European Journal of Cardiovascular Medicine

Currently, Noncommunicable diseases (NCDs) accounts for most of the global deaths. Cancer probably ranks as the leading cause of death and the most critical barrier in decreasing life expectancy in the 21st century1.

According to estimates from World Health Organization (WHO) in 2015, cancer is the most common leading cause of death before age 70 years in 91 of 172 countries, and which ranks third or fourth in an additional 22 countries1.

Irrespective of sex, the most commonly diagnosed cancer is lung cancer (11.6% of the total cases) and also the leading cause of death (18.4% of the total cancer deaths). Next to this followed by female breast cancer (11.6%), colorectal cancer (10.2%), and prostate cancer (7.1%), stomach cancer (8.2%), and liver cancer (8.2%)2.

In males, lung cancer the most commonly diagnosed and the leading cause of death, followed by prostate and colorectal cancer for incidence, and liver and stomach cancer by mortality. Among females, Breast cancer the most commonly diagnosed cancer and the leading cause of death, followed by Colorectal and Lung cancer for incidence and reverse for mortality. 3 About the incidence and mortality, cervical cancer ranks fourth among all types of cancers. Lung cancer has two main subtypes, i.e., Small-cell lung carcinoma and Non-small cell lung carcinoma which accounts of about 15% and 85% respectively.4

The ionizing radiation which causes the localized release of energy to disrupt strong chemical bonds which in turn generates free radicals that are highly reactive. Cellular components such as peptides, lipids, and DNA all of which are affected directly or indirectly with the interaction of radiation. 5 Through various theories, radiation-induced lung injury was resulted from direct cytotoxicity upon normal lung tissue and more significantly the formation of fibrosis mediated by the number of various cytokines also triggered by cellular signal transduction process. 6

Pulmonary function tests (PFTs) are the non-invasive test that illustrates how well the lungs are functioning. These tests measure the lung volume, capacity, rates of flow, and gas exchange. Pulmonary function tests (PFTs), includes forced expiratory volume in one second (FEV1) and hemoglobin-level-adjusted carbon monoxide diffusing capacity (DLCO). PFTs are well established in assessing the lung damage in numerous diseases, including chronic obstructive pulmonary disease (COPD) and lung fibrosis. Lung function has been postulated to alter due to radiation; however, results are equivocal7. Mehta et al.

In his study stated that after radiotherapy FEV1 reduction was 12% or less and DLCO reduction was usually 13% or more from baseline. Furthermore, changes in PFT results may be used as surrogate parameters to assess Radiation-Induced Lung Toxicity (RILT), especially if changes can be predicted based on radiation dose-volume histogram (DVH) parameters, which in turn guide in radiation treatment planning. Such guidance might include choosing between a photon and proton-based therapy8.

Radiation-induced lung toxicity remains critical. Framing and adopting the objective measures of pulmonary toxicity are needed to prevent this toxicity and can individualize the patient treatment. The objective measures include the pulmonary function tests. According to the available literature, the data suggests that the pulmonary function declines post radiotherapy in a dose- dependent manner. Data quality and analyses were inadequate. Hence a number of research studies are required to analyze the data which in turn helps to improve individualization of advanced radiation therapy.

This is a Prospective and Observational Study was conducted among 25 patients admitted to The Department of Respiratory Medicine, at JJM Medical college, Davangere from April 2023 to March 2024.

Sample and selection of patients

A study of patients with non-small-cell Lung Carcinoma was included, with the below-mentioned Inclusion and Exclusion criteria.

Inclusion criteria

Histopathologically confirmed cases of non-small cell lung cancer cases. Eligible for undergoing Radiotherapy. Able to perform Spirometry. Able to undergo PETCT and others for Staging of lung cancer. Patients of any age with T1–2N0–1M0 (now defined as stage I/IIA) or T3N0M0 (currently defined as stage IIB) NSCLC, either considered not sufficiently fit for or declining surgery.

Exclusion criteria

Confirmed small cell lung cancer cases. Unable to perform Spirometry. Stages not come      under Radiotherapy modality as Treatment and also as a palliative.

Methods:

Once eligibility was verified, patients were included in the study after taking consent from patients and their relatives. Anthropological data like age, sex, height, weight was recorded. History was collected from the patients who were included in the study. Symptoms like Dyspnea, Cough (dry r non-productive),

Chest pain, Hemoptysis, Loss of Weight( >5% of the loss of body weight within 6months) with complete details like duration, aggravating factors, relieving factors, amount, diurnal r nocturnal variation, postural and seasonal variation etc. were collected.

To determine the Performance Score, we used the ECOG scale, which measures the overall functional performance of patients, the score on which is also an important therapeutic parameter. Patients are classified by score, which ranges from 0 to 4: 0 = asymptomatic; 1 = presenting with disease symptoms but able to perform activities normally 

2 = symptomatic and often requiring outpatient treatment; 3 = bedridden for more than 50% of the time; and 4 = completely bedridden32.

The 6MWT evaluates the maximum distance that the patients can walk in six minutes. The 6MWT was performed in a corridor, with a clear line of length 30m on the floor. During the procedure, the patients were instructed, through the use of standardized verbal encouragement once a minute, to walk at their fastest pace. Before and after the test, we recorded the following variables: Blood pressure; Heart Rate;

Respiratory Rate; SpO2; and degree of dyspnea, as determined by the Borg scale. The criteria for interrupting the test were following the guidelines of the American Thoracic Society40.

Spirometry was done for the patients who were stable, able to perform, not with unstable angina, not with active hemoptysis, etc. Inhaled bronchodilators and corticosteroids were withheld 4hrs before testing. Adviced cases not to wear tight clothing also anthropometric data were collected before the test. Also, clinical parameters like blood pressure, pulse rate, and saturation were recorded and documented.

Spirometry was done in comfortable seating or standing position and asked the patient to blow out the air completely before taking in the mouthpiece. The mouthpiece held airtight with lips and asked to blew completely and immediately asked to take in the air and stopped by taking out the piece. After an effort asked the

patient to sit relax for getting ready for next effort. Likewise best 2 efforts were considered, and short-acting bronchodilator was sprayed into his/her mouth and asked to sit for 15-20 min and again repeated the test as above.

Finally, 2 best efforts were considered, and software will analyze the data and report will be produced with the best efforts of lung volumes, curves, and reversibility also.

Statistical Analysis

Data were analyzed using SPSS version 29 software, and the results were expressed in the form of Mean ± Standard Deviation format. Independent T-Test was performed to rule out the significant statistical relation between variables to find out the effect of one/more variables over other. Also Paired P- Tests are done to find out the relation between before and after phenomenon among the same variables.

Age of Patients in the study group was from range 45 – 85years. The mean age of the study group was 63.12 with Standard Deviation (SD) of 9.615 Hence these were categorized into the following ranges to assess the distribution if the percentage of ages diagnosed with Non-small Cell Lung Cancers.

Table – 1: Age distribution of patients in the Study

Table-2: Sex distribution of patients in the Study

Among the study group out of 25 patients, 15 are Males, and 10 are Females. To express in percentages, 60% are males and 40% are females.

Table-3: Distribution of type of cancers in the study group

Table-4: Distribution of Mean and SD of lung volumes in the study group

Table-5: Distribution of Mean of lung volumes among histological subtypes

Among 25 cases from the study group, 10 cases were investigated to have the Obstructive pattern, and the remaining 15 cases showed Restrictive pattern based on spirometry findings as per GOLD criteria taking 70% as a baseline to differentiate. The mean of FEV1/FVC, FEV1, FVC among obstructive and restrictive patterns-

Table-6: Distribution of Mean of lung volumes in different spirometry patterns

Out of 10 cases, 6 cases have already had a history of COPD with Moderate to Severe and very severe obstruction. Among 15 cases with the restrictive pattern, 8 cases were presented to the hospital with Pleural Effusion.

After 3 months of Radiotherapy, again lung function was assessed for the patients by spirometry. 9 cases were lost follow-up. Among the remaining 16 cases, 9 cases were investigated as having the Obstructive pattern, and the remaining 7 cases had a Restrictive pattern. Also found follow-up cases were found to have loss of weight in 5 cases but as per Independent T-Test did not found any significant relation with Lung function.

Table- 7: Distribution of spirometry pattern in the study group

It was observed that in the obstructive pattern, improved FEV1/FVC, FEV1, FVC were observed after radiotherapy and in restrictive pattern reduced the above lung volumes observed. Data were analyzed using Paired P-Test and found a significant relation in FEV1/FVC, FVC with p-value <0.05.

Table - 8: Distribution of Means of lung volumes in different spirometry patterns

Data about lung volumes before and after radiotherapy were analyzed in cases with the past history of COPD, it was found that reduced lung volumes after radiotherapy. To derive statistical relation Independent P-Test performed shown significant P value. 6MWT also followed the same pattern as lung volumes after RT.

Table - 9: Distribution of lung volumes before and after RT in COPD history Cases

Similarly, data about lung volumes were analyzed among cases presented with pleural effusion and found a decrease in the mean of lung volumes after radiotherapy. Also, only 3 cases were able to follow up after RT out of 9 cases only. It was observed that a decrease in 6MWT in 2 cases and improvement of distance walked in 1 case with mass with effusion.

Table – 10: Distribution of lung volumes before and after RT in pleural effusion Cases

Among the study group, the 3 cases presented with Endobronchial mass has shown a significant increase in lung volumes after radiotherapy, and also similar pattern seen in distance walked in 6MWT.

Table - 11: Distribution of lung volumes before and after RT in Endobronchial Cases

Among 25 cases, 15 were diagnosed to be Adenocarcinoma type, and 10 were diagnosed to be as squamous cell type of Carcinoma, i.e., 60% of adenocarcinoma histological subtype were documented when compared to 40% of squamous cell sub type.

From the study, 10 cases were with FEV1/FVC < 0.70 and 15 cases were with> 0.70, i.e., 40% cases are with FEV1/FVC with the value less than 70% and 60% cases are with FEV1/FVC with value more than 70%. Out of 10 cases, 6 cases had a history of COPD and also on Inhaler treatment. Among them, 1 case was with FEV1/FVC > 0.70 and 5 cases with < 0.70. FEV1 in those cases were in the range of 47 – 79% predicted, 1 case which had FEV1/FVC >0.70 had FEV1 of 77% predicted with mild obstruction and cases with FEV1/FVC < 0.70 had FEV1 in the range of moderate obstruction. Forced vital capacity was in the range of 60 – 90 % ( P < 0.05).

Except for 2 cases with the history of COPD the other 4 cases with the history of COPD were diagnosed as Squamous cell carcinoma. According to A L Durham and I M Adcock in lung cancer journal titled the relation between COPD and Lung cancer found that Squamous cell type was the most commonly associated lung cancer subtype with COPD9-14. Also, mortality rate high in lung cancers with COPD when compared to without COPD disease and surgical intervention of tumor in COPD cases reduces Quality of life and also lung functions. Hence assessment of lung function is very important in those cases.

From the study, after radiotherapy in cases with COPD history, 2 cases had improved FEV1 and no significant change in FVC, but in the remaining cases, a Significant decrease in FEV1 noted along with little change in FVC. Also found the increase in Dyspnea grading scale observed after RT in 4 cases and as a regular investigation done in them observed radiographic infiltrates among 3 of them with fever and increased cough suspected to be Radiation pneumonitis of grade 3 pneumonitis based on SWOG scale needed oxygen supplementation.

From the study group, 9 cases were presented with pleural effusion, and among them, 6 cases are with presented to have a mass lesion in the parenchyma. After confirmed diagnosis, Thoracocentesis did, and the mass lesion was subjected for CT guided biopsy and cases without mass lesion were underwent thoracoscopy and tissue pleural biopsy done and confirmed.

Out of the effusion cases also all the cases were diagnosed as Adenocarcinoma subtype histologically which is the most common presenting as malignant pleural effusion. Supporting to the study according to Noriyoshi Sawabata, Akihide Matsumura et al., titled Malignant minor pleural effusion detected on thoracotomy for patients with non–small cell lung cancer: is tumor resection beneficial for prognosis? Observed 43 patients (45%) with malignant minor pleural effusion of which 4 cases (9%) were bloody and histologic diagnosis was also adenocarcinoma in 38 cases, squamous cell carcinoma in 4, and large cell carcinoma in 1 in their retrospective study15-19.

The obstructive pattern in chronic obstructive pulmonary disease patient’s after receiving radiotherapy was found to be worsened when compared to pre- treatment with RT may be due to lung toxicity developed on irradiation for upper lobe masses and lower lobes which were already with emphysematous that led to an overall reduction of lung volumes. Forced expiratory volume in 1 second per unit of vital capacity (FEV1/VC) presented an increase and decreased after radiation. All the patients in our study were found to be under grade 3 performance status according to Eastern Co-operative Oncology Group (ECOG). No patient had scored the status above 4. Concerning the obstructive pattern, the obstruction was found to be decreased after receiving radiotherapy in patients with endobronchial mass; this may be due to the reduction of the size of a tumor on irradiation of mass relieving dyspnoea and improved lung volumes. Conditions like Malignant effusions and all Peripheral mass lesions, it was observed that the restrictive pattern was found to be typically increased after receiving radiation. While in few patients the restriction was improved. This may be due to the baseline differences like the staging of the disease, radiation dose, and concurrent chemotherapy. A similar pattern was seen in 6minute walk test – It was observed that after receiving radiotherapy, a noticeable Improvement in distance walked who presented with endobronchial lesions in early stages of cancers whereas in other cases it was reduced.

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