Novel Diagnosis and Treatment of Cancer

#### **Chapter 1**

## Liquid Biopsy: A New Strategy for Future Directions in Lung Cancer Treatment

*Maria Palmieri and Elisa Frullanti*

#### **Abstract**

The gold standard for cancer diagnosis has always been based on radiological imaging followed by surgical tissue biopsies for molecular testing and pathological examination and surgical resection to remove the tumoral mass when possible. However, the resulting information is a limited snapshot in space and time, which poorly reflects clonal heterogeneity or tumor evolution and metastasis. Over a decade since its inception, the ability to use non-invasive methods such as a liquid biopsy to analyze tumor biomarkers has transformed the vision of future cancer care into a better patient experience thanks to real-time monitoring and early diagnosis. The liquid biopsy essay is an effective tool for detecting cancers at an early stage, when there are very few tumor-derived materials circulating in the bloodstream, being a very sensitive technique. For this reason, liquid biopsy is particularly suitable for early-stage diagnosis (stage I or II) of lung cancer whose diagnosis often occurs in the final stages of the disease as well as monitoring cancer progression and driving target therapies.

**Keywords:** liquid biopsy, lung cancer, CfDNA, new strategies, Circulating Tumor DNA (CtDNA)

#### **1. Introduction**

#### **1.1 An early opportunity to catch cancer**

A cancer patient's torturous journey begins with formulating the diagnosis. The detection of tumor mass, the stage, and the molecular profile are all clues that lead to the proper treatment. The advent of new technologies allows us to deepen our knowledge of molecular data useful to physicians to guide them toward specific therapies.

Cancer is the World's second biggest killer after heart disease, in which some of the body's cells grow uncontrollably and spread to other parts of the body. Currently, 90% of cancer patients do not die from the primary tumor but are killed by its distant metastases. Current treatment of patients with metastatic cancer is generally driven by the molecular characteristics of the primary tumor. Detection and monitoring of the disease are carried out with tissue sampling in a common and invasive difficult way for patients with solid tumors. Recently, sequential peripheral blood tests have been introduced as a non-invasive technique, resulting in the use of liquid

biopsy [1]. Liquid biopsy refers to a test, usually carried out from blood samples, to analyze tumor molecular biomarkers that can diagnose cancer and inform clinical decision-making [1].

Here, we will explore the possible molecular biomarkers that can be used:


The analytes mentioned above are the most studied as they are detected more easily alone or in combination, but exosomes, RNA, extracellular vesicles and, last but not least, methylation must also be counted among others.

To date, the gold standard for cancer analysis in clinical practice is tissue biopsy. This implies that, despite the advantages of liquid biopsy that immediately appear very clear, it is necessary to demonstrate that this non-invasive approach is actually better than the current one. The greatest limitation of all tissue biopsies is the lack of representativeness of tumor heterogeneity and plasticity. Tumors are highly heterogeneous, even down to the single cell level, and their characteristics change over time and under treatment pressure. The recovery of the sample through tissue biopsy is a highly invasive practice for the patient and is not easily repeatable over time, thus making the information of the data obsolete over time. For its part, the liquid biopsy can be defined as minimally invasive and allows the monitoring of the evolution of the tumor characteristics over time thanks to the possibility of being able to repeat the practice of blood sampling and in a sequential way also during the course of treatment (**Figure 1**).

Even if the initial approach leads us to think of using the liquid biopsy rather than the tissue biopsy, we should start thinking of starting to collect different data deriving from both approaches to really have clear and comprehensive information that guides cancer treatment.

*Liquid Biopsy: A New Strategy for Future Directions in Lung Cancer Treatment DOI: http://dx.doi.org/10.5772/intechopen.109211*


#### **Figure 1.**

*Liquid biopsy versus tumor biopsy for clinical-trial recruitment [4].*

#### **1.2 The potential use of liquid biopsy through the patient's journey**

Thanks to the sensitivity and specificity achievable with high-depth sequencing, liquid biopsy can be used for the early diagnosis of cancer, and in the next future also as a screening in healthy people. To justify this use, however, it is necessary to demonstrate that the tests are better than those currently in use. Indeed, some studies have shown that ctDNA analysis was able to diagnose lung cancer in the early stages (stage I or II) [5], as well as the detection of some mutations (i.e. *TP53* or *KRAS* genes) which is possible many years earlier, when the individual is still asymptomatic, compared to the time of the classic diagnosis [6].

Additionally, liquid biopsy can be extremely useful in detecting residual molecular disease (MRD) after treatment. In fact, it is very common that after specific medical treatments the current radiological imaging techniques are not able to detect the MRD [7] responsible for relapse.

However, before liquid biopsy enters the clinical routine, several clinical trials are needed for normalization and experimentation and would help answer several unsuspended questions. In fact, clinical trials allow facing challenges such as [8]:


A recent study [9] shows that at the moment the analyses of cfDNA are mainly included in clinical trials for cancers that have a higher incidence and mortality such as lung, breast, and colon cancer. Additionally, the study found some main drawbacks that were common among several trials that risk demoralizing and/or confusing the patient:


#### **1.3 The liquid biopsy for non-small cell lung cancer**

Lung cancer is the leading cause of cancer death in industrialized countries. In the USA it represents the leading cause of death in men and has now passed breast cancer in females leading to first place in mortality. For non-small cell lung cancer (NSCLC), treatment decisions follow the assessment of the staging of pathological node tumor metastases (pTNM). The more advanced the clinical stage, the more this is associated with the risk of death. However, it is estimated that only 40% of patients have stage 2–3 and have a minimal residual disease (MRD), and this means that the remaining 60% are likely to be over-treated with the possibility of giving rise to high toxicity risks. Somatic molecular alterations in NSCLC can lead to oncogene activation through multiple genetic mechanisms (point mutations, insertions, deletions, gene rearrangements, etc.) and the treatment of cancer has thus evolved from broad chemotherapeutic approaches to therapies targeted against specific molecular abnormalities that drive tumor growth. A robust and accurate assessment of molecular alterations within tumor cells is mandatory in routine clinical practice to determine which patients are suitable for these targeted therapies.

The TRACERx study (Tracking Cancer Evolution through Therapy) is a British national observational study for patients with NSCLC who have undergone surgery. Through this study, they try to evaluate the natural history of the evolution of the disease in order to understand the biology of MRD when it is impossible to access a tissue biopsy again. By monitoring 30 tumor variants, they were able to identify cases of disease recurrence by detecting MRD prior to clinical surveillance. They are currently looking to implement over 200 variants and limit of detection (LOD) of the technique in well over 1000 plasma samples. Therefore, thanks to this pioneering study it is possible to use two approaches:


Historically, the first clinical application of liquid biopsy in advanced NSCLC was the detection of *EGFR* mutations (**Figure 2**). From these pioneering studies, the scientists moved on to the analysis of next-generation sequencing (NGS) which allowed expanding the investigation to other driver mutations as well, that could provide prognostic and predictive information [10].

The first methods used were those of RT-PCR (real-time PCR) capable of detecting *EGFR* mutations and at the moment the only one approved by the FDA for the

*Liquid Biopsy: A New Strategy for Future Directions in Lung Cancer Treatment DOI: http://dx.doi.org/10.5772/intechopen.109211*

#### **Figure 2.**

*Timeline of the development of liquid biopsy [10].*

detection of the T790M resistance mutation of the *EGFR* gene [11]. Indeed, in 2016, the Food and Drug Administration (FDA) approved the liquid biopsy test for patients with NSCLC to verify EGFR-targeted therapy, while a European consortium from the European Liquid Biopsy Academy (ELBA) using biomarkers such as ctDNA, CTC, exosomes, and tumor educated platelets (TEP) [12].

Currently, ESMO guidelines recommend testing at least *EGFR* mutations, *BRAF* mutations, *ALK* fusions, *ROS-1* fusions, *MET* exon 14 skipping mutations, *RET* rearrangements and PD-L1 expression levels in non-squamous advanced NSCLC [13]. This panel could be further implemented considering *KRAS* mutations, *HER2* mutations, *MET* amplification, and *NTRK* rearrangements [13].

#### **2. Conclusion**

In conclusion, we can state that the liquid biopsy is significantly helping the management of patients with lung cancer by crossing the threshold of the use of off-label drugs in therapeutic pathways [14], but we must be aware that liquid biopsy cannot replace the PDL-1 expression assay for investigation of the tumor immune microenvironment, as well as cytological analysis of tissue biopsy. Therefore, in order to obtain the most complete treatment possible, we must consider liquid biopsy not as a competitive approach to the already existing ones, but as another valid mutation detection option.

#### **Declaration**

The authors have no conflicts of interest.

*Tumor Microenvironment – New Insights*

### **Author details**

Maria Palmieri1,2 and Elisa Frullanti1,2\*

1 Department of Medical Biotechnologies, University of Siena, Siena, Italy

2 Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy

\*Address all correspondence to: elisa.frullanti@dbm.unisi.it

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Pantel K, Alix-Panabières C. Circulating tumour cells in cancer patients: Challenges and perspectives. Trends in Molecular Medicine. 2010;**16**(9):398-406. DOI: 10.1016/j. molmed.2010.07.001

[2] Meng S, Tripathy D, Frenkel E. et al, Circulating tumor cells in patients with breast cancer dormancy. Clinical Cancer Research. 2004;**10**(24):8152-8162. DOI: 10.1158/1078-0432.ccr-04-1110

[3] Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: Monitoring cancer-genetics in the blood. Nature Reviews. Clinical Oncology. 2013;**10**(8):472-484. DOI: 10.1038/ nrclinonc.2013.110 Epub 2013 Jul 9

[4] Corcoran RB. Liquid biopsy versus tumor biopsy for clinicaltrial recruitment. Nature Medicine. 2020;**26**:1815-1816. DOI: 10.1038/ s41591-020-01169-6

[5] Phallen J, Sausen M, Adleff V, et al. Direct detection of early-stage cancers using circulating tumor DNA. Science Translational Medicine. 2017;**9**(403):aan2415. DOI: 10.1126/ scitranslmed

[6] Gormally E, Vineis P, Matullo G, et al. TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: A prospective study. Cancer Research. 2006;**66**(13):6871- 6876. DOI: 10.1158/0008-5472. can-05-4556

[7] Pantel K, Alix-Panabières C. Liquid biopsy and minimal residual disease— Latest advances and implications for cure. Nature Reviews Clinical Oncology. 2019;**16**(7):409-424. DOI: 10.1038/ s41571-019-0187-3

[8] Lustberg M, Stover D, Chalmers J. Implementing liquid biopsies in clinical trials. The Cancer Journal. 2018;**24**(2):61-64. DOI: 10.1097/ ppo.0000000000000309

[9] Cisneros-Villanueva M, Hidalgo-Pérez L, Rios-Romero M, et al. Cell-free DNA analysis in current cancer clinical trials: A review. British Journal of Cancer. 2022;**126**(3):391-400. DOI: 10.1038/ s41416-021-01696-0

[10] Bonanno L, Dal Maso A, Pavan A, et al. Liquid biopsy and non-small cell lung cancer: Are we looking at the tip of the iceberg? British Journal of Cancer. 2022. DOI: 10.1038/s41416-022-01777-8

[11] Sacher AG, Paweletz C, Dahlberg SE, Alden RS, O'Connell A, Feeney N, et al. Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer. JAMA Oncology. 2016;**2**:1014

[12] Revelo AE, Martin A, Velasquez R, Kulandaisamy PC, Bustamante J, Keshishyan S, et al. Liquid biopsy for lung cancers: An update on recent developments. Annals of Translational Medicine. 2019;**7**(15):349. DOI: 10.21037/atm.2019.03.28

[13] Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2018;**29**:iv192-iv237

[14] Danesi R, Fogli S, Indraccolo S, Del Re M, Dei Tos AP, Leoncini L, et al. Druggable targets meet oncogenic drivers: Opportunities and limitations of target-based classification of tumors and the role of molecular tumor boards. ESMO Open. Apr 2021;**6**(2):100040

#### **Chapter 2**

## Minimally Invasive Surgery for the Management of Lung Cancer

*Gaetana Messina, Mary Bove, Giorgia Opromolla, Vincenzo Di Filippo, Mario Pirozzi, Marianna Caterino, Sergio Facchini, Alessia Zotta, Giovanni Vicidomini, Mario Santini, Alfonso Fiorelli, Fortunato Ciardiello and Morena Fasano*

#### **Abstract**

Lung cancer is the leading cause of cancer-related death and the most diagnosed cancer. The treatment of Non-Small Cell Lung Cancer (NSCLC) depends on clinical staging. Surgical radical resection is recommended for patients with stage 1 or 2 of disease and represents the treatment of choice. In the last decades, the surgical approach for lung cancer changed moving from an open approach to a minimally invasive approach, represented by Video Assisted Thoracic Surgery (VATS) and Robot-Assisted Thoracic Surgery (RATS). In this chapter, we illustrate the characteristics of lung cancer, the diagnosis, the classification, the staging and the preoperative evaluation. Then we focus on the surgical treatment of lung cancer and on how it has changed during the years. We explain the open approach represented by the traditional posterolateral thoracotomy and by the muscle-sparing thoracotomy. We illustrate VATS approach and evolution: from the hybrid approach to the pure VATS that can be triportal, biportal or even uniportal. Then, we focus on RATS approach, characterized by the use of multiple ports in the same intercostal space and how it evolved toward the uniportal approach. The objective is to combine the advantage of uniportal VATS (lower postoperative pain, enhanced recovery) and RATS (better visualization, more degrees of movements).

**Keywords:** NSCLC, thoracic surgery, VATS, RATS, Uniportal, minimally invasive surgery

#### **1. Introduction**

#### **1.1 Epidemiology**

Lung cancer is one of the main causes of death in several countries. The incidence of lung cancer is 3% in men and 1% in women. 236.740 new cases of lung cancer and 130.180 deaths have been recorded in 2022 [1]. 5-years survival rate is 21.7%, in particular it is 15% for men and 19% for women [2]. It represents the first cause of death for tumor for men and the second for women.

Cigarette smoking is the main risk factor for lung cancer, because of its carcinogenic chemicals. Relative risk of lung cancer is related to number of cigarettes smoked per day, years of smoking and level of tar in cigarettes. Exposed non-smokers also have an increased relative risk of developing lung cancer.

Many agents, such as asbestos, beryllium, cadmium, chromium, diesel fumes nickel, are known as carcinogens. They increase the risk of lung cancer in exposed people, especially in smokers. About 80–90% of lung cancer is caused by smoking. The risk of lung cancer is increased in ex-smokers than in never smokers [3]. Some genetic factors, such as overexpression of Epidermal Growth Factor (EGFR), are related to the development of non-small cell lung cancer (NSCLC) [4].

#### **1.2 Lung cancer screening**

The National Lung Screening Trial (NLST) was the first trial to demonstrate that early diagnosis of lung cancer with annual low-dose CT scan in individuals with highrisk factors reduces the mortality rate related to this disease of 20% compared to chest radiographs. In this trial, individuals with high-risk factors were current or former smokers with a 30 or more pack-year smoking history, 55 to 74 years of age with no evidence of lung cancer [5]. Different organizations such as European Respiratory Society (ERS), European Society of Radiology (ESR), European Society of Thoracic Surgeons (ESTS), European Alliance for Personalized Medicine (EAPM), European Society of Medical Oncology (ESMO) e Swiss University Hospitals recommend lung cancer screening with low-dose CT scan. Anyway, low-dose CT screening and followup do not substitute smoking cessation.

#### **1.3 Classification and prognostic factors**

World Health Organization (WHO) divides lung cancer into two main categories non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The 80% of lung cancer is represented by NSCLC. It is divided into two groups: (1) non-squamous: adenocarcinoma, large-cell carcinoma and other subtypes; (2) squamous cell carcinoma [6]. **Table 1** summarizes WHO classification of lung cancer.

In the last decades, the histological definitions of NSCLS become critical for the development of new therapies based on the histotype. Diagnosis can be obtained with morphological criteria based on hematoxylin and eosin stain or specific stains, such as May-Grunwald-Giemsa, but immunohistochemistry is crucial for the definition of poorly differentiated NSCLC or Not Otherwise Specified (NOS).

Immunohistochemical investigation can be conducted both on histological or cytological samples.

The study of the molecular characteristics of lung cancer, the individuation of disease-associated mutations (EGFR mutations) or immune biomarkers (PD-L1) is crucial for target therapy, that is effective in patients with specific mutations [7].

#### **1.4 Clinical manifestations**

Lung cancer can manifest with symptoms like cough, dyspnea, pain, fatigue or hemoptysis. Symptoms related to advanced stages of disease are weight loss, pleural effusion, dysphagia, lymphadenopathy, paraneoplastic syndromes [8].



#### **Table 1.**

*WHO classification of lung cancer.*

#### **2. Diagnosis**

Clinical suspicion of lung cancer is based on clinical evaluation and history (smoking history, symptoms, age, previous cancer history, family history, other lung disease). Chest X-ray is generally the first investigation performed. Incidental radiological finding of a suspected lung cancer is frequent and it often presents as a solitary or peripheral nodule. Suspicion findings have to be investigated by CT with contrast (**Figure 1**). Radiological features of the pulmonary nodule that suggest the diagnosis of lung cancer are: size, shape and density. The size of the neoformation and especially its growth over time is closely related to the risk of malignancy. However, the doubling of the volume of the nodule in less than 7 days indicates benign lesion (inflammation/infection). Spiculation, irregular margins and pleural retraction are associated with an increased risk of malignancy. Density of the neoformation can be homogeneous or inhomogeneous and varies from solid lesions to "ground glass" or partially solid lesions [9, 10].

Positron Emission Tomography/Computed Tomography (PET/CT) is playing a significant role as a potential diagnosis and staging test in patients with non-small cell lung cancer (NSCLC) [11] and allows, moreover, to direct the biopsy on suspect areas with elevated glucidic metabolism, increasing the likelihood of reaching a diagnostic result.

**Figure 1.**

*Examples of lung cancer at CT scan: (A) tumor located at right upper lobe; (B) tumor located at right lower lobe.*

Tissue diagnosis employs several techniques:


If a preoperative tissue diagnosis cannot be obtained, the alternative is intraoperative diagnosis (wedge resection or needle biopsy). The choice of diagnostic technique mainly depends on the location of the lesion (central or peripheral) but also on the size of the tumor and the clinical condition of the patient [12, 13].

In case of abnormal mediastinal and/or hilar lymph nodes at CT and/or PET, needle aspiration EBUS or EUS-guided is recommended. If malignant nodal involvement is not found by this techniques, surgical staging is recommended [12].

#### **3. Staging and TNM classification**

Lung cancer staging is necessary to establish the prognosis and the therapeutic program. Staging involves performing a contrast-enhanced CT scan of the chest and upper abdomen to determine local invasiveness, nodal involvement and distant metastasis, particularly in the liver and adrenal glands. The evaluation of these parameters defines the staging of the neoplastic disease according to the TNM system. TNM classification is universally accepted and routinely applied in clinical practice. The T category describes the size and the extension of the primary tumor; the N category defines regional lymph node involvement; the M category establishes presence of distance metastases. **Table 2** summarizes VIII edition of the TNM classification for lung cancer [13].


*1 The uncommon superficial spreading tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a.*

*2 Solitary adenocarcinoma,* ≤*3 cm with a predominately lepidic pattern and* ≤ *5 mm invasion in any 1 focus. 3 T2 tumors with these features are classified as T2a if* ≤*4 cm in greatest dimension or if size cannot be determined, and T2b if >4 cm but* ≤*5 cm in greatest dimension.*

*4 Most pleural/pericardial effusions with lung cancer are due to tumor. In a few patients, however, multiple microscopic examinations of pleural/pericardial fluid are negative for tumor. In these the effusion should be excluded as a staging descriptor.*

*5 This includes involvement of a single distant (nonregional) lymph node.*

**Table 2.** *TNM classification.*

In cases where CT does not show evidence of distant metastases, imaging staging should be completed with 18-FDG PET-CT, which has higher sensitivity and specificity than contrast-enhanced CT and higher sensitivity than (18)F-FDG PET in staging NSCLC in detecting extrathoracic and bone metastases. PET/TC has, however, low sensitivity in detecting brain metastases [14]. Staging brain MRI with contrast is used to evaluate the presence of cerebral metastases in patients with neurological symptoms or in the investigation of a suspected CT lesion [15].

Staging is divided into clinical staging (presurgical) and pathologic staging (after surgical resection of the tumor, lymph nodes or metastases) (**Table 3**).

#### **4. Treatment of early stage lung cancer**

Radical surgery allows to obtain a full recovery or to significantly improve the prognosis in patients with early stage disease and is not recommended for patients with advanced disease. Surgery needs to be taken in consideration in NSCLC stage I, II and in selected stage IIIA/IIIB (T1-T2, N2 single station, non-bulky). It should be performed in high-volume centers, by expert surgeons. It has been demonstrated that the outcome of patients undergoing lung resection for lung cancer is better for those treated in high-volume centers [16]. Before surgery, lung cancer patients need to be studied in order to define their operability. A tumor that can be completely resected with surgery is considered resectable. Even if a tumor is anatomically resectable, it is necessary to evaluate if the patient can tolerate surgery and is functionally operable according to his functional preoperative situation and, most importantly, his predicted postoperative status, especially with regard to respiratory and cardiovascular function. Cardiorespiratory evaluation is mandatory for patients that are candidate to a lung resection surgery, in order to predict the operatory risk and postoperative lung function. Lung function is evaluated mainly with: spirometry, Diffusion Lung CO (DLCO), hemogasanalysis, ergometric tests, lung perfusion scintigraphy. In case of lower values (FEV1 and DLCO <80%), Cardio Pulmonary Exercise Testing (CPET) is indicated and if the maximal oxygen consumption (VO2max) is less than 10 mL/kg/min the risk of serious postoperative complications is high. For cardiovascular assessment, the use of recalibrated thoracic Revised Cardiac Risk Index (RCRI) is recommended (**Table 4**).

An RCRI <2 has been reported to be associated with a low-cardiac risk, and no additional tests are needed. However, an RCRI >2 has been associated with an increased cardiac risk and a cardiac consultation with non-invasive testing is recommended [17, 18].

#### *Tumor Microenvironment – New Insights*


#### **Table 3.**

*Staging of NSCLC.*

Brunelli et al. [19] proposed a physiologic evaluation resection algorithm for major anatomic resection (lobectomy or greater).

For positive and low-risk or negative cardiac evaluation, we calculate postoperative FEV1 (ppoFEV1) and postoperative DLCO (ppoDLCO):

*Minimally Invasive Surgery for the Management of Lung Cancer DOI: http://dx.doi.org/10.5772/intechopen.109151*


#### **Table 4.**

*Recalibrated thoracic revised cardiac risk index.*

	- If VO2max is >20 ml/kg/min or > 75%, the patient is considered at low risk for major anatomic resection.
	- If VO2max is 10–20 ml/kg/min or 35–75%, the patient is at moderate risk for major anatomic resection.
	- If VO2max is <10 ml/kg/min or < 35%, the patient is at high risk for major anatomic resection.
	- If stair climb is >22 m or shuttle walk is >400 m, the patient is considered at low risk for major anatomic resection.
	- If stair climb is <22 m or shuttle walk is <400 m, cardiopulmonary exercise test (CPET) is recommended.

For positive high-risk cardiac evaluation, cardiopulmonary exercise test (CPET) is mandatory:


• If VO2max is <10 ml/kg/min or < 35%, the patient is at high risk for major anatomic resection.

A multidisciplinary evaluation is necessary to discuss the different therapeutic options and their potential results. The surgical procedure depends on the extent and the localization of the tumor and on the cardiopulmonary reserve of the patients. Preoperative or intraoperative cytohistologic diagnosis is recommended before anatomic lobectomy, bilobectomy or pneumonectomy. Anyway, when the diagnosis is technically difficult to obtain, or it is at high risk for the patient and the radiological and clinical probability of lung cancer is high, it is possible to perform an anatomic resection without tissue confirmation of lung cancer.

Anatomic lobectomy with mediastinal lymphadenectomy is the gold standard treatment for lung cancer.

When the lesion is not resectable through a lobectomy, for instance if it infiltrates the main bronchus or the main artery, or if it invades the fissure to the adjacent lobe, pneumonectomy is indicated.

If anatomically applicable and if negative margin can be achieved, sleeve lobectomy is preferred over pneumonectomy.

Anatomic segmentectomy is acceptable for Ground Glass Opacities (GGO) or for very early stage of disease (Tis or T1a) or in patients who are not eligible for lobectomy. It is possible because GGO more often are diagnosed as in situ adenocarcinoma or minimally invasive adenocarcinoma. When segmentectomy is performed, parenchymal resection margins should be 2 cm or more, or they should be the size of the nodule or larger. In these cases, segmentectomy is preferred over wedge resection [20].

#### **5. Surgical techniques**

#### **5.1 Thoracotomy**

The first pulmonary resection for lung cancer was performed in 1912. At the beginning, surgical resection for lung cancer was pneumonectomy. In 1960s, lobectomy was recognized as the gold standard treatment. Traditional surgical approach was a 15–20 cm posterolateral thoracotomy. This traditional approach implies the resection of multiple muscle layers (latissimus dorsi and serratus anterior) and ribs divarication with metal retractors. Ribs fractures are common during divarication and sometimes ribs segments are resected to avoid fractures and to improve surgical exposure. This kind of thoracotomy allows an optimal view of the hilum and the use of two hands by the surgeon. This incision can result in pain and shoulder and chest wall dysfunction. 44% of patients undergoing thoracotomy develop chronic pain for 1 year after the procedure and 29% of patients experience pain for more than 1 year after surgery [21].

Noirclerc et al. [22] were the first to describe the muscle-sparing thoracotomy. The objective of this approach is to preserve muscles, in particular the latissimus dorsi. This technique reduces postoperative complications and consents a better postoperative mobilization of the shoulder, compared to traditional posterolateral thoracotomy.

#### **5.2 Video-assisted thoracic surgery (VATS)**

During the last decades, Minimally Invasive Surgery (MIS) was applied for lung cancer surgery. The first Video-Assisted Thoracoscopic Surgery (VATS) for lung resection was performed in the early 1990s [23]. At the beginning, the term VATS indicated the use of a videothoracoscope during thoracic surgery procedures, performed through traditional thoracotomy. For example, Okada et al. [24] described a hybrid approach, with a mini-thoracotomy and a camera port, used to see areas not visible with direct vision. Substantially, hybrid approach integrated direct and thoracoscopic vision. Then, there was the development of "pure" VATS using only thoracoscopic vision.

Most centers use a 3–5 cm utility incision located anteriorly, one port for the optic and another port located posteriorly. Gossot et al. [25] described pure thoracoscopic lobectomy using three incisions with a mini-thoracotomy for the extraction of the lobe. McKenna Jr. et al. [26] use three or occasionally four ports.

Hansen et al. [27] perform a standardized anterior three-port approach, with the ports located always in the same place, independently of the lobe to resect: a utility incision of 4–5 cm is located anteriorly at the 4th intercostal space, the 1–1,5 cm camera port is located anteriorly at the level of the diaphragm (8th intercostal space) and a posterior 1,5 cm incision is done at the same intercostal space.

Burfein and D'Amico perform double-port VATS lobectomy [28]: a 2 cm camera port is located at the 7th or 8th intercostal space in the mid-axillary line and a utility incision of 4,5 cm is located anteriorly at the 5th or 6th intercostal space. The doubleport technique is characterized by a different lung exposure and the camera has to be moved between the camera port and the utility incision during surgery.

In all cases, systematic lymph node dissection is performed.

Compared to open approach, VATS lung resection is associated with lower postoperative pain, lower incidence of postoperative complications (including atrial fibrillation, atelectasis, prolonged air leak), shorter length of hospitalization, lower postoperative mortality. The reduced hospitalization also consents a rapid access to adjuvant chemotherapy [29]. Different studies analyzed the oncological equivalence of VATS compared to open approach. Some studies aimed to analyze the effectiveness of nodal dissection in VATS compared to that obtained with thoracotomy. Medbery et al. [30] affirmed that there is no difference in staging if nodal dissection is performed in high-volume centers. According to Watanabe et al. [31] a complete lymphadenectomy is possible in VATS also in N2 stage intraoperatively diagnosed. A retrospective study of the National Cancer Data Base (NCDB) showed no difference in nodal staging and overall survival between patients operated in VATS or in open resections [26]. It is also demonstrated that there is no difference in long-term survival [32].

During the years, VATS surgery evolved to a uniportal approach, with only a single incision used for all instruments and for lobe extraction. Rocco et al. [33] were the first to describe the uniportal approach in 2004 for wedge resection, not performing lobectomies. Gonzales-Rivas et al. [34] did the first uniportal VATS lobectomy in 2010. The utility incision is done at the 5th intercostal space, its size is the same of the utility incision used for triple or double-port approach. The surgeon and the assistant are placed both in front of the patient in order to have the same vision and to coordinate movements. A 30 degrees camera is used and it follows the instruments, giving

a vision that closely resembles that of the open approach. Uniportal VATS lobectomy follows the same principles of all major pulmonary resection in VATS. Dissection of veins, arteries, bronchus and fissure is performed, with a complete mediastinal lymphadenectomy.

Different studies compared the outcome of uniportal and "multiportal" VATS, demonstrating a reduction of complications, length of hospitalization and duration of drain tube. Uniportal VATS also allows for a reduction in postoperative pain due to several factors. Firstly, it involves only one intercostal space, minimizing the overall surgical trauma. Secondly, the absence of trocars eliminates the potential compression on the intercostal nerve that may occur during the movements of the camera in traditional multiport VATS procedures [35]. An interesting evolution of the uniportal VATS was the development of the subxiphoid approach, in order to reduce the pain due to intercostal nerve damage [36]. It also can be used to treat bilateral disease, even if the visualization is limited, compared to transthoracic techniques [37]. More studies are necessary to compare subxiphoid to transthoracic approach.

General anesthesia with single lung ventilation is required for lung surgery and it is obtained through a double lumen endotracheal tube or through a bronchial blocker. The patient is positioned in lateral position. Both the surgeon and the assistant stay in front of the patient in order to have the same vision. In general, the port position is the same for every lobectomy. A 30° videothoracoscope and long and curved instruments are usually used. Hilum dissection is performed bluntly with instruments, suction device, peanuts or energy devices. Vascular and bronchial elements are isolated and resected through linear endo-staplers. Also the fissure is divided with endo-stapler device. The specimen is extracted using an endo-bag. The chest tube is inserted in the camera port at the end of surgery. Then, the lymphadenectomy is done mainly using energy device.

Lymphadenectomy is necessary for the correct staging of the disease. Systematic lymph node dissection is recommended. Anyway some authors recommend the lobe-specific mediastinal lymphadenectomy. According to them, nodal metastasis is related to the localization of the primary tumor: upper lobe tumors tend to metastasize upper lymph nodes and lower lobe tumors tend to spread to the inferior and subcarinal nodes [38]. Systematic mediastinal lymph node dissection allows the detection of more metastatic lymph nodes and a better oncologic outcome than lobespecific nodal dissection [39]. Gooseman and Brunelli [40] recommend systematic lymphadenectomy and in particular, even for the selected cases in which lobe-specific nodal dissection could be accepted (peripheral T1 squamous cell carcinoma), they recommend always the dissection of subcarinal lymph nodes.

The surgeon has to be prepared to convert to thoracotomy in case of technical difficulties in dissection or in case of bleeding.

#### *5.2.1 Right upper lobectomy*

The first step involves performing a mediastinal release maneuver. The lung is retracted anteriorly and the posterior pleura is dissected at the level of the bronchial bifurcation. It helps the dissection of the bronchus from the anterior approach. Then, the lung is retracted posteriorly and the dissection of the veins is performed. Once identified and dissected the upper lobe vein, it is resected with vascular endo-stapler. The resection of the vein exposes the pulmonary artery. The arterial branches to the upper lobe (truncus anterior and ascending arteries) are dissected and divided through vascular endo-stapler. Then, the bronchus is divided through bronchial stapler and the fissure is completed with endo-stapler device. The specimen is extracted in an endo-bag through the utility incision.

#### *5.2.2 Left upper lobectomy*

The lung is retracted anteriorly and the posterior pleura is dissected in order to identify the posterior artery and to facilitate the maneuvers with the anterior approach. The lung is retracted posteriorly and, after the identification of the veins, the upper lobe vein is dissected and divided through endo-stapler, exposing the pulmonary artery and the upper lobe bronchus. The arterial branches for the anterior, posterior and apical segments and the lingular branches are exposed and divided through vascular endo-staplers. Then, the upper bronchus and the major fissure are divided through endo-staplers. The specimen is extracted in an endo-bag through the utility incision.

#### *5.2.3 Middle lobectomy*

The middle lobe vein is dissected and divided. Then the fissure to the lower lobe and the bronchus to the middle lobe are divided through endo-staplers. Then the artery branches are dissected and divided and at the end the fissure to the upper lobe is completed through endo-stapler. The specimen is extracted in an endo-bag through the utility incision.

#### *5.2.4 Lower lobectomies*

The first step of lower lobectomies is represented by the division of the inferior pulmonary ligament. This confers mobility to the lobe and exposes the vein to the lower lobe. The lower lobe vein is dissected and divided with endo-stapler (**Figure 2**). Then the procedure can continue in two ways: the surgeon can dissect the arterial branches to the lower lobe (for the apical segment and for the basal pyramid) and the bronchus to the lower lobe within the fissure. The other option is represented by the fissureless technique: after the dissection and resection of the vein, the lower lobe is retracted cranially and the plane between the bronchus and the artery is dissected and

#### **Figure 2.** *Right lower lobectomy: (A) right lower lobe vein dissection; (B) right lower lobe division through endo-stapler.*

#### **Figure 3.**

*Right lower lobectomy: (A) dissection right lower lobe bronchus; (B) division of right of right lower lobe bronchus through endo-stapler.*

#### **Figure 4.**

*Right lower lobe artery: (A) dissection and (B) division of right lower lobe artery through endo-stapler.*

the bronchus is divided through endo-stapler (**Figure 3**). Then, the arterial branches are divided and the fissure is divided at last (**Figure 4**). The specimen is extracted in an endo-bag through the utility incision.

#### **5.3 Robotic-assisted thoracic surgery (RATS)**

The most recent minimally invasive technique applied to thoracic surgery is robotic approach. The progress in the field of robotic technology generated interest in thoracic surgeons, that started to perform Robot-Assisted Thoracic Surgery (RATS). The first robotic lobectomies were described by Morgan et al. [41] and by Ashton et al. [42] in 2003. Since then, robotic lobectomy started to be performed in different centers. Cerfolio et al. [43] described their initial results using a completely portal 4-arm robotic operation with insufflation of carbon dioxide. The four ports are located at the same intercostal space (7th intercostal space). They achieved a complete R0 resection, performing a median number of 5 mediastinal lymph node station dissections. They recorded a significant reduction in morbidity and hospital stay compared to thoracotomy. When compared to VATS, Kent et al. [44] reported less postoperative pain and a rapid return to normal activities.

#### *Minimally Invasive Surgery for the Management of Lung Cancer DOI: http://dx.doi.org/10.5772/intechopen.109151*

In 2021, Yang et al. [45] were the first to describe a uniportal RATS lobectomy for a tumor located in the right upper lobe. A single 4 cm incision was made at the 4th intercostal space on the mid-axillary line. The 30° camera arm was placed on the upper end of the incision and the two instrument arms were placed intercrossed inside the chest. With this approach, they were able to perform a radical lobectomy and lymphadenectomy. The recovery was fast and the patient was discharged three days after surgery.

RATS consents a three-dimensional (3D) high-definition view, intuitive articulation of the robotic hands and more flexibility of instruments, with seven degrees of motion. Its superior instrumentations consent to perform accurate and safe dissection, in particular lymph node dissection that is crucial for the correct staging of lung cancer. It also can be used for difficult cases at high risk of conversion such as central tumors, sleeve lobectomy and pneumonectomy. To date, studies comparing VATS and RATS lobectomy do not show significant differences in terms of outcome. For this reason, a challenging question arises regarding the cost-benefit analysis [46, 47].

#### **6. Conclusions and future perspectives**

At the beginning of the era of minimally invasive thoracic surgery, a great limit of the technique was represented by the vision, because of the low definitions of cameras. Surgeons preferred the direct vision to have a better control of the procedure. The progress in the field of technologies consented to have high-definition cameras also with additional features, such as 3d vision or integration with augmented reality surgery navigation systems. Nowadays, cameras are largely used by surgeons even in thoracotomy approach to improve visualization and lightning. The progress made in the field of instrumentations has been appreciated by surgeons and instruments made for minimally invasive surgery such as endo-staplers are now used also for open approach, because of their thickness and flexibility.

Another challenge for VATS surgery is the use of rigid instruments that have to be moved through the rigid chest wall. Human hand consents to perform several traction and counter-traction movement and provides tactile feedback. With the development of minimally invasive surgery, that limits the tactile feedback, surgeons started to operate mainly relying on the vision. This happens, in particular, in RATS. Since the chance to palpate nodules or ground glass opacities is little in VATS and even null in RATS, surgeons has to rely only on visual signals. For this reason, they can use intraoperative ultrasound or they can mark nodules with coils in hybrid operating room [48]. Also artificial intelligence is developing in order to help surgeons during procedures.

The field of minimally invasive thoracic surgery is developing in two directions: reducing the number and the size of the surgical access (uniportal VATS) and increasing the use of RATS. The objective is to combine the advantage of uniportal VATS (lower postoperative pain, enhanced recovery) and RATS (better visualization, more degrees of movements).

*Tumor Microenvironment – New Insights*

### **Author details**

Gaetana Messina1 \*, Mary Bove1 , Giorgia Opromolla1 , Vincenzo Di Filippo1 , Mario Pirozzi2 , Marianna Caterino2 , Sergio Facchini<sup>2</sup> , Alessia Zotta<sup>2</sup> , Giovanni Vicidomini1 , Mario Santini1 , Alfonso Fiorelli1 , Fortunato Ciardiello2 and Morena Fasano2

1 Thoracic Surgery Unit, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Campania, Italy

2 Department of Precision Medicine, Università della Campania "L. Vanvitelli", Napoli, Campania, Italy

\*Address all correspondence to: adamessina@virgilio.it

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## Trends of Pediatric Cancer in India

*Sajna Panolan, Srinivas Govindarajulu, S. Kalpana, Valarmathi Srinivasan and Joseph Maria Adaikalam*

#### **Abstract**

Compared to developed countries, only a limited number of studies systematically engage with India's experience with the burden of childhood cancer and its implications for public healthcare in the country. This study aims to assess the long-term trend in the incidence of cancerous conditions, demographic factors, and the burden of the disease among children. The study has used the Madras Metropolitan Tumor Registry (MMTR), covering cancer cases reported among children (0–14 years) in Chennai for the last 34 years (1982–2016). The study analyses the incidence of the pediatric tumor for different age groups, gender, and type of cancer and the long-term trend over the years and compares the same with existing studies. The trend indicates that more cases are reported during 2007-11and the least number of cases are reported during 2012–2016 (respectively 16.7% and 11.9% of total cases reported).

**Keywords:** childhood cancer, pediatric cancer, tumor, trend, Chennai

#### **1. Introduction**

Globally, the incidence of childhood cancer has been increasing steadily and throws new challenges in public health management and policy making. Its nature, types and risk factors vary across the countries. As a developing country, India's experience with its given context is very important in understanding the role of epidemiological, demographic, socio-economic factors, and policy engagements in addressing public healthcare challenges. Several studies are looking into the experience of developed countries in addressing the cancer prevalence of cancer among children, their treatment, and attempts to connect them with countries' epidemiological transition. Compared to this, only a limited number of studies systematically engage with India's experience with the burden of childhood cancer and its implications for public healthcare in the country.

Available evidence indicates that India also experiences a steady increase in the number of children affected by different types of cancer. The details suggest that leukemia is the most common cancer affecting children followed by lymphoma and retinoblastoma. The profile of children affected by cancer shows variation across the age groups. The incidence of retinoblastoma, renal tumors, neuroblastoma, and hepatic tumors was found higher among children aged below five years whereas lymphoma, leukemia, bone tumors, and central nervous system tumors were found more among children aged above five years [1].

Globally, the annual number of new cases of childhood cancer exceeds 2, 00,000 and more than 80 percent of the reported cases are from the developing world [2]. Thirteen percent of the annual deaths worldwide are cancer-related and 70 percent of them are in the low- and middle-income countries [3]. Childhood cancer (age at diagnosis 0–14 years) is associated with a variety of malignancies and its incidence varies by age, sex, ethnicity, and geography, as reported by canceretiology [4, 5]. The incidence of childhood cancer across the countries ranges from 75 to 150 per million children per year. For instance, only 0.5 percent of all cancer cases reported in England occur in children less than 15 years of age whereas in India this proportion appears higher at 1.6–4.8 percent with variation by place of residence. This is related to the population structure (33% of the population in India is less than 15 years of age compared to 18% in England) [6, 7]. Though it remains less than the cases reported in the developed world, about 1.6 to 4.8 percent of all cancer reported in India are found in children below 15 years of age, and the overall incidence of 38 to 124 per million children, per year [8].

As 75 percent of the world population lives in these countries, developing countries bear more than half of the global cancer burden [9]. Because of population growth, aging and urbanization, changing dietary habits, better control of infections, and increasing tobacco consumption, developing countries are anticipated to bear a greater cancer burden, including that of greater lympho-hemopoietic malignancies [10]. India found to have 3 million persons is reported with cancer at any time, with 0.8 million new cases of cancer diagnosed each year [11]. There is a constant rise in cancer cases, but the trend and pattern vary according to the geographical region [12].

India's experience with a fast-growing economy and change in lifestyle-related behaviors can be connected to increasing cancer load [13, 14]. The relative differences in the incidence of lympho-hemopoietic malignancies in urban and rural populations can be connected with the differences in the environmental and socioeconomic factors affecting the dietary habits and lifestyle in rural and urban areas [15]. They tend to follow the larger trends noticed in terms of disease risk connected with the relative contributions of environment and genetics in the etiology of specific cancers. Studies consider their contribution to risk due to variation in exposure to carcinogens (in the external environment, or through lifestyle choices), or in genetic susceptibility to them [16].

This study broadly highlights the intensity of childhood cancer and its implications for child healthcare and health management in the global, national and local contexts. It aims to assess the long-term trend in the incidence of cancerous conditions, demographic factors, and the burden of the disease among children in Chennai from 1982 to 2016.

#### **2. Materials and methods**

This study has used the Madras Metropolitan Tumor Registry (MMTR), a population-based cancer registry (PBCR) based at the Cancer Institute (WIA), Chennai covering all cases reported among children (0–14 years) in Chennai for the last 34 years (1982–2016). All cases of childhood cancer from 0 to 14 years of age that were registered from 1st January 1982 to 31st December 2016 were included in this study. The study analyses the data on the incidence of the pediatric tumor for different age group, gender, and type of cancer and the long-term trend over the years and compare the same with existing studies. Childhood cancers (age at diagnosis

0–14 years) comprise a variety of malignancies, with incidence varied by age, sex, and ethnicity that provided insights into cancer etiology. The analysis looks into the types and incidence rate of cancer across the different age groups of children. The proposal was reviewed and approved by the ethical and scientific committees of the university.

#### **3. Result and discussion**

The analysis covers 34 years (1982 and 2016) and shows the trend of the cancerous condition of children of madras. The long-term trend indicates that more number of cases is reported during 2007–2011 (639cases) constitutes 16.7 percent of the total cases reported during this period. At the same time, the least number of cases are reported during 2012–2016 (458cases), constituting 11.9 percent of the total cases reported (**Figure 1**).

**Table 1** describes the Sex-wise distribution of pediatric cancer during this period and shows that more number of cases are reported among male children (2313 cases) constituting 60.3% of total cases reported (3834). Compared to this, only 1521 cases (39.7%) are reported among female children.

**Figure 2** describes the age group distribution of pediatric cancer reported from 1982 to 2016. When the children are classified into three agegroups, the data shows that more pediatric cancer is reported in 0–4 years of age (1417 cases) accounting for 37 percent of the total cases reported (3834 cases). The details show that the highest number of cases (370 cases, constituting 9.7%) was reported at three years of age.

**Table 2** shows the distribution of reported cases among the major religious groups. Compared to other religious groups, more pediatric cancer cases were reported in the Hindu community, (3172 cases) constituting 82.7 percent of the total 3834 cases. A large number of cases were reported among children from Muslim (392 cases, 10.2%), and Christian (247 cases 6.4%) communities.

**Figure 1.** *Number of cases reported: 1982–2016.*


**Table 1.**

*Sex-wise distribution of reported cases (1982–2016).*


**Table 2.**

*Religion-wise distribution of reported cases 1982–2016.*

**Figure 2.** *Distribution of reported cases across the age groups (share in %).*

**Table 3** describes the distribution of different types of pediatric cancer reported during this period. The trend indicates that lymphoid leukemia is the most common type of cancer reported (1002 cases, constituting 26.1% of 3834 cases). Non-Hodgkin's lymphoma, Myeloid Leukemia, Hodgkin's disease, Brain Tumor, Eye Cancer, and other type's cancers.

**Table 4** shows that the pattern of reported cases changes across the years. Types of major cancer reported between different periods show that more number of cases were reported during 2007–2011 (639 cases, 16.7%). Major types include Non-Hodgkin's lymphoma (39 cases, 6.1%), brain tumor (29 cases, 4.5%), rectum cancer

*Trends of Pediatric Cancer in India DOI: http://dx.doi.org/10.5772/intechopen.106051*


#### **Table 3.**

*Major types of cancer reported 1982–2016.*

(37 cases, 5.8%), kidney cancer (33cases, 5.2%), and other cancers (219cases, 34.3%). The other categories of cancer include cancers of the Nose, Pinna, fingers, nasopharyngeal cancers, etc.

**Figure 3** shows the distribution of reported cases with their types and gender. The trend indicates that most types of cancer reported remain high among the male children, except myeloid leukemia (7.1%), eye cancer (4%), bone cancer (2.7%), liver cancer (1.2%), kidney cancer (4.1%) and other types of cancers (33.9%).

**Table 5** shows the incidence of different types of pediatric cancer for different age groups. More pediatric cancers are reported in 0–4 years of age (1417 cases, 37%) out of 3834cases. Which include myeloid leukemia (14.7%), eye cancer (6.4%), adrenal gland cancer (3.8%), liver cancer (2.3%), and multiple myeloma (1.5%). Compared to this, more cases of lymphoid leukemia (29.1%), non-Hodgkin's lymphoma (9%), Hodgkin's disease (7%), brain tumor (5.2%), rectum cancer (5.1%), testis cancer (2.3%), kidney cancer (4.2%), and unspecific leukemia (1.3%) were reported in 5–9 years of age. The number of cases reported on Bone cancer (2.5%), and other cancer (29.3%) was found high among the children 10–14 years of age.

The overall incidence of pediatric cancer has gradually decreased in Chennai during the period 2012–2016, compared to the previous years. Leukemia emerges as the most common pediatric cancer as indicated by many studies (**Table 4**). The results broadly follow some of the existing studies like the highest incidence occurring between 0 and 4 years of age (**Table 2**) and non-Hodgkin's disease exceeds Hodgkin's disease (**Table 4**) as reported in India between 2012 and 2014 (Suman


#### **Table 4.**

*Major types of cancer: Trends across specific intervals (share in %).*

Das et. al) [17]. Similarly, overall cancer in children is more common among males than females (Stiller C 2007; [18] Gurney JG. et al. 2006) [19]. Existing studies report that both Hodgkin's and Non-Hodgkin's disease had the highest incidence among 10–14 years age group for both sexes (Suman Das.et al. 2017) whereas the present study finds that the Non-Hodgkin's disease and Hodgkin's disease had the highest incidence among 5–9 years of age group (**Table 5**). Our analysis also highlights that brain tumor had the highest incidence among 5–9 years of the age group for both sexes (**Table 5**). Eye and liver tumors had the highest incidence among the 0–4 years age group while bone and gastrointestinal tumors had the highest incidence among the 10–14 years age group for both sexes (**Table 5**).

#### **Figure 3.**

*Sex-wise distributions of reported cases and types of cancer (share in %).*


#### **Table 5.**

*Incidence of pediatric cancer across age group (share in %).*

#### **4. Conclusion**

The analysis covers three thousand eight hundred and thirty-four cases of pediatric cancer registered at Madras Metropolitan Tumor Registry from 1982 to 2016.

Overall, the results indicate a gradual decline in childhood cancer during this period and indicate that maximum cases are reported during 2007–2011. The results confirm some of the established patterns including a higher incidence of cancer among male children (60.3%), and a high incidence among the children in 0–4 yearsage group. Leukemia is the most common pediatric cancer and it constitutes 27 percent in males and 25 percent in females. Overall cancers are more reported in the Hindu community, while specific types like myeloid leukemia, NHL, brain tumor, and multiple myeloma are found high in the Jain community. Lymphoid leukemia and rectum ca are more common in the Muslim community.

The pediatric tumor showed wide variation concerning different age groups. The genetic and environmental factors played role in the etiology of pediatric cancer. Most pediatric cancer is curable if it has been detected early. Thus, the study offers some important insights and updates on the pediatric cancer trends in the city of Chennai and may serve as a reference source for clinicians and researchers on pediatric oncology and policymakers engaged in public health.

### **Author details**

Sajna Panolan\*, Srinivas Govindarajulu, S. Kalpana, Valarmathi Srinivasan and Joseph Maria Adaikalam The Tamil Nadu Dr. M.G.R. Medical University, Chennai, Tamil Nadu, India

\*Address all correspondence to: sachusajnap@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### Section 2
