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IntroductionVarious studies have suggested use of socket grafting materials after dental extraction for socket preservation. However, there is no single material that has been accepted as standard for preserving the socket. The purpose of this systematic review was to analyze the evidence for the use of biphasic calcium phosphate for socket regeneration. Materials and MethodsThe team conducted a systematic literature search in accordance with the protocol registered at PROSPERO. PubMed, OVID, and EMBASE databases were used in the search. The articles were then screened using RAYYAN open-source software for the synthesis of evidence. ResultsOf the 240 articles found in the search, two studies could be included in the review. ConclusionBiphasic calcium phosphate (60% hydroxyapatite, HA and 40% beta-tricalcium phosphate, β-TCP) has a significant effect in the socket preservation and quality of bone regeneration.

Abstract Objective To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors. Methods Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals. Results Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy. Conclusion CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.

Abstract Introduction With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. Methods Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife® image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide. Results During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. Conclusion We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.

Abstract Objective Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective. Methods Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment. Results Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression. Conclusion Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study.

PurposeCabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.MethodsThis was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR).ResultsSixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa.ConclusionsDespite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib.

Introduction: Various studies have suggested use of socket grafting materials after dental extraction for socket preservation. However, there is no single material that has been accepted as standard for preserving the socket. The purpose of this systematic review was to analyze the evidence for the use of biphasic calcium phosphate for socket regeneration. Materials and Methods: The team conducted a systematic literature search in accordance with the protocol registered at PROSPERO. PubMed, OVID, and EMBASE databases were used in the search. The articles were then screened using RAYYAN open-source software for the synthesis of evidence. Results: Of the 240 articles found in the search, two studies could be included in the review. Conclusion: Biphasic calcium phosphate (60% hydroxyapatite, HA and 40% beta-tricalcium phosphate, ß-TCP) has a significant effect in the socket preservation and quality of bone regeneration. [ABSTRACT FROM AUTHOR]

The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR- activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR- TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to- mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR- mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC., Introduction Lung cancer is a major cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. In 2004, somatic mutations in the [...]

Orthodontic mini-implants or transient anchorage devices can be used to shift difficult teeth. There is substantial evidence showing the effectiveness of Temporary Anchorage Devices (TAD) and their anchorage requirements. However, there are also reports of failures and complications like soft tissue inflammation, tissue overgrowth, peri-implantitis and mini-implant fracture. The present case report of 22 years old female patient, discusses a rare occurrence of tissue overgrowth over the mini-implant on right buccal mucosa in relation to 45, 46 regions. A 1.3×9 mm stainless steel mini-implant was used as an interim anchorage device. The tissue overgrowth was attributed to soft tissue inflammation around the mini-implant. Under adequate anaesthesia, the tissue was removed using a laser, and the mini-implant was retrieved using tissue forceps. After achieving hemostasis, simple interrupted sutures were placed. It is recommended to administer antibiotics, analgesics, and along with postoperative instructions. When used correctly, mini-screws are valuable tools that enhance the effectiveness of orthodontic treatment. However, there is a scarcity of case studies discussing the complications and side-effects of mini-implants. Clinicians should carefully evaluate both general and unique side-effects and complications at the insertion site. This case report demonstrates the successful removal of an orthodontic mini-implant following diode laser ablation of hyperplastic tissue. [ABSTRACT FROM AUTHOR]