Partnering bevacizumab with irinotecan as first line-therapy of metastatic colorectal cancer improves progression free survival-A retrospective analysis.

Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.

Doubling the Dose of Bevacizumab Beyond Progression in Metastatic Colorectal Cancer-the Experience of a Tertiary Cancer Center.

Background: Colorectal cancer (CRC) is the third most common cancer in Europe, with an annual increase in incidence ranging between 0.4 and 3.6% in various countries. Although the development of CRC was extensively studied, limited number of new therapies were developed in the last few years. Bevacizumab is frequently used as first- and second-line therapy for management of metastatic CRC (mCRC). The aim of this study is to present our experience with using bevacizumab beyond disease progression at different dosage levels in mCRC patients, in terms of overall survival, progression-free survival, time to treatment failure, and toxicities. Methods: We performed a consecutive retrospective analysis of patients with confirmed mCRC who were treated with bevacizumab at "Prof Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania. We included patients who had received bevacizumab as first- or second-line therapy and further stratified them according to the dose administered as a second-line (either standard dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, or double dose of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks-depending on the classical chemotherapy partner). All patients had received bevacizumab beyond progression (BYP) which is defined as continuing bevacizumab administration through second-line treatment despite disease progression. In each group, we evaluated the prognostic factors that influenced survival and treatment outcome. Results: One hundred and fifty-one (151) patients were included in the study. Themedian age of patients receiving double dose bevacizumab (DDB) and standard dose bevacizumab (SDB) was 58 years (range 41-71) and 57 years (range 19-75), respectively. The median overall survival in the DDB group was 41 months (range 27-49) compared to 25 months (range 23-29) in the SDB group (p = 0.01 log-rank test). First-line oxaliplatin-based treatment was used more frequently regardless of group, while irinotecan-based more frequently used as a second-line treatment (p = 0.014). Both oxaliplatin- and irinotecan-based regimens were found to be suitable partners for BYP. Statistical analysis revealed that dose intensity, primary tumor location, and cumulative exposure to BYP had significant influence on survival. Conclusion: Doubling the dose of bevacizumab after first progression may improve survival in mCRC patients. Increasing bevacizumab dose intensity could override the prognostic impact of primary tumor location in patients receiving double the dose of bevacizumab after first disease progression.

Paraneoplastic cerebellar degeneration associated with anti-Yo antibodies in an ovarian cancer case: A case report.

Paraneoplastic neurologic syndromes (PNS) are a rare heterogeneous group of disorders associated with malignancy that can result in significant functional impairment. One syndrome in particular, paraneoplastic cerebellar degeneration (PCD), may be severely disabling. PCD is a rare neurological syndrome, associated with active or subclinical cancer, characterized by acute or subacute onset cerebellar ataxia due to tumor-induced autoimmunity against cerebellar antigens. Treatment of paraneoplastic syndromes is generally unsatisfactory, but early diagnosis and treatment of PCD, which includes neurological treatment, immunotherapy and oncological treatment of associated malignancy, may improve the neurological prognosis. We reported the case of a 59-year-old woman who presented PCD as the first sign of ovarian cancer. Laboratory investigations showed the presence of anti-Yo antibodies in the serum. The brain MRI revealed specific modifications for PCD. After oncological treatment, intravenous immunoglobulin therapy and corticosteroid therapy, the oncological response was satisfactory, but no improvement of the neurologic symptoms was achieved.

The importance of a multidisciplinary team in rectal cancer management.

INTRODUCTION: The aim of this study was to evaluate the impact of the interval between surgery and adjuvant treatments regarding the overall survival and recurrence-free survival in patients from a developing country. For stages II and III rectal cancer, international guidelines recommend neoadjuvant chemoradiotherapy (CRT) regardless of the tumor location. In the developing countries there is a shortage of radiotherapy centers, specialists, which lead to long waiting lists for radiotherapy. These problems might lead to protocol deviations. METHODS: We conducted a retrospective study on 161 patients with rectal cancer treated with surgery, postoperative CRT and with or without chemotherapy for a total of 6 months, at The Oncology Institute Cluj-Napoca between 2006-2010. All patients had 5 years of follow-up. RESULTS: A total of 161 patients were enrolled in this study. The majority of patients were locally advanced stages (89.44%). The well known prognostic factors, such as TNM stage, performance status, CEA serum level, perineural, vascular and lymphatic invasion, and node capsular effraction had a statistically significant influence on overall survival. In 21.12% of patients the first adjuvant treatment was started in the first 4 weeks after surgery. Only 13.04% of patients started the concomitant CRT within the limit of 6 weeks after surgery. Concerning the time between surgery and CRT, we did not observe a statistically significantly difference in OS if the radiotherapy started after the first 6 weeks (p=0.701). The OS rate for locally advanced rectal cancer patients was 69.44%. CONCLUSIONS: In rectal cancer, the importance of the first therapeutic act is crucial. Following international guidelines provides a survival advantage and a better quality of life. In case of adjuvant treatment, it is recommended to start this treatment as soon as the local infrastructure allows it.

Solid pseudopapillary tumor of the pancreas: clinical-pathological features and management of 13 cases.

BACKGROUND AND AIM: Solid pseudopapillary tumor (SPT) of the pancreas is a rare pathological condition, representing less than 3% of all exocrine pancreatic tumors. SPT usually occurs in young females, without notable symptoms, with a low malignant potential and excellent prognosis. METHOD: We conducted a retrospective study during the period January 2005 - January 2015. SPT patients admitted in our institution were reviewed by describing demographic data, clinico-pathologic and radiological features, therapeutic management and prognosis records. RESULTS: Thirteen patients with SPT were identified (10 females), with a median age of 30 years. The main clinical presentation was abdominal pain (92.3%). The tumor was mostly located in the body or tail of the pancreas (77%), and the mean size was 8.2 cm. Regarding the surgical approach there were 5 distal pancreatectomies with splenectomy, 3 body and tail pancreatectomies, 2 body and tail pancreatectomies with splenectomy, 2 pancreato-duodenectomy, 1 partial enucleation and of all only 2 partial resections. Postoperative hematoxylin- eosin staining and immunohistochemistry confirmed the diagnosis in all cases. None of the patients had lymph nodes metastases. Only one local invasion. There was one case of death due to postoperative complications. Four cases followed adjuvant systemic chemotherapy. The mean follow-up was 18 months, without evidence of recurrence during this period. CONCLUSION: SPT should always be considered in the differential diagnosis in young women with a pancreatic tumor. Complete surgical excision is the treatment of choice, and is usually curative. The decision to administer systemic therapy must be individualized. Malignant behavior and late recurrences mandates long-term follow-up for patients with SPT.

The Importance of Ubiquitin E3 Ligases, SCF and APC/C, in Human Cancers.

A normal evolution of the cell-cycle phases consists of multiple consecutive events, which makes it a highly complex process. Its preservation is regulated by Cyclin-Cdks (cyclin-dependent kinases) interactions and protein degradation, which is often controlled by the ubiquitin-mediated proteolysis. The goal of this review is to emphasize the most important features of the regulation of the cell-cycle involved in cancerogenesis, by presenting the involvement of E3 ubiquitin ligases SCF (Skp1-Cul1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome) in human malignancies. Also, we discuss the importance of the ubiquitin proteasome pathway blockade in cancer treatment. We know that a better understanding of the regulatory biology of the cell cycle can lead to the development of new target therapies for cancer.