Ridge preservation using a new 3D collagen matrix: a preclinical study.

OBJECTIVES: The success of ridge preservation techniques in reducing bone resorption is well documented, but no clear guidelines have been provided regarding the type of the biomaterial or technique to be used. This experimental animal study aimed at comparing the effectiveness of two ridge preservation techniques. MATERIALS AND METHODS: Following the extraction of the distal roots of the mandibular second and fourth premolars of four dogs, the sockets were preserved using a combination of a collagen membrane intimately covering the socket plus a collagen matrix or a collagen membrane alone. The mandibular quadrants were randomly assigned to one of the treatment groups. Histomorphometrical analyses as well as microscopic observations were performed. RESULTS: After 5 months of healing, the histological analysis revealed a similar picture of bone formation in both groups. No significant differences between the buccal and lingual dimensions were calculated between the two treatment groups. The mucosa covering the alveolar ridges is significantly more abundant in post-extraction sockets preserved with the double-layered approach. CONCLUSIONS: The double-layered approach used to treat post-extraction sockets may result in a better preservation of the mucosal seal than the single-layered approach. CLINICAL RELEVANCE: The use of the new collagen matrix associated with a collagen membrane could be a clinical option to preserve post-extraction ridges, especially when an improvement in soft tissue dimension and quality is desired. However, the cost-benefit ratio of this approach should be thoroughly evaluated in further studies.

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.

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.

Treatment beyond progression in metastatic colorectal cancer: to double or not to double the dose of bevacizumab?

PURPOSE: Bevacizumab or cetuximab represent the standard treatment in association with classical chemotherapy in confirmed metastatic colorectal cancer (mCRC). Bevacizumab could be continued after the first disease progression with an overall survival (OS) advantage, compared to chemotherapy alone, but the optimal dose remains a debatable issue. METHODS: In a retrospective analysis of mCRC patients treated with bevacizumab, we selected patients with administration beyond progression, and stratified them according to the dose received- same dose bevacizumab (SDB) as first-line chemotherapy or double dose bevacizumab (DDB). For each group we evaluated OS, time to treatment failure (TTF) and progression-free survival in the first-line (PFS1) and in the second-line (PFS2). RESULTS: In the first-line therapy, oxaliplatin backbone regimen was used in 73% SDB, compared with 22.5% DDB patients, while irinotecan was used in 75% DDB and 27% SDB patients. Second-line oxaliplatin was given to 50% DDB and 29.7% SDB patients, while irinotecan was administered to 47.5% DDB and 70.3% SDB patients. The median values were: OS - 41 months in the DDB group and 25 months in the SDB group (p = 0.01); TTF - 24 months in the DDB group and 19 months in the SDB group (p=0.009); PFS1 - 17 months in the DDB group and 12 months in the SDB group (p=0.008); PFS2 - 9 months in the DDB group and 5 months in the SDB group (p = 0.03). CONCLUSIONS: Doubling the dose of bevacizumab at progression seems to provide OS and PFS advantage for mCRC patients.

The impact of two-socket preservation approaches on the soft and hard tissue healing: a short-term study in dogs.

The present study was designed in the context of the uncertain circumstances related to the best therapeutic option for ridge preservation. The research aimed to investigate the quality of early healing processes developed in the former sockets preserved with a collagen matrix alone or associated with a bone substitute in comparison with naturally-healed sockets, using an animal model previously validated. In both quadrants of the mandible of two dogs, the distal sockets of the second and fourth premolars served as experimental sites. Two sockets healed naturally, three sockets were preserved with the collagen matrix and three sockets were preserved with the collagen matrix plus a bone substitute. After one month of healing, the samples were harvested and histologically processed. The soft tissue covering the preserved ridges displayed an obviously thicker epithelial layer containing mostly areas of parakeratinized epithelium alternating with keratinized ones in comparison with naturally-healed sockets. In the apical third of the sockets, a mature bone structure was recorded for all three types of post-extraction approaches. While in naturally-healed and collagen matrix-preserved specimens the central third of the sockets contained bone with a mature aspect, in collagen matrix plus bone substitute-preserved sockets an immature appearance was observed. In the external third of the sockets, only in matrix-preserved alveoli a well-developed cancellous bone was present. The bovine bone substitute seemed to delay hard tissue development. The use of the collagen matrix could be a clinical option to preserve post-extraction ridges especially when an improvement in soft tissue quality is desired.