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Prabhat Singh Malik
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 3
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-22 - Liquid Biopsy in the Detection of EGFR Activating and Resistance Mutations in Advanced Pulmonary Adenocarcinoma (Now Available) (ID 1761)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Approximately 30% of the advanced pulmonary adenocarcinoma (PADC) patients are found to be mutated with epidermal growth factor receptor (EGFR). Nearly 60% of EGFR mutated patients develop T790M resistance mutation against which third generation TKIs are available. Detection of T790M mutation is a challenge due to non availability of enough tumour tissues in patients receiving first-generation EGFR-TKI treatment. Liquid biopsies (cell- free DNA) are promising for detection of EGFR activating and resistance mutations. The current study focuses on detection of EGFR mutations in cell-free DNA from patients with histologically confirmed EGFR mutation status.
Method
50 PADC patients (22 males; 28 females with mean age 63 years) were studied for EGFR mutations. Out of them 40 were TKI naïve and 10 patients were treated with EGFR-TKIs. Follow up biopsy from TKI treated patients was not available for resistant mutation studies. Real-time PCR and Digital droplet PCR techniques were adopted for studying EGFR exon 19 (deletions), 20 (T790M) and 21 (L858R) mutations in tissue and plasma samples respectively.
Result
Clinically all patients were in stage III-IV and 52% were never smokers. Out of 40 TKI naive cases, 20 cases were positive for EGFR activating mutations in tissue and 17 in plasma. Twenty cases were negative for EGFR mutations in both tissue and plasma. In 10 EGFR-TKI treated patients, founder activating mutation was still present in plasma of 7 cases and 3 of them also showed T790M resistance mutation. Two patients carrying this resistant mutation died subsequently. Remaining three TKI treated patients did not harbour even founder activating mutation in the plasma.
Conclusion
We observed a concordance of 88% (44/50) between liquid biopsy and tumour tissue. Our study highlights role of liquid biopsy as an alternative for detecting EGFR activating and resistance mutations in advanced PADC. EGFR mutation analysis in liquid biopsy can be helpful in those patients where the tissue biopsy is not possible.
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EP1.01-71 - Thymidylate Synthase and Folate Receptor Alpha Expression as Potential Biomarkers for Efficacy of Pemetrexed in NSCLC (Now Available) (ID 1878)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Predictive biomarkers for chemotherapy in advanced non-squamous NSCLC are lacking. Thymidylate synthase (TS) and folate receptor alpha (FRA) are target enzymes for pemetrexed. Here we investigated TS and FRA expression and their role as a prognostic and predictive biomarker for efficacy of pemetrexed-based chemotherapy.
Method
We performed immunohistochemistry on pre-treatment tumour specimens for TS and FRA expression and correlated it with patient’s demographic and clinical characteristics, treatment responses and survivals in a retrospective training cohort of patients with advanced non-squamous NSCLC treated with pemetrexed-based chemotherapy. Similar analysis for validation was performed in a prospective cohort of patients participating in a randomized control trial “to compare efficacy and safety of pemetrexed-carboplatin versus paclitaxel-carboplatin as induction regimen in advanced non-squamous NSCLC”. Chi-square test was used to co-relate TS and FRA expression with clinico-pathological characteristics. Kaplan-Meier methods, Log-rank test and Cox proportional-hazards model were used for survival analysis.
Result
In the retrospective training cohort median age was 57 (26-70) years with male predominance (ratio=2:1). TS and FRA expression were evaluable in 55 and 47 patients respectively. In this cohort TS and FRA expression didn’t co-relate with best overall response rates (ORR), however, low TS expression and positive FRA expression were associated with improved progression free survival (PFS), albeit non-significant. In the prospective validation cohort median age was 52 (28-65) years with 70% males. In this cohort TS and FRA expression were analysed in 113 and 97 patients respectively. High TS expression was significantly associated with better ORR in patients treated with paclitaxel-carboplatin (p=0.04) but there was no co-relation of TS expression with response rates in pemetrexed-carboplatin group. Younger patients (age<40 years) had more TS ‘low or negative’ status (p=0.04). High TS expression was associated with ALK positivity (p=0.02), bone metastases (p=0.01) and brain metastases (p=0.002). Positive FRA expression was associated with EGFR positivity (p=0.004) and liver metastases (p=0.020). Positive FRA expression was associated with improved PFS in patients treated with pemetrexed-carboplatin (median: 9.23 versus 4.27 months, p=0.01), paclitaxel-carboplatin (median: 10.87 versus 6.47 months, p=0.08) as well as improved OS (median: OS not reached versus 10.13 months, p=0.01), especially in patients treated with pemetrexed-carboplatin (median: 18.73 versus 10.46 months, p=0.08).
Conclusion
In conclusion, the results from this study suggest that TS or FRA expression doesn’t predict efficacy of Pemetrexed, however, high TS expression may predict better ORR in patients receiving paclitaxel-carboplatin. FRA expression may serve as a prognostic factor in patients receiving chemotherapy irrespective of the regimen.
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EP1.01-77 - Locally Advanced Non Small Cell Lung Cancer - Treatment Outcome in Real World Setting (Now Available) (ID 1626)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Lung cancer is one of the leading cancers in India. About two-thirds present in advanced /metastatic stage. The mainstay therapy for advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation. Locoregional failure constitutes the predominant failure pattern.
A larger proportion of the patients are treated with palliative intent. The current study evaluates the demographic profile, treatment pattern, and outcome and radiation practice for palliative treatment at a tertiary care academic medical institution.
Method
Medical records of patients treated between June 2016- June 2018 were evaluated Clinical presentation, treatment details and outcome was recorded. Case records with incomplete workup or treatment was excluded.
Result
A total of 181 patients of NSCLC were registered of which 108 were metastatic at presentation 96 patients received palliative radiotherapy and are analysed. 11 patients has pulmonary metastasis and 85 had extrapulmonary metastasis of which 21 patients had multiple extrapulmonary disease.
Ninety-six patients received palliative radiotherapy. 84 patients had ≤ 1comorbidity. Most of the patients were aged ≤65years (80%) with a female preponderance. Cough, chest pain and dyspnea each were present in one-third of patients. Twenty-six patients had bony pain, 18 had symptoms of raised intracranial pressure and 7 patients had SVCO.
Adenocarcinoma was the commonest histology observed in 86.4% patients. Bone was the most common site of metastasis, seen in 65(65.7%) patients; followed by brain in 23(24%).
Palliative radiotherapy was given to primary in 13(13.5%), brain in 27(28%), bone in 56(58%). Palliative radiotherapy to weight bearing sites was treated with 8Gy in single fraction. Whole brain radiotherapy was treated with 20Gy in 5 fractions. 65% of patients received palliative chemotherapy. Platinum- taxane and platinum- pemetrexed regimens were the most common regimen practiced for among squamous and adenocarcinoma histology respectively. Median follow up was 6.6 months (2 to 37 months). Median time for oncological intervention was 1.2 months (0.1 to 5.4months). Median PFS was 6months (IQR 3- 11.2months)
Conclusion
The study concludes that a large proportion of patients present in advanced/metastatic disease. In the metastatic setting bone metastasis was the most common site followed by brain. The outcome is dismal and newer treatment techniques /modalities may result in improved outcome in this group of patients.
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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-20 - Diagnostic and Prognostic Utility of Differentially Expressed Circulating MicroRNAs in Indian NSCLC Patients (Now Available) (ID 875)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
The presence of circulating tumour DNA, mRNA and non-coding RNAs, such as microRNA (miRNA), in the serum and plasma of cancer patients has sparked great interest because conventional diagnostic tests tend to be imperfect and more invasive, posing logistic difficulties for serial tumour sampling. Hence, identification of differentially expressed circulating miRNAs in the serum of non-small cell lung cancer (NSCLC) patients may have potential as cancer biomarkers for diagnosis, prognosis and predicting therapeutic response.
Method
For the identification of differentially expressed miRNAs in the serum of NSCLC patients, we performed small RNA sequencing with illumina HiSeq 2000 platform (n=10; 4 NSCLC patients and 6 controls). The expression profile of miRNAs in each subject was analyzed using miRNAkey software and fold change was performed to identify differentially expressed miRNAs in NSCLC as compared to controls. We validated the expression of few differentially expressed miRNAs in the serum of 75 NSCLC patients and 40 controls using miScript qRT-PCR assay. The expression of miRNAs was correlated with overall survival (OS), progression-free survival (PFS), response to therapy and various clinico-pathological parameters.
Result
The mean age of NSCLC patients and controls was 56.2 years and 55.3 years, respectively (p = 0.3242). Majority of the NSCLC patient and controls were male. 67% of NSCLC patients and 53% of controls were smokers (p = 0.099). Global miRNA profiling revealed 16 differentially expressed miRNAs (cut-off: fold change > 2.0, or p < 0.05, or both) in the serum of NSCLC patients as compared to controls. Our qRT-PCR data revealed significant down-regulation of miR-15a-5p, miR-320a, miR-25-3p, miR-192-5p, let-7d-5p, let-7e-5p, miR-148a-3p and miR-92a-3p in the serum of NSCLC patients as compared to controls. None of the miRNAs were correlated with survival outcome and therapeutic response. The expression of miR-320a, miR-25-3p and miR-148a-3p significantly correlated with stage, while miR-375 expression significantly correlated with lymph node involvement and pleural effusion.
Conclusion
The expression of majority of miRNAs was down-regulated in the serum of NSCLC patients as compared to controls. Some of the miRNAs, such as miR-375 and miR-320a, are less studied for their involvement in the pathogenesis of NSCLC. Hence, future mechanistic studies are warranted to elucidate their role in disease biology and as candidate biomarkers for diagnosis and prognosis of NSCLC.
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EP1.17 - Treatment of Early Stage/Localized Disease (ID 207)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.17-13 - Operated Stages I-IIIB NSCLC Among Young Indian Cohorts - Clinical Profile and Outcomes (Now Available) (ID 2233)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Lung cancer is the third highest cause of mortality in India. Young lung cancers are on a rise and the characteristics of operable NSCLC among these group needs evaluation. We aim to compare the differential risk factors of Indian young NSCLC patients compared to the older group who underwent resection.
Method
A retrospective analysis of NSCLC patients operated from May 2012 to December 2018 at DR.BRAIRCH, All India Institute of Medical Sciences, New Delhi,India. Patients were divided into two groups, group (Gp)-YON includes young patients (defined as age 50 years or less) and Gp-OLD includes those older than 50 years. Factors analysed were demographics, histology, stage, disease free survival(DFS) and overall survival(OS) rates.
Result
A total of 143 patients of NSCLC underwent resection (including those post neoadjuvant chemotherapy). Gp-YON includes 37 (26%) and Gp-OLD 106 (74%) patients. Significant differences were observed between Gp-YON vs GP-OLD among non-smokers 40% vs 26% (p=0.025). Young females were higher in number 27% vs 18% but was insignificant (p=0.229). Other factors between the two groups like performance status(ECOG-2) 5% vs 4% (p=0.297), histologic subtypes(p>0.05)-squamous cell carcinoma(49% vs 55%), adenocarcinoma(38% vs 43%) and NSCLC(not otherwise specified) (2% vs 4%) did not reach statistical significance. The distribution of cases in various stages were stage IA(13% vs 18%), IIA (24% vs 17%), IIB (18% vs 16%) , IIIA 35% vs 36%) and IIIB (10% vs 13%). Stage for stage evaluation was insignificant(p>0.05). Family history, FEV1, intraoperative blood loss, postoperative complications, chest tube drainage and postoperative hospital stay were also insignificant (p>0.05). Distant metastases was lesser in Gp-YON (27% vs 16%, p=0.046). Median follow up was 40.7 months (95%CI 29.7-47.2).The median DFS in Gp-YON (23.3 months, 95% CI: 17.1-28.5) was higher than Gp-OLD (13.6 months, 95% CI: 10.1-15.3). Median OS in Gp-YON (38months, 95% CI: 32-45) was also higher than Gp-OLD (24months, 95% CI: 19-27). Only independent adverse prognostic factor was NACT(neoadjuvant chemotherapy) (HR,2.254, CI:0.98-5.15,p=0.050).
Conclusion
The number of young operable lung cancer is increasing in India (26%). Non-smokers contribution is significant. Incidence among young females is slightly higher. Patients receiving NACT has an adverse prognosis. Histologic type has no predilection to young age. No survival difference among young compared to old with respect to TNM substages. Distant metastases is lesser in young. Short-term follow up shows that overall young patients have a better DFS and OS as observed from our study.
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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-25 - Definitive Radiotherapy in Lung Cancer – A Glimpse Over the Narrow Window (ID 2128)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Lung cancer is one of the leading global malignancies. Locally advanced NSCLC (LA-NSCLC) comprises of a significant proportion of patient burden. Despite advances in the treatment definitive radiotherapy is delivered only to a small proportion of patients.
The current study was carried out to analyze various factors associated with change of curative treatment plan to palliative treatment at a tertiary cancer Centre
Method
Medical records of patients of LA-NSCLC lung cancer treated between June 2016 to June 2018 were evaluated. Clinical presentation, evaluation, treatment details and outcome were recorded. Patients who were not eligible for radical treatment were excluded. All patients were taken for radical treatment but could not receive definitive radiotherapy were analyzed
Result
Of 67 patients of LA-NSCLC 8 patients that were non metastastic were planned for upfront palliative intent.25 patients needed change in their treatment plan to palliative treatment. Majority of them were ≥ 65years. Median number of chemotherapy cycles was 2 (0-6). Patients were assessed after 2 cycles of chemotherapy for concurrent chemoradiation as our institute practice. Patients were assessed at the end of 2nd chemotherapy. Reasons for ineligibility was noted and categorized into patient, tumor and treatment factors.
Factors for change in treatment plan were divided as (i) Patient related factors included, treatment defaults, poor compliance, financial and social reasons, ECOG performance status at the end of chemotherapy, comorbidities, which accounted for 30.3%. (ii)Tumor related factors included, disease progression, poor response to chemotherapy, which accounted for 54.5%. (iii)Treatment factors included ,risk of toxicity due to large volume disease, volume not able to cover in one radiotherapy portal, poor respiratory reserve, which added up for remaining 15.2% of patients.
Palliative radiotherapy to primary tumor alone was delivered in 25 patients,5 patients received palliative radiotherapy to primary and brain2 patients received palliative radiotherapy to bone and I received radiation to brain alone.
The median time to diagnose and stage was 0.65months (0.06 to 3.6 months). Median time to start chemotherapy was 0.8 months (0.16 to 7.3 months).
Conclusion
Eligibility for definitive radiotherapy is a dynamic decision which need to be reviewed at every stage of treatment. Timely radical intervention need not necessarily translate into radical radiotherapy. Feasibility of definitive radiotherapy pass through a narrow window and multiple factors play pivotal role in it.
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EP1.18-26 - Treatment Patterns and Clinical Outcomes in Locally Advanced Non Small Cell Lung Cancer: Experience from Tertiary Care Centre (Now Available) (ID 42)
08:00 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Lung Cancer comprises a significant global cancer burden.About two-thirds patients with non small cell lung cancer, present in advanced/metastatic stage, of which the locally advanced group account for 30%.Combined modality approach with definitive chemoradiation is feasible in only a small proportion of patients. Several factors play a role in deciding the treatment and outcome In developing countries access to cancer centres and waiting period for oncological intervention and radiation therapy also significantly affect the management.The current study evaluates the demographic profile, treatment pattern, outcome and Radiotherapy practice and patient care at a tertiary care academic medical institution.
Method
Archives patients of locally advanced Non Small Cell lung cancer(LA-NSCLC) treated at our centre between, June 2016-June 2018 were included in our study. Clinical , demographic characteristics, treatment patterns, outcomes was recorded. Radiotherpy practice and patient care process including integration of radiation therapy with other specilities,waiting time, compliance to treatment was documented. Case records with incomplete work up or treatment was excluded. Univariate and multivariate analysis of factors on survival and overall survival was analysed.
Result
174 patients were treated during the study period. The distribution as per histology include Squamous cell carcinoma 54, Adenocarcinoma 108,Others (adenosquamous,poorly differentiated) 12. The median age was 57 years(35-84) with male preponderance .Only 67 patients belonged to locally advanced group and remaining 107 presented with metastastic disease. 59 patients of LA-NSCLC group were planned for definitive chemoradiation comprising of two cycles of induction chemotherapy followed by concurrent chemoradiation. 34 patients eventually underwent the planned treatment.The reason for conversion to palliative radiotherapy included disease progression during induction chemotherapy(18),poor performance status(7),large volume disease and risk of toxicity with radical dose ,defaulters(3). Median follow up was 11 months (range 0.7-29), overall survival 9.4 months(range 1.7-44.8). Median overall treatment time was 44 days.Progression free survival 8.9 months(range 1.6-28.6).Time to start any oncological intervention was 1 month(0.1-4.3) and time to start radiotherapy was 2.1 months(0.1-5.4). Adherence to treatment was 91.2%.Age ≥65 and performance status ≥2 were significant for overall survival in univariate analysis but did not confer any significance in multivariate analysis.
Conclusion
The study concludes that more than 60%of patients with Non small cell lung cancer present with metastatic disease. Only about a third are suitable for definitive chemoradiation and eventually only 20% undergo the planned treatment. Adherence to treatment is good in definitive setting
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-48 - Whole Exome Sequencing (WES) in Non-Small Cell Lung Carcinoma (NSCLC): Identification of Novel Biomarkers (Now Available) (ID 1712)
09:45 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Significant advancement has been made in the treatment of patients with pulmonary adenocarcinoma (ADC) on the basis of the molecular profile. However, no such molecular target exists for squamous cell carcinoma (SCC) or small cell lung cancer (SCLC). WES has been in wide use for the discovery of new genetic markers, which may offer more information for the development of personalized medicine for all subtypes of lung cancer. The aim of the current study is to find out novel genetic markers for NSCLC which can be used as a universal biomarker for the treatment.
Method
WES of 20 advanced NSCLC patients (10 ADC and 10 SCC) was done on the Illumina HiSeqX10 with paired end 151bp chemistry. The Male: female ratio was 5.6:1 and a median age 56 years. Only 3 patients were non-smoker and in one case smoking history was unknown. 75% of patients were present with co-morbidities, all patients were either in stage III or IV and performance status was either 1 or 2.
Result
Table 1: WES data statistics and the total number of variants identified: S.No WES data Numbers 1 Average raw data 13.6 GB 2 Average processed data 12.1 GB 3 Average reads aligned 80.2% 4 Average total variations 34173 5 Average SNPs 26030 6 Average INDEL 81423 7 Average frameshift deletions 2185 8 Average frameshift insertions 3571 9 Average non-frameshift deletions 368 10 Average non-frameshift insertions 1292 11 Average non-synonymous 13418 12 Average stop gain 10337 13 Average stop loss 38 14 Average synonymous SNPs 11607 15 Average variations reported in databases 20269 16 Unknown mutations 659 WES data statistics has been depicted in table 1 including number of variants identified. After excluding common variants (MAF > 0.05), a total of 23 rare variants (0 < MAF < 0.01), possibly linked to lung carcinoma was identified in the exome. Further stringent filtering showed allele frequencies of mutations in GPRIN2 (G protein-regulated inducer of neurite outgrowth 2), KCNJ18 (potassium voltage-gated channel subfamily J member 18) and TEKT4 (Tektin 4) genes which were present in all the cases. The variations of amino acid substitutions were i) TEKT4: p.A223T and p.A405T (rs75603622); ii) GPRIN2: p.V241M (rs9422022), p.V47M (rs3127819); iii) KCNJ18: p.L211F (rs1435776313), p.I262S (rs1450551937)
Conclusion
Although the mechanism of GPRIN2, KCNJ12 and TEKT4 in tumorigenesis is unclear; our results suggest that these may play a major role in NSCLC and it is worth to be investigated in future. Validation of these genes is under process.
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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-11 - Dose Dense Paclitaxel and Carboplatin as Neoadjuvant Therapy for Resectable/Borderline Resectable NSCLC - A Phase II Trial (Now Available) (ID 1604)
09:45 - 18:00 | Author(s): Prabhat Singh Malik
- Abstract
Background
Neoadjuvant chemotherapy in locally advanced NSCLC is controversial. Available data suggest modest benefit and ideal regimen is unknown. Dose dense approach has not yet been tested in neoadjuvant setting.
Method
This phase II trial tested a novel approach of dose dense paclitaxel at 80mg/m2on d1, d8, d15 with three weekly carboplatin at AUC-6 for 4 cycles. Only patients with ECOG PS 0-2 with non-bulky N2 (defined as single lymph node < 2cm or multiple LNs or conglomerate, all < 2cm) were included in the study. Response assessment was done after two and four cycles. Primary end point was objective response rate. Relative dose intensity was calculated to define safety and tolerability. Secondary end points included progression free survival (PFS) and recurrence free survival (RFS) for patients who underwent surgery. IEC approved the study and the trial was registered with CTRI (ref no-CTRI/2016/05/006916).
Result
A total of 33 patients were included in the study. Male to female ratio was 1.75:1. The median age was 54 years (40-78) and majority were smokers (78.8%). Most common histology was squamous cell carcinoma (57.6%) followed by adenocarcinoma (36.4%). Sixteen patients (48.48%) had N2 disease by PET out of which only three were TBNA positive, all were non bulky (<2cm). Around 76% of patients were able to complete the planned 4 cycles of treatment with only one patient having CTCAE ver 5 grade ¾ toxicity. Objective response rate was 61.3%. Relative dose intensity of 80.25% was maintained in patients who completed 4 cycles. Around 58% patients required dose modification, most common reasons included peripheral neuropathy (47%), myalgia (16%), diarrohea (10.5%) and neutropenia (10.5%). A total of 138 grade ½ toxicity events were reported in the study over 12 courses of chemotherapy, with nausea (48.5%), myalgia (42.4%), neutropenia (30.3%), peripheral neuropathy (27.3%) and diarrhea (27.3%) being the most common. Thirteen patients underwent surgery with majority undergoing lobectomy (77%). After a median follow-up time of 19.3 months, median PFS was 11.1 months (95%CI 7.26-18.16) and median overall survival was 26.63 (95% CI 15.03-NR). TNM stage on CT/PET and PET response to NACT significantly correlated with progression free survival on univariate analysis. In patients who underwent surgery, median RFS was 17.36 months (95%CI 6.5-31.86) and 2 year RFS rates were 25%.
Conclusion
Dose dense therapy with paclitaxel/ carboplatin is feasible, safe and efficacious and can be considered for N2 negative/ low node burden patients.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-06 - Epidermal Growth Factor Receptor (EGFR) Mutation Spectrum in Pulmonary Adenocarcinomas: Indian Experience (ID 2447)
10:15 - 18:15 | Author(s): Prabhat Singh Malik
- Abstract
Background
Incidence of lung cancer is rising in India, which is the major cause of mortality worldwide. The identification of EGFR mutations and ALK fusions in lung cancer has changed the treatment paradigm. The use of tyrosine kinase inhibitor (TKI) is now well established in clinical practice as it improves treatment outcomes. Molecular testing using tumor tissue is the gold standard for targeted therapies. The aim of the present study is to analyze the exact frequency of EGFR activating, rare and coexisting mutations in pulmonary adenocarcinoma (ADC).
Method
A total of 783 ADC (755 biopsies and 28 cytology aspirate smears) cases were studied. The male: female ratio was 1: 0.3 with age ranging from 20 to 78 years. During grossing, two tumor blocks were made, one for immunohistochemistry studies and other for mutation testing. In high- cellularity, low- tumor fraction cases, tumor enrichment was done by manual microdissection. We used more than one aspirate smears/biopsy blocks in cases with low- cellularity, high- tumor fraction. Probe-based real-time PCR (RT-PCR) technique was used to analyze EGFR hotspots mutations (exons 18 to 21). Before proceeding for molecular testing, histo/cytomorphology, tumour content and DNA quality were determined. For checking the quality of DNA, RT-PCR was done using wild type EGFR exon 2 primers.
Result
About 99% cases passed through the quality check of DNA and only 1.02% (8/783) cases failed. Overall, 234 patients (29.8%) were positive for EGFR mutations. The distribution of different types of EGFR mutations is shown in the Table 1. The common EGFR mutations were Exon 19 del and Exon 21 L858R which were equally distributed between both the genders. The EGFR mutations were more in non-smokers. T790M was present at baseline in around 3% TKI naive cases and it coexisted mostly with Exon 19 del. Cytological smears also showed EGFR mutations in the same pattern as tissue biopsies and a concordance was seen in cases where matched tissue and cytology smears were available.
Table1: EGFR mutation spectrum in pulmonary adenocarcinomas
EGFR Exon
Percentage
Single Mutations = 89.7% (210/234)
EGFR most common mutations
Exon 19 del
61.5%
Exon 21 L858R
29.1%
EGFR TKI resistant mutation at baseline
Exon 20 T790M
2.8%
Rare EGFR Single Mutations
Exon 18 G719X
2.4%
Exon 20 S768I
1.4%
Exon 21 L861Q
1.4%
Exon 20 Ins
1.4%
EGFR double mutations = 10.2% (24/234)
Common double mutations
Exon 19 del: Exon 20 T790M
11
Exon 19 del: Exon 21 L858R
5
Rare double mutations
Exon 18 G719X: exon 20 S768I
2
Exon 21 L858R: exon 20 S768I
2
Exon 20 T790M: Exon 18 G719X
1
Exon 20 T790M: Exon 20 Ins
1
Exon 19 del: Exon 21 L861Q
1
Exon 19 del: Exon 18 G719X
1
Conclusion
With judicious use and triaging of lung cancer diagnostic specimens, it is possible to perform successful mutation testing in >98% cases. EGFR mutation was positive in about a third of ADC including rare, TKI resistant and coexisting mutations in approximately 10% cases which may have significant therapeutic implications. In patients with limited amounts of tissue, cytology samples can be used for EGFR mutation testing as a promising alternative.
