Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation.

The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.

The utility of serum amylase as a prognostic marker in multiple myeloma.

Background: Ectopic production of amylase by tumor cells is known since 1951. Elevated amylase in multiple myeloma (MM) was first described in 1988. It has been postulated that translocation of chromosome 1, where amylase gene is situated, is responsible for ectopic production from the malignant plasma cells. Anecdotal reports have shown hyperamylasemia in MM to be associated with extensive bone disease, rapid progression, and shorter survival. Serum amylase estimation is a ubiquitous test. This prospective study was conducted to ascertain the degree of elevated amylase, its clinical utility, and implications in MM patients. Materials and Methods: In an 18-month period, all consenting patients with newly diagnosed or relapsed MM were tested for serum amylase levels. The study excluded patients with elevated lipase, abnormal creatinine clearance, and evidence of intestinal obstruction or perforation. Patients with amylase value >100 U/L were designated to have "elevated amylase level" for the purpose of this study. Results: We enrolled 58 patients with MM, of which 29.3% (n = 17) were found to have elevated serum amylase levels. The median age of patients with elevated amylase was 65 years. The male-to-female ratio was 1.9:1. There was no statistical association between age, gender, type of heavy chain class, light chain, or high-risk cytogenetics. Among patients with the International Staging System (ISS), Stages I, II, and III, 20.8% (n = 5), 31.3% (n = 5), and 41.2% (n = 7) were noted to have elevated amylase levels. A statistically significant association was noted between the presence of extramedullary disease (EMD) and elevated amylase level (P = 0.028). Higher mortality (29.4% versus 17%) and shorter mean survival of (30.2 ± 3.3 months versus 51.7 + 4.9 months) were recorded in patients with elevated amylase levels in comparison to those with normal levels. Conclusions: Elevated serum amylase level in MM is indicative of advanced ISS stage, the presence of EMD, higher risk of mortality, and shorter survival. Serum amylase can be used as a cost-effective tool in myeloma management.

Prospective Evaluation of Response to Treatment, Survival Functions, Recurrence Pattern and Toxicity Profile in Indian Patients with Oligo-Brain Metastasis Treated with Only SRS.

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2-3 mm and a dose of 20-30 Gy in 1-5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total,: 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49-67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR - 8.1-28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20-2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17-118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3-73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20-28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population.

Case series of concurrent occurrence of sarcoidosis and breast cancer - A diagnostic dilemma.

Sarcoidosis is a multi-system granulomatous disorder characterized by involvement of multiple systems with or without lymphadenitis. Pulmonary complications are common and may lead to morbidity. Breast cancer is one of the commonest malignancy among women across the world. There is an increased risk of malignancies in sarcoidosis. This association with cancer creates a diagnostic dilemma due to the predominant involvement of nodes and organ systems in both conditions. Here we report three cases of sarcoidosis with breast cancer diagnosed over one year.

Pretreatment neutrophil-to-lymphocyte ratio predicts lymph node metastasis in triple-negative breast cancer.

Background: The purpose of the study was to investigate the value of pretreatment neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in triple-negative breast cancer (TNBC) and to see its bearing on the clinical and pathological stage of the disease. Methods: This was a retrospective analysis of cases of TNBC treated at our center from 2006 to 2013. The pretreatment complete blood count was recorded from which the NLR was calculated as the percentage of neutrophils divided by the percentage of lymphocytes. The association between pretreatment NLR with the stage of the disease, clinical and pathological lymph node status, and disease-specific survival was analyzed. Results: A total of 208 patients were eligible for the analysis. The median follow-up period was 48 months. The NLR was found to have a strong correlation with the pathological nodal status and the clinical stage (75% cases node-positive in the high NLR group versus 36% in the low NLR group; P < 0.01). At the time of analysis, 74% of our study population was alive and well. There was no significant correlation between the NLR and the overall survival. Conclusions: Based on our study, we conclude that the pretreatment NLR is strongly associated with lymph node metastasis and clinical stage in TNBC patients. It is probably not useful as a prognostic marker, as it does not seem to have any significant bearing on the overall survival.

A systematic review of clinical and laboratory parameters associated with increased severity among COVID-19 patients.

BACKGROUND AND AIMS: Corona virus disease 2019 (COVID-19) has been an extremely difficult pandemic to contain and it has affected more than 148 countries worldwide. The main aim of this systematic review is to provide a comprehensive summary of clinical and laboratory parameters that are associated with and indicative of increased severity among COVID-19 patients. MATERIAL AND METHODS: All the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19 were retrieved and evaluated for inclusion. RESULTS: As per our review, the mean age of patients in the severe group was 59.3 years compared to 46.5 years in non severe group. COVID-19 was more severe among men than women. Clinical presentation was variable among different studies. and dyspnea was the factor indicating severe disease. Laboratory parameters associated with increased severity were lymphopenia <0.8 × 109/L, thrombocytopenia 100 × 109/L, leucocytosis TC > 11 × 109/L, procalcitonin >0.5 ng/mL, d dimer >2 mcg/mL, aspartate transaminase elevation >150U/L, LDH >250U/L. CONCLUSION: This systematic review suggests that COVID-19 is a disease with varied clinical presentation and laboratory parameters. The commonest clinical symptoms were fever, cough and dyspnea. The laboratory parameters associated with severe disease were lymphopenia, elevated LDH, D dimer and Procalcitonin.

Effect of Lorazepam in Reducing Psychological Distress and Anticipatory Nausea and Vomiting in Patients Undergoing Chemotherapy.

OBJECTIVES: To evaluate the efficacy and safety of lorazepam in reducing psychological distress and chemotherapy-induced nausea and vomiting. METHODOLOGY: It was a prospective interventional study with seventy patients for a period of 1 year. In which, patients' anxiety, distress and status of nausea, and vomiting were assessed in the first four chemotherapy cycles before drug intervention. During the subsequent chemotherapy cycles, the outcomes of the intervention were reassessed along with patient's quality of life (QOL). RESULTS: Out of seventy patients, 62 showed improvement in their distress level after the drug intervention and patient counseling. Lorazepam along with other antiemetic drugs reduced chemotherapy-induced delayed nausea and vomiting. During the course of the study, 15 patients experienced drowsiness as an adverse reaction to lorazepam. The overall QOL of the population was also improved with lorazepam. CONCLUSION: Lorazepam along with patient counseling can improve patient's psychological distress and thus their QOL. The off-labeled use of lorazepam can be utilized for controlling chemotherapy-induced nausea vomiting.

The Role of Gefitinib in Patients with Non-small-cell Lung Cancer in India.

BACKGROUND: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC). We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India. MATERIALS AND METHODS: Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis. RESULTS: The median follow-up for the cohort was 311 days (range 11-1544 days). Median time to progression was 161 (range 9-883) days. Complete and partial remission was seen in 1 (2%) and 6 (9%) patients, respectively, with overall response rate of 11%. Twenty-four (38%) patients had stable disease. Gefitinib was well tolerated with no significant side effects. CONCLUSION: Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.