[On adjuvant therapy after limited resections for NSCLC Stage IA in patients with high risk of recurrence: waiting for the announced 8th Edition 2017 of TNM Staging System]. / Sulla terapia adiuvante dopo resezioni limitate per NSCLC Stadio IA in pazienti ad alto rischio di recidiva: in attesa della annunciata 8a edizione 2017 del TNM Staging System.

The adjuvant therapy in NSCLC Stage IA still remains a controversial issue even in the interdisciplinary decision making after limited resections of the neoplasm as an alternative to lobectomy. The Authors accept from literature that this mainly concerns specific sub-group of patients, the istopathological post-resection diagnosis of whom highlights linfovascular o perineural as well as visceral pleura invasion. There is confidence that the presently depersonalizing rigidity in the guidelines implementation is overcome in the presence of clear istological signs of invasion. As a consequence the interdisciplinary team should reasonably consider as correct the adjuvant treatment.

[The longsurvivors for non-small cell lung cancer: remarks on the present and in perspective]. / Le lungosopravvivenze nel carcinoma broncogeno non-microcitoma: riflessioni criticamente "obbligate" sul presente e in prospettiva.

The Authors fully share cricitisms voiced in international literature to NSCLC longsurvivors, in particular those remarkes related to advanced disease patients following various anti-tumor treatments ( mostly multimodal). To this point, even the NCCN version 3.2014 guidelines prove inadequate as they mostly focus on longsurvivors post-NSCLC early stage surgical resection. Although AIOM Working Group's recommendations for follow-up seem to be more adequate, still they lack depth with respect to advanced-stage bronchogenic carcinoma. The Authors quote a number of case report related to advanced disease longsurvivors, and draws his attention on the peculiar role of pneumologists in the follow-up for such patients: in particular, as regards respiratory pathologies prior or subsequent to different anti-tumor treatments (i.e., BPCO, interstitial lung diseases, pulmonary thromboembolism, etc.).

DNA flow cytometric studies of 66 human lung tumors analyzed before treatment. Prognostic implications.

To investigate the prognostic implications of DNA flow cytometry in human lung tumors, we analyzed specimens from patients with neoplastic and non-neoplastic lung disease. Most non-neoplastic and normal (taken at the resection border) lung samples yielded a single cell population with diploid DNA content (only two normal lung specimens from two cancer patients had aneuploid DNA content). At least one aneuploid cell subpopulation was seen in 91 percent of NSCLC and 50 percent on SCLC. To show intratumor heterogeneity, multiple-site sampling was done whenever possible in both primary tumor and metastatic sites, revealing a high incidence of multiclonality (50 percent). Although diploid tumors were rare, they associated with a higher survival rate than aneuploid monoclonal and multiclonal tumors with hypoploid and/or hypertetraploid clones, which had the lowest survival. Cellular DNA content analysis in patients with lung tumors may be useful in prognostic evaluation.

Lonidamine plus cyclophosphamide in the treatment of adanced non-small cell lung cancer in the elderly: a phase II study.

AIM AND BACKGROUND: The aim of this Phase II trial was to verify the therapeutic activity and tolerability of chemotherapy with lonidamine (LND) plus cyclophosphamide (CTX) in advanced non-small cell lung cancer (NSCLC) in the elderly. The rationale of the combination is reported. CTX showed mild toxicity, with a 12% objective response (OR) in monochemotherapy; LND potentiated the in vitro antiproliferative activity of alkylating agents, mainly CTX, without increasing myelotoxicity, particularly important in the elderly. METHODS: The schedule consisted of CTX, 600 mg/m2/i.v. on day 1 every 21 days for 6 cycles; LND, 450 mg/die/p.o. from day 1 to progression. RESULTS: Between November 1990 and April 1991, 41 patients with stage III-IV NSCLC were enrolled; 35 were assessable for response. Median age was 73 years (range, 71-79 years); 13 patients (32%) presented stage III A, 20 (49%) stage III b, and 8 (19%) stage IV disease. Cardiovascular conditions and/or chronic respiratory failure contraindicated surgical treatment in stage III A patients. Of enrolled patients, 14.6% experienced PR, 48.8% SD and 14.6% dropped out of the study. Median time to progression was 4 months (range, 2-9 months) and median survival 9 months (range 3-45 months). No patient showed WHO grade IV LND-related toxicity. In 1 patient (2.5%), LND was discontinued after 5 therapy cycles due to WHO grade III myalgia; in 80% of patients, LND oral dosage was reduced to 300 mg/day due to WHO grade II myalgia, and 20% of patients completed treatment with the full dose. CONCLUSIONS: CTX plus LND can be considered a well tolerated therapeutic approach in the elderly with NSCLC with good PS and good liver, renal and cardiac conditions, but 14.6% PR is a slightly better result as compared with 12% PR obtainable with CTX alone as reported in the literature, even though most patients presented with advanced disease and no specific toxic effect was observed. Therefore, a confirmatory randomized trial (CTX vs CTS plus LND) would hardly be useful.

Treatment of inoperable non-small cell lung carcinoma stage IIIb and IV with cisplatin, epidoxorubicin, vindesine and lonidamine: a phase II study.

AIMS AND BACKGROUND: The polychemotherapeutic regimen PEV (cisplatin, epidoxorubicin and vindesine) + lonidamine proved to be valid in terms of activity and efficacy in the treatment of patients with advanced, previously untreated non-small cell lung carcinoma. The goal of the study was to verify whether a different dose of lonidamine, together with an increase in cisplatin and epidoxorubicin compared to the standard regimen, is able to improve the activity and efficacy of PEV without increasing toxicity. PATIENTS AND METHODS: Thirty-one patients were treated with cisplatin (80 mg/m2/i.v.), epidoxorubicin (70 mg/m2/i.v.) and vindesine (3 mg/m2/i.v.) every 28 days for 6 courses in combination with lonidamine (600 mg/day on days 1 and 2 of each course followed by 450 mg/day until progression of disease or intolerance). All the patients were monitored for clinical response, median duration of response and survival and for toxicity. RESULTS: The clinical response in the 29 assessable patients was: 41.4% partial remission, 48.3% stable disease, and 10.3% progression of disease. The median duration of response was 8.5 months (range, 4-26+) and median survival was 12 months (range, 4-26+). Survival was above the median in 15 stage IIIb patients, and 2 patients were long survivors at 26+ months. The toxicity of PEV + lonidamine was mild; there were no toxic deaths nor acute toxicity of grade 4 according to the WHO scoring system. CONCLUSIONS: Our polychemotherapeutic regimen proved to be valid in terms of activity and efficacy, and a further dose increase in single chemotherapeutic agents as well as lonidamine could therefore be justified.

[Netilmicin in single daily doses for the bacterial bronchopulmonary complications in patients with advanced bronchogenic carcinoma]. / La netilmicina in monodose giornaliera nelle complicanze batteriche broncopolmonari in pazienti con carcinoma broncogeno avanzato.

In 40 patients with bacterial bronchopulmonary complications during polychemotherapy for advanced bronchogenic carcinoma, once-daily netilmicin (4.5 mg/kg every 24 h) brought about complete resolution of the infective process in 90% of the cases and eradication of the responsible pathogen in 82%. This result must be considered good in view of the patients' precarious condition due to their advanced neoplastic disease.

[Revisiting iatrogenic damage in pneumology past and current implications compared]. / Le attuali implicazioni pneumologiche del danno polmonare iatrogeno alla luce di una rivisitazione rispetto al passato.

Current features of iatrogenic damage by pneumological practice are taken into account and compared with those traced in the past by Daddi and colleagues. The Authors stress the major chances occurred over time and moreover they emphasize the correlated implications that took place with prevention, therapies, informed consent and defensive medicine. Especially in oncological as well as non-oncological field the more relevant iatrogenic damages are represented by the pulmonary interstitial disease and pulmonary thromboembolism. However, from the revisiting is emerged that at present time are strongly increased the possibility and the means for preventing the onset of iatrogenic damage as well as the possibility of reducing the size of lesions consequent upon the pharmacological, surgical and radiotherapeutics treatments.