Feasibility and therapeutic potential of the 68Ga/177Lu-DOTATATE theranostic pair in patients with metastatic medullary thyroid carcinoma.

BACKGROUND: This study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients. MATERIALS AND METHODS: Patients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). RESULTS: Twenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52-29.48). There were no cases of significant toxicity. CONCLUSION: Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

Peptide Receptor Radionuclide Therapy Using 177 Lu-DOTATATE in Advanced Neuroendocrine Tumors (NETs) in a Limited-Resource Environment.

Background This study was conducted to evaluate the clinical efficacy and safety of peptide receptor radionuclide therapy (PRRT) using 177 Lu-DOTA0-Tyr3-octreotate (DOTATATE) in patients with neuroendocrine tumors (NETs). Methods Sixteen patients with pathologically verified NETs including eight females and eight males were enrolled in this study. Before PRRT, the patients underwent 68 Ga-DOTATATE positron emission tomography/computed tomography or 99m Tc-octreotide scintigraphy for evaluation of somatostatin receptor expression. Response to treatment was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). In addition, for evaluation of toxicity, monthly blood analysis was performed including hematology, renal function (creatinine) test, and liver function test. The Eastern Cooperative Oncology Group (ECOG) status performance was applied to estimate the patients' general condition in a scale of 0 (fully active) to 5 (dead). In addition, overall survival (OS) was calculated as the time interval from the start of PRRT to death from any reason. Results Sixteen patients including eight females and eight males with a median age of 60.5 years (range: 24-74) were enrolled in this study. The patients underwent PRRT with a median cycle of 3.5 (range: 1-7) and a median dose of 20.35 (range: 7.4-49.95 GBq). At the end of data collection, PR, CR, SD, and PD were seen in 11, 2, 1, and 2 patients according to the RECIST, respectively. Three patients expired during or after the PRRT period. The median ECOG and Karnofsky Performance Scale was 1.5 and 75 before PRRT, which improved significantly to 1 and 80 after PRRT, respectively ( p < 0.05). According to the Kaplan-Meier test, the median OS was 23 months (95% confidence interval: 7.90-38.09). According to the National Cancer Institute's Common Terminology Criteria for Adverse Events, three patients showed grade I and three patients showed grade II leucopenia. Furthermore, three and seven patients had grade II and grade I anemia, respectively. Conclusion Since PRRT using 177 Lu-DOTATATE has a favorable response rate and few adverse effects and improves the quality of life in NETs, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of AlvotereⓇ (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy.

BACKGROUND: Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non-small cell lung cancer, and prostate cancer. OBJECTIVE: This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel. METHODS: Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets. FINDINGS: A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants' mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens. CONCLUSIONS: The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

Feasibility and Therapeutic Potential of Peptide Receptor Radionuclide Therapy for High-Grade Gliomas.

PURPOSE: This pilot study tested the principle that 177Lu-DOTATATE may be applied to patients with high-grade gliomas (HGGs) that are either inoperable or refractory to the standard conventional treatments and also assessed whether this approach could be a viable therapeutic plan in this dilemma. METHODS: In this prospective study, 16 subjects experiencing HGGs that were either inoperable or refractory to the standard conventional treatments were included. All the patients checked for somatostatin receptor expression on the tumors. The patients were treated with 1 to 4 cycles of IV 177Lu-DOTATATE. The primary end point was radiological response after peptide receptor radionuclide therapy, and the secondary end point was improved quality of life using Karnofsky Performance Score and Eastern Cooperative Oncology Group score. RESULTS: In total, 16 subjects (10 males and 6 females) with a mean age of 55.68 ± 13.17 years (26-73 years) participated in the study. Of them, 8 patients were new HGG cases, and 8 patients had recurrent tumors. The participants' responses to treatments were complete remission in 12.5% of (n = 2), partial remission in 31.25% (n = 5), disease stability in 18.7% (n = 3), and disease progression in 37.5% (n = 6). In total, pretreatment and posttreatment Karnofsky Performance Score and Eastern Cooperative Oncology Group scores did not improved (P > 0.05). The patients were followed up from 1 month to 26 months (median, 3 months). CONCLUSIONS: This preliminary result suggests that peptide receptor radionuclide therapy using 177Lu-DOTATATE may be associated with positive effects in patients with HGGs (grade III-IV). However, this approach should be evaluated in a more homogeneous group of patients with more favorable performance status.

Potential application of lutetium-177-labeled prostate-specific membrane antigen-617 radioligand therapy for metastatic castration-resistant prostate cancer in a limited resource environment: Initial clinical experience after 2 years.

In recent years, lutetium-177 (177Lu)-labeled prostate-specific membrane antigen (PSMA)-617 has become a promising new therapeutic agent in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we report on an early experience of 177Lu-PSMA therapy with an evaluation of its efficacy and safety in mCRPC patients. Twenty-one mCRPC patients with a mean age of 70.3 ± 9.6 (54-88)-year-old were treated with one to four therapy cycles (median two cycles) and administered activity of 3.7-29.6 GBq (mean of 15.4 GBq). A prostate-specific antigen (PSA) decline ≥ 50% was considered to be a biochemical response (BCR). To evaluate the clinical response, the Eastern Cooperative Oncology Group (ECOG) status was used. Within 2 weeks before and 1 and 2 months after each therapy cycle, hematology, renal function, liver status, alkaline phosphatase, and PSA were checked. The Common Terminology Criteria for Adverse Events was used for grading adverse events induced by 177Lu-PSMA. Furthermore, overall survival (OS) was calculated and analyzed. During the treatment, a BCR was seen in 62% of patients; 19% of patients showed progression and 19% of patients showed stable disease. ECOG status was improved after treatment, and OS was 62.7 weeks. After the treatment, two patients showed Grade II toxicity of white blood cells, Grade I thrombocytopenia was observed in two patients, one patient showed Grade II toxicity in serum creatinine and transient Grade I toxicity in creatinine was seen in two patients. In total, our initial experience demonstrates that 177Lu-PSMA therapy has the potential to positively affect the development and maturation of radioligand practices in selected mCRPC patients, even in resource limited, developing country environments. However, some challenges, such as practitioner training, poor initial acceptance by colleagues and financial concerns, particularly in developing nations, still exist.

A Double-Blind, Randomized Comparison Study between Zytux™ vs MabThera® in Treatment of CLL with FCR Regimen: Non-Inferiority Clinical Trial.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux™ in comparison to MabThera® in treatment of CLL. MATERIALS AND METHODS: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux™, and group B was treated with MabThera®. A non-inferiority margin of 20% for the primary outcome was defined to examine the similarity between Zytux™ and MabThera®. RESULTS: Baseline demographic characteristics showed no statistically significant difference between the two groups. The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux™ demonstrated a similar profile of adverse reactions in comparison to MabThera®. Moreover, the overall response rate was 88% and 89% for Zytux™ and MabThera®, respectively (CI -0.17, 0.18). CONCLUSION: Results showed non-inferiority of Zytux™ in terms of efficacy and adverse events as a biosimilar version of MabThera®.

Prevalence and Genotype Distribution of Hepatitis C Virus Infection among Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: This study was conducted to determine the prevalence and genotype distribution of hepatitis C virus (HCV) infection among patients with type 2 diabetes mellitus (DM). SUBJECTS AND METHODS: We included 556 consecutive patients with confirmed type 2 DM attending the Diabetic Clinic of the Bushehr University of Medical Sciences and 733 nondiabetic subjects as controls. Serum levels of fasting blood sugar (FBS), alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH), and triglycerides (TG) were measured by enzymatic colorimetric methods, and the presence of anti-HCV antibodies was determined by enzyme-linked immunosorbent assay. Semi-nested reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed on all anti-HCV-seropositive samples. Data were analyzed using the Statistical Package for the Social Sciences 17, and descriptive statistics, χ2 test, Fisher exact test, and the Student t test were used for analysis. RESULTS: The seroprevalence of HCV in the diabetic patients was 1.98% (11/556), which was higher than HCV prevalence among the nondiabetic controls (4/733, 0.54%) (p = 0.032). No significant differences in ALT, AST, FBS, TG, and TCH levels were found between the HCV-seropositive and HCV-seronegative diabetic patients, although HCV-seropositive diabetic patients tended to have higher ALT, AST, and TCH levels, but lower TG and FBS levels than HCV-seronegative patients. In logistic regression analysis, only AST levels were significantly associated with HCV seropositivity among diabetic patients. The AST level of 41-80 IU/L was the only significant predictive variable for HCV seropositivity in the diabetic patients (odds ratio, 4.89; 95% CI: 1.06-22.49; p = 0.041). Of the 11 HCV-seropositive diabetic patients, 10 (91%) had HCV viremia with genotype 3a. CONCLUSION: Patients with type 2 DM had a higher prevalence of HCV infection than controls, and HCV seropositivity was independent of biochemical parameters.

Vaccine-associated paralytic poliomyelitis in a patient with acute lymphocytic leukemia.

We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an immunocompromised patient with acute lymphocytic leukemia who was initially diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 poliovirus from the patient's cerebrospinal fluid made this a case of vaccine-related poliovirus (VRPV) infection. The patient developed paralysis and respiratory distress and deceased a few months after onset of paralysis with respiratory failure. This tragic case report highlights the emergence of VAPP and indicates the importance of timely diagnosis of VRPV infections to improve clinical management of VRPV-infected patients and to prevent the devastating consequences of silent introduction of VRPVs in treatment wards and eventually in the society.

The correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients.

BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19+CD24hiCD38hi cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19+CD24hiCD38hi cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients. METHODS: We selected 47 patients with invasive ductal breast carcinoma and 50 healthy controls and obtained their blood samples. RESULTS: The proportion of circulating CD4+CD25+Foxp3+ Tregs and CD19+CD24hiCD38hi cells was significantly increased in breast cancer patients. We also found that increased proportion of Tregs in breast cancer is correlated with HER2 amplification, advanced clinical stages, serum TGF-ß1 and increased CD19+CD24hiCD38hi cells in the peripheral blood. CONCLUSION: Altogether, our data suggest that as much as Tregs, CD19+CD24hiCD38hi B cells could also have a part in the suppression of immune response in breast cancer.

Seroprevalence and Molecular Evaluation of Toxoplasmosis in Patients Undergoing Chemotherapy for Malignancies in the Bushehr Province, Southwest Iran.

BACKGROUND: Toxoplasmosis is a life-threatening infection in organ transplant recipients, people receiving corticosteroid or radiation therapy, people with malignancies, and AIDS patients. OBJECTIVES: The current study aimed to determine the prevalence of toxoplasmosis in patients receiving chemotherapy for malignancies in the Bushehr province of southwest Iran. METHODS: Blood samples were taken from 86 patients who were continuously referred to the chemotherapy center in Bushehr province and evaluated by ELISA to determine anti-Toxoplasma IgG and IgM antibodies. Moreover, a blood buffy coat of each sample was assessed by polymerase chain reaction (PCR), targeting a 529 bp gene of T. gondii. PCR products of the positive samples were sequenced to determine the genotype of the parasite. RESULTS: Anti-Toxoplasma IgG antibodies were detected in the sera of 21 (24.4%) cases. All of the patients were negative for anti-Toxoplasma IgM antibodies. No statistically significant correlation was found between seropositivity to Toxoplasma and duration of chemotherapy or having contact with cats. PCR detected a 529 bp band of T. gondii in the buffy coats of two out of 86 (2.3%) cases. The sequence analysis demonstrated that both cases were 95% identical to type III (VEG strain) of T. gondii. CONCLUSIONS: Findings of this study demonstrated the presence of type III T. gondii in the buffy coats of patients undergoing chemotherapy. Given that toxoplasmosis is a life-threatening infection in immunocompromised patients, these patients should be screened for toxoplasmosis before and during chemotherapy to prevent acute toxoplasmosis.

Clinical Manifestations of ß-Thalassemia Major in Two Different Altitudes; Bushehr and Shahrekord.

BACKGROUND: Patients with ß-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it's the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of ß-thalassemia major (TM) patients. SUBJECTS AND METHODS: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient's clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed. RESULTS: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P>0.05). Patient's cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05). CONCLUSION: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals.

Abrupt Development of Plasma Cell Leukemia in a Patient with Chronic Anemia under Follow-up.

Plasma cell leukemia (PCL) is a very rare and progressive hematologic malignancy with unpleasant prognosis, which present with monoclonal proliferation of plasma cells in peripheral blood. Here we report a 52-year-old female case of PCL which diagnosed by morphology and immunohistochemistery (IHC) study. IHC revealed CD20+/CD38+/CD138+/CD56-/kappa-/lambda+. We diagnose PCL on peripheral blood. IHC can be helpful for prognostic determination.

Diffuse Hepatic and Spleen Uptake of Tc-99m MDP on Bone Scintigraphy Resembling Liver-Spleen Scintigraphy in a Patient of Plasma Cell Tumor.

The present case demonstrates a diffuse intense hepatic and, to a lesser degree, spleen, Tc-99m MDP uptake on a routine bone scintigraphy resembling liver-spleen imaging. A 49-year-old female with a history of anaplastic plasma cell tumor and suffering from bone pain was referred for bone scintigraphy to evaluate possible bone metastases. The bone scintigraphy showed diffuse hepatic and spleen uptake of Tc-99m MDP resembling liver-spleen imaging. Furthermore, bone uptake of Tc-99m MDP was significantly diminished and there were no abnormal foci throughout the skeleton. The bone scintigraphy of the present case of an anaplastic plasma cell tumor suggests the possible presence of amyloidosis.

High prevalence of Helicobacter pylori infection in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a multisystem disease of unknown etiology. There are several clues which may indicate an ethiopathogenesis role for Helicobacter pylori infection in this disease. METHODS: In a case control study in an out patient department, 48 patients with BD were compared to age, sex matched controls regarding presence of H. pylori infection by serology and urea breath test (UBT). RESULTS: Ongoing H. pylori infection was more prevalent among patients with BD using result of UBT with odds ratio of 3.1 (95% CI: 1.34 - 7.26, PV < 0.001). CONCLUSION: H. pylori infection may have a role in the pathogenesis of BD.