Dr S.T. Sathya Meonah PhD.,
Small cell lung cancer (SCLC) is one of the high – grade malicious maladies of the respiratory system.
Approximately one in six cancers accounts for Small cell lung cancers.
The prognosis of the malignancy is so unpredictive, although response to the first line treatment is often propitious.
Two variations of SCLC are evident in patients, namely limited SCLC and extensive SCLC.
Combination of chemotherapeutic drugs, namely cisplatin or carboplatin with etoposide and radiotherapy is generally considered as the first line conventional therapy.
Disease relapse is common leading to poor survival rate of less than a year.
Some factors like patient’s general health status, magnitude of tumour invasion and the duration to relapse after first-line treatment significantly affect the overall prognosis.
Staging of SCLC
Another staging system have been introduced by The International Association for the Study of Lung Cancer Retrospective Staging Project as the Tumour Nodes Metastasis (TNM) staging system. In this system, SCLC has been staged as LS (stages belonging to I-IIIB) and ES (stages with wide metastases).
As the disease exhibits aggressive proliferation when compared to Non-Small Cell Lung Cancer (NSCLC) and other type of cancers, staging the disease prior to treatment is obligatory.
Factors affecting survival rate of SCLC
Immunity to the human body is rendered by both the innate and acquired immune systems. Tumours normally induce both these immunological responses.
Proliferation of malignant tumours occur when the tumour growth escapes immunological supervision.
Researchers indicate that the general immunity of SCLC patients have been highly compromised with unknown immune defects leading to bad prognosis.
The body’s resistance against formation, growth and metastasis of diverse tumours is greatly compromised.
CD4+ T-cell and SCLC
Li et al., reported that tumour cell lines of SCLC secrete inhibitory molecules that significantly supress activated CD4+ T cell proliferation.
The subsets of these CD4+ T cells are primarily responsible for generating cell mediated and humoral mediated immunity and also exhibit anti-tumour response.
Two subsets of CD4+ cells viz, helper cells and regulatory cells help coordinate and regulate immune effector response. The regulatory (reg) subsets of T cells have the potential to prevent other T cells from expression and activation.
These reg subsets express forkhead box protein P3 (FOXP3) which has been recently identified as a cancer biomarker. If the regulation of immune subsets become abnormal, the expression for FOXP3 protein surges.
Although the mechanism is not well established, the FOXP3 protein infiltrates through tumour clones, and an increased level of the protein is associated with poor survival.
Patients suffering from SCLC along with neuromuscular disease, Lambert Eaton syndrome have been reported to have favourable prognosis following cancer treatment compared to patients suffering from SCLC alone.
IgG antibodies enter the voltage-gated calcium channels and inhibit the influx of Ca2+ into the channel causing muscular debility.
Maddison et al., (1999) reported that these antibodies inhibit the inflow of Ca2+ ions into SCLC cell linesand control tumour growth. He also reported that four SCLC patients with LEMS syndrome showed good prognosis with no recurrence of the tumour for a median of 6 years.
Another study reported increased ratio of anti-tumour effector T-cells compared to T-regulatory cells. Similarly, Koyama et al., reported the immunologic balance between immune cells and reg cells exhibiting immunity against onconeural antigens induced in SCLC patients with paraneoplastic syndrome.
Due to its swift growth and dissemination, about 70% of patients have tumour growth disseminated beyond the hemithorax, the mediastinum or the supraclavicular lymph nodes from the origin site. These patients belong to the Extensive stage SCLC as classified by Veterans Administration Lung Study Group.
Many a report has revealed that higher the ratio of anti-tumour effector cells, greater the overall survival (Koyama et al., 2008). All these reports serve to add significance to immunotherapy-based treatments approaches.
Small Cell Lung Cancer is still a threatening disease around the globe. Multiple treatment modalities have been assessed time and again to control its pathogenesis.
Please stay tuned for more factual information on the cellular and molecular configuration of the carcinoma and the possible treatment methods.