Extended dosing (12 cycles) vs conventional dosing (6 cycles) of adjuvant temozolomide in adults with newly diagnosed high-grade gliomas: a randomized, single-blind, two-arm, parallel-group controlled trial.

Purpose: Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas. Methods: Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months. Results: A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months. Conclusion: Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles. Trial registration: Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.

Surgical skill level classification model development using EEG and eye-gaze data and machine learning algorithms.

The aim of this study was to develop machine learning classification models using electroencephalogram (EEG) and eye-gaze features to predict the level of surgical expertise in robot-assisted surgery (RAS). EEG and eye-gaze data were recorded from 11 participants who performed cystectomy, hysterectomy, and nephrectomy using the da Vinci robot. Skill level was evaluated by an expert RAS surgeon using the modified Global Evaluative Assessment of Robotic Skills (GEARS) tool, and data from three subtasks were extracted to classify skill levels using three classification models-multinomial logistic regression (MLR), random forest (RF), and gradient boosting (GB). The GB algorithm was used with a combination of EEG and eye-gaze data to classify skill levels, and differences between the models were tested using two-sample t tests. The GB model using EEG features showed the best performance for blunt dissection (83% accuracy), retraction (85% accuracy), and burn dissection (81% accuracy). The combination of EEG and eye-gaze features using the GB algorithm improved the accuracy of skill level classification to 88% for blunt dissection, 93% for retraction, and 86% for burn dissection. The implementation of objective skill classification models in clinical settings may enhance the RAS surgical training process by providing objective feedback about performance to surgeons and their teachers.

Comprehensive assessment of nutritional status and nutritional-related complications in newly diagnosed esophageal cancer patients: A cross-sectional study.

BACKGROUND & AIMS: Malnutrition is prevalent in upper gastrointestinal cancer patients. The purpose of this study was a comprehensive assessment of nutritional status in newly diagnosed patients with esophageal cancer. METHODS: Newly diagnosed esophageal cancer patients were referred to a chemo-radiation referral center in Mashhad, Iran, between February 2017 to February 2019. Anthropometric indices, a Patient-Generated Subjective Global Assessment (PG-SGA) tool, body composition, dietary intake, nutritional-related complications, and laboratory tests were assessed. RESULTS: One hundred and eighty-nine patients with a mean age of 67.1 ± 12 and a male to female ratio of 98 to 91 were included. Ninety-seven (51.3%) of patients had experienced significant weight loss and 56 (29.6%) were underweight at diagnosis. According to PG-SGA, 179 (94.7%) needed nutritional interventions. Reduced muscle mass and low handgrip strength were observed in 70 (39.4%) and 26 (14.4%) of patients, respectively. Inadequate intakes of energy (less than 24 kcal/kg/day) and protein (less than 1.2 g/kg/day) were found in 146 (77.8%) and 171 (91%) patients, respectively. The mean total daily energy and protein intakes of subjects were 943.8 ± 540 kcal/day, and 30.6 ± 21 g/day, respectively. The most common nutritional-related complications were as follows: dysphagia (84.8%), anorexia (31.6%), constipation (62.1%), esophageal pain (48.4%), and dyspepsia (41.1%). CONCLUSION: Our study demonstrated a high prevalence of malnutrition in newly diagnosed esophageal cancer patients. This fact demonstrates the importance of early screening of nutritional status via PG-SGA tool, clinical evaluation, dietary intake evaluations, and laboratory tests, based on which effective nutritional interventions and Symptoms management may be introduced in these patients.

Nutritional Status in Patients with Esophageal Cancer Receiving Chemoradiation and Assessing the Efficacy of Usual Care for Nutritional Managements.

BACKGROUND: Malnutrition is prevalent in esophageal cancer patients which affects cancer prognosis. The purpose of this study was a comprehensive assessment of nutritional status during Chemoradiation (CRT). METHODS: Newly diagnosed adults with esophageal cancer were recruited for this study. Patient-Generated- Subjective Global Assessment (PG-SGA), anthropometric indices, body composition, dietary intake, laboratory tests, and nutritional-related complications were assessed before, after, and 4 to 6 weeks after CRT. RESULTS: Seventy-one cases were enrolled. The mean age was 66.8±12 years. Patients' mean weight loss was 2.42±2.4 kilograms during treatment. A significant reduction observed in mean MUAC (26.68±4.9 vs. 25.42±5.1 cm), fat mass percentage (24.11±11.8 vs. 22.8±12.5), fat free mass index (16.87±2.4 vs. 16.47±2.6 kg/m2) and hand grip strength (43.2±19 vs. 36.1±20 kg) during CRT (all p-values <0.0001). We had also a non-significant change in mean energy intake (19.5±11 vs. 18.3±11 kcal/kgw. day) and protein intake (0.56±0.4 vs. 0.66±0.5 g/kgw.day) during CRT.  In our assessment before, immediately after and 4-6 weeks following CRT, we recorded energy intake insufficiency in 55.7%, 58.7% and 27.3% and protein intake inadequacy in 89.8%, 89.1% and 72.7% of cases, respectively. The most common complications were dysphagia (56.7%), anorexia (25%), and constipation (47.9%) at admission. Dysphagia improved in some cases (42%), but anorexia (35%), early satiety (25%), Esophagitis (25%), dysosmia (21%) and dysgeusia (17%) were increased as CRT complication. yet, 25% of patients had dysphagia and 34.4% had constipation 4-6 weeks after CRT. The twelve-months mortality was significantly associated with lower BMI after CRT, primary PG-SGA score, weight loss, BMI<18.5, MUAC, physical performance, living in rural or urban areas, addiction. CONCLUSION: Our study demonstrated a high prevalence of malnutrition among esophageal cancer patients which worsened during Chemoradiotherapy. Our findings warrant early screening and monitoring of nutritional status and effective nutritional interventions with symptoms management during treatment in these patients.
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Overexpression of cancer-testis antigen melanoma-associated antigen A1 in lung cancer: A novel biomarker for prognosis, and a possible target for immunotherapy.

AIM: We investigated melanoma-associated antigen A1 (MAGE-A1) expression in lung cancer tissues and its correlation with prognostic factors. MATERIALS AND METHODS: In this cross-sectional study, samples from 101 patients with lung cancer were obtained between 2007 and 2014 and stained for MAGE-A1 by immunohistochemistry. Correlation with prognostic factors was assessed by t test, and χ 2 , and Pearson's tests. RESULTS: Eighty non-small-cell lung cancer (NSCLC) and 21 small-cell lung cancer specimens were stained for MAGE-A1. MAGE-A1 was detected more commonly in adenocarcinomas and was expressed more frequently in male and patients >60 years. CONCLUSIONS: MAGE-A1 was found in several lung cancer patients. MAGE-A1 was expressed more commonly in NSCLC, elderly, and men. Further investigations are needed to assess MAGE-A1 as potential cancer biomarkers.

EGFR Expression in Patients with Esophageal Squamous Cell Carcinoma and its Association with Pathologic Response to Preoperative Chemoradiotherapy: A Study in Northeastern Iran.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide. It is the most common histological type of esophageal carcinoma in low-resource countries. ESCC is prevalent in Asian countries, accounting for more than 95% of esophageal cancers. The epidermal growth factor receptor (EGFR) is involved in cancer development, as its gene is often mutated and/or amplified in cancer cells. According to recent statistics, esophageal cancer is the eighth most common cancer in Iran. METHODS: In this retrospective study, we assessed EGFR overexpression, using immunohistochemistry (IHC) in 68 patients with ESCC, undergoing neoadjuvant chemoradiotherapy and esophagectomy in 2011-2014. The treatment protocol included external beam radiotherapy (40 Gy), concomitant with cisplatin 20mg/m2 and 5- fluorouracil (5-FU) 1000 mg/m2 for 4 consecutive days during the first and fourth weeks of treatment. To compare the two groups (EGFR positive and negative) in terms of complete pathologic response, Chi-square test was performed using SPSS version 16. RESULTS: The median age of the patients was 59 years (range: 27-70 years), with a female-to-male ratio of 1.06. Overall, 70% of the subjects showed EGFR overexpression. Complete pathologic response to neoadjuvant treatment was significantly higher in EGFR-positive patients (40% vs. 15.8%, P = 0.05). In all cases, 1- and 3-year overall survival rates were 86.6% ± 4.1 and 48% ± 6.9, respectively. The 1- and 3-year disease free survival rates were calculated as 71.8% ± 5.4 and 44.3% ± 6.5, respectively. The overall survival rate was relatively higher in cases with EGFR overexpression, although the difference was not statistically significant (5-year survival rate: 47.9 ± 8.2 vs. 30.9 ± 13, P = 0.23). CONCLUSION: EGFR overexpression was reported in the majority of patients with ESCC in northeastern Iran. Moreover, EGFR overexpression was significantly associated with complete pathologic response.

Treatment Outcomes and Prognostic Factors in Adult Astrocytoma: In North East of Iran.

BACKGROUND: Astrocytomas are the most common primary adult brain tumors. OBJECTIVES: In this study, we investigated the impact of some potential prognostic factors on survival in patients with low and high grade astrocytomas. PATIENTS AND METHODS: This retrospective cohort study was performed on patients with brain astrocytoma who were referred to oncology departments, Omid and Ghaem hospitals, Mashhad University of Medical Sciences (2000 - 2011). RESULTS: 415 patients with a median age of 43 and a male to female ratio of 252:163 (1.54) were recorded. Grade I to IV astrocytoma were found in 40 (9.6%), 88 (21.2%), 71 (17.1%) and 216 (52%) patients. With a median follow up time of 37 months for low grade and 13 months for high grade astrocytoma, the 5-year survival in grades I to IV was 92.1%, 69.1%, 49.2% and 9.6% respectively. In low grade astrocytomas, patients with grade I tumors, being ambulatory (5-year survival: 88% vs. 60.3%, P < 0.001) and performing optimal surgery (5-year survival 86% vs. 59.3%, P < 0.001) were associated with more favorable survival. In high grade astrocytomas, patients with grade III tumors, age < 50 (5-year survival 29.6% vs. 14.6%, P < 0.001), being ambulatory (5-year survival 39.4% vs. 10.5, P < 0.001), performing optimal surgery (5-year survival 46.1% vs. 4.3%, P < 0.001) and receiving chemotherapy (5-year survival 23.7% vs. 18.7%, P = 0.02) were associated with significantly higher overall survival. CONCLUSIONS: Performing optimal surgery and good performance status were associated with more favorable survival in both low and high grade astrocytomas. In high grade a strocytomas, patients younger than 43 and those who received chemotherapy had better overall survival.

A Comparison of 5-HT3 Receptor Antagonist and Metoclopramide in the Patients Receiving Chemotherapeutic Regimens Including CMF, CAF and CHOP.

BACKGROUND: Chemotherapy- induced nausea and vomiting (CINV) occur frequently causing problems with an unacceptably high incidence that significantly affect patients' daily functioning and health-related quality of life. The present study was aimed to compare acute CINV for granisetron as 5-HT3 receptor antagonist and metoclopramide in the patients receiving chemotherapeutic regimens including cyclophosphamide and adriamycin. An attempt is made to examine whether it is possible to successfully replace granisetron with metoclopramide in control of acute CINV. METHODS: A total of 137 patients with breast cancer (78.8%) and lymphoma (17.5%) from two oncology departments in the first course of chemotherapy were enrolled. They received granisetron 3mg/IV and dexamethasone 8mg for the first referring and in the second referring metoclopramid 30mg/IV and dexamethasone 8mg/IV thirty minutes before chemotherapy and metoclopramide 20mg/IV during chemotherapy. The patients recorded the incidence of chemotherapy induced nausea and vomiting (CINV) and other side effects including headache, extra pyramidal manifestations and delayed nausea. RESULTS: Median age of studied patients was 49±15 year. The patients who received granisetron and dexamethasone had less acute nausea (during the first 24 hours after chemotherapy) than those who received metoclopramide. Also our study showed that controlled CINV episodes in patients who received CMF regimen were better than the regimen including adriamycin (CAF, CHOP) into both granisetron (p=0.06) and metoclopramid (p=0.04). The most common adverse event related to these drugs was extra pyramidal manifestations for 16 and 10 patients who had received granisetron and metoclopramide respectively. While the number of the patients who had sever delayed CINV (2-7 days after chemotherapy) episodes with granisetron (7 cases) was lower than those who took metoclopramide drug (14 cases). The number of patients who experienced extrapyramidal manifestations in metoclopramide group was lower than granisetron group. CONCLUSION: There were not any significant clinically serious adverse events in any patients undergoing chemotherapy due to cancer. Thus, the safety profiles of granisetron and metoclopramide were comparable in this study. The patients who were treated with cyclophosphamide, and adriamycin, the efficacy of dexamethasone and metoclopramide in controlling acute nausea and vomiting nearly equaled to those of granisetron. Thus the present study supports the use of metoclopramide due to its lower cost and nearly the same efficacy and safety compared to granisetron in CMF regimen.

Assessment of clinicopathologic features in patients with pituitary adenomas in Northeast of Iran: A 13-year retrospective study.

BACKGROUND: Intracranial lesions of the pituitary gland are common pituitary adenomas, accounting for 6-10% of all symptomatic intracranial tumors. In this retrospective study, the clinicopathologic features and survival rate of pituitary adenomas were evaluated. METHODS: The present retrospective study was conducted on 83 patients with pituitary adenomas, referring to radiation oncology departments of Ghaem and Omid Hospitals, Mashhad, Iran, over a period of 13 years (1999-2012). Data obtained from clinical records including clinical features, type of surgery (if performed), treatment modality, overall survival rate, and progression-free survival rate were analyzed. RESULTS: Eighty-three patients including 44 males (53%) and 39 females (47%) participated in this study. The median age was 40 years (age range: 10-69 years). Chiasm compression was reported in 62 patients (74.4%), and 45.78% of the subjects suffered from headaches. Functional and non-functional adenomas were reported in 44 (53.01%) and 39 (46.99%) patients, respectively. In cases with functional and non-functional adenomas, the disease was controlled in 95 and 84.5% of the subjects for 3 years, respectively. Furthermore, 1- and 3-year survival rates for functional adenoma were 84.6 and 23%, respectively; the corresponding values were 90.9 and 22.7% in non-functional adenomas, respectively. CONCLUSION: In this study, a significant correlation between headache severity and type of adenoma was observed. So, application of surgery and radiotherapy together could be a highly effective approach for treating functional adenomas, although it is less efficient for the non-functional type.

Prognostic significance of metastatic lymph node ratio in patients with gastric cancer: an evaluation in north-East of iran.

BACKGROUND: In this study we have evaluated the prognostic impact of Metastatic Lymph node Ratio (MLR) in gastric cancer patients whose have undergone curative surgical resection. METHODS: A total of 121 patients with gastric adenocarcinoma undergoing curative surgical resection (R0) in our institutions between 2003 and 2010 have been included in this study. MLR has classified into 3 groups as follows: MLR0; 0, MLR1; >0-0.33 and MLR2; 0.34-1. We have used Kaplan-Meier method to calculate survival rates and log rank test to compare survival curves between groups. Cox proportional hazards model has utilized for multivariate analysis. RESULTS: The median age of patients was 65 (range; 32 to 89) with a male to female ratio of 91/30 (3.03). 88 patients have undergone total gastrectomy (72.5%) and 33 subtotal gastrectomy (27.5%). With a median total retrieved lymph node of 11 (range; 6 to 44), the MLR0 to MLR2 has calculated in 28(23.1%), 31(25.6%) and 62 (51.2%) patients respectively. MLR2 (>0.33) has significantly associated with higher Tumor stage (T1-T2: 18.7% vs. T3: 56.2%, p=0.002). With a median follow up time of 12 months (range; 2-88), the 3-year survival in patients with MLR0, MLR1 and MLR2 was 75.1%, 54.8% and 9.5% respectively (p value<0.001). Tumor location (p<0.01), tumor stage (p<0.01) and lymph node stage (p<0.001) were also significant predictor of survival. MLR has also significant correlated with survival in 91 patients with less than 15 obtained lymph nodes (p<0.001). Cox-regression multivariate analysis has shown MLR as the most important and independent predictor of survival (p<0.001). CONCLUSION: MLR with cutoff point of 0.33 could be used as an independent prognostic factor in gastric cancer patients whose have undergone curative surgical resection. This factor could effectively predict survival even in cases with insufficient (<15) retrieved lymph nodes.

Treatment Outcomes and Prognostic Factors in Pediatric Non-brainstem Astrocytoma in North East of Iran.

BACKGROUND: Central Nervous System (CNS) tumors have accounted for approximately one fourth of all pediatric malignancies. CNS tumors have been the most common solid malignancies among the children. In this study, we have evaluated survival and prognostic factors in children with non-brain stem astrocytoma. METHODS: Children with non-brain stem astrocytoma, referring to radiation oncology centers of Ghaem and Omid hospitals of Mashhad, have included in this retrospective study, in years 2000-2010. Patients' demographic data, past medical history, clinical symptoms, extent of tumor resection and treatment modality have recorded. Disease-free survival and overall survival have measured using Kaplan-Meier method. RESULTS: We studied 87 patients with male to female ratio of 44/43 (1.02), and median age of 10 yrs (range: 2-15 yrs). Tumor grade distribution was as follows: grade I: 20 (23%) subjects; grade II: 34 (39.1%) subjects; grade III: 20 (23%) subjects; and grade IV: 13 (14.9%) subjects. The median follow-up duration was 38 months (6 to 110), and 16 months (4 to 100) for patients with low- and high-grade tumors. The 2-year survival rates in grades I-IV were 100%, 84.7%, 60% and 10.8%, respectively. Tumor resection less than gross total and non-ambulation have associated with a significantly inferior survival in both groups multivariate analysis, with high- and low-grade tumors. CONCLUSION: For all the cases of the pediatric non-brainstem astrocytoma, tumor grade had dramatic influences on their survival. Performing gross total resection was crucial for achieving favorable outcomes in both low-grade and high-grade cases. Moreover, according to the results, having major motor deficits has associated with lower survival.

Concurrent Chemoradiotherapy without Brachytherapy in Locally Advanced Cervical Cancer.

BACKGROUND: Concurrent chemoradiotherapy (EBRT + cisplatin) plus intracavitary brachytherapy is the standard of care in patients with advanced cervical cancer. However, a number of patients could not undergone brachytherapy due to massive residual tumor or anatomical distortion. In this study, we have evaluated the treatment outcome in patients with locally advanced cervical cancer, undergone conventional EBRT plus cisplatin based chemotherapy. METHODS: IN THIS STUDY, WE HAVE SELECTED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA (STAGE: IIB to IIIB) undergone external beam radiotherapy and chemotherapy without brachytherapy at our institute between October of 2007 and October of 2009. The patients have received 50 Gy within 5 weeks to whole pelvic that has followed by a localized boost dose on tumor to 70 Gy concurrently with cisplatin 35 mg/m2 weekly. The treatment has related toxicities, and survival (overall and disease free) have evaluated. RESULTS: 30 cases with a median age of 55 (range; 40 to 73) have been studied. According to FIGO classification, the clinical stages were as follows: stage: IIB 23, IIIA 4, and IIIB 3 cases. Three months after treatment, 19 patients (63.3%) have achieved complete response. With a median follow up time of 18 months (range; 10-33 months), 8/23 cases (34.7%) with stage IIB and 2/7 (28.5%) among stage IIIA-IIIB remained disease free at the end of follow up. Data have shown a 2-year overall survival rate of 58.7% ± 9% and 2- year disease free survival of 37.7% ± 9% . Most toxicities were grade I and II. 2 (6.6%) grade III diarrhea and 4 (13.3%) grade III neutropenia have recorded. CONCLUSION: Although a considerable number of patients have achieved complete response using concurrent chemoradiotherapy without brachytherapy, the overall treatment outcomes especially for stage IIIA-IIIB were unsatisfactory. Using modern radiation therapy techniques with increased delivered boost dose could improve treatment results.

Expression of Bcl-2 and Bax in advanced or metastatic prostate carcinoma.

PURPOSE: To evaluate the correlation of Bcl-2 and Bax protein expressions with biochemical failure-free survival in patients with advanced or metastatic prostate carcinoma (PCa) undergoing androgen deprivation therapy. MATERIALS AND METHODS: This retrospective study was performed on patients with locally advanced (≥ T3) or metastatic PCa, who were referred to Omid Hospital between years 2003 and 2007. All subjects had undergone androgen deprivation therapy. Samples were analyzed immunohistochemically for Bax and Bcl-2 expression. The H-score was calculated for each sample based on intensity and percentage of stained cells. H-score > 50 was considered positive. RESULTS: Thirty-seven patients (13 metastatic and 24 locally advanced) were eligible for analysis. Thirty-six (97.3%) samples were positive for Bax and 26 (70.3%) for Bcl-2 expression. The median H-score for Bax and Bcl-2 was 200 (range, 40 to 300) and 85 (range, 0 to 220), respectively. While there was no correlation between Bax expression and Gleason score, high Bcl-2 expression (H-score > 85) was significantly associated with Gleason score > 7 (P = .004). The median time to progression in the advanced and metastatic groups was 22 (range, 10 to 37) months and 16 (range, 9 to 26) months, respectively. High Bcl-2 expression (P = .01) and prostate-specific antigen > 20 ng/mL (P = .01) were significant predictors of lower biochemical progression-free survival. CONCLUSION: High Bcl-2 expression was associated with higher Gleason scores and lower biochemical-free survival in patients with advanced PCa undergoing androgen deprivation therapy.