Evaluation of delays during diagnosis and management of lung cancer in India: A prospective observational study.

OBJECTIVE: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear. METHODS: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment. RESULTS: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival. CONCLUSION: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care.

Association of COVID-19 With Emergence of Comorbidities: A Hospital-Based Cohort Study.

BACKGROUND: In 2019, the emergence of SARS-CoV-2 marked the beginning of the COVID-19 global pandemic, which reached its peak in 2020. Initially designated as a novel coronavirus, SARS-CoV-2 emerged as a respiratory illness and later began causing multi-organ complications in recovered patients. METHODS: This article presents a hospital-based retrospective cohort study conducted via telephone interviews with patients in a tertiary hospital. After obtaining verbal consent from the subjects, the study utilized a semi-structured questionnaire to gather data. RESULTS: In the 54-person cohort group, 64.8% were males and 35.1% were females. The mean duration of the male patients' hospital stays was greater than that of the female patients. However, the mean lag time between the onset of comorbidities and recovery from COVID-19 was shorter in females than in males. Upon further analysis, it was revealed that female patients are more susceptible to the development of multiple comorbidities at once, occurring in 37.5% of the female patients in this study. Diabetes mellitus alone had the highest incidence rate (12.9%), followed by ST-elevation myocardial Infarctions (7.4%) and thrombocytopenia (5.5%). Of the cohort group, 51.8% developed comorbidities after exposure to COVID-19, while about 14.8% of the control group developed comorbidities from March 2020 onwards, i.e. from the commencement of the COVID-19 global pandemic. The relative risk assessed for this study is 3.5. The study's attributable risk is 71.42%. CONCLUSION: The incidence of comorbidities in the cohort group was greater than that in the control group, demonstrating COVID-19 as a risk factor for post-exposure comorbidities. It is clear that there is a direct association between COVID-19 and the development of comorbidities, which is inferred with a relative risk of 3.5.

Lung cancer in Asian Indian females: Identification of disease-specific characteristics and outcome measures over a 12-year period.

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India. Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females. Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males. Conclusion: Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes.

Prognostic factors for treatment response and survival outcomes after first-line management of Stage 4 non-small cell lung cancer: A real-world Indian perspective.

Background: Indian data on treatment outcomes and survival in advanced non-small cell lung cancer (NSCLC) remain scarce. Materials and Methods: A retrospective review of 537 advanced NSCLC patients treated at a tertiary care facility in North India from January 2008 to March 2018 was done to assess treatment response and survival in terms of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Median age of enrolled patients was 60 years (range: 26-89 years). The majority were males (78.2%) and smokers (66.5%). Adenocarcinoma (51.2%) was the most common pathological type. Most patients had good performance status (PS) (the Eastern Cooperative Oncology Group [ECOG] 0 or 1 in 55.7%) and received conventional chemotherapy (86.6%). ORR and DCR after 3-4 months of first-line treatment were 55.2% and 71.75%, respectively (n = 223). Never smokers had better ORR as well as DCR compared to chronic smokers whereas treatment with tyrosine kinase inhibitors achieved significantly better ORR, and patients with good PS had better DCR compared to those with poor PS. Median PFS (n = 455) was 7.0 months (95% confidence interval [CI]: 3.7-14.0) and median OS was 11.7 months (95% CI: 5.5-29.9 months). Good PS and nonsmoking status were independent predictors of better PFS on multivariate analysis. For OS, good PS, nonsmoking behavior, and treatment with epidermal growth factor receptor inhibitors were independent predictors. Conclusion: In advanced NSCLC, never-smokers, and patients with good baseline ECOG have favorable treatment and survival outcomes. Treatment with targeted therapy results in better ORR and OS but did not affect PFS.

Clinical profile of small-cell lung cancer in North India: A 12-year analysis from a tertiary care center.

Introduction: The small cell variant is a relatively uncommon but aggressive form of lung cancer. The present study aims to analyse the clinical characteristics, treatment outcomes and prognostic factors of an ambispectively enrolled large cohort of small cell lung cancer (SCLC) in the Indian population over a decade-long period. Materials and Methods: All patients diagnosed with SCLC between 2008 and 2020 at a tertiary care lung cancer clinic were included. The clinical details, demographics, details of investigations, treatment and survival outcomes were recorded and analysed. Results: A total of 361 patients were included. The majority were males (86.4%) with a mean (SD) age of 57.3 (12.3) years. Further, 34.9% were current smokers, with the median smoking index being 520 (interquartile range [IQR]: 260-1000). The majority had good performance status, that is, the Eastern Cooperative Oncology Group scale (ECOG) 0 or 1 (65%), and Karnofsky Performance Scale (KPS) ≥70 (85.9%). Also, 73.3% had extensive stage disease. The median time from symptom onset to definitive diagnosis was 91 days. Treatment details were available for 179 patients: chemotherapy only (n = 128), combined chemo-radiotherapy (n = 41) and radiotherapy only (n = 10). The median (IQR) progression-free survival (PFS) was 182 (94 to 306) days and the median (IQR) overall survival (OS) was 205 (94 to 429) days. On univariate analysis, factors that significantly affected survival included smoking index and performance status. However, on multivariate analysis, only the performance status significantly affected PFS, whereas none of these factors were significant for OS. Conclusions: SCLC predominantly affects males with a heavy smoking index. The diagnosis is usually made late; survival remains poor and is predominantly affected by the performance status.

Not just skin deep: Multiple cutaneous nodules as first presenting sign of small cell cancer.

A 65 years old male, chronic smoker (30 pack years), presented with complaints of dyspnea (mMRC grade2), cough (dry in nature), loss of appetite, loss of weight ( > 5 kgs), weakness, bony pains, feverish feeling and easy fatigability for last 2-3 months.Contrast enhanced CT chest showed bilateral extensive paraseptal and centriacinar emphysematous changes, right upper lobe spiculated heterogeneously enhancing soft tissue lesion and significant conglomerate mediastinal lymphadenopathy encasing lower trachea and great vessels.As patient was high risk for development of pneumothorax related to image guided sampling of right upper lobe lesion in view of extensive emphysema; patient was referred to us for EBUS-TBNA (endobronchial ultrasound guided transbronchial needle aspiration) guided mediastinal lymph nodes sampling. But on head to toe examination revealed round, firm, non-tender, skin coloured, 2-3 cm size skin nodules (2 on left lateral chest wall, 1 on right lateral chest wall and 1 in proximity to umbilicus).Fine needle aspiration cytology (FNAC) was attempted from two of skin nodules which was suggestive of small cell lung cancerSkin metastasis as initial presentation is reported rarely in small cell lung cancer.The index case emphasize on importance of detailed physical examination in cases of lung cancer to look for any skin manifestation of the disease, although encountered rarely.Moreover detection of skin nodules helps in staging and prognosis of diseases.

A randomized comparison of sample adequacy and diagnostic yield of various suction pressures in EBUS-TBNA.

INTRODUCTION: The evidence for using vacuum suction during EBUS is sparse and the optimal suction pressure for obtaining adequate samples has not yet been determined. Our aim was to assess the influence of suction on the adequacy and diagnostic yield of EBUS-TBNA. MATERIAL AND METHODS: This single-center, prospective, randomized, non-inferiority trial assessed whether no-suction and 10 mL suction are inferior to 20 mL suction for adequacy and diagnostic yield of EBUS-TBNA aspirates. RESULTS: Three hundred twenty three lymph nodes were sampled using EBUS-TBNA. Baseline characteristics of lymph nodes were comparable in the three suction groups. The overall adequacy of EBUS-TBNA aspirates in the no-suction, 10 mL, and 20 mL suction was 90%, 83.49%, and 77.88%, respectively. The differences in adequacy were 12.1% (95% CI: 3.9-20.3) and 5.6% (95% CI: -3.3-14.5) for no-suction vs 20 mL, and 10 mL vs 20 mL suction, respectively. No-suction and 10 mL were not inferior to 20 mL suction in terms of sample adequacy. At a superiority margin of 3.92%, no-suction was superior to 20 mL suction in terms of sample adequacy (p < 0.05). The overall diagnostic yield was comparable (63.6%, 52.3%, and 57.7% in 0, 10 mL, and 20 mL, respectively; p-value was not significant). The proportion of aspirates which were predominantly bloody was similar (no-suction - 10.9%, 10 mL - 13.8%, 20 mL - 15.4%; p = 0.62). CONCLUSIONS: EBUS-TBNA with or without the application of vacuum suction does not influence specimen adequacy and diagnostic yield.

A comprehensive comparison between young and older-age non-small cell lung cancer patients at a public referral centre in Delhi, India.

PURPOSE: Given the increasing number of non-small cell lung cancer (NSCLC) patients in India, a comparative analysis between patients under 40 years and those of older age at a major public referral centre would provide insight into the phenotypic patterns of this group. METHODS: NSCLC patients who were accessioned within the lung cancer clinic database of the Pulmonary Medicine Department at the all India institute of medical sciences - Delhi between 2008 and 2019 were reviewed. Patients 40 years or younger and 60 years or older were selected and categorised as young and older patients, respectively. Baseline clinical characteristics, histologic profiles, treatments administered and survival outcomes were compared between both groups. RESULTS: Following the database review, 154 young and 1,058 older patients were selected for inclusion. Clinically, young patients were more often female (26.0% versus 14.5%, p < 0.001), retained a more independent performance status (64.1% versus 45.5%; p < 0.001) and never smoked (63.7 % versus 18.8%, p < 0.001). Regarding disease profiles, young patients were more frequently diagnosed with adenocarcinoma (p < 0.001) and 12 young patients had adenoid cystic carcinoma. Rates of stage IV disease at presentation were higher among young patients (78.0% versus 63.0%, p < 0.001). Regarding treatment, no differences in systemic therapies administered or survival were identified. CONCLUSION: In India, young NSCLC patients are frequently non-smokers and diagnosed with advanced disease. Despite better performance status, young patients do not share better outcomes. Efforts should be directed towards optimising intensive treatment for young patients.

Mediastinal germ cell tumour masquerading as loculated pleural effusion.

Benign mediastinal teratomas often discovered while patients are still asymptomatic. Almost all arise in the anterosuperior mediastinal compartment. Most symptoms result from compression of adjacent structures. We report a case of a large teratoma arising from the anterior mediastinum that presented a confusing clinical picture of loculated pleural effusion which was successfully diagnosed and treated by surgical excision.

Knowledge, anxiety and the use of hydroxychloroquine prophylaxis among health care students and professionals regarding COVID-19 pandemic.

INTRODUCTION: Data regarding knowledge and attitude about COVID-19, the prevalence of acceptance of hydroxychloroquine prophylaxis and anxiety amidst COVID-19 pandemic among health care students/professionals in India is scarce. MATERIAL AND METHODS: A cross-sectional study was conducted during May 2020, using an online survey via Google forms. A self-administered validated structured questionnaire was applied, which comprised 28 questions among health care students/professionals at a tertiary care centrein North India. RESULTS: A total of 956 respondents were included (10.2% nurses, 45.2% medical students, 24.3% paramedical students, 11.7% resident doctors and 8.6% consultant doctors). Overall knowledge score was 9.3/15; the highest for preventive practices (4/5), followed by clinical knowledge (2.7/5) and the use of personal protective equipment (PPE) (2.6/5). The overall score was the highest in consultant doctors (10.8) while the lowest in nurses (8.5) and paramedical students (8.4) (p < 0.001). Less than half of the respondents had knowledge about the correct sequence of doffing PPE and the use of N95 mask. About 21.8% of the participants experienced moderate to severe anxiety; higher among nurses (38%), followed by paramedical students (29.3%); and anxiety was higher when knowledge score was low (27.6% vs 14.7%); both factors were independent predictors on multivariate analysis (p < 0.001). Only 18.1% of the respondents applied HCQ prophylaxis - the highest proportion constituted consultants (42.7%), and the least - paramedical students (5.2%); (p < 0.001) and HCQ use was more frequently used if they had a family member of extreme age group at home (23.3% vs 12.2%; p < 0.001). CONCLUSIONS: The knowledge about correct PPE usage is low among all groups of HCWs and students, and there is a high prevalence of anxiety due to COVID-19. The lower COVID-19 knowledge scores were significantly associated with a higher likelihood of anxiety and inadequate use of HCQ prophylaxis. The appliance of HCQ prophylaxis had no significant association with anxiety levels of the respondents.

Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: A real-world multicentric cohort analysis from India.

BACKGROUND: The development of various targeted therapies against Epidermal Growth Factor Receptor (EGFR) has been a major step in therapeutic advancements in lung cancer. However, the response to tyrosine kinase inhibitors (TKI) therapy in a real-world setting has not been well elucidated. METHODS: As part of a retrospective analysis, patients with EGFR mutated non-small cell lung cancer at 4 tertiary care Institutions in North India between December 2007 and August 2018 were evaluated. The overall response rate, disease control rate, progression-free survival (PFS) and factors affecting PFS were analyzed. RESULTS: A total of 483 patients were included, including 52.4% males, with mean (±SD) age of 56.7 (±12.4) years. Majority (63.8%) had good performance status (Eastern Cooperative Oncology Group 0 or 1) and 77.4% were nonsmokers. Among the EGFR mutations, exon 19 deletion was the most common mutation detected (68.1%), followed by L858R mutation in exon 21 (26.9%). Extra-thoracic metastasis was present in 69.5% patients and majority of them had ≤ 2 metastatic sites (85.1%). TKIs were used as the first-line therapy in 64.8% patients, and gefitinib was the most frequently used TKI (67.3%), followed by erlotinib (26.7%). The overall response rate and disease control rate were 65.9% and 90.7% respectively. The median PFS was 9.3 months and brain was the exclusive site of progression in 18.0% patients. On univariate analysis, the factors that significantly affected PFS were, the number of metastatic sites and the type of EGFR mutation. On multivariate analysis, the number of metastatic sites was the only factor that affected the PFS [HR (95% CI): 2.5 (1.7-3.6); Pvalue <0.001]. Skin toxicity was the most common adverse event (32.3%), followed by involvement of the gastro-intestinal tract (22.5%). CONCLUSION: In this one of the largest multicentric Indian study of treatment outcomes in EGFR-mutated non-small cell lung cancer in a real-world setting, we found that increased tumor burden (number of metastatic sites > 2) was the only significant factor associated with a worse PFS.

Clinical profile of lung cancer in North India: A 10-year analysis of 1862 patients from a tertiary care center.

INTRODUCTION: Over the past few years, the demographic profile of lung cancer has changed. However, most reports are limited by small numbers, short follow-up period, and show an inconsistent pattern. A comprehensive evaluation of changing trends over a long period has not been done. MATERIALS AND METHODS: Consecutive lung cancer patients were studied over a 10-year period from January 2008 to March 2018 at the All India Institute of Medical Sciences, New Delhi, and relevant clinical information, and survival outcomes were analyzed. RESULTS: A total of 1862 patients were evaluated, with mean (SD) age of 59 (11.1) years, and comprising 82.9% males. Majority were smokers (76.2%) with median smoking index of 500 (interquartile range [IQR]: 300-800). Adenocarcinoma (ADC) was the most common type (34%), followed by squamous cell carcinoma (SCC - 28.6%) and small cell lung cancer (SCLC) (16.1%). Over the 10-year period, ADC increased from 9.5% to 35.9%, SCC from 25.4% to 30.6%, and non-small cell lung cancer -not otherwise specified (NSCLC-NOS) decreased from 49.2% to 21.4%. The proportion of females with lung cancer increased although smoking rates remained similar. Majority of NSCLC (95%) continued to be diagnosed at an advanced stage (3 or 4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements were present in 25.3% and 11.5% ADC patients, respectively. The median overall survival was 8.8 months (IQR 3.7-19) for all patients and 12.57 (IQR 6.2-28.7) months among the 1013 patients who were initiated on specific treatment (chemotherapy, targeted therapy, radiotherapy, or surgery). Never-smokers were younger, more likely to be female and educated, had a higher prevalence of ADC and EGFR/ALK mutations, and had better survival. CONCLUSION: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival.

Guidelines for diagnostic flexible bronchoscopy in adults: Joint Indian Chest Society/National College of chest physicians (I)/Indian association for bronchology recommendations.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

The time required to diagnose and treat lung cancer in Delhi, India: an updated experience of a public referral center

Background: Delays that postpone the evaluation and management of malignancy may lead to considerable morbidity. The primary objective of this study was to assess the time required to diagnose and treat lung cancer at an Indian public referral center that predominantly serves lower-income patients. Methods: A review of patients diagnosed with lung cancer between January 2008 and December 2016 was completed. We computed the median time intervals and inter-quartile ranges between symptom onset, definitive diagnostic investigation, confirmed histologic diagnosis, and chemotherapy initiation. Median intervals were correlated with baseline demographics and disease characteristics using Kruskal-Wallis test. Results: One thousand, three hundred and-seventy patients were selected. A majority (94.5%) with non-small cell lung cancer were diagnosed with advanced disease. After developing symptoms, patients required 101 [56­168] days to undergo a definitive diagnostic study, 107 [60­173] days to confirm a diagnosis, and 126 [85­196.8] days to initiate treatment. Patients who were previously treated for tuberculosis required more time to receive chemotherapy compared to those who were not (187 [134­261.5] days vs. 113 [75­180] days, p < 0.0001). A specialty Lung Cancer Clinic was implemented in 2012, and the mean referrals per month increased nearly four-fold (p < 0.0001), but the time required to administer treatment was not shortened. Conclusion: Among lower-income Indian patients, the most prominent delays occur prior to diagnosis. Efforts should be directed toward encouraging physicians to maintain a high index of clinical suspicion and educating patients to report concerning symptoms as early as possible.