Prognostic value of circulating chromogranin A and soluble tumor necrosis factor receptors in advanced nonsmall cell lung cancer

BACKGROUND: Increased levels of chromogranin A (CgA), a protein secreted by many neuroendocrine cells, have been detected in sera of patients with neuroendocrine tumors or renal, hepatic, or heart failure. In patients with heart failure, serum CgA correlates with tumor necrosis factor-alpha (TNF) and soluble TNF receptors (sTNF-Rs), with important prognostic implications. The prognostic value of CgA and sTNF-Rs was investigated in advanced nonsmall cell lung cancer (NSCLC), a histologically heterogeneous group of tumors that may undergo neuroendocrine differentiation. METHODS: CgA and sTNF-Rs were analyzed in the sera of 88 patients with NSCLC before chemotherapy by enzyme-linked immunoadsorbent assay (ELISA) and in tumors by immunohistochemistry. RESULTS: Thirteen percent of patients had CgA values greater than the highest value observed in normal subjects (distribution range, 9-724 ng/mL and 28-196 ng/mL, respectively). Immunohistochemical studies showed no correlation between CgA expression in tumors and serum levels. Conversely, circulating CgA was associated with worse Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P = .0005), more advanced stage (P = .042), and survival, with CgA being an independent prognostic factor of poor outcome (hazards ratio [HR] 1.31 for 100 ng/mL increase; 95% confidence interval [95% CI], 1.08-1.60 [P = .0071]). sTNF-R1 and sTNF-R2 were also associated with ECOG PS (P = .0001 and P = .02, respectively). sTNF-Rs was weakly correlated with circulating CgA (r = 0.39 for TNF-R1 and r = 0.40 for TNF-R2), suggesting a regulatory link between sTNF-Rs and CgA secretion. CONCLUSIONS: Increased serum levels of CgA in NSCLC are independent from protein expression in tumors and more likely related to neuroendocrine response associated with worsening of patient condition. In addition to ECOG PS and stage, CgA is an independent indicator of poor prognosis.     

Views of persons with schizophrenia on their own disorder: an Italian participatory study

OBJECTIVE: This study explored the views of 241 patients with schizophrenia about their own disorder. METHODS: Patients' knowledge of their diagnosis, confidence that they will be well again, and perception of limitations in their own life as a result of the disorder were explored in relation to patients' opinions about the social consequences of schizophrenia. Study results were presented to participants, and suggestions were collected regarding how these study results should be used. RESULTS: Seventy-two respondents (30%) reported that a psychiatrist told them that they have schizophrenia. Respondents who were confident that they would be well again had a lower duration of contact with psychiatric services and a less pronounced perception of affective and social difficulties related to schizophrenia. Respondents who did not feel limited in their life by the disorder reported less social distance and more optimism about the usefulness of treatments. CONCLUSIONS: Participatory studies may provide ideas for a more constructive interaction between patients and professionals.     

A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project

BACKGROUND:

Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long‐term treatment‐related toxicity also may be a more important issue in younger individuals.

METHODS:

A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5‐fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin.

RESULTS:

Forty‐six patients (ages 9‐17 years) were considered eligible for the study over a 10‐year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5‐year overall and progression‐free survival rates were 80.9% and 79.3%, respectively (median follow‐up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported.

CONCLUSIONS:

This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long‐term follow‐up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes. Cancer 2011. © 2011 American Cancer Society.     

Thalassaemia—A global view

The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care therapy includes regular transfusions to maintain a haemoglobin level of around 10 g/dL, together with iron chelation therapy to prevent iron overload. Novel therapies, bone marrow transplantation, and gene therapy are treatment options that are unavailable in many countries with stressed economies. This Wider Perspectives article presents the strategies for management of an adolescent refugee patient with beta thalassaemia, as it would be performed by expert haematologists in six countries: Italy, Lebanon, Oman, the Sudan, Thailand and the United States. The experienced clinicians in each country have adapted their practice according to the resources available, which vary greatly. Even in the current modern era, providing adequate transfusions and chelation is problematic in many countries. On the other hand, ensuring adherence to therapy, particularly during adolescence, is a similar challenge seen in all countries. The concluding section highlights the disparities in available therapies and puts the role of novel therapies into a societal context.     

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data

Background

The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.

Methods

The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.

Results

From February 2022 to November 2022, 145 patients were enrolled. After a median follow-up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator-assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune-mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non-viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.

Conclusion

The results reported in this first real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial in terms of PFS, ORR and safety.     

Sustained increase in physical fitness independently predicts improvements in cardiometabolic risk profile in type 2 diabetes

Aims

To investigate the relationship between changes in physical fitness and cardiovascular risk factors and scores in patients with type 2 diabetes receiving either a behavioural counselling intervention to increase moderate-to-vigorous-intensity physical activity (MVPA) and decrease sedentary-time (SED-time) or standard care.

Materials and Methods

This is a pre-specified ancillary analysis of the Italian Diabetes and Exercise Study_2, a 3-year randomized clinical trial in which 300 physically inactive and sedentary patients were randomized 1:1 to receive either a one-month theoretical and practical counselling each year or standard care. Mean changes from baseline throughout the 3-year period in MVPA, SED-time, cardiorespiratory fitness (VO_2max), muscle strength, flexibility, cardiovascular risk factors and scores were calculated for study completers (n = 267) and considered irrespective of study arm.

Results

Haemoglobin (Hb) A_1c and coronary heart disease (CHD) risk scores decreased with quartiles of VO_2max and lower body muscle strength changes. Multivariable linear regression analysis showed that increases in VO_2max independently predicted decreases in HbA_1c, blood glucose, diastolic blood pressure (BP), CHD and total stroke 10-year risk and increases in HDL cholesterol, whereas increases in lower body muscle strength independently predicted decreases in body mass index (BMI), waist circumference, triglycerides, systolic BP, CHD and fatal stroke 10-year risk. These associations remained after including changes in BMI, waist circumference, fat mass and fat-free mass, or MVPA and SED-time as covariates.

Conclusions

Improvement in physical fitness predicts favourable changes in cardiometabolic risk profile, independent of changes not only in (central) adiposity or body composition but also in MVPA and SED-time.

Trial Registration

ClinicalTrials.gov; NCT01600937; URL https://clinicaltrials.gov/ct2/show/NCT01600937 .