Audit of Presentation, Primary Site, and Pattern of Treatment in 778 Indian Patients with Brain Metastasis in 15 Years (2007-2022).

BACKGROUND AND AIM: Audit of brain metastasis (BM) patients treated with radiation therapy (RT) in a tertiary cancer center from South India was carried out to assess the incidence of BM by site with a specific focus on their primary origin, with an aim to evaluate the relationship between the primary site and the site of metastases, pattern of care, and RT over the years. MATERIALS AND METHODS: All consecutive BM patients who received RT with whole-brain radiation therapy (WBRT), hippocampal avoidance WBRT (HA-WBRT), and radiosurgery SRS between 2007 and 2022 after radiologic confirmation of a known case of malignancy or histology-proven BM were audited. RESULTS: From January 2007 to December 2022, hospital information system (HIS)-identified 778 patients with BM treated with RT were audited. Incidence of BM was 0.64% in 2008 and over the years, it had increased to 0.89% in 2020, 0.93% in 2021, and 1.24% in 2022. Usage of SRS was almost nil in 2007, whereas in 2022, it was 40%. Also, 593 (76%) patients were treated with WBRT, 157 (20%) with SRS, and only 23 (3%) received HA-WBRT. Lung and breast cancers (40%) were the most common primary, and among rare primary tumors were those of larynx (two), tonsil (one), tongue (three), pancreas (one), and blood disorders (two). Lung primary presented with frontal lesion in 51%, parietal lesion in 43%, cerebellar lesion in 38%, and temporal lesion in 33% of cases. CONCLUSIONS: Audit of BM in the Indian population suggests a shift in treatment paradigm from WBRT to SRS as a primary modality in oligo-brain metastasis with a good performance status. This audit provides us information regarding geographic variation in presentation and primary site.

Unchartered waters: Significance of fall in Ki67 index after short-term preoperative endocrine therapy in early breast cancers.

BACKGROUND: Endocrine treatment for breast cancer acts largely by inhibiting tumor cell proliferation. The biomarker Ki67 is linked to the proliferative index of the tumour. OBJECTIVE: To identify the factors affecting the fall in Ki67 value in early-stage hormone receptor (HR) positive breast cancer patients receiving short-term preoperative endocrine therapy in an Indian cohort. METHODS: Women with hormone receptor positive, invasive, nonmetastatic, and early breast cancer (4 week) did not affect the fall in Ki67. CONCLUSION: Preoperative therapy with Letrozole resulted in a more significant fall in Ki67, as compared to therapy with Tamoxifen. Determining the fall in Ki67 value in response to preoperative endocrine therapy could provide an insight into the response to endocrine therapy in luminal breast cancer.

Ki 67: a Promising Prognostic Marker in Early Breast Cancer-a Review Article.

Ki67 index is considered to be a reliable indicator of the proliferative activity of breast cancer. Additionally, the Ki67 proliferative marker may play a role in assessing response to systemic therapeutic strategies and can act as a prognostic biomarker. But its limited reproducibility which stems from a lack of standardization of procedures, inter-observer variability, and preanalytical and analytical variabilities all have hampered the use of the Ki67 index in clinical practice. Currently, clinical trials have been evaluating Ki67 as a predictive marker for needing adjuvant chemotherapy in luminal early breast cancer patients receiving neoadjuvant endocrine therapy. But the inconsistencies existing in the estimation of the Ki67 index limit the utility of Ki67 in standard clinical practice. The purpose of this review is to evaluate the benefits and drawbacks of utilizing Ki-67 in early-stage breast cancer to prognosticate the disease and predict the risk of recurrence.

Fall in Ki67 Index After Short-Term Preoperative Letrozole: a Gateway to Assess the Response in Hormone-Positive Early Breast Cancers.

Endocrine treatment for breast cancer acts largely by inhibiting tumor cell proliferation. The study aimed to explore the fall in proliferative marker Ki67 in patients receiving preoperative endocrine therapy and the factors associated with it. A prospective series of hormone receptor-positive postmenopausal women with early N0/N1 breast cancer were enrolled. Patients were requested to take letrozole OD while they await surgery. The fall in Ki67 after the endocrine therapy was defined as the percentage of the difference between the pre-and postoperative Ki67 value with the preoperative Ki67. Sixty cases matched the criteria of which 41 (68.3%) of women showed a good response to preoperative letrozole (fall in Ki67 > 50%; p-value < 0.001). The average mean fall in Ki67 was 57.083 ± 37.97. Postoperative Ki67 after the therapy was less than 10% in 39 (65%) patients. Ten patients (16.6%) had a low Ki67 index at baseline, which continued to remain low after preoperative endocrine therapy. The duration of the therapy did not affect the percentage of Ki67 fall in our study. Short-term changes in the Ki67 index in the neoadjuvant settings may predict outcomes during adjuvant use of the same treatment. Proliferation index on residual tumor holds prognostic importance, and our results reflect that greater attention should be given to the percentage of reduction of Ki67, rather than focusing purely on a fixed value. This could help predict patients who respond well to endocrine therapy, while those who respond poorly may require further adjuvant treatment.

Preservation of cognitive function after brain irradiation.

OBJECTIVE: Approximately 50-90% of brain metastatic patients who receive radiation therapy (RT) exhibit cognitive decline which may affects the quality of life of cancer survivors. Hence preservation of cognitive functions in brain metastatic patients becomes important. This review aims to evaluates the pathology or mechanism of cognitive function impairment after brain irradiation and strategies available to preserve cognitive function after radiation therapy. DATA SOURCES: Published articles evaluating the pathology behind radiation induced cognitive impairment and strategies to resolve or preserve cognitive impairment were searched for in scientific databases (eg: PubMed, Scopus, Cochrane database, Google scholar) using keywords including memantine, brain metastases, radiation therapy, pathophysiology, pathogenesis, mechanism and prevention. DATA SUMMARY: Several hypotheses have been offered to explain the mechanism of radiation induced cognitive decline. Among them, vascular hypotheses play a significant role. Some pharmacological agents have been also tested in patients receiving radiotherapy, memantine was found beneficial based with the reference to existing data. CONCLUSION: Future studies are required to evaluate the impact of memantine in different types of radiation therapy procedures and its effects on quality of life of brain metastatic survivors.

Association of apolipoprotein E ε4 allele with cognitive impairment in patients with epilepsy and interaction with phenytoin monotherapy.

Cognitive impairment implicates many factors beyond phenytoin monotherapy in patients with epilepsy. Apolipoprotein E ε4 allele has been reported to play a role in severe memory impairment that ultimately progresses to Alzheimer's disease (AD); however, knowledge about its role in cognitive impairment in patients with epilepsy is lacking. Our study proposes the possible involvement of the APOE ε4 allele in cognitive impairment in patients with epilepsy which is further worsened by phenytoin monotherapy. Assessment of the APOE ε4 allele in a population with epilepsy will help to identify the patients vulnerable to cognitive impairment and, therefore, the corrective therapy that needs to be addressed.

A comparative effect of atorvastatin with other statins in patients of hyperlipidemia.

OBJECTIVE: The objective of the study was to evaluate the safety and efficacy of atorvastatin compared with simvastatin and pravastatin in patients of hyperlipidemia. MATERIALS AND METHODS: This was a randomized, parallel group, open-label study conducted at KG hospital, Coimbatore, Tamilnadu, India. Twenty hyperlipidemia patients each taking atorvastatin 20 mg, pravastatin 20 mg and simvastatin 20 mg tablets were selected for the study after clinical and baseline investigations. The patients were reviewed after 3(rd) and 5(th) month of statin therapy for lipid profile. The liver enzyme levels (SGOT, SGPT, ALP), albumin, bilirubin, protein and biochemical infraction parameters (Creatine Kinase, Creatine Kinase - Myocardial Band) after 5(th) month of treatment with statins were also reviewed. RESULTS: The results showed that atorvastatin significantly reduced the lipid levels (LDL-C, TC, TG, VLDL) when compared to simvastatin and pravastatin after 3(rd) and 5(th) month of treatment. Atorvastatin increased the HDL-C levels significantly when compared to simvastatin and pravastatin after 5 months of treatment. Atorvastatin also significantly reduced the CK levels when compared to pravastatin but no increase in liver enzyme levels was observed. CONCLUSION: The study showed that atorvastatin is more effective when compared to simvastatin and pravastatin in patients with hyperlipidemia.