Volumetric Modulated Arc Therapy as an Example of the Advanced Capability of Modern Radiotherapy.

BACKGROUND: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges. OBJECTIVES: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies. METHODS: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT. RESULTS: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases. CONCLUSIONS: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Combined acetyl-11-keto-ß-boswellic acid and radiation treatment inhibited glioblastoma tumor cells.

Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated in vitro and in vivo the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth in vivo compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA in vivo. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells in vitro and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients.

Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer.

BACKGROUND: Radiotherapy is one of the primary therapies for localized prostatic carcinoma. Therefore, there is an emerging need to sensitize prostatic cancer cells to chemotherapy/radiotherapy. Modified citrus pectin (MCP) is an effective inhibitor of galectin-3 (Gal-3), which is correlated with tumor progression, proliferation, angiogenesis, and apoptosis. PURPOSE: This study was directed to evaluate the efficacy of combining ionizing radiation (IR) with MCP on PCa cells. STUDY DESIGN: Effects of treatments on PCa cells survival were evaluated using XTT assay, flow cytometry, and clonogenic survival assay. Expression of selected proteins was estimated using western blotting. Cell motility, migration, and invasion were determined. Contribution of reactive oxygen species production to treatment effects on cell viability was tested. RESULTS: Radiotherapy combined with MCP reduced viability and enhanced radiosensitivity associated with a decrease in Gal-3, cleavage of the precursor of caspase-3, increased expression of the pro-apoptotic protein Bax, and downregulation of DNA repair pathways, poly-ADP-ribose polymerase, and proliferating cell nuclear antigen. MCP significantly reduced the invasive and migratory potential of PCa cells. Combining sodium pyruvate with MCP and IR mitigated the effect on cell viability. CONCLUSION: Our findings demonstrated that MCP sensitized PCa cells to IR by downregulating anti-apoptotic Gal-3, modulating DNA repair pathways, and increasing ROS production. For the first time the correlation between MCP, radiotherapy, and Gal-3 for prostatic cancer treatment was found. In addition, MCP reduced the metastatic properties of PCa cells. These findings provide MCP as a radiosensitizing agent to enhance IR cytotoxicity, overcome radioresistance, and reduce clinical IR dose.

Single-institution Experience of SBRT for Lung Metastases in Sarcoma Patients.

OBJECTIVES: Lung metastasectomy is regarded as the standard procedure for improving the prognosis of patients with metastatic sarcoma. Few reports are available in the literature describing the value of stereotactic body radiation therapy (SBRT) of lung metastases from primary sarcoma as an alternative to surgical treatment. We therefore sought to expand the evidence base for this modality. MATERIALS AND METHODS: Twenty-two patients with metastatic sarcoma to lung were treated by SBRT. The retrospective analysis of overall survival, toxicity, and local control of 53 treated lesions is presented in the study. Lung lesions were grouped into 2 categories for follow-up: <10 mm or ≥10 mm diameter. RESULTS: Of 34 lesions <10 mm, 24 achieved complete response, 3 partial response, and 7 stable disease. The results of 18 lesions measuring >10 mm were as follows: 5 complete response, 5 progressive disease, and 8 stable disease. No progressive disease of all SBRT treated lesions was found at a median follow-up of 95 months (SD 32). Five-year overall survival of the entire group was 62% from the time of diagnosis and 50% from start of treatment. The treatment was well tolerated with minimal, mainly skin toxicity. CONCLUSION: SBRT is an effective tool that might be used as an alternative to operative treatment of lung metastases in sarcoma patients.

AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors.

Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors.