Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
Brief Commentary
Cardio Oncology with ACOS
Case Report
Case Series
Conference Review
Consensus Statement
Current Issue
Editorial
Erratum
Letter to Editor
New Drug Update
News
Original Article
Position Paper
Response to the letter
Review Article
Short Communication
View/Download PDF

Translate this page into:

Editorial
7 (
3
); 61-63
doi:
10.25259/IJMIO_23_2022

Editorial

Department of Clinical Hematology, Mahatma Gandhi University of Medical Sciences and Technology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
Department of Medical Oncology, Mahatma Gandhi University of Medical Sciences and Technology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
Corresponding author: Purvish Parikh, Department of Clinical Hematology, Mahatma Gandhi University of Medical Sciences and Technology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. purvish1@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Parikh P, Malhotra H, Sharma LM, Yadav A, Gupta N. Editorial. Int J Mol Immuno Oncol 2022;3:61-3.

The case report by Harikrishnan et al. is interesting because their patient with adenocarcinoma of lung had an epidermal growth factor receptor (EGFR) exon 19 deletion at initial presentation and subsequently demonstrated EGFR exon 20 insertion mutation at recurrence.[1]

Next-generation sequencing (NGS) showed activating mutation of exon 19 deletion but no other targetable genetic alterations. The logical initial therapy consisted of Gefitinib, the first-generation EGFR TKI inhibitor.[2] It is not surprising that the patient responded (partial response) at 6 months and subsequently developed disease progression – a common occurrence after a period of 12–18 months.[3]

Repeat NGS from the brain metastasis revealed EGFR, p. Asn 3 771_His773du p (exon 20 insertions). The originally identified exon 19 deletion was no longer seen. Interestingly, there was no evidence of T790M mutation, a common cause of EGFR TKI resistance. Again the authors correctly changed the systemic treatment to Afatinib, an effective second-generation EGFR TKI inhibitor.[4]

In this editorial, we would like to focus on three other aspects of the case.

AGE AT PRESENTATION

This patient was 47 years old when he was confirmed to have a diagnosis with lung cancer. Since the solitary pulmonary nodule (SPN) was identified 3 years earlier, his age would have been 44 years. A large study of 1862 consecutive patients with lung cancer between January 2008 and March 2018 (10 years) has been reported by All India Institute of Medical Sciences, the premier institution in New Delhi.[5] It documented a mean age of 59 years (range 46–70 years), which is similar to that seen elsewhere as well as remains unchanged over the years.[6,7] While younger patients with lung cancer have been documented, this patient developed the disease at an age which is an outlier (<2.35%) for Gaussian distribution. Could be the reason to be linked to the comorbidities? (vide infra).

COMORBIDITIES

This young man had rheumatic heart disease, moderate aortic regurgitation, and subclinical hypothyroidism. These are significant comorbidities, the former two not commonly seen in today’s day and age.

Several publications have documented a high risk for the development of cancers in those who have rheumatic diseases.[8] Some commonly recognized paraneoplastic syndromes include hypertrophic osteoarthropathy, carcinomatous polyarthritis, palmar fasciitis, vasculitis, polymyalgia rheumatica, erythromelalgia, amyloidosis, remitting seronegative synovitis, panniculitis, multicentric reticulohistiocytosis, dermatomyositis, and lupus like and scleroderma like syndromes.[8]

In addition, some autoimmune and rheumatic diseases have a direct real increased risk of malignancies. The exact cause is not known. Factors implicated include immunosuppressive therapy, Epstein bar virus, smoking, and even genetic susceptibility. For patients with rheumatoid arthritis, the risk of developing a malignancy is 2–3 times higher than in the normal population.[9] Interestingly, among solid tumors, this increased risk has been documented only for lung cancer.

Levels of many tumor-associated antigens (e.g., CA 15-3, CA 125, and CA 19-9) have been reported to be high in the serum of patients with autoimmune diseases as well as in their tumor cells.[10]

Drugs used in the treatment of rheumatic diseases can also lead to the development of cancers (e.g., cyclophosphamide, methotrexate, cyclosporine, and azathyoprine).[11] Meta-analysis shows that this risk could be 3.3 times higher than the normal population.[12] We do not have the details of whether this patient received any such medications.

Fortunately, a large and retrospective study conducted from 2003 to 2019 confirms that the survival of lung cancer patients who also have a rheumatic disease (n = 177) is not inferior to the cohort without such comorbidities (n = 219).[13]

This was true for OS, DFS, and the rate of recurrence of locoregional disease. Of concern was the fact that more patients with the autoimmune disease did not receive standard of care. Would that imply a protective role of the latter in cancer patients?[14]

WAS THERE A DELAY IN THE CORRECT DIAGNOSIS?

This patient was first identified to have SPN – which would have been Stage I disease if it was NSCLC. Three years later, the lesion has increased in size, and a PET CT scan indicated that, now, the stage was at least III (increased uptake in mediastinal, hilar, right upper paratracheal, and subcarinal lymph nodes). It was unfortunate that multiple biopsies were inconclusive, and finally, a wedge resection of the lung SPN was necessary to confirm the diagnosis of NSCLC. By refusing to undergo lobectomy (as recommended by his doctors), the patient lost the chance of potentially curative therapy. This is a global problem that is difficult to tackle.[15]

CONCLUSION

This case report of lung cancer has several unique features. Young age at diagnosis, associated comorbidities of significance (like a rheumatic disease), delays in diagnosis in a case of SPN, patient’s refusal to undergo potentially curative surgery, and the transition from EGFR exon 19 mutation to EGFR exon 20 insertion mutation.

References

  1. , , . A rare case of Exon 19 deletion transforming to Exon 20 insertion in a case of adenocarcinoma of lung. 2022 Ahead of Print
    [CrossRef] [Google Scholar]
  2. , , , , , , et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa survival evaluation in lung cancer) Lancet. 2005;366:1527-37.
    [CrossRef] [Google Scholar]
  3. , , , , , , et al. Clinical experience with gefitinib in Indian patients. J Thorac Oncol. 2008;3:380-5.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , . Indian subset analysis of a phase iiib open-label study of afatinib in epidermal growth factor receptor tyrosine kinase inhibitor-naïve patients with epidermal growth factor receptor mutation positive non-small cell lung cancer. Oncol J India. 2021;5:116-8.
    [CrossRef] [Google Scholar]
  5. , , , , , , et al. Clinical profile of lung cancer in North India. A 10-year analysis of 1862, patients from a tertiary care center. Lung India. 2020;37:190-7.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , , , et al. Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience. Indian J Cancer. 2012;49:74-81.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , , , et al. Differential effect of age on survival in advanced NSCLC in women versus men: Analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab. Lung Cancer. 2012;76:410-5.
    [CrossRef] [PubMed] [Google Scholar]
  8. , . Rheumatic diseases and malignancies. Maedica (Bucur). 2012;7:364-71.
    [Google Scholar]
  9. , , , . A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10:R45.
    [CrossRef] [PubMed] [Google Scholar]
  10. , , , , , , et al. Increased production of the soluble tumor-associated antigens CA 19-9, CA 125, and CA 15-3 in rheumatoid arthritis: Potential adhesion molecules in synovial inflammation? Ann N Y Acad. 2007;1108:359-71.
    [CrossRef] [PubMed] [Google Scholar]
  11. . Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med. 1985;21:44-9.
    [CrossRef] [Google Scholar]
  12. , , , , , , et al. Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: Does the risk change with the time since start of treatment. Arthritis Rheum. 2009;60:3180-9.
    [CrossRef] [PubMed] [Google Scholar]
  13. , , , , , , et al. Lung cancer survival in patients with autoimmune disease. JAMA Netw Open. 2020;3:e2029917.
    [CrossRef] [PubMed] [Google Scholar]
  14. , . Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-30.
    [CrossRef] [PubMed] [Google Scholar]
  15. , . Impact of delays in lung cancer treatment on survival. Chest. 2021;160:1934-58.
    [CrossRef] [PubMed] [Google Scholar]
Show Sections