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| LETTER TO EDITOR |
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| Year : 2020 | Volume
: 3
| Issue : 4 | Page : 869-870 |
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Prognostic role of inflammatory markers: Hype or reality?
Richa Vaish1, Rohit O Mundhada1, Neha Mittal2
1 Department of Surgical Oncology, Head-and-Neck Services, Tata Memorial Hospital; Department of Surgical Oncology, Head-and-Neck Services, Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Hospital; Department of Pathology, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| Date of Submission | 21-Oct-2020 |
| Date of Acceptance | 15-Nov-2020 |
| Date of Web Publication | 25-Dec-2020 |
Correspondence Address:
Richa Vaish
Room No 621, Homi Bhabha Block, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/crst.crst_334_20
How to cite this article:
Vaish R, Mundhada RO, Mittal N. Prognostic role of inflammatory markers: Hype or reality?. Cancer Res Stat Treat 2020;3:869-70 |
We read with great interest the article by Mittal et al. titled “Exploring the prognostic significance of the pretreatment inflammatory markers in hypopharyngeal cancers: A retrospective analysis” and the accompanying editorial by Mehra.[1],[2] The authors have explored the association of pretreatment inflammatory markers, namely the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the combination of platelet count and NLR with the survival outcomes in hypopharyngeal cancers. Although it is an interesting hypothesis, it has the inherent limitations of a retrospective study, a heterogeneous cohort, and the small numbers which the authors have enumerated.
Hanahan and Weinberg published an article elucidating the six hallmarks of cancer, namely self-sufficiency in growth signaling, insensitivity to anti-growth signals, evading apoptosis, sustained angiogenesis, tissue invasion and metastasis, and limitless replicative potential.[3] Two more emerging hallmarks with a decade of research, are reprogramming of energy metabolism and evading the immune surveillance. The acquisition of these hallmarks is enabled by two characteristics, which are genomic instability and inflammation.[4] The tumors are infiltrated by the immune cells, which can have a wide range of density. This infiltration, which is predominantly an innate immune reaction to overcome the tumor, paradoxically promotes tumorigenesis by delivering various bioactive molecules to the tumor microenvironment.
This theory forms the premise of the hypothesis that inflammatory markers are associated with tumor aggressiveness. Various markers of inflammation such as the C-reactive protein, NLR, PLR, and serum albumin have been studied extensively for prognostication of survival in various solid tumors, including those in the head-and-neck region for almost a decade now. These, however, have failed to gain universal acceptance and incorporation in the standard staging system due to their obvious limitations.
The dynamic and nonspecific nature of these markers with the physiological and pathological differences among people of different ethnicities and origins precludes their widespread use. Head-and-neck cancers are frequently associated with comorbidities such as chronic obstructive pulmonary disease (COPD), which is secondary to smoking tobacco. COPD is known to be associated with systemic inflammatory response, thus jeopardizing the prognostic value of these markers in head-and-neck cancers.[5] Other factors which limit the use of these markers are the low socioeconomic status of these patients, poor oro-dental hygiene, and co-existent/superimposed secondary infections. The systemic markers are intended to be a surrogate of the tumor microenvironment, but how much do they mirror it, is still unknown. The inflammatory markers are dynamic, and therefore, a cross-sectional study of these markers may not provide an actual representation of the tumor microenvironment. The data have mainly emerged from retrospective or small, poor-quality prospective studies. These studies have proposed various cutoffs for these markers, with a wide range of PLR values from 111 to 186.2 and NLR values from 1.9 to 6.0.[6],[7] These values are generated by internal prognostic grouping and lack external validation, thereby hindering their widespread application.
However, despite these limitations, this is a conceptually attractive hypothesis based on the sound premise of the biology of interaction between the tumor and its microenvironment. Nevertheless, it needs large prospective studies with external validation to standardize the cutoff values and large randomized controlled trials to assess their implications on the management and clinical utility.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Mittal S, Krishnamurthy A, Kothandaraman SK, Dhanushkodi M, John A. Exploring the prognostic significance of the pretreatment inflammatory markers in hypopharyngeal cancers: A retrospective analysis. Cancer Res Stat Treat 2020;3:437-44.  [Full text] |
| 2. | Mehra R. Reevaluating how we define inflammation in head-and-neck cancers. Cancer Res Stat Treat 2020;3:564-5. [Full text] |
| 3. | Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70. |
| 4. | Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74. |
| 5. | Oudijk EJ, Lammers JW, Koenderman L. Systemic inflammation in chronic obstructive pulmonary disease. Eur Respir J Suppl 2003;46:5s-13s. |
| 6. | Bardash Y, Olson C, Herman W, Khaymovich J, Costantino P, Tham T. Platelet-lymphocyte ratio as a predictor of prognosis in head and neck cancer: A systematic review and meta-analysis. Oncol Res Treat 2019;42:665-77. |
| 7. | Cho JK, Kim MW, Choi IS, Moon UY, Kim MJ, Sohn I, et al. Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: A meta-analysis and validation study. BMC Cancer 2018;18:969. |
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