSCLC and warrants further investigation in the neoadjuvant setting. Accrual is ongoing to reach a planned target of 42 evaluable patients. No significant financial relationships to disclose.

Celecoxib

Induction chemotherapy

10.1200/jco.2005.23.16_suppl.7324

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N-Acetylcysteine protects human bronchi by modulating the release of neurokinin A in an ex vivo model of COPD exacerbation

Biomedicine & Pharmacotherapy (2018)

Luigino Calzetta Paola Rogliani Francesco Facciolo Barbara Rinaldi Mario Cazzola

N-Acetylcysteine (NAC) reduces the risk of exacerbation of chronic obstructive pulmonary disease (COPD). Although NAC also has anti-inflammatory activity, the detailed mechanism leading to its protective role remains to be elucidated. We tested the impact of NAC against the effects of lipopolysaccharide (LPS) in an ex vivo model of COPD exacerbation, and investigated the role of neurokinin A (NKA) in this context. Isolated airways from COPD patients were incubated overnight with LPS (100 ng/ml). NAC was tested at concentrations resembling the plasma levels elicited by oral administration of NAC at 200 mg/day (very low dose), 600 mg/day (low dose) and 1.200 mg/day (high dose). NAC at high concentrations normalized the peroxidase activity, H2O2, malondialdehyde (MDA), nitric oxide, glutathione (GSH), total antioxidant capacity (TAC), and interleukin 6 (IL-6) (overall change 34.32% ± 4.22%, P < 0.05 vs. LPS-treated). NAC at low concentrations modulated peroxidase activity, H2O2, MDA, GSH, TAC, and IL-6 (overall change 34.88% ± 7.39%, P < 0.05 vs. LPS-treated). NAC at very-low concentrations was effective on peroxidase activity, H2O2, GSH, and IL-6 (overall change 35.05 ± 7.71%, P < 0.05 vs. LPS-treated). Binary logistic regression analysis indicated that the modulatory effect of NAC on NKA levels was associated with a reduction of pro-oxidant factors and IL-6, and selectively blocking the NK2 receptor abolished such an association. This study demonstrates that, along with its well-known antioxidant activity, the protective effect of NAC against the detrimental effect of LPS is due to the modulation of NKA and IL-6 levels.

Ex vivo

10.1016/j.biopha.2018.04.011

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Citations (25)

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC

Frontiers in Oncology (2023)

Filippo Tommaso Gallina Daniele Marinelli Riccardo Tajè Daniele Forcella Gabriele Alessandrini

Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy.Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines.A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma.Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.

Lymphadenectomy

Univariate analysis

10.3389/fonc.2023.1229939

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Citations (3)