Assessment of potential drug-drug interactions in hospitalized cancer patients.

INTRODUCTION: Drug-drug interactions (DDIs) pose a significant threat to patients with cancer, resulting in several adverse events in an oncology setting. Our study aims to identify potential DDIs in inpatient oncology wards, assess their severity, and provide recommendations to avoid these interactions. MATERIALS AND METHODS: This prospective study was conducted in 79 hospitalized cancer patients over a period of 9 months (from August 2021 to May 2022) at the Amrita Institute of Medical Sciences, Kochi receiving at least two oncological or non-oncological drugs for 5 days. RESULTS: Significant differences were found in drug count (61.6% vs. 38.4%), hospitalization duration (63.1% vs. 36.9%), and medications for comorbidities (63% vs. 37%) between patients with and without DDIs (p < 0.001, <0.001, and 0.01, respectively). The study identified 321 DDIs, with 14 (4.4%) X interactions, 93 (30%) D interactions, 161 (50%) C interactions, and 53 (15.6%) B interactions. Severity-wise, 76 (23.7%) were major, 190 (59.1%) were moderate, and 55 (17.2%) were minor. CONCLUSION: Our study showed that drug count, medications for comorbidities, and hospitalization duration significantly increase the risk of DDIs in hospitalized oncology patients. Around 96.4% of recommendations for potential interactions were accepted and implemented, highlighting the huge opportunities and requirements for improvement, implementation, and management of drug interactions in oncology settings.

Endometriosis in clear cell and endometrioid carcinoma ovary: its impact on clinicopathological characteristics and survival outcomes.

Background: Malignant transformation in endometriosis was first described by Sampson in 1925. There is now sufficient evidence of its association specifically with endometrioid (EOC) and clear cell ovarian cancer (CCOC). Whether endometriosis-associated ovarian cancer (EAOC) is a distinct clinicopathological entity from non-endometriosis-associated ovarian cancer (NEAOC) remains uncertain. Objectives: This study aimed to assess the impact of endometriosis on clinical characteristics and survival outcomes in EOC and CCOC. Methods: This is a retrospective single-institution analysis of patients diagnosed with CCOC AND EOC between 2010 and 2021. Demographic and clinical presentation data were obtained from medical records. Patients were followed up till March 2023. Statistical analysis was done using the IBM SPSS Statistics 20 Windows. Results: Of the 77 cases of CCOC and EOC ovary, 38 had histopathologically proven endometriosis. There was no difference in age (51.62 and 50.05 years, respectively), body mass index, parity, menopausal status and CA 125 levels at presentation. Ascites was more frequent in the absence of endometriosis (30% versus 8.1%, p = 0.015). However, this did not translate to a statistical difference in the stage, with the majority presenting in the early stage. (94% versus 83%). All 78 patients underwent primary cytoreduction with equal rates of optimal resection.There was no difference in the mean disease-free interval between EAOC and NEAOC (107.6 and 109.4 months, p 0.484). Recurrences were predominantly pelvic in both groups. The disease-specific survival was 111.7 and 120.1 months, respectively, with and without endometriosis. This was however not statistically significant (p 0.751). Conclusion: In the Indian population, endometriosis did not have any impact on the age at presentation, CA 125 levels, stage of the disease and survival outcomes in EOC and CCOC ovary.

Impact of COVID-19 on the Diagnosis and Surgical Care of Patients with Breast Cancer-a Retrospective Observational Cohort Study from Kerala, South India.

The COVID-19 pandemic has strained the healthcare system worldwide. Our study aimed to evaluate the impact of the COVID-19 pandemic on the diagnosis and surgical care of patients with breast cancer in Amrita Institute of Medical Sciences, Kochi. This is a single-centre retrospective observational cohort study conducted in a tertiary care institution intended to analyse the management of patients with breast cancer before and after the pandemic outbreak. The number of mammograms dropped from 3689 in the pre-pandemic phase to 1901 in the post-pandemic phase, whilst the number of core biopsies remained almost the same (391 before the pandemic and 367 after the pandemic). The number of new patients decreased by 57.7% (from 614 to 354). However, the number of breast cancer surgeries has remained almost the same (318 before the pandemic and 287 after the pandemic). The number of breast conservation surgeries dropped from 127 in 2019 to 93 in 2020 (p-value = 0.01). Conversely, 24 patients underwent neoadjuvant chemotherapy in 2019, and this number increased to 37 in 2020, representing a statistically significant increase (p = 0.04). Even during a pandemic, cancer care is possible with proper resource allocation and by adopting a multidisciplinary approach.

Primary Neuroendocrine Carcinoma of the Larynx: A Case Report.

Neuroendocrine tumours can originate from any part of the body. The most common site in the head and neck is the larynx, accounts for less than 0.6%. The neuroendocrine carcinomas (NECs) of the larynx are rare tumours with high incidence of widespread metastases and poor prognosis. Here we report a 50-year-old male with localised primary moderately differentiated NEC of the larynx. He was treated with surgery followed by adjuvant chemotherapy and concurrent chemoradiation. He is free of his disease and is doing well.

Deciphering the role of transforming growth factor-beta 1 as a diagnostic-prognostic-therapeutic candidate against hepatocellular carcinoma.

Transforming growth factor-beta (TGF-ß) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-ß family, TGF-ß1 modulates most of its biological outcomes. Despite the abundant expression of TGF-ß1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-ß1 levels, contributing to poor prognosis and survival. Additionally, elevated TGF-ß1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms. TGF-ß1 has a prime role as a diagnostic and prognostic biomarker in HCC. Moreover, TGF-ß1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors. This review provides clinical relevance and up-to-date information regarding the potential of TGF-ß1 in diagnosis, prognosis, and therapy against HCC.

Flupirtine in the Management of Taxane-induced Pain in Cancer Patients.

Objectives: Paclitaxel and docetaxel are two commonly used chemotherapeutic agents in the treatment of various types of cancers. However, debilitating taxane-induced arthralgia and myalgia are among the most common adverse reactions associated with taxanes, which has greatly influenced medical practitioners. Most of the mild and moderate analgesics were found to be less effective in the management of taxane induced pain. So we used flupirtine, a non-opioid analgesic, in the treatment of taxane-induced pain. Materials and Methods: In this study, we analysed the baseline pain score and follow-up data of 60 patients receiving a taxane-based chemotherapy regimen. Baseline data of these study populations experiencing significant taxane-induced pain were compared with follow-up data after treating them with analgesic flupirtine (200 mg/day). The baseline and follow-up data representing pain were assessed with the help of the Visual Analogue Scale (VAS), and the quality of life was determined using the Brief Pain Inventory (BPI) scale questionnaire. Results: The mean baseline and follow-up VAS score was compared using paired sample t-test, which showed a significant reduction in taxane-induced pain after treatment with flupirtine (P < 0.001). Similarly, the mean BPI score representing the quality of life before and after treatment with flupirtine was compared, and a notable improvement in quality of life was seen after treatment with flupirtine. The mean and follow-up data of aspartate aminotransferase and alanine aminotransferase levels of patients were also compared to assess the adverse drug reaction profile of the drug, and the analyzed data was found to be statistically insignificant (no significant liver toxicity) which indicates that drug can be used effectively for a period of <2 weeks. Conclusion: We believe that flupirtine can be used as an effective analgesic in dire situations where patients require opioid analgesics for the management of taxane-induced pain, provided that the drug is given for <2 weeks to avoid drug-related hepatotoxicity.

Therapeutic Drug Monitoring as a Tool for Therapy Optimization.

The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetic) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; and oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-size-fits-all-fixed-dosing approach. Therapeutic drug use can be monitored based on pharmacokinetic, pharmacodynamic, and pharmacometric methods. Based on the experiences of therapeutic drug monitoring of various agents across the globe, we can look ahead to the possible developments of therapeutic drug monitoring in India.

Clinical Profile of Lung Cancer in Females- A Single Institution Study.

The global incidence of lung cancer among women is rising. By 2030, lung cancer in women is expected to increase by 43%. The factors thought to predispose women to lung cancer are exposure second hand smoke, air pollution and biofuels used for cooking. Our objectives was to study the clinical and pathological features of lung cancer in women. Material: A retrospective review of medical records of women with lung cancer who attended Amrita institute of medical sciences, Kochi, between 2015-2019 was done. Data was collected using our institution's Electronic medical records (EMR). Demographic details and clinicopathologic features were extracted from the EMR manually. Data was tabulated using Microsoft Excel. Categorical variables were expressed as frequencies and percentages., Observation :Out of the 1683 lung cancer cases seen during 2015-2019, 389 (23.1%) were females. 250 patients for whom complete data was available was included in this study. Majority of the women were above 50 years old (N= 216, 86.4%). The median age of diagnosis was 64 years (range 33- 95 years). 14 patients (5.0%) had history of pulmonary tuberculosis. The median duration of symptoms was 8.7 weeks (IQR 4.3 -13). Cough (N=173, 69.2%), dyspnoea (N=117, 46.8%) and chest pain (N = 105, 42%) were the most common symptoms. Data regarding the use of cooking medium used (biofuel/LPG) was available only in 107 patients. 15/107 (14%) patients were using biofuels for cooking. 75.2% of them presented in advanced stages (Stage IV N=188). The most common sites of metastasis were bone (N=88, 35.2 %), lung (N = 55, 22%), lymph nodes (N=55, 22%) brain (N= 38, N= 15.2%), liver (N=32, 12.8%) and adrenal gland (N=31, 12.4%). 113 patients had one and 77 patients had multiple metastatic sites. The site of primary tumour was-right upper lobe N=67 (26.8%), Right middle lobe N =11 (4.4 %%), Right Lower lobe N=46 (18.4%), Left upper lobe N=65 (25%) and left lower lobe N=52(20.8%). Adenocarcinoma was the predominant histological type (N=224, 89.6%) followed by squamous cell carcinoma (N=12, 4.8%). Actionable mutations observed were EGFR in 44% and ALK 2% and BRAF 1.2%. Conclusion: Male to female ratio in our study (4.3:1) was higher compared to the lung cancer demographics from other states in India. This finding along with rising global incidence warrants special attention and screening for women with suspicious symptoms. The incidence of EGFR mutation was also high (44%) compared to other studies from India.

Belzutifan: A Narrative Drug Review.

Von Hippel-Lindau disease is an autosomal dominant disorder characterised by renal cell carcinomas, pancreatic neuroendocrine tumours, central nervous system hemangioblastomas, retinoblastomas, and tumours of the reproductive tract. This disease results from loss of function mutations in the tumour suppressor gene known as the Von Hippel-Lindau gene, located on chromosome 3. Loss of function mutation in the Von Hippel-Lindau gene results in the accumulation of a protein known as a hypoxia-inducible factor, which promotes cellular proliferation and angiogenesis, leading to cancer. Belzutifan inhibits the hypoxia-inducible factor by binding to the Per-ARNT -Sim-B binding pocket on the hypoxia-inducible factor -2α, inhibiting cellular proliferation and angiogenesis. In our thorough literature review, we identified 37 relevant articles. Belzutifan showed clinically meaningful response rates for both Von Hippel-Lindau disease-associated renal cell carcinomas and non-renal cell cancers. The pharmacokinetic profile of belzutifan was much better than its congener molecules due to the optimisation of its dihalide groups from germinal to vicinal. The pharmacodynamic effect of belzutifan was confirmed by its ability to decrease serum erythropoietin, which is a direct result of hypoxia-inducible factor- 2α inhibition. The significant side effects observed were anaemia, hypoxia, fatigue, hypertension, visual impairment and weight gain. Multiple clinical trials are currently underway to determine the role of beluztifan as part of combination regimens in treating Von Hippel-Lindau diseaseassociated malignancies.

Recurrent extramedullary plasmacytomas without multiple myeloma: A case report with review of the literature.

BACKGROUND: Extramedullary plasmacytoma (EMP) is an uncommon presentation and usually occurs in conjunction with multiple myeloma (MM). An EMP without developing MM at any point is an extremely rare presentation, and only seven such cases have been reported in the literature to date. PRESENTATION OF CASE: We present a case of EMP, who presented with multiple recurrent lesions in rare sites like nasal cavity, testis and skin without the involvement of bone marrow at any point of disease course. He was treated with multiagent chemotherapy (DT-PACE) and continues to be in remission at 29 months post-chemotherapy, which is the longest amongst all the cases reported so far. DISCUSSION AND CONCLUSIONS: There are no clearly defined guidelines to treat EMP. Our case had a clinical presentation at very unusual sites and was treated with DT-PACE regimen as against the previous seven reported cases and had the most prolonged period of remission.

Discovery of Anticancer Hybrid Molecules by Supervised Machine Learning Models and in Vitro Validation in Drug Resistant Chronic Myeloid Leukemia Cells.

The concept of hybrid drugs for targeting multiple aberrant pathways of cancer, by combining the key pharmacophores of clinically approved single-targeted drugs, has emerged as a promising approach for overcoming drug-resistance. Here, we report the design of unique hybrid molecules by combining the two pharmacophores of clinically approved BCR-ABL inhibitor (ponatinib) and HDAC inhibitor (vorinostat) and results of in vitro studies in drug-resistant CML cells. Robust 2D-QSAR and 3D-pharmacophore machine learning supervised models were developed for virtual screening of the hybrid molecules based on their predicted BCR-ABL and HDAC inhibitory activity. The developed 2D-QSAR model showed five information rich molecular descriptors while the 3D-pharmacophore model of BCR-ABL showed five different chemical features (hydrogen bond acceptor, donor, hydrophobic group, positive ion group, and aromatic rings) and the HDAC model showed four different chemical features (hydrogen bond acceptor, donor, positive ion group, and aromatic rings) for potent BCR-ABL and HDAC inhibition. Virtual screening of the 16 designed hybrid molecules identified FP7 and FP10 with better potential of inhibitory activity. FP7 was the most effective molecule with predicted IC50 using the BCR-ABL based 2D-QSAR model of 0.005 µM and that of the HDAC model of 0.153 µM, and that using the BCR-ABL based 3D-pharmacophore model was 0.02 µM and that with HDAC model was 0.014 µM. In vitro study (dose-response relationship) of FP7 in wild type and imatinib-resistant CML cell lines harboring Thr315Ile or Tyr253His mutations showed growth inhibitory IC50 values of 0.000 16, 0.0039, and 0.01 µM, respectively. This molecule also showed better biocompatibility when tested in whole blood and in PBMCs as compared to ponatinib or vorinostat.

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.

Pilot Nanostring PanCancer pathway analysis of colon adenocarcinoma in a tertiary healthcare centre in Kerala, India.

The prevalence of microsatellite instability and deoxyribonucleic acid mismatch repair deficiency in colorectal adenocarcinoma (CRC) cases is higher in India compared to western populations. No major study on the molecular pathogenesis is currently available in the Indian population. We conducted a pilot study to explore the differences in molecular pathogenesis of microsatellite stable (MSS) and microsatellite unstable CRC from a tertiary care centre in Kerala, South India. Using Nanostring PanCancer panel assay in Stage II colorectal adenocarcinoma, tumour tissues (n = 11) were compared against normal colon tissues (n = 4). Differentially expressed (DE) genes were identified and super-imposed onto colon adenocarcinoma cohort of The Cancer Genome Atlas (TCGA) data (TCGA Colon Adenocarcinoma (TCGA COAD)), from the Genome Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource (TIMER) to compare the gene associations. Significant DE genes were 59 out of 730 (false discovery rate adj. p-value < 0.05), 18 of which had a fold-change |FC(log2)| ≥ 2. On superimposition to TCGA COAD, 33 genes were significant in both TCGA and current study. ETV4 was expressed significantly higher in MSS with no immune cell infiltration. Other significant DE genes with high FC(log2), unique to the study were INHBA, COL1A1, COL11A1, COMP, SFRP4 and SPP1, which were clustered in STRING network analysis and correlated with tumour-infiltrating immune cells in TIMER, suggesting a specific interaction pathway. The preliminary study suggests a distinct pathogenesis of MSS CRC involving ETV4 in the Indian population and warrants further clinically extensive and high-dimensional expression studies.

Intracranially injectable multi-siRNA nanomedicine for the inhibition of glioma stem cells.

BACKGROUND: Nanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene-targeted siRNA nanoparticle gel (NPG) for the combinatorial silencing of 3 aberrant genes, thus inhibiting the tumorogenic potential of GSCs. METHODS: NPG loaded with siRNAs targeted against FAK, NOTCH-1, and SOX-2 were prepared by the self-assembly of siRNAs with protamine-hyaluronic acid combination. Electron microscopy, DLS, and agarose gel electrophoresis were used for the physicochemical characterization. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma-derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-derived xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity. RESULTS: The siRNA nanoparticles with an average size ~ 250 nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumor growth in orthotopic rat brain tumor model. CONCLUSION: Intracranially injectable n-siRNA NPG targeted to multiple stem-cell signaling impairs glioma initiation capabilities of GSCs and inhibited tumor growth in vivo.

Cancer and severe mental illness in low- and middle-income countries: The challenges and outlook for the future.

OBJECTIVE: Patients with severe mental illness (SMI) face health inequalities that lead to under treatment of diseases such as cancer and result in increased mortality. There is literature addressing this issue for SMI patients in high-income countries but few for those in low- and middle-income countries. This review aims to draw attention to the health inequalities and the compounding factors faced by SMI patients in low- and middle-income countries. The relevance of integration of psycho-oncology in the care of SMI patients with cancer is integral to reduce disparities and address varied contributory factors. METHODS: The literature review was conducted by searching through two databases which includes PubMed and Google Scholar. We searched for articles using keyword search terms: severe mental illness, SMI, schizophrenia, bipolar disorder, cancer, low- middle-income countries, low- and middle-income countries, psycho-oncology, HPV vaccine, cancer incidence, cancer mortality, cancer control, cancer screening, cancer treatment and palliative care. RESULTS: A total of 80 research articles were included in our literature review. We found that there was an increased requirement for adapting to the changing disease landscape in low- and middle-income countries. An improvement on aspects such as vaccination, screening and prevention is necessary, and also efforts to change social stance towards SMI is crucial. CONCLUSION: There is an increase incidence of cancer in low- and middle-income countries, and the number of patients with SMI in low- and middle-income countries is also rising. This is due to social, psychological, economical and healthcare factors. Low- and middle-income countries must consider improving these aspects in order to adapt to the changing landscape.

Vulvar carcinoma in Fanconi Anaemia: A case report with review of literature.

Fanconi anaemia is a rare autosomal recessive disorder associated with bone marrow failure and congenital malformations. The impaired DNA repair pathways in Fanconi anaemia predispose patients to a high risk of cancers of squamous cell origin, particularly in the head and neck region. Cancers of the vagina and vulva are rare in Fanconi anaemia. Here, we report a case of a 44-year-old female with Fanconi anaemia who developed an ulcerated lesion on the clitoris that extended into the labia majora. A biopsy of the lesion showed well-differentiated squamous cell carcinoma. The patient was treated with wide local excision of the vulval lesion. The patient developed neutropenia post-procedure but recovered in one week time. We have followed up the patient regularly since the procedure. No further issues have been detected to date.

Prevalence of the use of traditional complementary and alternative medicine amongst cancer patients in a tertiary care center in Kerala, India.

BACKGROUND: Unmet needs of cancer patients prompt them to seek care from Traditional, Complementary and Alternative Medicine (TCAM) practitioners. OBJECTIVE: To investigate the prevalence of TCAM use in a multi-specialty tertiary cancer center in South India. MATERIALS AND METHODS: A cross-sectional survey of cancer patients who used TCAM during the study period. The patients were recruited based on covenience sampling method. RESULT: 320 cancer patients were approached, out of which 279 (87.2%) patients responded, and the prevalence of TCAM use was 34.4%. Home remedies (36%) figure prominently, with family advice (40%) being the primary influence for the TCAM use. The key expectation was an improvement in the quality of life (49%). TCAM use was pronounced during the chemotherapy phase (50%). Most patients (76%) using TCAM reported satisfaction with the treatment. Majority of the patients did not disclose concomitant use of TCAM to their treating physicians (71%). CONCLUSION: TCAM use by cancer patients is prevalent in Kerala. The study results point towards a need for large scale surveys, implementation of pharmacovigilance, patient education and research to identify and integrate TCAM interventions in cancer care that are safe and have beneficial effects.

Cancer nanomedicine developed from total human serum: a novel approach for making personalized nanomedicine.

Aim: To develop a method for making total serum nanoparticles (TSN) loaded with cytotoxic chemodrugs for cancer therapy. Materials & methods: TSN loaded with paclitaxel (PTX) or piperlongumine (PL) were prepared using high-pressure homogenization and tested for immunogenicity in healthy animals and antitumor properties in pancreatic cancer xenograft models. Results: TSN-PL nanoparticles of average size 104 nm and encapsulation efficiency approximately 50% showed enhanced dose-dependent cytotoxicity compared with TSN-PTX or clinically used combination of gemcitabine and nano-PTX in two pancreatic cell lines. Significant antitumor efficacy was also established in the pancreatic xenograft model. Conclusion: We developed a unique method of converting total blood serum into chemo drug-loaded nanoparticles and demonstrated its efficacy in vitro and in vivo.