Duloxetine for the Prevention of Oxaliplatin Induced Peripheral Neuropathy: A Randomized, Placebo-Controlled, Double-blind Clinical Trial.

PURPOSE: Peripheral neuropathy is a dose-limiting adverse effect of oxaliplatin. The aim of this study was to evaluate the efficacy and safety of duloxetine in the prevention of oxaliplatin-induced peripheral neuropathy (OIPN). METHOD: Cancer patients receiving oxaliplatin based chemotherapy were randomized into two arms. Duloxetine 60 mg capsule was given in the first 14 days of each chemotherapy cycle to one arm and placebo was similarly given to another. We compared the two arms based on the incidence of neuropathy and the results of the nerve conduction study (NCS). Grade of complained neuropathy was recorded according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Thirty-two patients mostly rectal cancer (90.6%) were randomized to duloxetine and placebo arms. Highest grade of neuropathy in each cycle was not significantly different between the two groups. Six weeks after treatment incidence of neuropathy of any grade was 52.9 in duloxetine arm compared to 76.9% in placebo arm (P: 0.26). Patients in the duloxetine arm had a lower percentage of chemotherapy cycles (mean) in which they reported distal paresthesia (51% vs. 84%, P = 0.01) and throat discomfort (37% vs. 69%, P = 0.01). Results of NCS were mostly comparable between the two arms except for the velocity in two of the examined nerve which was significantly higher in duloxetine group. Duloxetine was safe and well-tolerated. CONCLUSION: Although a definite conclusion might be difficult to draw but administering duloxetine for 14 days in each chemotherapy cycle could not decrease the incidence of acute OIPN based on CTCAE grading system.

Radioprotective Effects of Combined Melatonin and Famotidine Treatment on Radiation Induced Apoptosis in Peripheral Blood Leukocytes of Breast Cancer Patients and Normal Individuals.

OBJECTIVE: The aim of this study was to evaluate the effects of individual or combined use of two antioxidants, melatonin and famotidine on radiation induced apoptosis in leukocytes from breast cancer (BC) patients. MATERIALS AND METHODS: In this experimental study, the DPPH assay was used to determine the appropriate doses of melatonin and famotidine for treatment of BC and control leukocytes. The leukocytes were cultured in complete RPMI1640 medium and treated with either agent for two hours. Cells were exposed to 4 Gy gamma rays generated from a Co-60 source at a dose rate of 0.85 Gy for 48 hours before harvesting. The cells were placed on slides and the neutral comet assay was performed. A total of 500 cells were stained with ethidium bromide and assessed for the amount of apoptosis under a fluorescent microscope x400 magnification. RESULTS: We observed significantly more apoptosis following radiation alone in the leukocytes from BC patients compared with normal individuals (P<0.01). Individual use of famotidine and melatonin induced very low frequencies of apoptosis that was not significantly different from the control (P>0.05). However, when combined with radiation, there was a decreased frequency of apoptosis in leukocytes of both normal and BC patients (P<0.05). The effect of famotidine was more pronounced than melatonin. CONCLUSION: Melatonin, despite its potent antioxidant property, does not significantly affect radiation induced apoptosis in leukocytes derived from normal individuals; however, it has a moderately significant protective effect on in leukocytes derived from BC patients. Therefore, when used with radiation it might not intervene with the radiotherapy (RT) regimen of BC cancer patients. Famotidine is a good radioprotector for normal tissue. However, the efficacy of RT might be reduced with an accumulation of famotidine in tumour tissues.

Comparison of Iodide-125 and Ruthenium-106 Brachytherapy in the Treatment of Choroidal Melanomas.

BACKGROUND: To compare iodine-125 (125I) with ruthenium-106 (106Ru) episcleral plaque radiation therapy in terms of the effectiveness and non-inferiority for choroidal melanoma treatment. OBJECTIVE: To report the non-inferiority of new made iodine-125 (125I) compared with ruthenium-106 (106Ru) episcleral plaque radiation. PATIENTS AND METHODS: A retrospective, non-randomized comparative case series. In this series the patients treated with 125I and 106Ru episcleral plaques for choroidal melanoma between September 2013 and August 2017 at Farabi Hospital are compared. Local control of choroidal melanomas after 125I and 106Ru plaques implantation and vision changes are the main outcome measures. RESULTS: A total of 35 patients were identified (125I = 15, 106Ru = 20). No significant difference between two groups in visual acuity, diameter and thickness changes were observed after treatment. Multivariate linear regression (MLR) analysis showed that final diameter was only, independently and significantly, correlated with the pre-treatment diameter of the tumor (ß = 0.59, 95% confidence interval [CI]: 0.29, 1.34, P = 0.003). The same MLR analysis for the final thickness and visual acuity, after adjusting for age and sex showed no significant difference between two groups. A single patient treated with 106Ru had local tumor recurrence with no one in the 125I group. No statistical difference in the rate of ocular complications was observed. CONCLUSION: The treatment with our 125I plaques is as effective as 106Ru plaques in controlling choroidal melanoma tumor and preserving the vision during the two and half year of follow-up. The complication rates are alike. It means that the effectiveness of 125I is not only comparable to 106Ru but also superior when the outcome of the interest is the thickness of the tumors.

COVID19 Prevention & Care; A Cancer Specific Guideline.

On March 11th 2020, the coronavirus outbreak was declared a pandemic by the WHO. One of the groups that is considered high risk in this pandemic are cancer patients as they are treated with a variety of immune system suppressor treatment modalities and this puts them in a great risk for infectious disease (including COVID-19). Therefore, cancer patients require higher level measures for preventing and treating infectious diseases. furthermore, cancer patients may bear additional risk due to the restriction of access to the routine diagnostic and therapeutic services during such epidemic. Since most of the attention of health systems is towards patients affected with COVID-19, the need for structured and unified approaches to COVID-19 prevention and care specific to cancer patients and cancer centers is felt more than ever. This article provides the recommendations and possible actions that should be considered by patients, their caregivers and families, physician, nurses, managers and staff of medical centers involved in cancer diagnosis and treatment. We pursued two major goals in our recommendations: first, limiting the exposure of cancer patients to medical environments and second, modifying the treatment modalities in a manner that reduces the probability of myelosuppression such as delaying elective diagnostic and therapeutic services, shortening the treatment course, or prolonging the interval between treatment courses.

Optimization of low-energy electron beam production for superficial cancer treatments by Monte Carlo code.

CONTEXT: Low energy electron beam has been being used widely for superficial cancer treatments. In the current study a design for production of very low energy electron beam, by different thickness of Perspex spoilers, is presented that may be used for skin cancer. AIMS: MCNPX Monte Carlo code was used for modeling and simulations in the current study. An energy spoiler Perspex was modeled for degrading 4 MeV electron beam of Varian 2300 CD Linac. MATERIALS AND METHODS: The thicknesses of 3, 7, and 10 mm were applied before electron applicator at a distance of 42 cm from phantom surface. Dosimetric properties of new electron beams including Rp, Dmax, E0, as well as the penumbra of the beam were investigated. RESULTS: For the 3 mm spoiler, the superficial beam output decreased to 77%, and the Dmax, R90, R50, and RP were shifted to the depths of 4, 6, 9, and 12 mm, respectively. While for 10 mm filter the results were 5.2, 3.0 and 5.0 mm for R90, R50, and Rp, respectively. In addition, the surface dose was 93% and the Dmax was shifted to the depth of 1mm for the 10mm Perspex spoiler slab. CONCLUSIONS: The presented beam provides a novel surface dose, Dmax, and RP which can be applicable for treatment of skin cancers with minimum dose to the beyond normal tissues.

Outcomes of Neoadjuvant Chemoradiation in Patients with Gastro-esophageal Junction Adenocarcinoma: a Retrospective Cohort Study in Iran.

PURPOSE: The optimal treatment for locally advanced GEJ and cardia adenocarcinoma is controversial. Several studies have shown that treating these patients with neoadjuvant chemoradiotherapy followed by surgery leads to survival benefits, and there are also studies that have declared conflicting results. It seems that there is still room for discussion. We calculated the survival rates and pathologic responses in our patients with characteristics which we mentioned above. METHODS: Patients with locally advanced, non-metastatic GEJ and cardia adenocarcinomas (only patients with Siewert's type I and II), who were referred to Imam Khomeini hospital (Institute of cancer) between 2005 and 2014 and received neoadjuvant chemoradiation and underwent surgery were enrolled in this retrospective cohort study. Evaluations were done every 3 months. RESULTS: Thirty-two patients enrolled in this study. Median follow up time was 23 months (Reverse Kaplan-Meier method). The rates of 1-year survival, 2-year survival, 3-year survival, 4-year survival, and 5-year survival were 75%, 52%, 52%, 37%, and 37%, respectively. No local recurrences occurred among patients; however, four patients experienced distal recurrence in the following locations: two cases (6.3%) in the liver, one case (3.1%) in the lung, and one case (3.1%) in the peritoneum. The rate of complete pathologic response (T0N0) was 21.9%. CONCLUSIONS: Neoadjuvant chemoradiation in patients with locally advanced GEJ and cardia adenocarcinoma will lead to a survival benefit.

Assessment of the Agreement between Cerebral Hemodynamic Indices Quantified Using Dynamic Susceptibility Contrast and Dynamic Contrast-enhanced Perfusion Magnetic Resonance Imagings.

BACKGROUND: Brain tumor is one of the most common tumors. A successful treatment might be achieved with an early identification. Pathological investigation as the gold standard method for tumor identification has some limitations. Noninvasive assessment of tumor specifications may be possible using perfusion-weighted magnetic resonance imaging (MRI). Cerebral blood volume (CBV) and cerebral blood flow (CBF) could be calculated based on dynamic contrast-enhanced MRI (DCE-MRI) in addition to dynamic susceptibility contrast MRI (DSC-MRI) modality. Each category of the cerebral hemodynamic and permeability indices revealed the specific tumor characteristics and their collection could help for better identification of the tumor. Some mathematical methods were developed to determine both cerebral hemodynamic and permeability indices based on a single-dose DCE perfusion MRI. There are only a few studies available on the comparison of DSC- and DCE-derived cerebral hemodynamic indices such as CBF and CBV. AIM: The objective of the study was to validate first-pass perfusion parameters derived from T1-based DCE method in comparison to the routine T2*-based DSC protocol. MATERIALS AND METHODS: Twenty-nine patients with brain tumor underwent DCE- and DSC-MRIs to evaluate the agreement between DSC- and DCE-derived cerebral hemodynamic parameters. Agreement between DSC- and DCE-derived cerebral hemodynamic indices was determined using the statistical method described by Bland and Altman. The reliability between DSC- and DCE-derived cerebral hemodynamic indices was measured using the intraclass correlation analysis. RESULTS: The achieved magnitudes for DCE-derived CBV (gray matter [GM]: 5.01 ± 1.40 mL/100 g vs. white matter [WM]: 1.84 ± 0.74 mL/100 g) and DCE-derived CBF (GM: 60.53 ± 12.70 mL/100 g/min vs. WM: 32.00 ± 6.00 mL/100 g/min) were in good agreement with other studies. The intraclass correlation coefficients showed that the cerebral hemodynamic indices could accurately be estimated based on the DCE-MRI using a single-compartment model (>0.87), and DCE-derived cerebral hemodynamic indices are significantly similar to the magnitudes achieved based on the DSC-MRI (P < 0.001). Furthermore, an acceptable agreement was observed between DSC- and DCE-derived cerebral hemodynamic indices. CONCLUSION: Based on the measurement of the cerebral hemodynamic and blood-brain barrier permeability using DCE-MRI, a more comprehensive collection of the physiological parameters cloud be achieved for tumor evaluations.

Morbidity and Mortality Following Short Course Preoperative Radiotherapy in Rectal Carcinoma.

The aim of this study was to evaluate the morbidity and mortality in patients with operable stage II and III rectal cancers within one or two months after surgery, who has been treated pre-operatively with short course radiotherapy. Twenty-eight patients with rectal adenocarcinoma, consecutively referred to the Cancer Institute of Imam Khomeini Hospital from March 2009 to March 2010, were selected for the study after staging by endorectal ultrasound and CT of abdomen, pelvis, and chest; and if they had inclusion criteria for short course schedule, they were treated with radiotherapy alone at 2500 cGy for 5 sessions, and then they were referred to the surgical service for operation one week later. They were visited there by a surgeon unaware of the research who completed a questionnaire about pre-operative, operative, and post-operative complications. Of 28 patients, 25 patients underwent either APR or LAR surgery with TME. One patient developed transient anal pain grade I and one patient had dysuria grade I; they were improved in subsequent follow-up. Short course schedule can be performed carefully in patients with staged rectal cancer without concerning about serious complications. This shorter treatment schedule is cost-effective and would be more convenient for patients due to fewer trips to the hospital and the main treatment, i.e. operating the patient, will be done with the shortest time the following diagnosis.

An overview of neuro-oncology research and practice in Iran, three years with the NOSC initiative.

Research and practice of neuro-oncology compiles clinical neuroscience expertise from neurosurgery, radiation oncology, neuroradiology, medical oncology, neuropathology and related disciplines to optimize planning and therapy in central nervous system malignancies. Such an interdisciplinary context prompted health-care providers from all related disciplines to establish the Neuro-Oncology Scientific Club (NOSC) in Iran and let it flourish since 3 years ago. With the advent of advanced technologies and through continued share of experience, NOSC members have tried to provide more integrated diagnoses and therapeutic care to brain tumor patients across the country. NOSC activities revolve around some key tenets including dissemination of education and updates, facilitation of institutional collaborations; data registry and patients' awareness. By virtue of recent insights on molecular characterization of brain tumors such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma, a range of translational research is being followed within NOSC. The most recent NOSC meeting which was held in Tehran, recapitulated main advances and dealt with the current debates on functional neurosurgery, biological markers and neuroimaging, risk prediction models in high grade gliomas and clinical issues in pediatric neuro-oncology. This article gives an overview of current hotspots in neuro-oncology research and practice which are pursued within NOSC.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)--imaging manifestations of renal involvement.

A 23-year-old lady presented with abdominal fullness and distension as well as large abdominal masses in physical exam. Upon ultrasonographic evaluation, two large space occupying lesions anterior to kidneys, with no clear distinction from renal tissue, as well as bilateral hydronephrosis were found. The findings were confirmed by MRI. Histopathological analysis of renal masses and lymph nodes showed proliferation of histiocytes mixed with occasional multinucleated giant cells, immunostaining of which was positive for S-100 and CD68. We present renal scintigraphy features of this rare case of renal sinus histiocytosis with massive intraabdominal lymphadenopathy (Rosai-Dorfman disease).

Risk factors and clinical aspects of recurrent invasive cervical carcinoma.

OBJECTIVES: Recurrence of cervical cancer is one of the important and plausible discussions in oncology especially in patients with advanced stages. The purpose of this study was to introduce probability invasive cervical carcinoma recurrence as well as determining characteristics and the prognostic factors of this entity. METHODS: A retrospective study was designed to identify risk factors and pattern of uterine cervical carcinoma recurrence evaluating the outcome of 36 registered patients. Recurrence was defined based on clinical or para-clinical documentation over at least 6 months after complete remission following surgery or radiotherapy. Treatment consisted of a radiosurgical combination and exclusive radiotherapy. RESULTS: Mean age in selected patients is 54.8 ± 12.0 years. The pathological reports of primary diagnosis are squamous cell carcinoma in 94.44 % and adenocarcinoma in remaining patients. Mean duration of recurrence among patients is 2.75 ± 1.5 years after the initial treatment. Metrorrhagia is mostly revealing symptom which patients present in recurrent episode. Usually, the recurrence of cervical cancer is presented in pelvic cavity locally. Marginal involvement is documented in 50 % of cases and lymph node in 33.3 % of patients with recurrent episode being involved. Most important prognostic factors are improper treatment (16.66 % of cases) after initial diagnosis. CONCLUSIONS: Prognostic factors such as selection of appropriate method for treatment are an important point for reducing the rate of recurrence. Moreover, warning patients about symptoms and frequent episodes of follow up is necessary for early diagnosis of recurrence.