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Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients' IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5-ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28-37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs., (© 2024. The Author(s).)

Background: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy., Methods: The Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS., Results: Overall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 - 10.1), while mPFS was 7.0 months (95% CI: 5.7 - 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59)., Conclusion: We found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS., Competing Interests: Dr. SB received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, Astellas. Dr. SR received honoraria as speaker at scientific events and travel accommodation from BMS, Amgen, GSK, Ipsen, Astellas, Janssen, MSD. Dr. DB received honoraria as advisory role by Ipsen, Astellas, Janssen, Novartis, BMS, MSD, Pfizer, Merck and travel accommodation from Ipsen, Janssen, MSD, Merck. Dr. UD services as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS BMS, IPSEN, Janssen, Pfizer. Dr. SC received honoraria as speaker at scientific events/advisory boards and travel accommodation from BMS, Ipsen, MSD, Pierre-Fabre, Bayer, Gentili. Dr. PZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme MSD, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, Astrazeneca, Roche and Bayer. Dr. GPro services advisory boards/consulting for Astellas, AstraZeneca, BMS, Janssen, IPSEN, Merk, MSD, Novartis, Pfizer. Dr. CB received honoraria from advisory board/clinical trials/conference speaking/travel grant with Astellas, AstraZeneca, Bayer, BMS, Clovis, Exelixis, GSK, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi. Dr. MSo services advisory boards/consulting for Janssen, received research funding from Janssen, Roche and Merck and received travel accomodation from Ipsen, BMS, Janssen, Pfizer, Novartis, Astellas, Sanofi, Roche. Dr. FM services advisory boards for Pfizer and MSD. Dr. PR services advisory boards for MSD, AstraZeneca and Janssen. Dr. GF services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, Merck and received travel accomodation from Astellas, Janssen, Bayer. Dr. GB reports personal fees from AstraZeneca and Astellas for speaker bureau. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Murianni, Signori, Buti, Rebuzzi, Bimbatti, De Giorgi, Chiellino, Galli, Zucali, Masini, Naglieri, Procopio, Milella, Fratino, Baldessari, Ricotta, Mollica, Sorarù, Tudini, Prati, Malgeri, Atzori, Di Napoli, Caffo, Spada, Morelli, Prati, Nolè, Vignani, Cavo, Lipari, Roviello, Catalano, Damassi, Cremante, Rescigno, Fornarini and Banna.)

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented., Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy., Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027)., Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Longo, Della Corte, Russo, Spinnato, Ambrosio, Ronga, Marchese, Del Giudice, Sergi, Casaluce, Gilli, Montrone, Gristina, Sforza, Reale, Di Liello, Servetto, Lipari, Longhitano, Vizzini, Manzo, Cristofano, Paolelli, Nardone, De Summa, Perrone, Bisceglia, Derosa, Nardone, Viscardi, Galetta and Vitiello.)

Background: The study of health-related quality of life in survivors of gynecologic cancers is becoming increasingly important as 1.5 million survivors of gynecologic cancer in the United States and more are expected due to advances in diagnosis and treatment. This project investigated the perceived needs and lived experiences of survivors of gynecological cancer to help design supportive activities to be implemented in clinical practice., Methods: Patients were recruited in hospitals or through social media and responded to an online survey that was addressed to patients in Italy, specifically in Sicily, Puglia, and Campania. Patients with ovarian, endometrium, or cervix cancer were recruited among women attending Cannizzaro Hospital and Alleanza Contro il Tumore Ovarico (Alliance Against Ovarian Cancer) members., Results: Body image perception was changed in 82.3% of respondents, whereas familial relationships were described as changed by 27.5% of women. In 69.6% of patients, sexual habits were hindered by changes in the body, depression, pain, and awkwardness. Physicians informed patients about sexuality changes related to cancer extensively in 16.7% of cases and briefly in 19.6% of cases. The advice of a clinical sexologist was considered potentially helpful by 31.4% of patients and not potentially helpful by 47.1%, whereas 21.6% of patients had no opinion., Conclusions: Although sexual habits are often changed by cancer, women surviving gynecological cancer rarely seek medical advice in this area. Physicians should be trained to inform patients and to promote referrals to sexologists.

Purpose: To assess caregivers' characteristics and influence of the presence or absence of the caregiver on clinical outcomes of older (≥70 years) metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (ABI) or enzalutamide (ENZ)., Methods: Patients from the Meet-URO 5 ADHERE study were assessed with a 5-item caregiver evaluation questionnaire focusing on the presence, age, degree of kinship, working status and qualification of the caregiver. We investigated the association between the presence of a caregiver and the clinical characteristics and outcomes of enrolled patients., Results: No differences were found in the main clinical characteristics between patients with or without a caregiver, except for a lower median G8 score (p = 0.0453) in the caregiver group. A longer radiographic PFS (rPFS) was observed in the group without a caregiver, with a trend towards more prolonged overall survival (OS) in the same group., Conclusion: Our work suggests a detrimental effect of caregivers in managing older mCRPC patients treated with ABI or ENZ, especially those identified as frail by the geriatric G8 screening score. Further work is needed to identify and address patients' vulnerability areas, which could have a detrimental effect on prognosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Novel androgen receptor signaling inhibitors for prostate cancer (PC) impose the burden of self-administration on older patients overwhelmed by the requirement of many other concomitant medications., Patients and Methods: This study evaluated the proportion of non-adherence in a 12-month follow-up period and the first 3 months to abiraterone (ABI) or enzalutamide (ENZ). In a prospective multicenter observational cohort study, patients with metastatic castration-resistant PC (mCRPC) aged ≥70 years receiving ABI or ENZ pre- or post-docetaxel were enrolled. Treatment monitoring included pill counting, a self-assessment questionnaire, and clinical diaries at each clinical visit. Non-adherence rates were based on proportions of missed/prescribed pills ratios by pill counting., Results: Overall, 234 patients were recruited with median age of 78 years (range, 73-82); 86 (37%) were treated with ABI, and 148 (63%) with ENZ. The median follow-up for adherence was seven monthly cycles (IQR: 4-12). The two cohorts were well balanced for baseline characteristics. The percentage of non-adherence by pill counting was slightly higher for ABI than ENZ (5.2% vs. 4.2%, P < .001). By self-reporting, patients on ENZ tended to report more frequently than those with ABI forgetfulness as the reason for missing events (42% vs. 17%, P < .001). A lower Geriatric G8 score correlated with non-adherence (P = .004). Overall survival (OS) was 48.8 months. Patients on ABI had radiographic progression-free survival (rPFS) of 28.4 [24.2-32.5], while for ENZ patients, we reported a median rPFS of 23.1 [18.2-28.1] months., Conclusion: Physicians tend to treat older mCRPC patients with ENZ. Non-adherence rate is relatively low overall but can be higher with ABI than with ENZ and correlates with the Geriatric G8 score. Forgetfulness is a potential barrier for ENZ., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73-82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8-29.3) and OS 48.8 mo. (95% CI, 36.8-60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 ( p < 0.001 and p = 0.004) and PSA decline ≥50% ( p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only ( p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only ( p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care.

Background: Considerable numbers of patients with metastatic urothelial carcinoma (mUC) develop bone metastases (BoM). Their impact on the efficacy of immune-checkpoint inhibitors (ICIs) is not yet investigated., Methods: Between July 2014 and August 2020 data on pts treated with single-agent ICIs after failure of at least 1 previous line of chemotherapy for advanced disease, were retrospectively collected across 14 Italian centers. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UVA) and multivariable analysis (MVA)., Results: A total of 208 evaluable patients treated with ICIs were identified, including 122 (59%) without BoM (BoM-) and 86 (41%) with bone metastases (BoM+). After a median follow-up of 22.3 months, BoM+ patients showed shorter OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], P = .005) and shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], P < .001). Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, OS and PFS of BoM+ patients were shorter. Both presence of BoM and higher Bellmunt risk score were significantly associated with shorter OS and PFS in UVA and MVA., Conclusion: Patients treated with single-agent ICIs for BoM+ mUC have a dismal prognosis compared to BoM-. Further research is needed to understand the mechanism behind these outcomes., (Copyright © 2021. Published by Elsevier Inc.)

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients' privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5-8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals. Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in a patient-centered approach., (© 2021. The Author(s).)

Purpose: To evaluate adherence to abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC)., Methods: In an observational prospective cohort study, we monitored patients with mCRPC for their adherence to abiraterone or enzalutamide in the pre- or post-chemotherapy setting., Results: Fifty-eight patients with median age of 76 years (range 56-94), age-adjusted Charlson comorbidity score of 10 (range, 4-15), and geriatric G8 score of 14 (range, 6-17) were enrolled. Twenty-two (38%) patients were treated with abiraterone and 36 (62%) with enzalutamide, while forty-two (72%) were in the pre-chemotherapy setting. Forty-seven patients (81%) had a caregiver. Based on the pill counting, a non-adherence rate of 4.8% and 6.2% was observed for the whole period and the first 3 months, respectively, without a statistically significant difference between abiraterone and enzalutamide cohorts. A lower non-adherence rate (1.3%) was reported by patients during the whole period, mainly due to a misperception (77%) and forgetfulness (19%). Non-adherence rate to the fulfilling of the clinical diary was 38% for the whole period. Non-adherence in the whole period was related to the radiological response (p = 0.03) and geriatric G8 score (p = 0.005). By the receiver operating characteristic (ROC) curve based on the radiological response, non-adherence cut-off was 1.87% (p = 0.04). By this non-adherence cut-off, the G8 cut-off was 14.75 (p = 0.0003)., Conclusion: Non-adherence to abiraterone or enzalutamide for mCRPC may have an impact on disease response and be related to patients' frailty, suggesting their geriatric assessment and clinical interventions to monitor and increase their adherence.

Introduction: The treatment of metastatic urothelial cancer (mUC) following first-line standard platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) is not yet established., Material and Methods: We investigated the activity and toxicity of vinflunine at the dose, due to previous treatments, of 280 mg i.v. every 21 days until disease progression or limiting toxicity, with instrumental disease reassessment every 3 cycles, in 6 patients aged ≥18 years, with metastatic urothelial carcinoma of the upper or lower urinary tract, with performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG) of 0-2, adequate hematologic function and progressive disease (PD) following first-line platinum-based chemotherapy and second-line ICI., Results: The median age of the 6 patients was 67.5 years (range 63-77) and median PS 1 (range, 0-2). Four patients (67%) had a disease partial response (PR). With a median follow-up of 4.5 months (range, 3-9), 3 patients are alive (50%). The median progression-free survival following vinflunine (PFS-3) was 4 months (range, 1-8), as compared to the PFS-2 (following ICI) of 4 months (range, 2-9) and the PFS-1 (after platinum-based chemotherapy) of 6 months (range, 2-13). The PRs were not associated with the length of PFS-2 of PFS-1, the histologic subtype, primary and metastatic site of the tumour. No grade 3-4 toxicity has been observed; grade 2 asthenia occurred in 3 patients (50%), grade 1 nausea and constipation were observed in one patient (17%), respectively., Conclusion: Despite the low number of patients treated, the activity of vinflunine was substantial and suggests its role as chemotherapy line following previous chemotherapy and immunotherapy, deserving further retrospective or prospective investigations in this setting.

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population., Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017., Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001., Conclusion: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy.

Objective: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma., Methods: Patients with histologically confirmed locally advanced cervical carcinoma, aged ≥18 years, were treated with intravenous ifosfamide 5,000 mg/m² and mesna 5,000 mg/m², on day 1; intravenous paclitaxel 175 mg/m² and cisplatin 75 mg/m², on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy., Results: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively., Conclusion: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.

Synchronous or metachronous brain metastases (BMs) occur in about 33% of patients affected by non-small-cell lung cancer (NSCLC). To date, no reliable biological marker is able to identify patients who will develop BMs. In the present study, using a quantitative double-labeling immunofluorescence analysis, we evaluated the expression of chemokine CXCL12 and its receptor, CXCR4, in primary NSCLC histological specimens of patients with and without BMs. The immunoreactivity of CXCL12 and CXCR4 was significantly higher in NSCLC samples of patients with BMs. We performed Receiver Operating Characteristics (ROC) analysis in order to define optimal cut-off values for CXCL12 and CXCR4 immunoreactivity that could discriminate between NSCLC patients without and with BMs. ROC curves showed a good diagnostic accuracy and adequate predictive power for both CXCL12 and CXCR4. These findings suggest a possible role for the CXCL12/CXCR4 axis in the metastatic evolution of NSCLC, and its potential use as prognostic markers and drug targets.

The neuroendocrine differentiation in PC could potentially represent a new finding with diagnostic, prognostic and therapeutic implications. This study aimed at evaluating the clinical usefulness of CgA as a neuroendocrine (NE) serum-marker. We investigated the role of the serum concentration of CgA in a study group of patients with PC. CgA was significantly higher in the patients affected by PC as compared with the group of healthy subjects (HS) and those with chronic pancreatitis (CHP) (p<0.001). Also the HS group differed significantly from the CHP control group in the serum CgA levels (p<0.001). The serum carbohydrate antigen (CA19-9) level displayed a significant difference (p<0.001) between the PC and the HS group. The PC and CHP groups, as well as the HS and CHP groups showed also significant differences in the CA19-9 levels (p<0.001). One can conclude that the patients with higher CgA levels had poorer prognosis and survival, as compared to those with lower CgA levels. These results support the notion that the determination of serum CgA level before treatment may be a potential prognostic factor for PC.