Treatment related toxicity in BRCA1-associated epithelial ovarian cancer - is DNA repairing impairment associated with more adverse events?

AIM OF THE STUDY: The presence of BRCA germline mutations in patients with ovarian cancer has been shown to have predictive and prognostic significance, including increased platinum-sensitivity. The aim of the study was to evaluate if patients with BRCA1-associated ovarian cancer have more treatment related adverse events and, if so, does it have impact on chemotherapy outcomes. MATERIAL AND METHODS: We conducted a retrospective analysis of medical records of 172 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch between 2007 and 2013. Ninety-six of these patients have known BRCA mutation status - 21 patients were BRCA1(+) and 75 BRCA1(-). Analysed treatment related adverse events (AE's) were: haematological toxicity, nausea/vomiting, neuropathy and mucositis. RESULTS: Grade 3-4 haematological AE's were significantly more common among BRCA1(+) patients (OR = 3.86; 95% CI: 1.14-13.23; p = 0.02). There was no association between BRCA1 mutation status and neuropathy (p = 0.73) or nausea/vomiting (p = 0.91). Occurrence of above mentioned AE's has no significant association with PFS (p = 0.75, 0.64, 0.97 respectively) and OS (p = 0.64, 0.69, 0.73 respectively). CONCLUSIONS: Among patients with BRCA1-associated epithelial ovarian cancer we observed significantly more grade 3-4 haematological complications after chemotherapy. However, occurrence of AE's did not correlate with better outcomes in this subgroup.

Prospective, Observational Study of Aflibercept Use in Combination with FOLFIRI in Patients with Metastatic Colorectal Cancer: A Real-World Effectiveness Study.

BACKGROUND: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. METHODS: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. RESULTS: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9-9.9] and 27.0 months [95% CI, 23.9-30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). CONCLUSIONS: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed.

The Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting-A Nation-Wide Retrospective Analysis (RACER).

Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.

[Chemotherapy in disseminated thymoma--case report, own experience]. / Chemioterapia w leczeniu grasiczaka w stadium rozsiewu--opis przypadku, doswiadczenie wlasne.

Thymomas are thymic epithelial neoplasms. Surgery plays a major role in thymoma treatment but chemotherapy can significantly improve prognoses for this group of patients. Neoadjuvant chemotherapy (before surgery), adjuvant chemotherapy (after surgery), chemotherapy combined with radiotherapy and palliative chemotherapy in dissemination stage could be required in effective therapy. The aim of this paper is description of the effective systemic second line treatment in the case of 66 years old patient with advanced thymoma.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before chemotherapy as potential prognostic factors in patients with newly diagnosed epithelial ovarian cancer.

INTRODUCTION: Recent studies have shown that the presence of systemic inflammation correlates with worse outcomes in many types of cancers. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed as indicators of systemic inflammatory response. The aim of the study was to assess the prognostic value of NLR and PLR before starting chemotherapy among patients with newly diagnosed ovarian cancer. METHODS: We conducted a retrospective analysis of medical documentation of 315 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, between 2007 and 2013. 31 (12.1%) patients had metastatic disease at the time of diagnosis. Receiver-operating characteristic (ROC) curves for progression free survival (PFS) and overall survival (OS) prediction were plotted to verify cut-off points for NLR and PLR. PFS and OS were analysed for correlation with NLR and PLR, using the Cox regression model. Other potential prognostic variables included in multivariate analysis were: patient's age at diagnosis (<65 vs ≥65 years), Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2, FIGO stage of the disease and baseline Ca-125 level. RESULTS: In multivariate analysis, higher pretreatment NLR (p=0.002), poor ECOG-PS (p=0.0002), higher disease stage (p<0.0001) and baseline Ca-125 (p=0.03) level were independent negative prognostic factors for PFS. However, only ECOG-PS ≥2 (p<0.0001), high stage of the disease (p<0.0001) and high baseline Ca-125 level (p=0.0003) were independent negative prognostic factors for OS. CONCLUSIONS: Advanced stage of the disease with high Ca-125 level and poor patient performance status are the most important prognostic factors in ovarian cancer. Higher pretreatment value of NLR was an independent negative prognostic factor for PFS, with no significant impact on OS.

Adult Wilms' tumor - diagnosis and current therapy.

INTRODUCTION: Wilms' tumour is one of the commonest malignant tumours of childhood. It appears mainly in the first 5 years of life. Incidental examples of nephroblastoma in adults have been described in literature (about 3% of all described cases). There are diagnostic and therapeutic difficulties in that older age group. The preoperative diagnosis of nephroblastoma in adults is difficult because there are no specific radiographic findings that allow to distinguished it from the more common adult renal tumors. Histopathologically, there is no difference between adult and childhood Wilms' tumor. MATERIALS AND METHODS: The PubMed database and current literature search was conducted for reports on clinical and histopathological features of nephroblastoma in adults. We also reviewed the literature in terms of treatment strategy, toxicity and prognostic factors. RESULTS: Up till now, several biological factors have been identified that may be in future new prognostic factors. Modern treatment regiments improved OS in this group of patients (OS rates of 90%). The prognosis remain still worse for about 25% of patients with anaplastic, bilateral and recurrent disease. CONCLUSIONS: Due to the fact that nephroblastoma is a very rare type of cancer, adult patients should be treated in an individual way based on the available schemes used in children. Toxicity in adults is higher than in children.

Unfavorable prognosis of nephroblastoma in adults.

Wilms' tumor is the most common type of malignant kidney tumor in children. Due to the fact that this type of cancer is so rare in adults, however, there is a significant lack of treatment strategies in this age group. Moreover, the treatment of adults is often based on protocols used in children. The present report describes a case of a 25-year-old male with nephroblastoma stage IV, who had a primary surgery and underwent chemotherapy with CDVC (cyclophosphamide, doxorubicin, vepesid, carboplatin). During the systemic treatment, the authors observed progression of disease and serious side effects.