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Deepali Jain
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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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EP1.01-17 - Predictors of Survival Outcomes with Chemotherapy in Advanced NSCLC Patients with Performance Status 2 and Above and Without Driver Mutation (Now Available) (ID 1287)
08:00 - 18:00 | Author(s): Deepali Jain
- Abstract
Background
Platinum-based combination chemotherapy is recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its benefit is limited to patientswith performance status (PS) of 0 or 1. However, it is not clear whether these benefits apply to patients with poor performance status (PS 2 and above) and there are no predictors of outcome to suggest whom to treat .This population accounts for a significant portion (up to 30%) of patients of our practice and some of them have been treated with systemic chemotherapy based on clinician’s discretion.We have analyzed the outcome of these patientswho have been treated with chemotherapy despite poor performance status.
Method
We performed a retrospective analysis of patients of advanced NSCLC with poor PS (ECOG PS 2 or more) registered at our lung cancer clinic between January 2016 and December 2017 and treated with systemic chemotherapy. Patients with driver mutations who were treated with first line TKIs were excluded. Hospital case records were reviewed for baseline characteristics, treatment details and outcome data. Patients who haven’t come to the hospital in last 3 months were contacted on phone.
Result
A total of 95 patients were found to be eligible for this analysis. Median age was 62 years (30-84 years, including 23(24%) patients 70 years or above. At presentation out of these 95 patients, 63(66%) were smokers,31(32%) had cytological proven pleural/pericardial effusion, 10(10.5%) patients had brain metastasis and 34(35.5%) had extra thoracic metastasis (≥2 sites).Majority(64%) patients had ECOGPS 2 but 36 % had PS 3 or 4 also and 44(46%) had one or more associated comorbidities. The most common chemotherapy regimen used was weekly paclitaxel and carboplatin(57.8%) followed by pemetrexed and carboplatin (16.8%).Majority (64%) patients could complete 4or more cycles of chemotherapy however 15 patients (15.7%) could receive only one cycle and 20(21%) patients even received maintenance chemotherapy. Chemotherapy was interrupted due to poor tolerance in 20(21%) patients and grade ¾ toxicity seen in 22(23%) % patients. At least one point improvement in ECOG PS from baseline was observed in 43 patients (45%) after 4 cycles of chemotherapy. Objective response and disease control rates were 20 % and 48.42% % respectively.Aftera median follows up of 8.6 months, median progression free survival was 6.2 months (95%CI 5-10.33).On univariate analysis ,neutrophil –lymphocytic ratio (<5 vs >5 )and induction regimen (weekly Taxol+Platinum vs rest) were significantly associated(p=0.02 and p= 0.04 respectively) with better median PFS
Conclusion
Systemic chemotherapy in modified doses and schedules in advanced NSCLC patients with PS 2 and above is feasible and may be associated with better symptom palliation with clinical benefit and improvement in survival.neutrophil –lymphocytic ratio (<5 vs >5 )and induction regimen (weekly Taxol+Platinum vs rest) are predictors of better median PFS . Further studies addressing this neglected subgroup are indicated.
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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): Deepali Jain
- 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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EP1.01-91 - Outcomes with Systemic Chemotherapy with Weekly Regimen in Advanced NSCLC Patients with PS 2 and Above and Without Driver Mutation (Now Available) (ID 1173)
08:00 - 18:00 | Author(s): Deepali Jain
- Abstract
Background
Platinum-based combination chemotherapy is recommended as the standard treatment for patients with advanced NSCLC, but its benefit is limited to patientswith performance status (PS) of 0 or 1. However, it is not clear whether these benefits apply to patients with poor PS( 2 and above)). These patients have inferior outcomes and have been excluded from clinical trials. We have analyzed the outcome of these patients who have been treated with weekly chemotherapy despite poor performance status.
Method
We performed a retrospective analysis of patients of advanced NSCLC with poor PS (ECOG PS 2 or more) registered at our lung cancer clinic between January 2016 and December 2017 and treated with weekly chemotherapy. Patients with driver mutations who were treated with first line TKIs were excluded. Hospital case records were reviewed for baseline characteristics, treatment details and outcome data.
Result
A total of 68 patients were found to be eligible for this analysis. Median age was 63.5 years (30-77 years, including 17(25%) patients 70 years or above. At presentation out of these 68 patients, 50(73.5%) were smokers,22(32%) had cytological proven pleural/pericardial effusion, 7(10.2%) patients had brain metastasis and 35(51.5%) had extra thoracic metastasis (≥2 sites). Majority(61%) patients had ECOGPS 2 but 39 % had PS 3 or 4 also and 29(42%) had one or more associated comorbidities. The most common chemotherapy regimen used was weekly paclitaxel and carboplatin(82.8%) followed by single agent paclitaxel(17.8%).Majority (63%) patients could complete 4 or more cycles of chemotherapy however 9 patients (13.2%) could receive only one cycle and 16(23%) patients even received maintenance chemotherapy. Chemotherapy was interrupted due to poor tolerance in 10(14.7%) patients and grade ¾ toxicity seen in 16(23%) % patients. At least one point improvement in ECOG PS from baseline was observed in 33 patients (48.5%) after 4 cycles of chemotherapy and objective response and disease control rates were 23.5 % and 50% % respectively. After a median follows up of 13 months, median progression free survival was 7.3 months.
Conclusion
Systemic chemotherapy in modified doses and schedules in advanced NSCLC patients with PS 2 and above is feasible and may be associated with better symptom palliation with clinical benefit and improvement in survival. Further studies addressing this neglected subgroup are indicated.
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EP1.15 - Thymoma/Other Thoracic Malignancies (ID 205)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.15-03 - SMARCA4-Deficient Thoracic Malignancies: A Unifying Genetic Aberration Across Tumors of Divergent Differentiation (Now Available) (ID 1614)
08:00 - 18:00 | Presenting Author(s): Deepali Jain
- Abstract
Background
Mutations in ATPase-dependant chromatin remodelling units are one of the most common genetic alterations observed in human cancer. Germline mutations in SMARCA4 encoding for Brg-1 protein, a subunit of the SWI/SNF chromatin modifier unit, are well recognised as the causative genetic event in rhabdoid tumor predisposition syndromes that occur in infants and young children. In recent years, somatic mutations in SMARCA4 have been increasingly identified in many adult-onset malignancies ranging from well differentiated carcinomas to poorly differentiated high grade sarcomas in a variety of anatomical sites, including thorax. Documentation of such tumors is essential to our understanding of the pathogenesis and possible mechanisms of therapeutic targetting.
Method
Case 1: A 60-year-old male smoker presented with chronic emphyema thoracis of non-tubercular etiology which was treated by intercostal drainage. He had repeated episodes of blockade of chest drain over the next 6 months and eventually a thoracic window was surgically created. Five months following thoracotomy, patient presented with a mass growing at the site of the thoracic window . No other masses in the lung parenchyma or mediastinal lymphadenopathy was seen. Patient underwent an excision of the granulation tissue-like mass. Formalin fixed paraffin embedded sections were subject to microscopy and immunohistochemistry for vimentin, CD34, MIC2, p53, SALL4, pan-cytokeratin (AE1/AE3), EMA, p40, TTF-1, cytokeratin-7, Hepar-1, desmin, myogenin, CD31, S100, Melan-A, HMB-45, GATA-3, calretinin, WT1, INI-1, brg-1 and hematolymphoid markers.
Case 2: A 58-year old male smoker presented with hemoptysis and cough. On evaluation, an endobronchial mass was identified and was excised. Formalin fixed paraffin embedded sections from excised tumor mass was subject to microscopy and immunohistochemistry for cytokeratin 7, cytokeratin 19, epithelial membrane antigen, chromogranin, synaptophysin, cytokeratin 20, CD117, TTF-1, NUT1, Her2neu, GATA3, p40, S100, INI-1 and brg-1.
Result
Case 1: Microscopy revealed a tumor centred in the soft tissue of the chest wall ulcerating the overlying skin. No lung parenchymal involvement was seen. The tumor was arranged in sheets composed of monomorphic large tumor cells with abundant eosinophilic cytoplasm and prominent nucleoli showing frequent mitoses and foci of necrosis. No squamous or glandular differentiation was seen. Tumor cells were only immunopositive for vimentin, CD34, MIC2, p53, and SALL4, very focally immunopositive for CK (AE1/AE3) and showed retained INI-1 protein expression. Brg-1 expression was lost in tumor cells leading to a diagnosis of SMARCA4-deficient thoracic sarcoma.
Case 2: Microscopy revealed a high grade tumor arising from the main bronchi with parenchymal and tracheal extension ulcerating the overlying squamous epithelium. Tumor cells were arranged in lobules with peripheral palisading and central necrosis. The tumor cells were large with frequent cytoplasmic clearing and frequent mitoses. Tumor cells were immunopositive for CK-7, CK-19, EMA, CG while were negative for others. INI-1 was retained while brg-1 was lost leading to a diagnosis of SMARCA4-deficient carcinoma.
Conclusion
Two independant studies have delineated SMARCA4-deficient thoracic sarcomas and SMARCA4-deficient lung carcinomas as distinct clinicopathological entities. Despite a unifying genetic alteration, these tumors appear to show varied histomorphology and immunoprofiles. Long term follow-up and molecular analysis of such tumors is necessary.
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EP1.15-19 - Primary Endobronchial Hyalinising Clear Cell Carcinoma Presenting in Association with Active Pulmonary Tuberculosis (Now Available) (ID 1619)
08:00 - 18:00 | Presenting Author(s): Deepali Jain
- Abstract
Background
Hyalinising clear cell carcinoma (HCCC) is a rare tumor of putative salivary gland origin that most commonly presents as an oral submucosal lesion in middle aged to elderly adults. With a characteristic histomorphology of infiltrating cords and nests of clear tumor cells set in a hyalinised stroma, these tumors frequently harbour EWSR1:ATF1 fusions, the latter serving as a useful diagnostic marker in differentiation from other clear cell-rich tumors. Only four cases with primary pulmonary origin have been previously reported, all of which were incidentally detected small (<3 cm) intrabronchial masses in non-smoking middle aged men. We report the fifth case in a 44-year-old non-smoker who presented with hemoptysis and was found to harbour a 3.5 cm intra-bronchial HCCC in association with active pulmonary and mediastinal tuberculosis.
Method
A 44-year-old male, non-smoker, presented with 2 episodes of hemoptysis. On imaging, a heterogeneously enhancing FDG-lobulated soft tissue mass was noted within the left lower lobe bronchus with lobar collapse. FDG avid nodular lesions were also seen in the left lower lobe parenchyma with enlarged aortopulmonary window and bilateral hilar lymphnodes. No pleural effusion was seen. There was no evidence of any metastatic lesions. He underwent an endobronchial biopsy from the left main bronchus followed by left lower lobectomy and mediastinal lymphadenectomy. Formalin fixed paraffin embedded tumor sections were subject to special stains for detection of acid fast bacilli and fungi, immunohistochemistry for p40, TTF-1, chromogranin, synaptophysin, epithelial membrane antigen, smooth muscle actin, S100 and smooth muscle myosin heavy chain, and fluorescence-in-situ hybridisation for 22q12 locus using the Vysis EWSR1 dual color, break apart rearrangement probe.
Result
Microscopic sections from the endobronchial biopsy revelaled a subepithelial tumor arranged in nests, cords and trabeculae within a densely hyalinised stroma. Tumor cells were monomorphic with clear to eosinophilic cytoplasm and occasional mitoses. Left lower lobectomy specimen showed a grossly circumscribed solid tumor in the wall of the left main bronchus abutting the cartilage and demarcated from adjacent lung parenchyma by a thin fibrous capsule. Tumor cells were immunopositive for p40, epithelial membrane antigen, while were negative for TTF-1, and myoepithelial markers. FISH revealed presence of EWSR1-re-arrangement in tumor cells, confirming the diagnosis of HCCC. Numerous mililary parenchymal and pleural nodules with necrotic caseous material containing acid fast bacilli were also seen, consistent with tuberculosis. Further work-up did not reveal presence of tumor elsewhere ascertaining a primary lung origin. Patient was started on anti-tubercular therapy and adjuvant radiotherapy/chemotherapy was not given. Patient is currently on follow-up
Conclusion
From the limited numbers reported, primary pulmonary HCCCs appear to be indolent slow growing neoplasms with an excellent outcome after surgical excision. The differential diagnoses include the commoner squamous cell carcinomas with clear cell change, clear cell adenocarcinomas, mucoepidermoid carcinomas, metastatic clear cell renal cell carcinoma, and myoepithelial neoplasms. Knowledge of its typical histomorphology aided by prudent immunohistochemistry and demonstration of EWSR1 gene rearrangement or more specifically, EWSR1:ATF1 fusion transcripts should lead one towards the correct diagnosis.
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MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
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MA18.12 - Discussant - MA18.09, MA18.10, MA18.11 (Now Available) (ID 3793)
11:30 - 13:00 | Presenting Author(s): Deepali Jain
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-02 - Pemetrexed-Carboplatin Versus Paclitaxel (Weekly)-Carboplatin as First Line Chemotherapy in Advanced Non-Squamous NSCLC (Now Available) (ID 2952)
09:45 - 18:00 | Author(s): Deepali Jain
- Abstract
Background
Platinum doublet chemotherapy has been standard of care in treatment naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutation until recent approvals of first line immune check point inhibitors. Pemetrexed-platinum combination has been preferred over other combinations in non-squamous NSCLC (ns-NSCLC). However there has been no direct comparison to Paclitaxel-carboplatin.
Method
This open label randomized control trial was designed to compare Pemetrexed-Carboplatin versus Paclitaxel (weekly)-Carboplatin combination in treatment naive advanced/metastatic ns-NSCLC without driver mutations and ECOG PS 0-2. The study was powered to detect superiority of Pemerexed-Carboplatin over Paclitaxel-Carboplatin by 15% in terms of 6 months PFS rates (primary outcome) and total 182 events were required for the same. Patients received either Pemetrexed 500 mg/m2 and Carboplatin AUC 5 every 3 weekly cycle for 4 cycles (with standard vitamin supplementation) or Paclitaxel 80 mg/m2 day 1, day 8 and day 15 with Carboplatin AUC 5 every 4 weekly cycles for 4 cycles. Patients in both arms were allowed to receive Pemetrexed maintenance in absence of progressive disease after 4 cycles. Patients, in whom EGFR mutation or ALK rearrangement were detected after randomization, were allowed to receive appropriate targeted therapy after 4 cycles or earlier as per physician’s discretion. The trial was approved by institute ethics committee and registered with CTRI (CTRI/2016/12/007605).
Result
A total of 180 patients were enrolled between April 2016 and January 2019. The study was terminated early due to slow accrual, however at the time of analysis (31stMarch 2019) total 129 events (70.8% of required) had occurred. Finally, 164 patients were evaluable, 83 in Pemetrexed-Carboplatin arm and 81 in Pacitaxel-Carboplatin arm. After a median follow up time of 15 months, PFS rates at 6 months were not different in two treatment arms (43.3% vs 43.2%; p=0.98). Median PFS were 5.63 months (95%CI 3.73-7.3) in Pemetrexed-Carboplatin arm and 5.03 months (95%CI 2.63-7.43) in Paclitaxel-Carboplatin arm (p=0.61; HR 1.09(95%CI 0.77-1.54). Median overall survival wasn’t different, 13.4 months (95%CI 8.6-17.63) and 10.13 (95%CI 7.6-19.7) respectively (p=0.11; HR 1.07(95%CI 0.71-1.61). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were significantly higher in the Paclitaxel arm.
Baseline Characteristics of the patients Characteristics Pemetrexed arm
N (%)=83Paclitaxel arm
N(%)= 81p Median Age 52 years (29-65) 52 years (28-65) 0.6 Gende
Males
Females56 (67.47%)
27 (32.5%)
58 (71.6%)
23 (28.4%)0.61 Smoking Status
Non smokers
Smokers45 (54.22%)
38 (45.78%)39 (48.15%)
42 (51.85%)0.5 ECOG PS
0
1
29 (10.84%)
51 (61.45%)
23 (27.71%)3 (3.7%)
57 (70.37%)
21 (25.9%)0.18 Histology
Adenocarcinoma
NSCLC- NOS83 (100%)
076 (95%)
4 (5%)0.039 EGFR mutation
Positive
Negative
Not available20 (24.39%)
47 (57.32%)
16 (19.2%)18 (22.2%)
48 (59.26%)
15 (18.52%)0.94 ALK rearrangement
Positive
Negative
Not available
08 (9.76%)
50 (60.98%)
25 (30.12%)07 (8.64%)
50 (61.73%)
24 (29.61%)0.66 Stage (AJCC 7th)
Stage 3B
Stage 402 (2.41%)
81 (97.59%)03 (3.7%)
78 (96.3%)0.59 Pleural/Pericardial Effusion
Present
Absent32 (38.55%)
51 (61.45%)27 (33.33%)
54 (66.67%)0.48 Brain metastasis
Present
Absent/ Not evaluated16 (19.28%)
67 (80.7%)16 (19.75%)
65 (80.2%)0.93
Conclusion
Pemetrexed-Carboplatin is not superior to Paclitaxel (weekly) -Carboplatin as first-line regimen in advanced ns-NSCLC in terms of 6 months PFS rates.
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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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P2.09-24 - IASLC Global Survey for Pathologists on PD-L1 Testing for Non-Small Cell Lung Cancer (ID 906)
10:15 - 18:15 | Author(s): Deepali Jain
- Abstract
Background
PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories.
Method
The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s).
Result
344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system.
Conclusion
There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally.
