Paolo Pronzato

Background: Lung cancer is an oncological threat worldwide, including in Italy. New organizational approaches based on a network of cancer centers and multidisciplinary and technological innovation are required. The experience in the Liguria region, in northwestern Italy, in the management of lung cancer is presented with a focus on the organizational model. Methods: A retrospective observational analysis was conducted for the period from January 2019 to December 2023 using administrative regional data. Results: Of the total surgery treatments in Liguria, most were carried out at the IRCCS San Martino (about 47%), which is the hub’s center. Most cases involved males aged ≥65 years (p < 0.001). Passive mobility showed a decrease in recent years. Considering the type of access to clinical structures, almost all that were finalized to receive chemotherapy were from the day hospital regimen (99%). Conclusion: A comprehensive approach must be carried out for cancer patients to maintain high levels of care quality. In this challenging context, the Liguria region has implemented new organizational approaches based on the networking of cancer centers and multidisciplinary and technological innovation.

Introduction: Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes mucous membranes. The distinctive feature is the widespread and progressive deposition of melanin precursors in the dermis. Objectives: The purpose of this review is to define the clinical and demographic features of DMC and to promote a deeper insight into the clinical manifestation, histological findings, and pathophysiology behind DMC. Methods: We have conducted a systematic review of the literature on published DMC in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We also reported a case of DMC secondary to low-risk melanoma. Results: Overall, including our case report, we reported 53 articles described 62 DMC patients. Breslow level of primary melanoma was reported having a mean value of 3.3 mm. The mean survival rate from onset of DMC resulted being 4.36 months. Conclusions: Among the most widely accepted etiopathogenetic hypotheses are deposition of melanic precursors in the dermis following tumor lysis, melanocyte proliferation induced by neoplastic growth factors, and the presence of diffuse dermal micro-metastases of MM. However, unanimous consensus on the proposed etiopathogenetic models of DMC is still lacking.

GIM 13-AMBRA is a longitudinal cohort study aimed at describing therapeutic strategies and the relative outcome parameters in 939 HER2-ve MBC patients. Taxanes–based regimens, or taxanes + targeted agents, mainly Bevacizumab, were the preferred first choice in both Luminal (30.2%) and TNBC (33.3%) patients. The median PFS1 was 12.5 months (95% CI 16.79–19.64), without any significant difference according to subtypes, while the median Time to first Treatment Change (TTC1) was significantly lower in TNBC patients (7.7 months—95% CI 5.7–9.2) in comparison to Luminal A (13.2 months, 95% CI 11.7–15.1) and Luminal B patients (11.8 months, 95% CI 10.3–12.8). PFS2 was significantly shorter in TNBC patients (5.5 months, 95% CI 4.3–6.5 vs. Luminal A—9.4, 95% CI 8.1–10.7, and Luminal B—7.7 95% CI 6.8–8.2, F-Ratio 4.30, p = 0.014). TTC2 was significantly lower in patients with TNBC than in those with the other two subtypes. The median OS1 was 35.2 months (95% CI 30.8–37.4) for Luminal A patients, which was significantly higher than that for both Luminal B (28.9 months, 95% CI 26.2–31.2) and TNBC (18.5 months, 95% CI 16–20.1, F-ratio 7.44, p = 0.0006). The GIM 13—AMBRA study is one of the largest collections ever published in Italy and provides useful results in terms of time outcomes for first, second, and further lines of treatment in HER2- MBC patients.

Bravaccini: Up to now, the conventional tissue biomarkers (estrogen receptor [ER], PgR, human epidermal growth factor receptor 2 [HER2], and Ki-67) are

Background: Survival rates for metastatic melanoma (MM) patients have improved in recent years, leading to major expenses and health resource use. We conducted a non-concurrent prospective study to describe the burden of hospitalization in a real-world setting for patients with MM. Methods: Patients were tracked throughout all hospital stays in 2004–2019 by means of hospital discharges. The number of hospitalizations, the rehospitalization rate, the average time spent in the hospital and the time span between consecutive admissions were evaluated. Relative survival was also calculated. Results: Overall, 1570 patients were identified at the first stay (56.5% in 2004–2011 and 43.7% in 2012–2019). A total of 8583 admissions were retrieved. The overall rehospitalization rate was 1.78 per patient/year (95%CI = 1.68–1.89); it increased significantly with the period of first stay (1.51, 95%CI = 1.40–1.64 in 2004–2011 and 2.11, 95%CI = 1.94–2.29 thereafter). The median time span between hospitalizations was lower for patients hospitalized after 2011 (16 vs. 26 months). An improvement in survival for males was highlighted. Conclusions: The hospitalization rate of patients with MM was higher in the last years of the study. Compared with a shorter length of stay, patients were admitted to hospitals with a higher frequency. Knowledge of the burden of MM is essential for planning the allocation of healthcare resources.

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.

Objectives: Rare tumors (RT) collectively account for one quarter of all malignancies in Italy. The low frequency and the large heterogeneity in natural history and outcome of individual diseases, together with a scarcity of epidemiological information make them a challenge for clinical practice, as well as for public healthcare organizations. We conducted a retrospective study to quantify the burden of hospitalization in a real-word setting in patients diagnosed with these diseases in an Italian region. Methods: RT patients were tracked along all hospital stays from 2000 to 2019 using hospital discharge records. Frequency of hospitalizations, average time spent in hospital and median timespan between consecutive admissions were considered. Re-hospitalization rates were analyzed through a multivariable negative binomial regression analysis to adjust for confounding and allowing for over-dispersion in count data. Results: As a whole, 57,329 patients were identified at first stay for all studied tumors. A total of 183,959 admissions were retrieved, along a median of 3 hospitalizations per patient. Median timespan between hospitalizations shortened in the course of the study years (12.5 months in 2000–2004 to 5.4 months in 2015–2019). The overall re-hospitalization rate increased from 0.92 per patient/year (95% CI = 0.81–1.04) in 2000–2004 to 2.17 (95% CI = 1.90–2.47) in 2015–2019. Conclusions: Overall, the hospitalization rate of patients with a RT increased in the twenty years since the 2000 and particularly doubled starting from 2015. A higher burden of hospitalizations was found for tumors of the central nervous system, thoracic cavity, digestive tract and sarcomas. To the best of our knowledge this is the first paper related to access to Italian healthcare facilities of patients with these tumors.

Breast cancer is the most common tumor in middle-aged and older women. In 2003, the European Parliament recommended to Member States that all women with breast cancer should be treated by a multidisciplinary team and that a network of certified breast centers be organized (the centers have been called Breast Units (BUs)). With the present study, we aim to explore the impact of the introduction of the BU organizational model in the Liguria region, Italy, through different outcome indicators. An explorative retrospective analysis was conducted through the period from 2013 to 2019 to assess the impact of the introduction of the BU model in our region. We identified two periods: before (2014–2015) and after (2017–2018) the introduction of this organizational model to assess its value impact through the definition of six measurable outcome indicators. Length of hospitalization, repeated specialist outpatient diagnostic procedures and the rate of subjects who started radiotherapy treatment within 60 days improved after the introduction of BUs. The passive health migration rate only improved significantly for one local health unit (LHU), while reintervention and diagnosis–surgery time did not show any enhancement after the introduction of the BU model. The BU model seems to provide an increase in several aspects of the healthcare offered to breast cancer patients in Liguria, specifically in those areas where a shared guideline could assist healthcare workers. Future research, such as pilot studies, are needed to assess the impact of the introduction of the BU model in our reality.

To date, the 5-year overall survival rate of 60% for early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on an interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. In order to identify a prognostic score, we performed in-depth high-throughput analyses of plasma circulating markers, including exosomal microRNAs (Exo-miR) and peptides, in 67 radically resected NSCLCs. The miRnome profile selected the Exo-miR-130a-3p as the most overexpressed in relapsed patients. Peptidome analysis identified four progressively more degraded forms of fibrinopeptide A (FpA), which were depleted in progressing patients. Notably, stepwise Cox regression analysis selected Exo-miR-130a-3p and the greatest FpA (2-16) to build a score predictive of recurrence, where high-risk patients had 18 months of median disease-free survival. Moreover, in vitro transfections showed that higher levels of miR-130a-3p lead to a deregulation of pathways involved in metastasis and angiogenesis, including the coagulation process and metalloprotease increase which might be linked to FpA reduction. In conclusion, by integrating circulating markers, the identified risk score may help clinicians predict early-stage NSCLC patients who are more likely to relapse after primary surgery.

Background: Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor–positive disease. There are controversial data on its fertility preservation potential. Methods: The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: Of 281 randomly assigned patients, 80.4% had hormone receptor–positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor–positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92). Conclusions: Final analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor–positive disease.