Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

BACKGROUND: Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS: In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS: We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION: Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Decision making on antenatal screening results: A comparative Q-method study of women from two Chinese cities.

BACKGROUND: Although an integral part of ethical and quality health care, little is known about the informed decision making of Chinese women with different socioeconomic backgrounds within the context of antenatal testing. METHODS: To explore women's viewpoints on informed decision making regarding antenatal screening, a Q-methodology study that combines both quantitative factor analysis and interviews was conducted between June 2016 and February 2017 in Shanghai and Duyun. A total of 169 women (84 Shanghai and 85 Duyun) participated in the study of 41 ranked statements along a Q-sorting grid. RESULTS: Using by-person factor analysis, five distinct viewpoints are identified: (a) choice is shared with the partner/husband, but the mother has the right to make the final decision; (b) having antenatal tests is not about choice but about a mother's responsibility; (c) choice is a shared decision led primarily by the partner/husband and secondarily by the doctors; (d) choice should be made using the advice of doctors, but the decision should be made with the partner/husband; and (e) choice is a responsibility shared with the partner, family and doctors. CONCLUSIONS: The study reveals that women with better education and higher incomes demonstrate more autonomy than those with less education. The nuclear family clearly emerges as the main decision makers in health-care services in China. PATIENT AND PUBLIC CONTRIBUTION: The 169 participants shared their views and stories for at least an hour. They were debriefed after the interviews and contributed their thoughts on our study design and interpretation of the data.

Attitudes towards non-invasive prenatal diagnosis among obstetricians in Pakistan, a developing, Islamic country.

OBJECTIVES: Stakeholders' views are essential for informing implementation strategies for non-invasive prenatal testing (NIPT). Little is known about such views in developing countries. We explored attitudes towards NIPT among obstetricians in Pakistan, a developing, Islamic country. METHODS: A 35-item questionnaire was distributed and collected at eight events (a national conference and seven workshops in five cities) for obstetric professionals on advances in fetal medicine. RESULTS: Responses from 113 obstetrician show positive attitudes towards implementation of NIPT: 95% agreed prevention of genetic conditions was a necessity, and 97% agreed public hospitals should provide prenatal screening tests. However, participants also agreed the availability of NIPT would increase social pressure on women to have prenatal screening tests and to terminate an affected pregnancy (53% and 63%, respectively). Most participants would not offer NIPT for sex determination (55%), although 31% would. The most valued aspects of NIPT were its safety, followed by its utility and then accuracy. CONCLUSION: Participants generally supported the implementation of NIPT but raised concerns about social implications. Therefore, national policy is needed to regulate the implementation of NIPT, and pretest information and post-test genetic counselling are needed to mitigate social pressure and support parents to make informed decisions. © 2017 John Wiley & Sons, Ltd.

Knowledge, attitude and perceptions of Muslim cancer patients regarding cancer treatment during Ramadan: Results from a tertiary care hospital Karachi.

OBJECTIVE: To assess the knowledge and attitude of Muslim cancer patients regarding cancer treatment during Ramadan. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from July to August 2015, and comprised cancer patients. .Adult Muslim cancer patients receiving active oncological treatment or on surveillance were included. Patients on only supportive treatment were excluded. SPSS 19 was used for data analysis. RESULTS: Of the 265 patients, 87(32.8%) were males and 178(67.2%) were females. The overall mean age was 49±13.87 years. Besides, 184(70.9%) patients belonged to the middle class. Breast cancer was the most common cancer 106(40.6%). Overall, 153(57.9%) patients had stage II disease. Further, 201(80%) patients had 0-1 performance status. Moreover, 180(72%) patients were receiving different forms of chemotherapeutic agents. It was found that 113(54.3%) patients sought advice regarding fasting. Most of the patients who observed fast, i.e. 214(81%), had an early stage disease and 19(7.1%) were on hormonal therapy. Patients who did not fast mostly attributed this to fatigue 69(26.3%). Conclusion: Only half of the patients sought advice on fasting and those having early disease more. CONCLUSIONS: Only half of the patients sought advice on fasting and those having early disease more frequently observed fast.

Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta.

A combination of autozygosity mapping and exome sequencing identified a null mutation in SLC24A4 in a family with hypomineralized amelogenesis imperfect a (AI), a condition in which tooth enamel formation fails. SLC24A4 encodes a calcium transporter upregulated in ameloblasts during the maturation stage of amelogenesis. Screening of further AI families identified a missense mutation in the ion-binding site of SLC24A4 expected to severely diminish or abolish the ion transport function of the protein. Furthermore, examination of previously generated Slc24a4 null mice identified a severe defect in tooth enamel that reflects impaired amelogenesis. These findings support a key role for SLC24A4 in calcium transport during enamel formation.

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.

Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain.

A case report and literature review on primary intracranial malignant melanoma: Challenges and insights.

INTRODUCTION AND IMPORTANCE: Primary central nervous system (CNS) melanoma is a rare entity. Primary CNS malignant melanomas account for 1 % of melanomas and 0.07 % of intracranial tumours. These are highly aggressive and are associated with poor prognosis. Herein, we have discussed one such rare case of PIMM. CASE PRESENTATION: 62-year-old man with primary CNS melanoma underwent craniotomy and resection of left temporal lesion. Postoperative MRI showed no evidence of residual disease. He received 28 fractions of radiation. Follow-up MRI showed no evidence of disease. However, he later developed worsening symptoms and repeat imaging revealed disease progression with hydrocephalus and drop metastasis to spine. He underwent VP shunting and was started on Temozolomide. He progressively declined functionally and eventually died from his disease. CLINICAL DISCUSSION: Primary CNS melanoma is characterized by its rarity, challenging diagnosis, and aggressive behaviour. Current literature suggests limited treatment options, which depend on complete resection of the primary tumour. Molecular analysis may play a key role in deciding future treatment options, including immune checkpoint inhibitors and targeted therapies targeting the BRAFV600E mutation. CONCLUSION: Primary intracranial malignant melanoma (PIMM) is an extremely rare tumour of CNS, and its treatment paradigm is very limited based on available literature. Currently any long-term survival depends on the complete resection of tumour. Our case is unique as it talks about the limited therapeutic options in case of rapidly declining performance status in a resource constraint setting.

Oral mucositis & oral health related quality of life in women undergoing chemotherapy for breast cancer in Karachi, Pakistan: A multicenter hospital based cross-sectional study.

BACKGROUND: Oral mucositis is an inflammatory condition of oral cavity which is a common and serious side effect of cancer treatment. Severe oral mucositis compromises basic functions like eating and swallowing causing malnutrition also affecting overall patient's oral health related quality of life. The aim of the study was to find the frequency of oral mucositis in patients with breast cancer during their chemotherapy, the factors associated with oral mucositis & the overall patient's oral health related quality of life. METHODS: A cross-sectional study was conducted and a total of 160 women diagnosed with breast cancer, receiving chemotherapy and who had undergone at least one cycle of chemotherapy were recruited from two hospital settings. In-person interviews were done, patients were asked questions about their sociodemographic history, personal habits, oral history and oral findings, breast cancer stage, chemotherapy history and Oral Health Related Quality of Life. Their oral examination was done at the end of the interview to assess presence or absence of oral mucositis, using World Health Organization oral mucositis tool. Oral Health Related Quality of Life was assessed using Oral Health Impact Profile-14 questionnaire. RESULTS: Our results showed that out of 160 patients 88 (55%) of the breast cancer cases developed oral mucositis during chemotherapy. The mean Oral Health Impact Profile -14 scores in patients with oral mucositis was high 18.36±0.96 showing poor Oral Health Related Quality of Life. Occasional frequency of brushing was significantly associated with oral mucositis (Prevalence ratio:2.26, 95%_CI 1.06-4.84) compared to those patients who brushed once and twice daily. Low level of education showed negative association with oral mucositis (Prevalence ratio:0.52, 95%_CI 0.31-0.88). CONCLUSION: Our study showed significant positive association of occasional brushing with OM and protective association of low level of education with the development of OM. Emphasis should be given to oral hygiene instructions and dental education to cancer patients in oncology clinics with the prescription of mouth washes, gels and toothpaste to patients to decrease OM during chemotherapy.

Outcomes of patients with anal cancer treated with definitive chemoradiation: A single centre experience.

Background: Anal cancers are uncommon neoplasms that make up to <1% of all tumours globally. Concurrent chemoradiation remains the standard of care treatment for patients who present with non-metastatic anal squamous cell carcinomas (ASCCs). Methods: We aimed to evaluate the response rate and 2-year survival outcome of the definitive chemoradiation approach in patients with non-metastatic ASCCs of our population. We conducted a cross-sectional review of these patient populations who were treated and then followed after completion of treatment at our institute during the last 10 years. Results: A total of 17 patients were enrolled after fulfillment of the eligibility criteria. The responses were documented in 16 patients through magnetic resonance imaging or computed tomography of the pelvis, done at 3 months of treatment completion. More than 80% of the patients had complete radiological responses. Among the surviving participants, the 2-year disease-free survival rate was found to be more than two-thirds. Approximately 20% of the study participants had disease recurrence during the subsequent clinic visits following treatment completion. Conclusion: This review emphasises the impact of definitive chemo-radiation in achieving radiological and clinical responses in patients with non-metastatic ASCCs. Moreover, to our knowledge, this is the first review to highlight anal cancer's incidence and characteristics in Pakistan.

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.

Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information. Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making. Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories. Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 (P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative. Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.

Comparing Ki-67 and Oncotype-Dx Tests for Predicting Early Breast Cancer Outcomes: A Comprehensive Review The study explored the correlation between the expensive Oncotype-Dx (ODx) test and the more affordable Ki-67 index in predicting outcomes for certain breast cancers. Results from 16 out of 18 studies indicated a significant link between the 2 tests, suggesting Ki-67 could be a cost-effective alternative, especially in low- to middle-income countries.

Primary endo-bronchial muco-epidermoid carcinoma in a 22-year-old female: A case report.

INTRODUCTION: Muco-epidermoid carcinomas are primarily the subtypes of salivary gland tumors that can rarely originate within the respiratory tract. Our case highlights the occurrence of an unusual, localized, endo-bronchial muco-epidermoid cancer. We aim to strengthen the evidence of occurrence of this distinct variety of lung cancer in our country as little is known about this rare subclass of lung cancer. CASE PRESENTATION: We report a case of a 22-year-old female patient, belonging to Karachi, Pakistan, who presented with respiratory symptoms and upon work-up, was diagnosed with a low-grade, localized muco-epidermoid carcinoma of the lung. She underwent surgical resection successfully and was advised to get evaluated for adjuvant radiotherapy. CLINICAL DISCUSSION: Localized low-grade MEC respond well to surgical resection in contrast to high-grade MEC which is associated with poor prognosis thus requiring adjuvant radiotherapy to improve survival outcomes. CONCLUSION: Lung cancers can be unusually of muco-epidermoid origin. It has been uncommonly found in the world including Pakistan. Special attention with validated data is therefore needed, for developing guidelines for the optimal management of such neoplasms.

Unmasking the enigma: A case of Fumarate Hydratase-deficient renal cell carcinoma.

INTRODUCTION: Fumarate Hydratase-deficient-renal cell carcinoma (FH-dRCC) is an uncommon and extremely aggressive variant of renal cell carcinoma (RCC) resulting from inactivating mutations in the tumor suppressor gene, fumarate hydratase (FH). CASE PRESENTATION: We report a case of a young male who presented with the complaint of painless hematuria. Upon workup, he was found to have a renal mass with bony metastases. The histopathology was consistent with renal cell carcinoma with features of FH-deficient variant. Germline testing showed a pathogenic mutation in the FH gene. He was started on a treatment combination of Pembrolizumab and Axitinib along with Zoledronate for bone metastasis. His response to the combination therapy was short with early progression of disease. He was switched to a second-line treatment Bevacizumab and Erlotinib, which achieved significant disease response. DISCUSSION: Systemic therapy is the mainstay of treatment for metastatic disease. Although the novel agents approved for other subsets of RCC have been used, the responses are grim. There is no consensus on the sequence of further lines of treatment for FH-dRCC and is based on the physician's choice, availability of the drugs, cost, toxicity, and tolerance of the patient. CONCLUSION: This case report emphasizes the occurrence, presentation, management and prognosis of FH-dRCC, which is an aggressive entity, presenting at a young age with early distant metastases, not diagnosed appropriately due to its poorly characterized cytologic features. Being an infrequent neoplasm, it is an area that warrants oncological exploration to improve outcomes in these individuals. The combination of Erlotinib and Bevacizumab provides promising outcomes in terms of progression-free survival.

Cardiac sarcoma: A rare case of primary cardiac sarcoma.

INTRODUCTION AND IMPORTANCE: Primary cardiac sarcoma is a rare malignancy with a poor prognosis because of diagnostic delay, therapeutic difficulties, and high metastatic potential. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. However, there is a lack of evidence to guide the treatment. CASE PRESENTATION: We present a case of primary cardiac sarcoma. Our patient was presented in the department of emergency medicine (ED) in our institute with shortness of breath on exertion associated with orthopnea. Based on the history and cardiovascular examination, he underwent an echocardiogram, which revealed a sizeable echogenic density in the right ventricular outflow tract. He underwent surgical resection of the cardiac mass via median sternotomy and total cardiopulmonary bypass approach. The patient was eventually diagnosed with primary cardiac sarcoma, confirmed by tissue biopsy after surgical intervention. CLINICAL DISCUSSION: Through this report, we highlight the rarity of primary cardiac sarcomas, the importance of multidisciplinary tumor board (MDT) discussion and provide evidence of surgical excision being the treatment of choice, followed by systemic chemotherapy in selected cases. CONCLUSION: Cardiac sarcoma is a rare but highly malignant tumor with a poor prognosis. However, early diagnosis and surgical resection of a primary cardiac sarcoma can significantly increase the patient's survival and quality of life. Therefore, physicians should keep a high suspicion of a patient with clinical features suggestive of cardiac sarcoma, and echocardiography should be the diagnostic modality of choice in such patients.

Pakistani healthcare professionals' perceptions of communication with patients and their relatives about hereditary breast cancer: a qualitative study in a LMIC.

Pakistan has the highest incidence and mortality rates of breast cancer in Asia, with high numbers of patients diagnosed at a young age suggesting the possibility of an inherited cancer syndrome. Communication of hereditary breast cancer (HBC) risk information with patients could enable earlier detection of the condition in relatives and reduce mortality rates. This study aimed to explore perceptions of healthcare professionals (HCPs) in Pakistan about communication with patients and their relatives about HBC. Semi-structured qualitative interviews were conducted with eighteen HCPs during March to May 2020 in Lahore. Thematic analysis shows the HCPs were generally supportive of informing patients themselves about HBC, but believed it was the patients' role to inform their relatives. HCPs also highlighted important barriers to communication with patients about HBC, including (i) patients' low socioeconomic status and educational attainment; (ii) high prevalence of the social stigma of breast cancer; and (iii) lack of health resources and facilities to provide genetic testing for HBC. In conclusion, HCPs would value the development of interventions to support communication between HCPs and patients. They also highlighted the need for interventions to support intrafamilial communication about HBC. Much research and political support are needed to address patient, social, and systemic-level barriers to facilitate communication about HBC.

Chaotic transformation of parotid acinic cell carcinoma to metastatic dedifferentiated high-grade pathology - A rare case with clinical and emotional challenge.

INTRODUCTION AND IMPORTANCE: Acinic cell carcinoma (AciCC) is a rare entity in which high-grade transformation (HGT), formerly dedifferentiation, is uncommon. This case report presents a rare case of AciCC, with rapid transformation to metastatic high-grade dedifferentiated pathology after initial curative treatment. CASE PRESENTATION: A 58-year-old woman presented in the medical oncology clinic with a progressive swelling on the right side of her face. Magnetic resonance imaging revealed a 5 × 5 cm lobulated parotid gland lesion, and fine needle aspiration biopsy was consistent with carcinoma. After informed consent, a Modified-Blair incision was given as a standard approach to the right preauricular area under general anaesthesia, and a right superficial parotidectomy with the removal of the tumor and selective lymph node dissection was performed. Histopathology of the resected mass was reported as parotid AciCC. She was given adjuvant radiation therapy. A repeat PET CT scan ten weeks after the completion of her adjuvant radiation treatment showed local disease recurrence as well as multiple pulmonary deposits. A repeat biopsy was reported as DOG-1 positive dedifferentiated (high-grade) acinic cell carcinoma, and she was offered platinum-based palliative systemic chemotherapy. CLINICAL DISCUSSION: Parotid acinic cell carcinomas with high-grade transformation are rare. This case highlights its critical diagnostic markers, curative and palliative management and long-term follow-up. CONCLUSION: The transformation of parotid AciCC to high-grade, dedifferentiated pathology is unusual and belligerent. Hence, these tumors need intense treatment with a multimodality approach. Close follow-ups with history and physical examination, along with periodic imaging, should be considered for these patients.

Role of circulating-tumor DNA in the early-stage non-small cell lung carcinoma as a predictive biomarker.

Lung cancer is one of the most common solid malignancies. Tissue biopsy is the standard method for accurately diagnosing lung and many other malignancies over decades. However, molecular profiling of tumors leads to establishing a new horizon in the field of precision medicine, which has now entered the mainstream in clinical practice. In this context, a minimally invasive complementary method has been proposed as a liquid biopsy (LB) which is a blood-based test that is gaining popularity as it provides the opportunity to test genotypes in a unique, less invasive manner. Circulating tumor cells (CTC) captivating the Circulating-tumor DNA (Ct-DNA) are often present in the blood of lung cancer patients and are the fundamental concept behind LB. There are multiple clinical uses of Ct-DNA, including its role in prognostic and therapeutic purposes. The treatment of lung cancer has drastically evolved over time. Therefore, this review article mainly focuses on the current literature on circulating tumor DNA and its clinical implications and future goals in non-small cell lung cancer.

No difference in treatment outcome between patients with nodal versus extranodal diffuse large B-cell lymphoma.

Background and Aim: Diffuse large B-cell lymphoma (DLBCL) has been classified using various parameters, including the site of origin. Studies have reported conflicting outcomes when DLBLC patients were stratified according to the site of origin. This study aimed to investigate the response rate and survival outcomes in nodal versus extranodal DLBCL and compare the results to a region-matched study covering the 1988 - 2005 period. Methods: A single-center retrospective cohort study was conducted on all patients diagnosed with DLBCL and treated in a tertiary care hospital in Pakistan during 2014 - 2019. We calculated the mean and median for continuous variables and frequency and percentages for all categorical variables. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier survival curves. A Cox proportional hazards model was used to determine the hazard ratio (HR) for OS. Results: Of the 118 patients, 49 patients (41.5%) had nodal disease and 69 patients (58.5%) were diagnosed with extranodal DLBCL. The majority of patients in the nodal and extranodal cohorts presented with Stages III and IV disease (73.4% and 62.3%, respectively). A complete response to (immuno) chemotherapy was achieved in 71.4% of nodal DLBCL patients and 65.2% of extranodal DLBCL patients. The 5-year PFS and median PFS in the entire cohort were 0.8% and 17 m, respectively. The PFS and median PFS in the nodal and extranodal DLBCL cohort were 0% and 1.4%, respectively, and 15 m and 19 m, respectively. The 5-year OS and median OS in the entire cohort were 16.1% and 19 m, respectively. The OS and median OS in the nodal and extranodal DLBCL cohort were 8.2% and 21.7%, respectively, and 19 m and 21 m, respectively. Multivariable linear regression revealed that the ABC phenotype (nodal, HR = 1.37, 95% CI = 1.37 - 3.20; extranodal, HR = 1.65, 95% CI = 1.46 - 3.17; GBC as reference) and double and triple hit DLBCL (nodal, HR = 1.29, 95% CI = 1.19 - 2.81; extranodal, HR = 1.87, 95% CI = 1.28 - 2.43; and non-expressors as reference) are independent negative predictors of OS. Conclusions: DLBCL incidence in the Karachi region has remained comparable but patient composition in the extranodal DLBCL cohort has shifted to predominantly advanced stage. Nodal and extranodal DLBCL were associated with similar PFS and OS profiles and first- and second-line treatment responses. Cell of origin and antigen expression status was independent negative predictors of OS, disfavoring the ABC phenotype and lesions with c-MYC and BCL2 and/or BCL6 overexpression. Relevance for Patients: DLBCL is an aggressive type of non-Hodgkin's lymphoma, however; patients respond well to standard systemic chemotherapy. Extranodal type of DLBCL patients tend to have more residual disease after first-line systemic chemotherapy, but physicians should keep in mind that the subsequent line treatment mitigates its negative impact on survival.

Mean level of pretreatment neutrophil to lymphocyte ratio in patients with squamous cell carcinoma of the head and neck-Cross-sectional study.

Background: Squamous cell carcinoma of the head and neck have been characterized using various prognostic parameters. These include advanced age, lifestyle habits such as smoking, higher tumor stage at presentation & presence of metastasis. Many patients are diagnosed with head and neck cancers annually in Pakistan, but limited data is available for the prognosis of these patients. This study aims to investigate a new biomarker by estimating the mean level of pretreatment neutrophil to lymphocyte ratio (NLR) in patients with Squamous cell carcinoma of the head & neck. Methods: We conducted a cross-sectional study using non-probability consecutive sampling techniques for 222 biopsy-proven cases of head & neck squamous cell carcinoma. Clinical & pathological variables were analyzed, including the patient's profile and tumor characteristics. The NLR of each patient before treatment was calculated using the absolute neutrophil count divided by the absolute lymphocyte count in preoperative blood samples. An independent sample t-test was used to assess the mean difference. A p-value less than or equal to 0.05 was taken as statistically significant. Results: Of 222 patients, a male predominance was seen in the entire cohort. A median pretreatment NLR of 3.19 (2.47-4.97) was identified, and patients were classified into high and low NLRs based on this value. Data analysis revealed a statistically significant increase in NLR among patients with nodal metastasis. In addition, patients with NLR above the median cutoff value of 3.19 demonstrated that there was a significant increase in NLR values with high tumor (T) and nodal (N) classifications with a p-value of 0.001 and 0.003, respectively. Conclusion: Pretreatment neutrophil to lymphocyte ratio may be associated with increased nodal involvement. It may serve as a useful prognostic predictor for patients with squamous cell carcinomas of the head and neck. Identifying high-risk patients in the pretreatment phase with the help of such biomarkers will also facilitate early inclusion in clinical trials.