|LETTER TO THE EDITOR
|Year : 2021 | Volume
| Issue : 2 | Page : 299-301
Laboratory findings and treatment in non-small cell lung cancer (NSCLC): Single-center report
Chhavi Rajvanshi1, Aseem K Tiwari1, Swati Pabbi1, Geet Aggarwal1, Simmi Mehra1, Rajni Chauhan1, Dheeraj Gautam2, Ashok Kumar Vaid3
1 Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana, India
2 Department of Pathology, Medanta-The Medicity, Gurgaon, Haryana, India
3 Department of Medical and Haemato Oncology, Medanta-The Medicity, Gurgaon, Haryana, India
|Date of Submission||23-Oct-2019|
|Date of Decision||14-Dec-2019|
|Date of Acceptance||23-Sep-2020|
|Date of Web Publication||11-May-2021|
Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rajvanshi C, Tiwari AK, Pabbi S, Aggarwal G, Mehra S, Chauhan R, Gautam D, Vaid AK. Laboratory findings and treatment in non-small cell lung cancer (NSCLC): Single-center report. Indian J Cancer 2021;58:299-301
|How to cite this URL:|
Rajvanshi C, Tiwari AK, Pabbi S, Aggarwal G, Mehra S, Chauhan R, Gautam D, Vaid AK. Laboratory findings and treatment in non-small cell lung cancer (NSCLC): Single-center report. Indian J Cancer [serial online] 2021 [cited 2021 Sep 25];58:299-301. Available from: https://www.indianjcancer.com/text.asp?2021/58/2/299/315811
Lung cancer accounts for 18.4% of deaths all over the world as reported by GLOBOCAN 2018 (Global Cancer Statistics 2018). Small-cell lung cancer and non-small cell lung cancer (NSCLC) are the two main types of lung cancer. NSCLC is often diagnosed at an advanced stage. Mortality in the advanced stage of NSCLC does not decrease if only chemotherapeutic regimen is used for treatment. Technical advancement and research have now evolved to offer a more effective treatment called targeted therapies in NSCLC. Targeted therapy involves small molecular inhibitors that target oncogenic tyrosine kinases. Mutations in epidermal growth factor tyrosine kinase receptor (EGFR) leads to cancer., In this study, we have screened EGFR mutations in NSCLC. In addition to already reported mutations for EGFR in the COSMIC (https://cancer.sanger.ac.uk) database, we are presenting some novel mutations detected at our center. We also evaluated the correlation of chemotherapy plus targeted therapy with remission (complete or partial) and survival of patients.
This study was conducted in a tertiary care hospital in India over a period of 1 year from January 2018 to January 2019. All 80 consecutive samples of patients with suspected or confirmed NSCLC were included in the study. Out of them, we could not find sufficient tissue for DNA extraction in 18 biopsies; therefore, only 62 patient samples could be processed further. Formalin fixed paraffin-embedded (FFPE) tumor tissue blocks were used for DNA extraction. The Ion Torrent platform (Thermo Fisher Scientific, USA) was used to detect EGFR mutations using Ion AmpliSeqTM Cancer Hotspot Panel v2 primers and Ion PGM instrument. Results were analyzed with the help of Torrent Browser and Ion Reporter Software.
All patients were categorized into two groups: mutated EGFR and wild-type EGFR. Wild type EGFR received a treatment regimen in the form of chemotherapy alone and mutated EGFR received a regimen comprising chemotherapy and targeted therapy, both. Chemotherapy included standard drugs like zoledronic acid, pemetrexed, carboplatin, paclitaxel, etoposide, and carboplatin. Targeted therapy included erlotinib, osimertinib, and gefitinib. In our settings, patients usually turn up in advanced stages (stage IV), and the turnaround time of EGFR mutation is at least 2 weeks, sometimes longer. Two cycles of chemotherapy are given as an institutional protocol to provide symptomatic relief before mutation is verified and the final treatment regimen is instituted.
Treatment response was evaluated after 4 weeks in both wild type and mutant patients on the basis of response evaluation criteria in solid tumors (RECIST) criteria.,, Response to the therapy was evaluated by CT scan and radiological evaluation (2-[18F] fluorodeoxyglucose positron emission tomography).,,
The ordinal data obtained were expressed in terms of mean and standard deviation. The analysis was done using Microsoft Excel and SPSS software (Version 24.0; IBM, Bangalore, Karnataka, India).
As described in [Table 1], out of 62 patients' samples, a total of 12 different known mutations were found at exon numbers 18, 19, 20, and 21. We also found eight different novel EGFR mutations at exon numbers 20 and 21. Overall, a significant correlation of treatment regimen (chemotherapy plus targeted therapy) was found with remission of cancer disease (P-value = 0.003 and Chi-square value = 12.98). Combined chemotherapy plus targeted therapy achieved better results than chemotherapy alone in terms of complete or partial remission [Table 2]. Kumar et al. also suggest that radiotherapy (week end-less) in combination with neoadjuvant chemotherapy is an effective strategy to treat patients with locally advanced lung cancer. In addition to these results, we did not find any correlation between stage of the disease and EGFR mutation. No patient had recurrence during the study period in either wild type or mutated groups.
|Table 1: Mutations found in non-small cell lung cancer patients’ specimen using NGS (Next Generation Sequencing)|
Click here to view
|Table 2: Patients’ clinical outcome and correlation of outcome with chemotherapy versus targeted therapy|
Click here to view
The genetic evolution of tumors is a clue for the need for technical advancement as resistance to known tyrosine kinase inhibitors may develop in cancer patients. In addition to reported somatic mutations for which drug has been known, there is a need to detect and report other novel mutations in EGFR. Malik et al. also suggest that EGFR mutations strongly predict the efficacy of inhibitors of EGFR with response rates higher than 70%., Detection of new or novel mutations should motivate the development of alternative EGFR inhibitors to add to the armamentarium of drugs that would increase progression-free survival in lung cancer patients. Our findings shed light on the importance of doing EGFR mutation analysis and adding tyrosine kinase inhibitors in the treatment regimen of NSCLC.
There are a few limitations of the present study; first, cancer hotspot panel V2 included few genes other than EGFR, (P53, KRAS, BRAF) relevant to lung cancer but we evaluated only EGFR mutation. Second, there are other mutations, like ROS 1, ALK translocation, which are not included in the cancer hotspot and therefore could not be studied. These mutations may have a bearing on the patient outcome, which is not addressed in the present study.
It is important to find and report novel mutations. We found eight different novel EGFR mutations at exon numbers 20 and 21. Out of these, the most common was c2361G>A (point mutation) at exon number 20. Novel mutations help gain insight into disease pathogenesis and would possibly encourage the development of alternative EGFR inhibitors to add to the armamentarium of drugs for the treatment of lung cancer patients.
Declaration of patient consent
Patient consent was obtained for diagnosis and treatment in the hospital. This was an observational study and no additional sample was drawn for this study. All investigations, treatment, and monitoring were according to the current “Standard-of-Care” and personal identifiers like name and unique hospital identity were kept strictly confidential.
Financial support and sponsorship:
Conflict of interest
There are no conflicts of interest.
| » References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
Valaitis J, Warren S, Gamble D. Increasing incidence of adenocarcinoma of the lung. Cancer 1981;47:1042-6.
Qiu T, Guo H, Zhao H, Wang L, Zhang Z. Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology. Sci Rep 2015;5:1-7.
Ansari J, Palmer DH, Rea DW, Hussain SA. Role of tyrosine kinase inhibitors in lung cancer. Anticancer Agents Med Chem 2009;9:569-75.
Mitsudomi T. Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Transl Lung Cancer Res 2014;3:205.
Bindal N, Forbes SA, Beare D, Gunasekaran P, Leung K, Kok CY, et al.
COSMIC: The catalogue of somatic mutations in cancer. Genome Biol 2011;12:1-27.
D'addario G, Früh M, Reck M, Baumann P, Klepetko W, Felip EE, ESMO Guidelines Working Group. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21:116-9.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al
. New response evaluation criteria in solid tumours: Revised RECIST guideline. Eur J Cancer 2009;45:228-47.
Rankin S. PET/CT for staging and monitoring non small cell lung cancer. Cancer Imaging 2008;8:27.
Chen CH, Gow CH, Yu CJ, Shih JY, Hsu YC, Lee WY, et al
. Clinical response of gefitinib on malignant pleural effusions in patients with non-small cell lung cancer. J Cancer Mol 2008;4:23-8.
Thippeswamy R, Noronha V, Krishna V, Joshi A, Bal MM, Purandare N, et al
. Stage IV lung cancer: Is cure possible?. Indian J Med Paediatr Oncol 2013;34:121.
] [Full text]
Kumar R, Kumar H S, Paramanandhan M, Purohit R, Sharma N, Jakhar S L, et al.
Neo-adjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced NSCLC-A randomised prospective single institute study. J Can Res Ther 2020;16:860-6.
] [Full text]
Malik PS, Raina V. Lung cancer: Prevalent trends & emerging concepts. Indian J Med Res 2015;141:5-7.
] [Full text]
Berge EM, Doebele RC. Targeted therapies in non-small cell lung cancer: Emerging oncogene targets following the success of epidermal growth factor receptor. Semin Oncol 2014;41:110-25.
[Table 1], [Table 2]