Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2024 | Month : March | Volume : 18 | Issue : 3 | Page : OC01 - OC05 Full Version

Predictors of Response to Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Prospective Cohort Study


Published: March 1, 2024 | DOI: https://doi.org/10.7860/JCDR/2024/67668.19098
Arjun Kumar, Deepak Aggarwal, Kranti Garg, Varinder Saini

1. Assistant Professor, Department of Respiratory Medicine, Maharishi Markandeshwer Medical College and Hospital, Solan, Himachal Pradesh, India. 2. Professor, Department of Pulmonary Critical Care and Sleep Medicine, Government Medical College and Hospital, Chandigarh, India. 3. Associate Professor, Department of Pulmonary Medicine, Government Medical College, Patiala, Punjab, India. 4. Professor and Head, Department of Pulmonary Critical Care and Sleep Medicine, Government Medical College and Hospital, Chandigarh, India.

Correspondence Address :
Arjun Kumar,
Assistant Professor, Department of Respiratory Medicine, MMMC&H, Kumarhatti, Solan-173229, Himachal Pradesh, India.
E-mail: aknlnegi@gmail.com

Abstract

Introduction: Lung cancer carries the highest cancer-related mortality rates worldwide. Despite all recent advances, the mortality from lung cancer is still rising. A better understanding of the risk factors may help us predict responses to chemotherapy for better management.

Aim: To evaluate predictors of response to chemotherapy in advanced Non-Small Cell Lung Cancer (NSCLC) patients.

Materials and Methods: This was a prospective cohort study conducted in the Department of Pulmonary Medicine at Government Medical College and Hospital, Chandigarh, India. A total of 60 confirmed cases of advanced (stage IIIB and IV) NSCLC patients were enrolled consecutively for a duration of two years. Baseline clinical parameters, routine blood tests, spirometry, exercise capacity using the 6 Minute Walk Test Distance (6MWTD), and Computed Tomography (CT)-based tumour size were recorded. Certain pre-defined patient, disease, and therapy-related factors (age, gender, dyspnoea, baseline blood tests, tumour size, histology, etc.) were evaluated for their possible role as predictors of treatment response in advanced NSCLC patients. A positive response was defined if the response to chemotherapy was Complete Response (CR) or Partial Response (PR), and a negative response if the response was Progressive Disease (PD) or Stable Disease (SD) as per revised RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. Variables between the two groups were compared using the Mann-Whitney U test and Chi-square test. To find out the factors that may predict response to treatment, univariate and multivariate logistic regression analysis were used.

Results: Out of a total of 60 confirmed cases of NSCLC patients, only 40 patients were able to complete the four cycles of chemotherapy. The mean age of the patients was 58.5±9.6 years. There were a total of 35 males (87.5%) and five females (12.5%) in the study. Out of 40 patients, 27 (67.5%) had squamous cell carcinoma and 13 (32.5%) had adenocarcinoma. On univariate analysis, Neutrophil-Lymphocyte Ratio (NLR) had a statistically significant association with tumour response (p<0.001). On multivariate analysis, advanced age (p=0.05) and high (>3.81) NLR (p=0.002) were found as independent predictors of poor response to chemotherapy.

Conclusion: Pre-treatment high NLR and advanced age are significant factors for a poor response to chemotherapy treatment in advanced NSCLC patients.

Keywords

Cancer related mortality, Computed tomography, Squamous cell carcinoma

Lung cancer is the most common malignancy worldwide and carries the highest cancer-related mortality rates (1). Despite recent advances in the management of lung cancer, mortality continues to rise in middle and low-income countries (2). More than 9.3 percent of deaths in India are directly related to lung cancer (3). The histology of more than 80 percent of all primary lung cancers is of the NSCLC type (4). Despite numerous recent advances in terms of new diagnostic methods and therapeutic interventions, the outcomes of lung cancer have remained below average. Approximately two-thirds of NSCLC patients present in the advanced stages (Stage III and IV) of the disease at the time of diagnosis (5). The overall five-year survival rate for advanced NSCLC patients is 12 to 16 percent, which is two to three times lower (5 percent) in developing countries (6).

With the advent of new chemotherapeutic regimens, including targeted therapies, the response rate and survival in these patients have shown improvement. However, chemotherapy with or without radiotherapy is the only treatment modality available to patients who are not eligible for targeted therapy. Previous studies have reported variable responses to chemotherapy among different patients, suggesting that the cancer may display different biological behaviour and natural history in different population groups (7),(8),(9). Previous studies have shown that higher age, smoking status, high baseline Platelet-To-Lymphocyte Ratio (PLR), high NLR, Lactate Dehydrogenase (LDH), uric acid, hypercalcaemia, tumour histology, clinical stage IV, and malignant pleural effusion are associated with poor prognosis and shorter Overall Survival (OS) (10),(11),(12),(13),(14),(15). Most of these results were generated from western populations, and evidence is scarce on the predictors of response to chemotherapy from India (9),(10),(11),(12),(13),(14),(15). Hence, the authors conducted a study to evaluate predictors of response to chemotherapy in advanced NSCLC cancer patients in a tertiary care centre in North India.

Material and Methods

A prospective cohort study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Radiotherapy and Oncology at Government Medical College and Hospital, Chandigarh, India, from July 2016 to August 2018. This study was approved by the institutional medical sciences and ethical committee (No. 6915/GM/17).

A total of 60 confirmed cases of advanced NSCLC patients (clinical stage IIIB and IV as per 7th Tumor, Node, Metastasis (TNM) staging) (16) were consecutively enrolled.

Inclusion criteria: Histopathology/cytopathology-proven NSCLC cases (clinical stage IIIB and IV as per seventh TNM staging) (16) and willing to undergo palliative chemotherapy with or without radiotherapy and with a performance status of 0-2 (as per Eastern Cooperative Oncology Group (ECOG) (17).

Exclusion criteria: Patients ineligible for chemotherapy due to haemodynamic instability, those positive for Epidermal Growth Factor Receptor (EGFR) mutations and the ones not willing to undergo treatment were excluded from the study.

Procedure

Total of 60 patients were included in the study. They underwent detailed demographic information collection, including history and clinical examination, symptoms, smoking history, and co-morbidities. All patients underwent routine spirometry and exercise capacity assessment using 6MWTD (18). Based on revised RECIST 1.1, baseline tumour burden was calculated by CT-based tumour size measurement (19). Tumour-related factors like baseline tumour size, clinical stage, histology, and presence of malignant pleural effusion were recorded. Routine blood investigations, like Haemoglobin (Hb), NLR, creatinine, uric acid, LDH, and calcium, were also recorded. All patients received four cycles of palliative chemotherapy with or without radiotherapy as per standard guidelines after baseline evaluation.

Certain pre-defined (patient, disease, and therapy-related) factors were analysed for their role as predictors of treatment response (based on revised RECIST criteria 1.1) (19). The evaluation of target lesions’ response was done in terms of CR, PR, PD, SD. For statistical analysis, patients were divided into two groups: the “response” group if the response to treatment was CR or PR, and the “no response” group if the response to treatment was PD or SD.

Statistical Analysis

All baseline numerical variables were summarised using mean±standard deviation or median (Range) depending on the distribution. Categorical data were summarised as frequency (percentage). Continuous variables between two groups were compared using the Mann-Whitney U test, and categorical variables were compared using the Chi-square test. Univariate and multivariate logistic regression analyses were conducted to identify the factors that predict the response to treatment. In all statistical analyses, a p-value of ≤0.05 was considered significant. All analyses were conducted using Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics 21.0; Armonk, NY, USA).

Results

Out of a total of 60 confirmed cases of NSCLC patients, only 40 were able to complete the four cycles of chemotherapy. The remaining 12 died, and eight were lost to follow-up before completing treatment. The mean age of the patients was 58.5±9.6 years (range 40-76 years). There were a total of 35 males (87.5%) and five females (12.5%) in the study, resulting in a male to female ratio of 7:1. Dyspnoea was the most common presenting symptom, observed in 35 patients (87.5%), followed by cough and fever, seen in 33 (82.5%) and 18 (45%) patients, respectively (Table/Fig 1).

Out of the 40 NSCLC cases, 27 (67.5%) had squamous cell carcinoma, and 13 (32.5%) had adenocarcinoma based on histopathology. The mean serum NLR in the patients was 3.9±1.45 (Table/Fig 2). A significant difference in the NLR between patients with response and non-response to chemotherapy was observed (p-value <0.001), as shown in (Table/Fig 3). Receiver Operating Characteristics (ROC) curve analysis was also conducted, revealing that a NLR cut-off of ≥3.81 had reasonable sensitivity (93.8%) and specificity (83.3%).

The mean baseline FEV1 was higher in patients who showed treatment response than in patients with no response (mean FEV1 in the response group: 74.9±18.7% vs non-response group: 68.3±13.9%); however, the difference was not statistically significant (p-value=0.28) (Table/Fig 3).

In the study, a total of 24 patients (60%) showed a favourable treatment response (PR), 12 (30%) showed SD, and four (10%) showed PD (Table/Fig 4). Baseline NLR exhibited a significant association with tumour response (p=<0.001) in univariate logistic regression analysis. In multivariate regression using the significant parameters, age (OR: 0.88; 95% CI 0.78-1.01; p≤0.05) and NLR (OR: 0.08; 95% CI: 0.016-0.41; p=0.002) were found as the only independent predictors that predicted a poor response to treatment (Table/Fig 5).

Discussion

The present study analysed 40 confirmed cases of advanced NSCLC to evaluate factors that may predict outcomes in lung cancer patients after four cycles of chemotherapy. In the study, a total of 24 patients (60%) showed a favourable treatment response (partial/total response). Advanced age and high NLR were found as independent factors predicting response to four cycles of chemotherapy.

Out of the 40 confirmed NSCLC cases, 24 (60%) were diagnosed in stage IV (7th TNM), and there was no statistically significant difference in the treatment response seen among different tumour stages (p>0.05). In contrast, previous studies have indicated that higher tumour stage is associated with a worse prognosis in advanced lung cancer patients treated with chemotherapy (13),(15),(16). This variability might be due to the small sample size of the present study as well as differences in the study population, chemotherapy regimens, and staging criteria used in these studies.

In the multivariate model, NLR was found to be a statistically significant independent prognostic factor for a poor response to chemotherapy (OR 0.08 and 95% CI 0.016-0.41; p-value=0.002) in the present study. The peripheral NLR represents the burden of the ongoing inflammatory process in the tumour microenvironment. Neutrophils release active chemicals that assist tumour cells in migrating through the extracellular matrix and vasculature to distant metastatic sites (20). However, the exact mechanism by which the NLR impacts prognosis still remains unclear.

A retrospective study conducted in 401 patients with advanced NSCLC treated with first-line chemotherapy or targeted therapy showed that factors like ECOG-PS, tumour stage, histology, EGFR status, and NLR (HR 1.74, 95% CI 1.26-2.41; <0.001) were significant predictors of OS (21). In a recent meta-analysis of 19 studies comprising 7,283 patients with lung cancers, it was found that high NLR (p<0.00001) and high PLR (p=0.01) were significantly associated with poorer prognosis and worse OS (22). High NLR and PLR were significantly associated with deeper tumour invasion (p=0.006), extensive lymph node metastasis (p=0.01), poor differentiation (p=0.0002), and vascular invasion (p=0.002). The calculated NLR cut-off value for differentiating between treatment response and failure was 5 (22). However, in the present study, the ROC curve for the NLR cut-off value in detecting a response to treatment in advanced NSCLC was 3.81.

High post-chemotherapy NLR was correlated with a higher risk of mortality (HR=1.13, 95% CI 1.06-1.21; p<0.001) in the study by Lee Y et al., (23). However, high pre-chemotherapy NLR (HR=1.807, p=0.018 for PFS, HR=1.761, p=0.020 for OS) and multiple metastasis (HR=2.118, p=0.008 for PFS, HR=2.753, p<0.001 for OS) were found to be poor prognostic markers for Progression-Free Survival (PFS) and OS by a study by Yao Y et al., (24). Previous meta-analyses also confirmed that a high NLR was a predictor of poorer OS and shorter PFS in patients with advanced lung cancer (14),(22),(25),(26). The majority of these previous studies are retrospective and derived from Western populations. Being retrospective, they are susceptible to selection biases. Moreover, the presence of biological heterogeneity might have affected the interpretation of the results of the meta-analyses. The value of NLR can be influenced by the effect of various immuno-modulatory drugs like steroids, as well as concurrent infections. Particular inflammatory markers of infection, like C-Reactive Protein and procalcitonin, might be useful to exclude infections in such situations (22).

Tumour histology has also been evaluated for its effect on the treatment response in NSCLC in previous studies, where non-adenocarcinoma tumour histology was associated with worse survival outcomes (27),(28),(29). The present study didn’t find any significant association between tumour histopathology and response to chemotherapy. Few previously published studies also did not find any significant association between tumour histology and response to chemotherapy (15),(30),(31). This variation, though not fully understood, might be due to the small sample size in the present study.

Advanced age (>60 years) was associated with a poor treatment response to chemotherapy in the present study (OR 0.88, 95% CI 0.78-1.01; p=0.05). However, in a previous study performed by Albain KS et al., age >70 years was associated with improved outcomes in patients with advanced NSCLC treated with chemotherapy (32). An increase in age is usually associated with a decrease in functional capacity and an increase in co-morbidities that are likely to affect the treatment outcome.

Other baseline patient characteristics like smoking history, weight loss >5% of body weight, co-morbidity, lower (<18.5) BMI, ECOG >II, tumour stage IV, >2 metastatic sites have been shown to negatively impact the overall response and survival in NSCLC patients in other studies (10),(12),(15). However, the authors did not find these baseline characteristics statistically significant in the present study.

The previous study results showed that low serum albumin levels were associated with a poor prognosis and OS (33),(34). However, the present study revealed no statistically significant association with the treatment response (p=0.66). Apart from albumin, a higher concentration of serum uric acid has also been found to be associated with a good prognosis and increased overall patient survival in a few studies (27),(35). Nevertheless, the present study didn’t show any statistically significant difference between the uric acid level and the response to chemotherapy. Serum uric acid levels are influenced by various other factors, including food habits (increased purine-rich diets) and alcohol consumption.

In this study, there was a statistically significant correlation between a higher pre-treatment NLR and a poor response to conventional chemotherapy in EGFR mutation-negative advanced NSCLC patients. The findings suggest that NLR could be a potential cost-effective and easily available biomarker for chemotherapy response and prognosis.

Limitation(s)

The present study also had some limitations, including a short study duration, a small sample size, and the absence of enrolled EGFR mutation patients, which might have affected the results. Increasing the sample size in future prospective studies might help us validate the results and predict OS.

Conclusion

Factors like higher NLR and advanced age (>60 years) are significant predictors of poor response to conventional chemotherapy in EGFR mutation-negative advanced NSCLC patients. India is a high-burden country for lung cancer. Knowledge of such predictors of response before initiating treatment may help us categorise patients for better management and guide the tailoring of therapy.

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DOI and Others

DOI: 10.7860/JCDR/2024/67668.19098

Date of Submission: Sep 22, 2023
Date of Peer Review: Dec 13, 2023
Date of Acceptance: Jan 06, 2024
Date of Publishing: Mar 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Sep 23, 2023
• Manual Googling: Jan 01, 2024
• iThenticate Software: Jan 04, 2024 (13%)

ETYMOLOGY: Author Origin

EMENDATIONS: 7

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