The Use of Intraoperative Radiation Therapy (IORT) in Multimodality Management of Cancer Patients: a Single Institution Experience.

BACKGROUND: Intraoperative radiation therapy (IORT) is a highly conformal type of radiation therapy given at time of surgery aiming for better tumor local control. It increases the tumor radiation dose without exceeding normal tissues tolerance doses. PURPOSE: To assess the feasibility of IORT and short-term toxicities in patients with different cancer sites treated with multidisciplinary protocol including IORT. PATIENTS AND METHODS: Medical records of cancer patients who received IORT as a part of their multidisciplinary treatment at King Faisal Specialized Hospital and Research center (KFSH&RC), Riyadh, Saudi Arabia, from January 2013 until December 2017 were retrospectively reviewed. RESULTS: A total of 188 patients with 210 IORT applications were analyzed. Twenty-two patients had two applications at the same time. One hundred sixteen patients were males. Median age at time of diagnosis was 49.5 years (19-77). One hundred thirty-four patients had primary, while 54 cases had recurrent disease. Gastroesophageal cancer and soft tissue sarcoma were the most frequent diagnosis in 49 patients followed by colorectal cancer in 35 patients. Major surgeries with curative intent done in 183 patients (97.3%). Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 118 (62.8%) patients. The 30-day postoperative mortality rate was 3.2%. Fifty-four (28.7%) patients develop grades III-IV complications according to Clavien-Dindo grading system. CONCLUSION: The data presented discusses using of IORT treatment for different malignant tumors as a part of multimodality treatment. IORT seems safe and feasible; however, a longer follow-up period is needed for proper evaluation and to define the role of IORT in a tailored multimodality approach.

Biosynthesis of copper oxide nanoparticles mediated Annona muricata as cytotoxic and apoptosis inducer factor in breast cancer cell lines.

This study investigated for the first time a simple bio-synthesis approach for the synthesis of copper oxide nanoparticles (CuO NPs) using Annona muricata L (A. muricata) plant extract to test their anti-cancer effects. The presence of CuONPs was confirmed by UV-visible spectroscopy, Scanning electron microscope (SEM), and Transmission electron microscope (TEM). The antiproliferative properties of the synthesized nanoparticles were evaluated against (AMJ-13), (MCF-7) breast cancer cell lines, and the human breast epithelial cell line (HBL-100) as healthy cells. This study indicates that CuONPs reduced cell proliferation for AMJ-13 and MCF-7. HBL-100 cells were not significantly inhibited for several concentration levels or test periods. The outcomes suggest that the prepared copper oxide nanoparticles acted against the growth of specific cell lines observed in breast cancer. It was observed that cancer cells had minor colony creation after 24 h sustained CuONPs exposure using (IC50) concentration for AMJ-13 was (17.04 µg mL-1). While for MCF-7 cells was (18.92 µg mL-1). It indicates the uptake of CuONPs by cancer cells, triggering apoptosis. Moreover, treatment with CuONPs enhanced Lactate dehydrogenase (LDH) production, probably caused by cell membrane damage, creating leaks comprising cellular substances like lactate dehydrogenase. Hence, research results suggested that the synthesized CuONPs precipitated anti-proliferative effects by triggering cell death through apoptosis.

Choice of Antimicrobials in Surgical Prophylaxis - Overuse and Surgical Site Infection Outcomes from a Tertiary-Level Care Hospital.

Background: This study was aimed to describe the choice of Surgical Antimicrobial Prophylaxis at a tertiary-level care hospital in United Arab Emirates. It also associated the choice between two leading antimicrobials for the SAP to the site of surgery. Methods: A descriptive drug use evaluation was performed retrospectively to study choices of antimicrobials in surgical antibiotic prophylaxis. An analytical cross-sectional study design was used to develop a hypothesis regarding the choice of ceftriaxone. Data were collected from the medical records of Hospital from July 2020 to December 2020. Results were presented in numbers and percentages. Results: SAP data were collected from 199 patients, of which 159 were clean or clean-contaminated. Dirty surgeries (18) needed a higher level of antimicrobials as there were infections to be treated. For other surgeries with no infection, overuse of antimicrobials was found regarding the choice of antimicrobials. Surgical antibiotic Prophylaxis was administered within the recommended time prior to surgeries. Ceftriaxone was preferred over cefuroxime in all types of surgeries based on the timing of Surgical Antibiotic Prophylaxis, wound classification, and the surgical site. A statistically significant association for choice of ceftriaxone over cefuroxime was found regarding surgical sites (p-value <0.05). About 99% of the patients were prescribed discharge antimicrobials when 158 (80%) surgeries were clean or clean-contaminated. Conclusion: Overuse of antimicrobials was found in surgical antimicrobial prophylaxis. Ceftriaxone was preferred more than cefuroxime in all types of surgeries. No surgical site infections were reported. A follow-up comparative study is recommended to decrease antimicrobial use without increasing risk of surgical site infection.

LC-MS/MS Proteomic Study of MCF-7 Cell Treated with Dox and Dox-Loaded Calcium Carbonate Nanoparticles Revealed Changes in Proteins Related to Glycolysis, Actin Signalling, and Energy Metabolism.

One of the most prevalent death causes among women worldwide is breast cancer. This study aimed to characterise and differentiate the proteomics profiles of breast cancer cell lines treated with Doxorubicin (DOX) and Doxorubicin-CaCO3-nanoparticles (DOX-Ar-CC-NPs). This study determines the therapeutic potential of doxorubicin-loaded aragonite CaCO3 nanoparticles using a Liquid Chromatography/Mass Spectrometry analysis. In total, 334 proteins were expressed in DOX-Ar-CC-NPs treated cells, while DOX treatment expressed only 54 proteins. Out of the 334 proteins expressed in DOX-CC-NPs treated cells, only 36 proteins showed changes in abundance, while in DOX treated cells, only 7 out of 54 proteins were differentially expressed. Most of the 30 identified proteins that are differentially expressed in DOX-CC-NPs treated cells are key enzymes that have an important role in the metabolism of carbohydrates as well as energy, including: pyruvate kinase, ATP synthase, enolase, glyceraldehyde-3-phosphate dehydrogenase, mitochondrial ADP/ATP carrier, and trypsin. Other identified proteins are structural proteins which included; Keratin, α- and ß-tubulin, actin, and actinin. Additionally, one of the heat shock proteins was identified, which is Hsp90; other proteins include Annexins and Human epididymis protein 4. While the proteins identified in DOX-treated cells were tubulin alpha-1B chain and a beta chain, actin cytoplasmic 1, annexin A2, IF rod domain-containing protein, and 78 kDa glucose-regulated protein. Bioinformatics analysis revealed the predicted canonical pathways linking the signalling of the actin cytoskeleton, ILK, VEGF, BAG2, integrin and paxillin, as well as glycolysis. This research indicates that proteomic analysis is an effective technique for proteins expression associated with chemotherapy drugs on cancer tumours; this method provides the opportunity to identify treatment targets for MCF-7 cancer cells, and a liquid chromatography-mass spectrometry (LC-MS/MS) system allowed the detection of a larger number of proteins than 2-DE gel analysis, as well as proteins with maximum pIs and high molecular weight.

Protein profile of MCF-7 breast cancer cell line treated with lectin delivered by CaCO3NPs revealed changes in molecular chaperones, cytoskeleton, and membrane-associated proteins.

The second most predominant cancer in the world and the first among women is breast cancer. We aimed to study the protein abundance profiles induced by lectin purified from the Agaricus bisporus mushroom (ABL) and conjugated with CaCO3NPs in the MCF-7 breast cancer cell line. Two-dimensional electrophoresis (2-DE) and orbitrap mass spectrometry techniques were used to reveal the protein abundance pattern induced by lectin. Flow cytometric analysis showed the accumulation of ABL-CaCO3NPs treated cells in the G1 phase than the positive control. Thirteen proteins were found different in their abundance in breast cancer cells after 24 h exposure to lectin conjugated with CaCO3NPs. Most of the identified proteins were showing a low abundance in ABL-CaCO3NPs treated cells in comparison to the positive and negative controls, including V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP. Hornerin, tropomyosin alpha-1 chain, annexin A2, and protein disulfide-isomerase were up-regulated in comparison to the positive. Bioinformatic analyses revealed the regulation changes of these proteins mainly affected the pathways of 'Bcl-2-associated athanogene 2 signalling pathway', 'Unfolded protein response', 'Caveolar-mediated endocytosis signalling', 'Clathrin-mediated endocytosis signalling', 'Calcium signalling' and 'Sucrose degradation V', which are associated with breast cancer. We concluded that lectin altered the abundance in molecular chaperones/heat shock proteins, cytoskeletal, and metabolic proteins. Additionally, lectin induced a low abundance of MCF-7 cancer cell proteins in comparison to the positive and negative controls, including; V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP.

Dose Escalation with Simultaneous Integrated Boost (SIB) Using Volumetric Modulated Arc Therapy (VMAT) in Rectal Cancer.

PURPOSE: Assess feasibility-rate of PCR, short-term toxicity after neoadjuvant concurrent chemoradiation (NACRT) delivered via simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique for locally advanced rectal cancer. METHODS: Retrospective evaluation of patients with locally advanced rectal cancer treated with VMAT-SIB technique preoperatively at an academic tertiary care center in Riyadh, Saudi Arabia between February 2013 and March 2017. RESULTS: One hundred patients with depth of invasion staged as T3/T4 or T2 in 93 and seven patients, respectively. Lymph node metastasis was staged as N1/N2 or N0 in 87 and 13 patients, respectively. Circumferential radial margin (CRM) was involved radiologically prior to treatment in 50 patients. A dose of 55 or 50 Gy was given to 71 and 29 patients, respectively. All treatments were completed without interruption. Grade 3/4 toxicity was not observed. Low anterior resection and abdominoperineal resection were performed with negative proximal, distal, and radial margins in 72 and 28 patients, respectively. There were no immediate significant postoperative complications. Histologically, no residual tumor (grade 0) was noted in 20 patients (pCR). Regression grade 1, 2, and 3 were noted in 31, 34, and 15 patients. Average number of lymph nodes retrieved in the surgical specimen was 12 (range 6-22). Lymph nodes were negative for cancer in 80 patients. CONCLUSION: Dose escalation with SIB-VMAT as NACRT for rectal cancer is feasible. Moreover, it can increase the rate of pathological complete response with a favorable toxicity profile. Clinical benefit of this approach needs to be validated in a larger cohort of patients with longer follow-up.

Primary oral malignant melanoma metastasis to the brain and breast: A case report and literature review.

Primary oral malignant melanoma is a rare tumor, which is estimated to comprise 0.2-8.0% of all melanoma cases. This type of cancer is fairly uncommon, its prognosis is dismal, and it frequently exhibits a biologically aggressive behavior. The common location of primary oral malignant melanoma is the hard palate and maxillary alveolus. In ~85% of cases, the melanoma will metastasize to the liver, lung, bone and brain early in the course of the disease. The present study reports the case of a 50-year-old premenopausal woman who presented with primary oral malignant spindle cell melanoma (T3bN2aM0) and underwent complete surgical resection followed by an adjuvant course of radiation therapy. After 1 year, the patient presented with sudden onset slurred speech, and upon examination, was found to have left-sided hemiparesis and a hard left breast mass. Workup confirmed breast and brain metastasis. The patient developed lung metastasis 4 weeks later and was referred for palliative care.

Multiple enlarged lymph nodes in axilla A case report of Merkel Cell Carcinoma.

We present the case of a 59-year-old man with a growing mass in his left axillary area. A biopsy and immunostainings demonstrated neuroendocrine carcinoma, which is Merkel cell carcinoma (MCC). The disease is characterised by neurosecretory granules in tumor cells. MCC is a rare entity. The disease is predominantly seen in the inguinal region or the axilla and typically found incidentally. It presents clinically as multiple lymph nodes enlargement. Yet controversy exists regarding treatment modality of MCC. We report the first case of MCC in (Left) Axilla where there were two cases reported previously in (Right) Axilla. KEY WORDS: Lymph nodes enlargement, Merkel cell carcinoma, Radiotherapy.

Failure modes and effects analysis in image-guided high-dose-rate brachytherapy: Quality control optimization to reduce errors in treatment volume.

PURPOSE: Analyze the inputs which cause treatment to the wrong volume in high-dose-rate brachytherapy (HDRB), with emphasis on imaging role during implant, planning, and treatment verification. The end purpose is to compare our current practice to the findings of the study and apply changes where necessary. METHODS AND MATERIALS: Failure mode and effects analysis was used to study the failure pathways for treating the wrong volume in HDRB. The role of imaging and personnel was emphasized, and subcategories were formed. A quality assurance procedure is proposed for each high-scoring failure mode (FM). RESULTS: Forty FMs were found that lead to treating the wrong volume. Of these, 73% were human failures, 20% were machine failures, and 7% were procedural/guideline failures. The use of imaging was found to resolve 85% of the FMs. We also noted that imaging processes were under used in current practice of HDRB especially in pretreatment verification. Twelve FMs (30%) scored the highest, and for each one of them, we propose clinical/practical solutions that could be applied to reduce the risk by increasing detectability. CONCLUSIONS: This work resulted in two conclusions: the role of imaging in improving failure detection and the emphasized role of human-based failures. The majority of FMs are human failures, and imaging increased the ability to detect 85% of all FMs. We proposed quality assurance practices for each high-scoring FM and have implemented some of them in our own practice.

Hypofractionated Volumetric Modulated Arc Radiotherapy with simultaneous Elective Nodal Irradiation is feasible in prostate cancer patients: A single institution experience.

PURPOSE: To assess feasibility, toxicity and biochemical relapse-free survival (b-RFS) for a group of organ confined (OC) Saudi prostate cancer patients treated by hypo-fractionated Volumetric Modulated Arc Radiation Therapy (VMAT) Simultaneous Integrated Boost (SIB) Elective Nodal Irradiation (ENI) whole pelvic radiotherapy (WPRT). PATIENTS AND METHODS: Between March 2009 and January 2014, 29 OC prostate cancer patients; median age 64years, PS 0-1 were treated in King Faisal Specialist Hospital - Riyadh, Kingdom of Saudi Arabia using VMAT-SIB-ENI-WPRT, to a total dose of 70Gy in 28 fractions. Twenty Four patients (83%) were treated with neo-adjuvant; concurrent androgen deprivation therapy (ADT). Median follow-up (FU) was 42months (range: 18-72months). RESULTS: The 3-year actuarial b-RFS for low/intermediate and high risk groups were 100%, and 48%, respectively (p=0.09) with a median FU period of 34months (range: 14-53months). Gleason Score (p=0.02), and pretreatment PSA (p=0.01) were predictive for biochemical failure on univariate analysis; with no observed prostate cancer-related deaths. Grade 2 acute/late GI and GU toxicities were 28%/0% and 17%/10% respectively with no reported grade 3/4 toxicities. Four (50%) out of the 8 patients with baseline partial potency, retained sexual function on long term follow-up. CONCLUSIONS: Hypo-fractionation dose escalation VMAT-SIB-ENI-WPRT using 2 arcs is a feasible technique for intermediate/high risk OC prostate cancer patients, with acceptable rates of acute/late toxicities, much favorable planning target volume (PTV) coverage, and shorter overall treatment time. Prospective randomized controlled trials are encouraged to confirm its equivalence to other fractionation schemes.

Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer.

In this report, updated guidelines for the evaluation, medical, and surgical management of prostate cancer are presented. They are categorized according the stage of the disease using the tumor node metastasis staging system 7(th) edition. The recommendations are presented with supporting evidence level.

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions.

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.