Current Cancer Therapy Reviews - Volume 14, Issue 1, 2018

Purpose: To explore the role of stereotactic body radiotherapy (SBRT) in the management of primary or metastatic liver cancer. Materials and Methods: A systematic search of the PubMed database was conducted to identify indications and patient selection criteria, technique and dose prescription, oncologic outcomes and side effects of stereotactic body radiotherapy (SBRT) for liver cancer. Results: The role for radiotherapy in the management of liver cancer is increasing, thanks to recent developments and technological advances in diagnosis, surgery, conformal radiotherapy, and new chemotherapy regimens. SBRT delivers a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues. Integrated, multidisciplinary management significantly improves overall survival and quality of life. Conclusion: Stereotactic body radiation therapy is a non-invasive, effective and welltolerated treatment modality for patients with liver cancer.

Background: Stereotactic body radiotherapy (SBRT) is a recent addition to the armamentarium for treating clinically localized prostate cancer. SBRT is a special form of image-guided radiotherapy (IGRT) that involves the delivery of a small number of very high-dose fractions (e.g. 35 to 40 Gy, in 4 to 5 fractions). The slow-growing nature of prostate adenocarcinoma is thought to be associated to a low α[alpha]/β[beta] ratio of ~1.5, that is believed to confer a preferential sensitivity to ultra-hypofractionation. Literature documenting excellent long-term outcomes and relatively low toxicity with high dose-rate (HDR) brachytherapy (using similar dose-fractionation) provided a clinical rationale for SBRT. Methods: A review was performed of available literature focusing on the current status of SBRT for clinically localized prostate cancer, including trends, evidence of late toxicity and unresolved issues. Results: The adoption of SBRT for prostate cancer has been rapid, increasing from <1% in 2004 (in all patient groups), to 8.8% by 2012. Cost and convenience have contributed to this trend, despite the risk that the toxicity may be slightly higher. RTOG 0938 demonstrated the clinical tolerance and feasibility in a multi-institutional setting and is expected to form the basis for a definitive phase III trial comparing SBRT to a more conventional fractionation scheme. Whether the use of rectal spacers or modified dose constraints will improve the risk benefit ratio remains to be elucidated. More work is also needed to assess the role of SBRT as a boost after conventional radiation, in the setting of “salvage” therapy and as palliation for urinary tract obstruction due to prostate cancer. Conclusion: There appears to be a substantial and growing interest in SBRT for clinically localized prostate but much more work is needed to define its role relative to other forms of radiation including conventional external beam radiation and brachytherapy.

Background: Pancreatic cancer is a difficult malignancy to manage with little improvement in mortality rates over time. Local control remains a challenge. The objective of this review is to discuss patient selection and technical considerations for the safe utilization of stereotactic body radiotherapy (SBRT). Methods: An online search was completed to review available data. The current literature examining the use and delivery of SBRT for pancreatic cancer was reviewed and summarized. Patient selection criteria, technical considerations, and the implementation of SBRT are described. Results: Studies thus far have shown promising outcomes for SBRT in terms of potential for conversion from borderline or unresectable to resectable disease as well as the feasibility of delivering SBRT safely. Conclusion: SBRT represents an emerging treatment option for patients to improve local control through delivery of ablative, high-dose radiation while reducing radiation treatment time as compared to conventionally fractionated chemoradiation. Further studies are needed to explore the full potential and toxicities of SBRT in pancreatic cancer. The importance of technical considerations in this modality cannot be overstated.

Introduction: The role of stereotactic radiosurgery is increasing in the management of brain and spine metastases. We review the data supporting its use. Methods: We used data to compile recommendations for indications, prescription dose and dose constraints, treatment outcomes, and toxicities. Results: Stereotactic radiosurgery is demonstrated to be effective and safe in the management of brain and spine metastases, both upfront and for recurrence. Toxicities, particularly radiation necrosis and myelopathy, can be morbid and need to be followed for. Conclusion: While the data support its use, there needs to be continued research with improved technology, on the use of radiosurgery for larger brain metastases, and on the toxicities of radiosurgery and its management.

Background: Stereotactic body radiotherapy (SBRT) or radiosurgery has emerged as a viable highly precise technique that delivers a hypofractionated radiotherapy regimen with a high biologic effective dose. In addition to patient convenience, this dose is thought to provide acceptable local control while keeping toxicity to a minimum due to the typical small target size. The aims of this paper are to review recent outcomes with the application of SBRT in the management of head and neck cancer. Methods: Research and online content related to head and neck cancer SBRT were reviewed focusing on dose fractionation schedules, incorporation of systemic therapy and long term toxicity. Results: SBRT technique provided convenient precise approach in the management of primary as well as recurrent head and neck cancer with adequate local control rates and tolerable long term toxicity profile. Conclusion: The use of stereotactic body radiotherapy is still evolving and multiple studies are needed to optimize the dose fractionation of SBRT and its integration with systemic therapy.

Background: Colorectal cancer (CRC) also known as bowl cancer is still one of the leading causes of cancer related mortality worldwide. Generally tumor cells are protecting themselves by fibrin coat and it is resistant to fibrinolytic degradation. Such a coated tumor appears as ‘self’ to the immune system, and thus is not detected as a tumor by the immune system (i.e. natural killer cells). Hence, a potent proteolytic enzyme has to propose/ identify to dissolve the protective fibrin layer, exposing the tumor cell surface to chemotherapy and immune attack. In this research papain was considered to be the potential proteolytic agent, can break down the fibrin coat of cancer cell wall and ultimately the cancer cells are exposed to immune attack and help against the cancer. Secondly, the cytotoxic compound(s) directly deliver to cancer site without harm to normal cells. Methods: The attempt made to attain this objective, we were designed to fabricate the Papain loaded solid lipid nanoparticles (SLN) by melt dispersion-ultrasonication technique, and investigate the various formulation parameters. The papain loaded SLN was characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), Scanning electron microscopy (SEM), drug encapsulation efficiency, in vitro drug release, and in vitro cytotoxicity studies on HT-29 colorectal cancer cells. Results: The successful outcome of this research was that, the cetyl alcohol based SLN of papain were successfully prepared by using melt dispersion- ultrasonication method with maximum encapsulation efficiency with desired particle size. The release profile of the produced SLN was investigated in phosphate buffer media, and it showed prolonged release during 24 h. The drug release behaviour from the SLNs exhibited a biphasic pattern with the burst release at the initial stage and sustained release subsequently. Future perspective of this research is that need to investigate the SLN for the lymphatic uptake to produce local action on metastatic colorectal cancer. In vitro cell viability for P-SLNs was tested on colorectal Adenocarcinoma HT-29 cells by MTT assay. The results revealed that the in vitro cell viability against different concentrations of papain was 99% and 31 % which were treated with 5μg/ml and 80μg/ml concentration respectively. The cell viability of HT-29 cells was decreased signicantly from 94 % to 17 % treated with P-SLN at 5 μg/ml and 80 μg/ml concentration respectively. Therefore, the papain loaded SLNs exhibits a better performance on getting lower cell viability (or) equivalent high cytotoxicity than that of pure papain. Therefore, the SLNs delivery system plays a significant role in enhancing the cytotoxic efficacy of papain enzyme against colorectal cancer cells. Conclusion: In this research, we successfully formulated the P-SLN for the treatment of colorectal cancer therapy. We investigate the various formulation parameters, drug release profile and cytotoxic efficacy of P-SLN. Upon successful completion of this work, P-SLNs delivery system is predictable to produce enhanced cytotoxic efficacy against HT-29 colorectal cancer cells. The papain loaded SLNs can potentially be utilized as a drug delivery system for the treatment of colorectal cancer. In future, we will explore further to investigate the mechanism of anticancer activity and clinical investigation of P-SLN.