Complete response to capecitabine in a frail, elderly patient with metastatic colorectal cancer: A case report.

The clinical management of frail, elderly patients affected by colorectal cancer (CRC) remains a subject of debate. The present study reports the case of an elderly man with metastatic CRC (mCRC) who was successfully treated with capecitabine. The patient survived for 29 months, thus highlighting its potential activity in terms of obtaining a complete response and high efficacy. A 77-year-old man presented with adenocarcinoma of the rectum with multiple and synchronous liver metastases, in addition to several comorbidities. The patient received single-agent capecitabine chemotherapy (825 mg/mq twice a day) on days 1-14 of a 21-day cycle. Following 12 cycles of well-tolerated therapy, a computed tomography scan revealed a complete response with no evidence of liver metastases. An overall survival of 29 months was documented, and the patient eventually succumbed to a diabetes-related complication. In compromised patients with mCRC, reduced-dose capecitabine is an excellent therapeutic option due to its positive safety profile, activity and efficacy.

Diamond: immunohistochemistry versus sequencing in EGFR analysis of lung adenocarcinomas.

AIMS: Identification of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKIs). EGFR E746-A750del and L858R mutations are the most common gene alterations, also predicting the best clinical response to TKIs. We evaluated the accuracy of EGFR mutation-specific antibodies in a large cohort of lung adenocarcinomas, with different molecular settings and types of tissue samples. METHODS: 300 lung adenocarcinomas diagnosed on cytology (48 cell blocks), biopsy (157 cases) and surgical resections (95 cases) were selected. All cases were investigated for EGFR by sequencing and two mutation-specific antibodies (clone 6B6 for E746-A750del; clone 43B2 for L858R) were tested using an automated immunostainer. Discordant results were investigated by next-generation sequencing (NGS). RESULTS: Overall sensitivity and specificity of mutant-specific antibodies were 58.6% and 98.0%, respectively, and they increased up to 84% and 100% if only tumours harbouring E746-A750del were considered. In 13 discordant cases, NGS confirmed immunohistochemistry results in eight samples. CONCLUSIONS: The EGFR mutation-specific antibodies have a fair/good sensitivity and good/high specificity in identifying classic mutations, but they cannot replace molecular tests. The antibodies work equally well on biopsies and cell blocks, possibly permitting a rapid screening in cases with poor material.

Natural History of Non-Small-Cell Lung Cancer with Bone Metastases.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer.

BACKGROUND: An estimated 5 % ­ 10 % of all breast cancers are due to an inherited predisposition and, out of these, about 30 % are caused by germline mutations of the BRCA1 and BRCA2 genes. The prevalence of germline mutations in theBRCA1 and BRCA2 genes varies among ethnic groups. The aims of this study are to evaluate deleterious mutations and genomic rearrangements in BRCA1/2 genes and the CHEK21100delC mutation in a cohort of Italian women affected with hereditary breast and/or ovarian cancer. In addition we clarify the effect of the novel variants identified in BRCA2 gene bymRNA analysis and prediction software. METHODS: We enrolled 103 consecutive Italian patients affected with hereditary breast and/or ovarian cancer, aged23 ­ 69 years. RESULTS: We found BRCA1/2 mutations in 15/103 probands(14.6 % ). Among these, a BRCA2 gene mutation has not been described previously. In addition, we identified five novel BRCA2 variants (S1341, IVS1-59t > c, IVS11-74insA, IVS12 + 74c > g and I1167V). No genomic BRCA1/2re arrangements or CHEK2 1100delC mutation was found in our patients. The novel BRCA2 mutation NS1742del(p.N1742_S1743del) was an in-frame 6 bp deletion that results in loss of two amino acids. CONCLUSIONS: In silico analysis conducted for S1341, IVS1-59t > c, IVS11-74insA and IVS12 + 74c > g of BRCA2 predicted the variants as neutral and benign, whereas the results for I1167V was inconclusive. mRNA analysis for the novel BRCA2 intronic variant IVS11-74insA and the already published BRCA1 variant C197 shows that they have no effect on the splicing. These results are in agreement with in silico analysis.

First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial.

PURPOSE: Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. PATIENTS AND METHODS: Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned. RESULTS: At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. CONCLUSION: In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.