Diversity of small round cell sarcoma in soft tissues around bone among Indian patients.

Round cell tumors are a group of malignant tumors which shows overlapping microscopic features of small round monotonous cells with hyper-chromatic nucleus. It mostly occurs in children, adolescent, and young adults. The ancillary technique to confirm the differential diagnosis of round cells sarcoma is immuno-histo chemistry (IHC). Therefore, it is of interest to document the diversity of small round cell sarcoma in soft tissues around bones among Indian patients using IHC. A total of 334 cases among Indians were studied. Among them 160 cases were Non-Hodgkin's Lymphoma, 82 cases are poorly differentiated carcinoma and 92 cases of round cell sarcoma. Out of 92 cases, there were (40%) 27 cases of Wilms tumour, with the highest incidence. The highest incidence was observed in 0-14 years of age group with highest incidence in males. The distribution and diverse histology of different small round cell sarcoma offers challenge in the diagnosis by histopathology. Most frequent round cell tumour is Wilms tumour, followed by Rhabdomyosarcoma. Data shows the role of IHC in classifying soft tissue sarcoma but some time result of IHC remains inconclusive, where cytogenetic is important.

Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is one of the leading and aggressive cancers in this region of India. It is very difficult to diagnose in the early stage, as it lacks typical early signs and symptoms; thus, the diagnosis is often in the advanced stage, which ultimately leads to a poor 5-year survival outcome. Tumor markers including carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), CA 125, CA 242, and alpha fetoprotein are used as indicators in the diagnosis and prognosis of GBC. AIM: To compare tumor marker levels between GBC and benign GB diseases (GBDs) and to assess the combined use of tumor markers to increase the diagnostic accuracy for GBC. METHODS: Patients of either sex aged ≥ 18 years, with suspected GBC (GB polyp, irregular thick GB wall, GB mass, porcelain GB) on the basis of radiological imaging were included in this study. GB wall thickness using ultrasonography and tumor markers CEA, CA 125, CA 19-9, and CA 242 in all patients were recorded. All cases after surgical intervention were divided into two groups, GBC and benign GBD, according to histopathological examination findings. The cases were followed up and clinical findings, radiological findings, and levels of tumor markers were assessed. RESULTS: A total of 200 patients were included in this study, of whom 80 patients had GBC and 120 patients had benign GBD. The median (interquartile range) age was 52.0 (41.0-60.0) years and the majority of patients (132, 66.0%) were women. Tumor markers including CA 19-9, CA 125, CEA, and CA 242 were significantly elevated in patients with GBC (P < 0.001). There was a significant reduction in tumor markers at 3 and 6 mo from baseline (P < 0.001). The mean survival of patients with normal and elevated levels of tumor markers CA 125, CA 19-9, and CEA was comparable; however lymph node metastasis and CA 242 expression level were independent prognostic factors. CONCLUSION: Serum levels of tumor markers including CA 19-9, CA 125, CEA, and CA 242 were significantly associated with GBC. However, no significant association was observed between the presence of elevated levels of any tumor marker with respect to survival. Tumor marker assessment during follow-up may represent a treatment response.

Hepatitis B in hepatocellular carcinoma patients and its correlation with alpha-fetoprotein and liver enzymes.

Background: Hepatocellular carcinoma (HCC) in India ranges from 0.7 to 7.5 for men and 0.2 to 2.2 for women, per 100,000 population per year. The major risk factors for the development of HCC are infection with hepatitis B virus (HBV), hepatitis C virus, and cirrhosis of liver. Alpha-fetoprotein (AFP) and liver enzymes are widely used by clinicians for diagnostic purpose in HCC. Aims and Objective: This study was conducted in HCC patients related to HBV infection and to assess the significance of AFP and liver enzymes in it. Materials and Methods: Blood samples of 68 patients were taken. The samples were analyzed for AFP and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]). Liver enzymes were estimated by auto analyzer OLYMPUS AU400. AFP was analyzed by chemiluminescence immunoassay. Results: The mean values of AFP in serum hepatitis B surface antigen (HBsAg) negative and positive patients ranges from 22745.4 to 23269.3 ng/ml with P = 0.921. The mean value of ALP in HbsAg-negative patients was 418 U/ml, whereas in positive patients, it was 310 U/ml. Both the groups did not show any significant changes in AFP levels. The ALP showed slight rise in negative group. The other parameters did not show significant rise in all patients. Conclusion: These values suggest that there was no significant influence of viral etiology on AFP and liver enzymes level in HCC patients.

Genomic Pattern of GSTM1 and T1 Gene Null polymorphism of Head and Neck Cancer Patients in Eastern India.

OBJECTIVE: Homozygous deletion i.e., null polymorphism of the Glutathione S transferases genes hinders detoxification reactions by altering the sensitization of glutathione s transferases enzymes. Hence, we analysed the association between the GSTM1 and GSTT1 gene polymorphisms and head and neck cancer (HNC). METHODS: The study consists of 238 healthy controls and 160 diagnosed cases of HNC, who attended the Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences (a tertiary care hospital). DNA was extracted from whole blood of patients and control using Qiagen DNA extraction kit. GSTM1 and GSTT1 gene polymorphisms were examined using PCR and agarose gel electrophoresis. RESULTS: GSTM0 null polymorphism was 26.25% and 15.13% in cases and control respectively. GSTT0 null polymorphism was observed in 18.13% cases and 8.82% in control groups. The GSTM0 null polymorphism was present significantly in case group as compared to control group (OR = 1.997, p = 0.006). There was also significant association of GSTT0 null polymorphism with case group as compared to control group (OR = 2.288, p = 0.006). The combined genotypes were also analysed. GSTM0T1 genotype (n = 27) was found to be most common among HNC group followed next by GSTM0T0 double deletion (n =15). CONCLUSION: The result indicated that there was strong association of GSTM0 and GSTT0 null polymorphism in those patients. The combined genotypes i.e., GSTM0T1 and GSTM0T0 null polymorphism also showed significant association in HNC patients.

Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Effect of age and frailty on the efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma.

Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p = .024), ≥VGPR (OR, 1.68, p = .027), PFS (HR 0.55, p = .002), and improved OS (HR 0.63, p = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p = .08) and OS (HR 0.62, p = .062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p = .0060) and frail patients (15% vs. 44%; p = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM.