Mutation Analysis of Epidermal Growth Factor Receptor Gene in Non-Small Cell Lung Cancer for Selection of Patients Eligible for Tyrosine Kinase Inhibitor Therapy

Introduction: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy is effective as a first-line treatment of advanced non-small-cell lung cancer (NSCLC). This research study investigated the distribution of EGFR mutations in patients diagnosed with NSCLC to assist in selecting patients who could benefit from tyrosine kinase inhibitor therapy. Materials and Methods: This cross-sectional study was conducted between July 2017 and November 2022. A real-time multiplex ​Polymerase Chain Reaction (PCR) assay supplied by Roche Diagnostics was used to examine DNA obtained from 682 tumor biopsies collected from NSCLC patients. DNA amplification was performed in a Cobas z 480 instrument for mutation analysis. The PCR assay was designed using specific primers and probes to detect 43 different mutations targeting exons 18-21. Results: Among the 682 samples, 466 (68.3%) were males, and 216 were females. The male-to-female ratio was 2.1. Twenty per cent of the male and 37% of the female samples were positive for EGFR mutations. The most common mutations were the in-frame deletion of exon 19, followed by L858R in exon 21, exon 20 insertion and S769I, exon 18 G719X. In addition, three mutations, namely del exon 19, T790M and exon 20 insertions were also detected in a patient, suggesting an actively progressive disease. Conclusions: This study showed that EGFR mutations are more common in Pakistani female patients than males. Secondly, in-frame deletion of exon 19 and exon 21 mutation L858R are prevalent in most of the NSCLC patients. The prevalence of common and rare EGFR mutations in Pakistani patients provides an opportunity for a subset of patients' chance of therapy

Survival Analysis and Correlates with Molecular Epidemiology: 10-year Retrospective Series of High-Grade Glioma in Pakistan

Introduction: High-grade gliomas are malignant, recurring primary CNS tumors requiring extensive postoperative chemotherapy and radiation treatment. Isocitrate dehydrogenase (IDH), 1p19q, and ATRX mutations significantly influence survival and response to chemotherapy, as seen in many extensive studies from the Global North. This study aims to report data from the local region regarding progression-free survival and overall survival in light of molecular characteristics. Materials and Methods: A 10-year retrospective series was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, with 285 patients presenting from 2008 to 2018. Prospective follow-up data was collected, and complete molecular profiles were available for patients presenting from 2010 onwards. Survival analysis was conducted through the Kaplan-Meier method, with log-rank reported. Results: 70.53% (201) of patients were male, with a mean age at diagnosis of 43.33 ± 15.1 years. 265 patients within the cohort completed postoperative radiotherapy, while 141 patients underwent chemotherapy (PCV [Procarbazine, lomustine and vincristine] or Temozolomide). Mean survival, in months, within the cohort was as follows: glioblastoma (14.1), anaplastic astrocytoma (27.5), and anaplastic oligodendroglioma (39.8). Survival curves showed a lower survival for IDH wild-type (p<0.0001), ATRX mutated (p=0.029), and 1p19q non-deleted (p=0.008) tumors from Pakistan. Discussion: Our findings quantified long-term survival outcomes for high-grade glioma from Pakistan, analysing the various treatment patterns. Of particular importance, molecular sub-classification significantly predicted survival outcomes by IDH, ATRX, and 1p19 co-deletion mutations. Expanding brain tumour epidemiology will benefit assessing the efficacy of regional oncological centres and establishing standards of care

Pediatric Ewing Sarcoma of Kidney: A Case Series and Review of Literature

Introduction: Renal Ewing sarcoma is an aggressive and rare malignancy affecting children and adolescents. Limited data on its management contributes to uncertainties in treatment Case description: We present two pediatric cases of Renal Ewing Sarcoma. Both cases emphasize the significance of accurate diagnosis, multimodal treatment, and long-term follow-up in achieving favourable outcomes. Accurate diagnosis of renal Ewing sarcoma is crucial for effective management. Multimodal treatment involving neoadjuvant chemotherapy, surgical resection and staging with lymph node sampling, and chemotherapy continuation has shown promising results in our cases. Long-term follow-up is essential for monitoring disease progression and ensuring optimal outcomes. Practical Implications: There is limited data published about these renal tumors, especially in the pediatric population, and most studies lack long-term follow-up (6,7,20), with uncertain management due to limited data. This data will add to the newer and multimodal approach and form the basis for future meta-analysis to help formulate guidelines in upcoming international meetings. Continued research efforts are necessary to optimize strategies and improve the prognosis for pediatric patients with renal Ewing sarcoma

Systemic Diseases and Risk of Developing Gastrointestinal Cancer.

Importance: Gastrointestinal (GI) cancers are the second leading cause of cancer-related deaths worldwide. Observations: The global challenges GI cancers pose are high, especially in middle- and low-income countries. Patients with these cancers present with symptoms of poor appetite, weight loss, heartburn, abdominal pain, fatigue, and anaemia. Several risk factors contribute to GI cancers, including age, gender, obesity, pathogenic infections, smoking cigarettes, alcohol consumption, and dietary habits. Most of these cancers are sporadic. However, some patients are at high risk because of a family history of GI cancers. Systemic diseases affect multiple organs, and their chronic occurrence elicits inflammatory responses at various sites. These diseases also contribute to GI cancers. Conclusion and Relevance: In this review, we discuss that untreated systemic diseases, including diabetes, hepatitis, AIDS, ulcers, and hypertension, can potentially lead to GI cancers if they remain untreated for a longer period. Systemic diseases initiate oxidative stress, inflammatory pathways, and genetic manipulations, which altogether confer risks to GI cancers. Here, we describe the association between systemic diseases and their underlying mechanisms leading to GI cancers

Large Bowel Perforation in Patients with Colorectal Cancer: A South African Perspective

Introduction: Large bowel perforation (LBP) occurs in up to 10% of colorectal cancer (CRC) patients and is a potential surgical emergency. Data on LBP in CRC patients from resource-limited countries are required to improve the management of this condition in these settings. Our study aimed to describe LBP amongst CRC patients in KwaZulu-Natal, South Africa. Materials and Methods: This was a descriptive sub-analysis of LBP data from an ongoing CRC registry. This study explores free and contained perforations and describes LBP characteristics, surgical management, histological findings, overall survival, and CRC recurrence. Results: Ninety-four out of 2523 CRC patients had LBP (3.7%). The median age was 53.0 years (interquartile range: 43.0–64.0). The male-to-female ratio was 1.4:1. Thirty-three patients (35.1%) had a coexisting bowel obstruction. Tumor site perforations occurred in 87 patients (92.6%) and were mostly in the sigmoid colon (36.2%). Perforations were contained in 77 patients (81.9%). Eighty-nine patients (94.7%) underwent resection (elective resection: 76/89 patients, 85.4%). The post-operative inpatient mortality rate was 2.2%. Most patients had Stage III CRC (46 patients, 48.9%) and moderately differentiated tumors (77 patients, 81.9%). Overall survival at 12 months following CRC diagnosis was 55.4%. The early recurrence rate for CRC disease was 5.4%. Conclusion: Tumor site perforations predominated, and most were contained. Patients were younger when compared with the international literature. We reaffirm that diastatic-free and contained perforations are two distinct clinical entities

A Case Report on Rare Case of Pancreatic Metastasis from Primary Lung Adenocarcinoma: Treated Through a Non-surgical Approach

Introduction: Most frequent sites of metastasis from lung cancer are the liver, brain and adrenal. Pancreas is an infrequent site of solitary metastasis from the lung primary with limited treatment options. There is insufficient data on the prognosis and optimal management of such cases. Case Description: We report a case of 44 years old gentleman diagnosed with locally advanced Lung Adenocarcinoma Stage T4N3 who was treated radically with chemoradiation therapy, followed by a relapse of solitary pancreatic metastasis, which was treated with targeted therapy, erlotinib, because of the presence of EGFR mutation. Practical Implications: This case reports an excellent radiological and symptomatic response in a patient who received erlotinib for advanced non-small cell lung cancer (NSCLC). The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has led to better prognosis and longer progression-free survival for patients with advanced NSCLC. However, the long-term survival of patients with metastatic NSCLC is limited

Reduction in Average Length of Stay in Emergency Department of a Low-Income Country's Cancer Hospital.

Introduction: Prolonged length of stay (LOS) in emergency departments (ED) is a widespread problem in every hospital around the globe. Multiple factors cause it and can have a negative impact on the quality of care provided to the patients and the patient satisfaction rates. This project aimed to ensure that the average LOS of patients in a tertiary care cancer hospital stays below 3 hours. Materials and Methods: The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) approach was followed. Results: The average LOS was 166 minutes before implementing interventions. The two primary reasons for the increased length of stay were delays secondary to physician assessment and diagnostic lab reports. Strategies were defined to control these factors, which helped reduce the average length of stay to 142 minutes, a 30% reduction. Conclusion: A process improvement model similar to this project is recommended to enhance the quality of hospital services. It will provide valuable insights into the process flow and assist in gathering precise data on the various steps involved. The data collected can then be analyzed to identify potential causes and make informed decisions that can significantly improve hospital processes

Outcomes of Patients with FLT3 Positive Acute Myeloid Leukemia; an Experience from a Tertiary Care Hospital in Karachi, Pakistan

Introduction: Molecular genetic abnormalities in AML are essential for disease diagnosis and determining prognosis and clinical course. Mutations in FLT3 and NPM genes are the most frequent genetic abnormalities, which are also known to impact disease outcomes. FLT3 mutations have been identified in approximately 30% of denovo AML patients and are associated with poor prognoses. This study aimed to determine the response to induction chemotherapy, overall survival, and relapse rate in patients with FLT3-positive acute myeloid leukaemia. Materials and Methods: In this study, a retrospective analysis was performed of 75 newly diagnosed patients with AML registered between January 2015 and July 2022. Patient demographics and clinical-haematological parameters were noted, and molecular analysis for FLT3 ITD/TKD and NPM mutations was performed. All the patients received standard induction chemotherapy, and their response to treatment, overall survival, and relapse rate were assessed. Results: A total of 75 cases of AML were analysed. The mean age of the sample was 34.9 years, of which 65.3% were males and 34.7% were females. The patients were stratified into two groups: those who were positive for FLT3 while negative for NPM (FLT3+/NPM-), representing 17.3%, and those who were negative for both FLT3 and NPM (FLT3-/NPM-), representing 82.7% of cases. On day 28 post-induction, the complete remission rate was 69.2% in the FLT3 positive group and 77.4% in the FLT3 negative group. In the FLT3+/NPM- group, 55.6% of cases who were in remission at day 28 subsequently relapsed, compared to 50.0% of FLT3-/NPM- cases. The overall median survival time for the cohort and FLT3+ group was 1467 days, while that of the FLT3-group could not be estimated due to the very high survival rate. Conclusion: No significant differences in outcomes were observed in patients who were FLT3 positive compared to those who were FLT3 negative

A Longitudinal Metagenomic Comparative Analysis of Oral Microbiome Shifts in Patients Receiving Proton Radiation Versus Photon Radiation for Head and Neck Cancer

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center (MPTC) and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three-time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n=4) were compared to photon radiation (n=4). Additional control groups included healthy age- and sex-matched controls (n=5), head and neck cancer patients who never received radiation therapy (n=8), and patients with oral inflammatory disease (n=3). Results: Photon therapy patients presented with a lower microbial alpha diversity at all timepoints and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. Bacterial de novo pyrimidine biosynthesis pathway and nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for proliferation of pathogenic bacteria. Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status

Standardized Uptake Value (SUVmax) in Organ Confined Prostate Cancer in 68-Ga-PSMA PET-CT Scan and its Correlation with Prostate Specific Antigen level and Gleason Score

Introduction: A positron emission tomography (PET) scan and a computed tomography (CT) scan is an integral part of oncological imaging, and other modalities like magnetic resonance imaging, CT or bone scintigraphy have some limitations in staging the workup of prostate carcinoma. Combined with tissue-specific markers like PSMA (prostate-specific membrane antigen), positron emitter-based functional imaging results have improved. Our study aimed to determine the Standardized Uptake Value (SUVmax) in prostate adenocarcinoma that is confined to the organ in Ga-68-PSMA PET-CT scans and how it correlates with prostate-specific antigen (PSA) levels and Gleason Score (GS). Materials and Methods:  This cross-sectional study was conducted at SIUT (Sindh Institute of Urology and Transplantation), Karachi, and includes subjects referred for a Ga68-PSMA PET-CT scan from September 2017 to January 2022. Histopathologic-proven adenocarcinoma prostate patients with organ-confined disease and PSA levels obtained within six weeks before the PSMA-PET-CT scan were included in the study. PET-CT images were semi-quantitatively analyzed by measuring SUVmax, and the result was interpreted using statistical software SPSS version 22.0. Results: A total of 154 patients were analyzed. The mean age of patients was 66.57 ± 8.86 years. The GS of all patients ranges from 6 to 10. The mean and median PSA levels were 32.33 ng/ml (range: 0.004-306.00) and 14.20 ng/ml, respectively. The mean SUVmax of all prostatic lesions was 14.67±12.58, and the median value was 10.76. SUVmax was higher in patients with a PSA level of more than ten than those with a <10. The correlation of SUVmax with PSA and GS showed a significant correlation. Conclusion: The SUVmax of organ-confined prostate cancer correlates well with PSA level, and GS Median SUVmax and PSA directly relate to GS