Safety evaluation of the trastuzumab biosimilar in Iranian women with HER2-positive breast cancer undergoing adjuvant chemotherapy: a post-marketing surveillance.

BACKGROUND: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). RESEARCH DESIGN AND METHODS: The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. RESULTS: A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. CONCLUSIONS: The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06021379.

Investigation the effect of a magnetic field on the dose distribution of I-125, Ir-192, Yb-169, and Co-60 brachytherapy sources by Monte Carlo simulation.

Magnetic resonance imaging (MRI) during brachytherapy may alter the dose distribution of radioactive sources implanted in the tumor. This study investigates the impact of a magnetic field of 1.5 T, 3 T, and 7 T strengths on the dose distribution of high dose rate Co-60, Ir-192, and Yb-169, and low dose rate I-125 sources, using Geant4 Monte Carlo toolkit. After validating the simulation results by calculating the AAPM-TG43 dosimetric parameters, seven sources of each radioisotope were simulated in a water phantom, and their dose distributions were compared under the influence of a magnetic field. The simulation results indicate that using Co-60 brachytherapy under the MRI guidance is not recommended. Furthermore, the impact of a magnetic field of up to 7 T strength on the dose distribution of Ir-192, Yb-169, and I-125 sources is negligible, provided that there is no air pocket near brachytherapy sources.

Comparison of the performance of log-logistic regression and artificial neural networks for predicting breast cancer relapse.

BACKGROUND: Breast cancer is the most common cancers in female populations. The exact cause is not known, but is most likely to be a combination of genetic and environmental factors. Log-logistic model (LLM) is applied as a statistical method for predicting survival and it influencing factors. In recent decades, artificial neural network (ANN) models have been increasingly applied to predict survival data. The present research was conducted to compare log-logistic regression and artificial neural network models in prediction of breast cancer (BC) survival. MATERIALS AND METHODS: A historical cohort study was established with 104 patients suffering from BC from 1997 to 2005. To compare the ANN and LLM in our setting, we used the estimated areas under the receiver-operating characteristic (ROC) curve (AUC) and integrated AUC (iAUC). The data were analyzed using R statistical software. RESULTS: The AUC for the first, second and third years after diagnosis are 0.918, 0.780 and 0.800 in ANN, and 0.834, 0.733 and 0.616 in LLM, respectively. The mean AUC for ANN was statistically higher than that of the LLM (0.845 vs. 0.744). Hence, this study showed a significant difference between the performance in terms of prediction by ANN and LLM. CONCLUSIONS: This study demonstrated that the ability of prediction with ANN was higher than with the LLM model. Thus, the use of ANN method for prediction of survival in field of breast cancer is suggested.

Attitude of cancer patients toward diagnosis disclosure and their preference for clinical decision-making: a national survey.

OBJECTIVES: There is still contradictory evidence on disclosure preferences regarding cancer diagnosis. The aim of this study was to evaluate the preference of cancer patients for knowing the truth about their disease, as well as the factors that might have an impact on these preferences. METHOD: This study was conducted in 11 cancer centers in Iran. A questionnaire was used to collect data, and all patients above 15 years of age who were willing to participate were included in the study. The patients were asked if they were aware of the malignant nature of their disease, and if they came to know about their disease at the time of initial diagnosis, or later. The patients were then asked about the way they looked upon their disease. In the final part of the questionnaire, the participants were asked the level of involvement they prefer to have in making treatment decisions. RESULTS: In total, 1226 patients were enrolled in this study, only 565 (46.7%) of whom were aware of their disease at the time of diagnosis, and 878 (72.7%) at the time of interview, while 980 (85.2%) were willing to receive information about their disease. Patients' awareness was significantly associated with age under 50 years, female gender, having breast, skin or head and neck cancer, and having medical care in Shiraz or Hamadan while it was not associated with the stage or accompanying illness. CONCLUSION: While the majority of Iranian cancer patients prefer to be aware of the nature of their disease and have an active role in treatment decision making, they do not receive this information.

The impact of multiple recurrences in disease-free survival of breast cancer: an extended Cox model.

AIMS AND BACKGROUND: Identifying the risk factors of recurrence of breast cancer is important for both the physician and patient. Analysis of the first recurrence may lead to an inaccurate evaluation of the factor's effects because it does not completely reflect the history of the disease and may result in the loss of valuable information. The present study aimed to determine the factors that influence breast cancer recurrence and to estimate disease-free survival, adjusting for multiple metastases in breast cancer patients. METHODS AND STUDY DESIGN: Patients were selected from a longitudinal study carried out at Fayazabakhsh Hospital in Tehran, Iran. Women who were diagnosed with breast cancer and who underwent either modified radical mastectomy or breast-conserving surgery between January 2006 and April 2008 were recruited to take part in the study. Breast cancer recurrence was defined as the occurrence of a tumor in the contralateral breast, local-regional relapse, or distant metastasis to other organs. Using an extended Cox model, the effect of age, tumor size, estrogen receptors, HER2, progesterone receptors as well as lymph node ratio was analyzed. RESULTS: Over a 5833 person-month follow-up, 25 of 133 patients (18.8%) had died and 108 patients (81.2%) were still alive, 9 of them with metastasis. Thirty-four patients (25.6%) experienced their first disease recurrence. A total of 11 patients had a second metastasis. The mean time to first metastasis was 19.93 months, and mean gap time between two metastases was 7.15 months. Risk of experiencing a metastasis or death in the third and fifth year after surgery was approximately 22% and 28%, respectively. Fitting multiple recurrent regression shows that high lymph node ratio, high histologic grade, large tumor size and HER2-positive tumors are prognostic factors for shorter disease-free survival. CONCLUSIONS: Our novel approach might be helpful in clinical practice to predict breast cancer recurrence after surgery and might be adapted to be used in other malignancies as well.

Artificial neural network for prediction of distant metastasis in colorectal cancer.

BACKGROUND AND OBJECTIVES: Artificial neural networks (ANNs) are flexible and nonlinear models which can be used by clinical oncologists in medical research as decision making tools. This study aimed to predict distant metastasis (DM) of colorectal cancer (CRC) patients using an ANN model. METHODS: The data of this study were gathered from 1219 registered CRC patients at the Research Center for Gastroenterology and Liver Disease of Shahid Beheshti University of Medical Sciences, Tehran, Iran (January 2002 and October 2007). For prediction of DM in CRC patients, neural network (NN) and logistic regression (LR) models were used. Then, the concordance index (C index) and the area under receiver operating characteristic curve (AUROC) were used for comparison of neural network and logistic regression models. Data analysis was performed with R 2.14.1 software. RESULTS: The C indices of ANN and LR models for colon cancer data were calculated to be 0.812 and 0.779, respectively. Based on testing dataset, the AUROC for ANN and LR models were 0.82 and 0.77, respectively. This means that the accuracy of ANN prediction was better than for LR prediction. CONCLUSION: The ANN model is a suitable method for predicting DM and in that case is suggested as a good classifier that usefulness to treatment goals.

Comparison of three adjuvant chemotherapy regimes using an extended log-logistic model in women with operable breast cancer.

OBJECTIVE: The main objective of the present study was to compare the effects of three common chemotherapy regimes in terms of disease-free survival (DFS) of breast cancer (BC) patients; the three explored regimes were taxane-based, anthracycline-based and CMF (cyclophosphamide methotrexate and 5-fluorouracil). MATERIALS AND METHODS: In this historical-cohort study, we obtained the information of 62 patients with confirmed BC in non-metastatic stage and followed them for 8 years. All the patients had undergone modified radical mastectomy surgery and had received adjuvant chemotherapy in three medical centers in Tehran, Iran. DFS was considered as the end-point. Afterwards, an extended log-logistic regression model was used to compare these regimes. RESULTS: The mean (SD) age of patients was 49.0 (10.3) years. The median time of follow-up was 20.0 months and the probability of 5-years DFS was 0.48. Survival analysis indicated that the type of chemotherapy (OR(CMF vs. taxane) = 0.33, OR(anthracycline vs. taxane) = 0.74), grade (OR(III vs. I or II) = 0.35), tumor size (OR(>5 cm vs. <5 cm)= 0.179) and nodal involvements (OR(Yes vs. No)= 0.36) affected DFS. CONCLUSION: The current study revealed that the efficacy of taxane-based, in terms of DFS, was more than CMF (p = 0.05). Moreover, taxane-based chemotherapy prolonged DFS more than anthracycline-based one although the difference was not significant (p= 0.63). Finally, considering the importance of tumor size, histological grade and number of involved lymph nodes in lengthening DFS, it is crucial to highlight the role of public education and screening programs in order to detect tumor in its early stages.

Treatment and prognosis of epithelial ovarian cancer: five year multi-center study.

OBJECTIVE: To study the response rate for common chemotherapy regimens, and the progression free survival analysis in ovarian cancer in Tehran. METHODS: Ninety-eight women with confirmed ovarian cancer who had surgery, followed by chemotherapy at the 3 hospitals in (Fayazbakhsh, Shohadayee Tajrish, and Imam-Hossein), Tehran, Iran, between 1997 and 2003 were enrolled in this retrospective descriptive study. Data regarding age, pathologic variations, surgical procedures, chemotherapy regimens, response rates, and time to progression of the disease were collected. Response rate was evaluated for 51 patients with epithelial cancer. RESULTS: From a total of 98 patients, there were 81 (82.6%) epithelial, 12 (12.2%) germ cell, 4 (4.1%) granulosa cell tumors, and one case of lymphoma. Staging with optimal residue was performed for 18 patients. Stage III was the most common stage (44.9%). In 71.4% of patients, complete or partial response was seen, while the other patients showed stable, or progressive disease. The most important prognostic factors were the initial stage (p=0.034), and the extent of surgical procedure (p=0.045). Median disease-free survival was 52.6 months. Although, higher response rate was produced by taxane-based regimen in comparison with cisplatin-cyclophosphamide regimen (78.2 % versus 71.4%), but it was not statistically significant (p=0.275). Median age (49.6 years) of our patients is lower than expected. Besides, a large proportion of the patients are referred in advanced stages. CONCLUSION: New chemotherapy practically has made no significant higher response rate.

McGill Quality of Life Questionnaire: reliability and validity of the Persian version in Iranian patients with advanced cancer.

OBJECTIVES: McGill Quality of Life Questionnaire (MQOL) is an instrument specifically designed to evaluate quality of life (QOL) in patients with advanced diseases. The primary objective of this study was to translate this questionnaire into Persian and assess its reliability and validity in Iranian patients suffering from an advanced cancer. The report also includes the correlations between patients' characteristics and their QOL scores. METHODS: MQOL was translated into Persian using a forward-backward method and administered to 62 patients with cancer at two hospitals in Tehran. Statistical analysis was performed to test reliability and validity of the questionnaire and to assess relationships between patients' characteristics and MQOL scores. RESULTS: In general, MQOL-Persian is a valid and reliable questionnaire to assess QOL in Iranian patients with advanced cancer. Test-retest reliability of the whole questionnaire is highly favorable for a questionnaire of this type (Pearson correlation = 0.87). Except for the existential subscale, all MQOL scores are internally consistent. There was no significant correlation between MQOL scores and patients' extent of knowledge about their disease. CONCLUSION: The Persian version of MQOL is, for the most part, a valid, reliable instrument in this setting. Because of cultural differences, the existential subscale may require adaptation. Further studies are needed to explore other aspects of QOL in Iranian patients with cancer.

Recurrence in breast cancer. Analysis with frailty model.

OBJECTIVE: To determine the value of known prognostic factors for metastasis in breast cancer by accounting for patient-specific effect of patients who received surgical treatment followed by adjuvant treatment using the frailty model. METHODS: One hundred seventeen women with breast cancer who underwent surgery followed by adjuvant therapy at 3 hospitals in Tehran, Iran between 1995 and 2003 were enrolled in this study. Women with defined breast cancer with no distant metastases at time of diagnosis that have undergone modified radical mastectomy or breast-conserving surgery were enrolled. Tumors were classified according to the Tumor, Node, Metastasis (TNM) system of the American Joint Committee on cancer. Grading was performed according to Scarff-Bloom-Richardson method. Estrogen receptor (ER) was measured by immunohistochemistry method. The patients have been followed regularly by routine clinical laboratory profile, serologic markers (CEA, CA15-3) and para-clinical examinations; furthermore, we have followed missing materials by other access ways such as calling. RESULTS: Median follow up time for patients was 26 months after surgery. During the follow up time 44 (38%) patients developed metastasis and 20 (45%) of these 44 patients experienced the second metastasis. The median disease-free survival for patients in the study was 49.6 month. The median time to experience second metastasis after the first one was 22.5 months. Risk of occurrence of a metastasis in the first year after surgery was 12%. Risk of experience a metastasis up to the second year was 32% and up to fifth years was 69%. Result of fitting a frailty model to data showed that size of tumor, number of positive lymph nodes and histologic grade had a significant effect on the risk of metastasis (p<0.05). Patients with tumor size larger than 5 cm were in higher risk of metastasis compared with others. Increase in the number of positive lymph nodes to more than 10, increased risk of metastasis. Patients with moderate or undifferentiated histologic grade were in higher risk of metastasis to well differentiated patients. Age, family history, lymph node stage, and ER had no significant effect. It was found that there was heterogeneity between patients after adjusting for other covariates because variance of frailty was 0.315. It means that based on the variance of the distribution of frailty, the relative risk of high-risk patients to low-risk patients was 7.2, wherein high-risk group is defined as a cluster at the 95th percentile and low-risk to a cluster of 5th percentile of the frailty distribution. CONCLUSION: Known risk factors describe the risk of metastasis partly and other unknown or unmeasured factors, such as genetics or environmental factors are important to describe the risk of metastasis in breast cancer.

Clinicopathological features of primary central nervous system lymphoma.

OBJECTIVE: To investigate the anatomic location, immunologic, and clinicopathological features of patients with primary central nervous system lymphoma (PCNSL). METHODS: From May 1993 to December 2004, at Shohada Hospital, Tehran, Iran, the clinical data of 110 PCNSL patients, including the age, sex, duration of symptoms, radiological findings, site of tumors, immune status, and history of immunocompromised state (such as organ transplantation, radiotherapy, steroid therapy or AIDS) were assessed. RESULTS: The mean age of the patients with PCNSL was 47.02 +/- 15.8 years. There were 42 female and 68 male patients. One hundred and six cases (96.3%) were diagnosed as B-cell lymphoma. Most of the PCNSL in our study are unifocal. More than 70% of tumors were in a cerebral hemisphere and periventricular location, usually involving the corpus callosum or basal ganglia. No patients had been in immunocompromised states. Symptoms of increased intracranial pressure or changes in personality, vision, or motor function are most common. Seizures are seen in approximately 10% of patients. The number of PCNSL cases showed a gradual rise in incidence. CONCLUSION: The results of this single hospital 12-year survey of PCNSL are in agreement with data from other single institutions and regional surveys concerning clinical features. However, in contrast with the literature, most of our patients were immunocompetent. The age at diagnosis is also lower than in most reports.