Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments.A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test.Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio [HR], 1.08; 95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference between the cisplatin and carboplatin arms according to sex, stage, performance status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin, respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%, respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity profile was significantly different for each of the arms: hematologic toxicity was higher with carboplatin, and nonhematologic toxicity was higher with cisplatin.Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.
Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.
Abstract Abstract #6066 Background: Herstatin is a naturally occurring product of the HER2 gene generated by alternative mRNA splicing. It functions as a secreted inhibitor that binds to the extracellular domains of EGFR and HER2, disrupting multiple receptor combinations in response to a variety of ligands. This mode of action supports the potential utility of herstatin in the development of novel therapeutics against breast cancer. The aim of the present study was to evaluate the association of herstatin with HER family expression at the m-RNA level, as well as with other clinicopathological characteristics of patients with high-risk operable breast cancer enrolled in a randomized phase III trial. The effect of herstatin on disease-free survival (DFS) and overall survival (OS) was also investigated.
 Patients and Methods: 595 high-risk breast cancer patients were treated with anthracycline-based chemotherapy in the adjuvant setting (HE10/97 trial). This was a two-arm trial (E-CMF vs. E-T-CMF) investigating postoperative dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was extracted from 279 formalin-fixed paraffin-embedded tumor tissue samples followed by kinetic one-step RT-PCR for assessment of mRNA expression of herstatin, EGFR, HER2, HER3, and HER4. Values of RNA above the median were considered as positive expression, except for EGFR, where the 75th percentile was used as a cut-off. DFS and OS were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox analysis for DFS and OS was also performed.
 Results: Positive herstatin expression was found to be significantly associated with ductal histology (χ2 test, p=0.004), and marginally associated with infiltrated lymph nodes (p=0.062). Furthermore, herstatin was found to be strongly correlated with HER2 expression (r=0.783, p<0.001) and weakly correlated with HER3 expression (r=0.144, p=0.02). Positive herstatin expression was associated with poor DFS and OS (log-rank, p=0.004 and 0.008, respectively). This remained unchanged when adjusted for treatment group, whereas no interaction between herstatin and treatment was identified. Interaction of HER2 overexpression (>75th percentile) with herstatin was found to be significant for OS (Wald, p=0.03), thus implying a possible prophylactic effect of herstatin in the subgroup of patients with HER2 overexpression.
 Conclusions: Herstatin was shown to be associated with a poor prognosis. Given the high correlation between herstatin and HER2, this finding may reflect the effect of HER2 on patient's prognosis. Our results suggest that the effect of herstatin may be altered in case of HER2 overexpression. This hypothesis should be investigated in future studies, focusing in patients with HER2 overexpression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6066.
Pancreatic cancer stands out as one of the most lethal forms of malignancies, representing 2% of all cancer cases and contributing to 5% of cancer-related fatalities. Therefore, early detection of pancreatic cancer is crucial for enhancing treatment outcomes. Various hereditary cancer syndromes have been linked to an elevated risk of developing pancreatic cancer, suggesting potential benefits from surveillance strategies for individuals at risk. Presently, precision medicine employs PARP inhibitor therapy for pancreatic cancer patients carrying germline variants in Homologous Recombination Repair (HRR) genes. Our objective was to ascertain the occurrence of germline pathogenic/likely pathogenic variants in genes predisposing to cancer among pancreatic cancer patients. Methodologically, we analyzed 184 pancreatic cancer patients referred to our laboratory for genetic examination. Utilizing a Next-Generation Sequencing (NGS) approach, we scrutinized 52 genes implicated in hereditary cancer predisposition. Our findings revealed that 21% of the patients analyzed harbored germline pathogenic/likely pathogenic variants. Within this subset, 48% exhibited positive results in pancreatic cancer susceptibility genes, namely ATM (17%), BRCA1 (12%), BRCA2 (7%), CDKN2A (7%), and PALB2. Significantly, 64.3% of the pathogenic variants were associated with genes involved in the HRR pathway (ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCL, MRE11, PALB2, RAD50, RAD51B and RAD51C). In conclusion, our study underscores the significance of multigene genetic testing for pancreatic cancer patients, with 21% of individuals yielding findings linked to pancreatic or other cancer predisposition. Moreover, patients carried pathogenic/likely pathogenic variants in HRR genes, potentially benefiting from targeted therapies such as PARP inhibitors or platinum-based treatments.
