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Shaf Keshavjee



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    MA22 - New Therapeutics, Pathology, and Brain Metastases for Small Cell and Neuroendocrine Tumour (ID 925)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 206 BD
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      MA22.06 - Preinvasive Multifocal Neuroendocrine Lesions with Primary Typical Carcinoid Lung Tumors: A Negative Prognostic Factor? (ID 12432)

      15:50 - 15:55  |  Author(s): Shaf Keshavjee

      • Abstract
      • Presentation
      • Slides

      Background

      Impact on survival in patients with surgically resected multifocal neuroendocrine lesions (MNET), such as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) or tumorlets, along with primary typical lung carcinoid (TC) is unclear. Aim of this study is to analyze whether synchronous preinvasive multifocal neuroendocrine lesions of the lung with primary TC tumors (MTNET+TC) may represent a negative prognostic factor.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective study, prospectively collected, for TC from two institutional databases was evaluated with a lifelong follow-up from surgery. Patients who did not receive surgery, underwent bronchial resection or lung transplant were excluded. Pathology specimens were all reclassified according the 2015 WHO and the eight AJCC Staging system. Kaplan-Meier(KM) method and Log-rank test reports significance between TC and were MTNET+TC were used. Hence a 1:1 propensity score matching analyses was done by adjusting the imbalance and comparing the overall survival and progression free rate between matched groups with a Cox proportional hazards regression model. A p value of 0.05 or less was considered significant.

      4c3880bb027f159e801041b1021e88e8 Result

      From January 1983 to December 2013 a total of 234 patients was outlined from the databases (TABLE). A total of 41 patients (17.5%) with MNET+TC were identified. Overall KM progression free survival achieved at 5 and 10 years respectively MNET+TC 93.2% and 83.8% compare to TC 98.4% and 96.1% (p =0.00039). Thirty-six MNET+TC were matched pairs vs. TC alone. Univariate Cox proportional hazards model for matched patients MNET+TC compared to TC was 2.78 (95% CI=0.84-9.3, p=0.095). Difference in progression free rate between matched groups was p<0.001.

      table_net_daddi.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Synchronous multifocal neuroendocrine preinvasive lesions (MNET) with primary typical carcinoid (TC) lung tumors can be a negative prognostic factor. Careful search of MNET should be always performed in clinical and pathological staging of a suspected primary TC. The increased risk of progression of MNET+TC warrants an accurate and lifelong follow-up.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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      OA11.06 - Two BRM Promoter Polymorphisms Do Not Predict Susceptibility or Prognosis of Thymoma (ID 12745)

      14:25 - 14:35  |  Author(s): Shaf Keshavjee

      • Abstract
      • Presentation
      • Slides

      Background

      Brahma (BRM) is a critical protein subunit in chromatin remodeling, and insertions/deletions at its two polymorphic promotor sites (BRM-741 and BRM-1321) have been reported as susceptibility and/or prognostic markers in lung, head and neck, esophageal, pancreatic, and liver cancers. There is also early evidence of potential association with immune-related diseases such as ulcerative colitis and rheumatoid arthritis. As epigenetic silencing of BRM can be pharmacologically reversed, BRM polymorphisms in cancer might have therapeutic implications. Thymoma is a unique cancer in that it has immunological disease associations. We evaluated whether BRM-741 and BRM-1321 polymorphisms influence overall risk, survival, and time-to-progression of thymoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Thymoma cases and matched healthy controls were recruited in a comprehensive cancer centre. Study participants’ peripheral blood samples were collected and genotyped for BRM promoter polymorphisms. Multivariable logistic regression assessed risk of thymoma in case-control analyses. Association of BRM variants with overall survival (OS) and time-to-progression or recurrence (TTP) was assessed by multivariable Cox regression.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 237 cases of histologically diagnosed thymoma and 948 age- and gender-matched healthy controls, thymoma patients had median age of 53 (range: 17-84) years; 121 (51%) were male; 76 (32%) had a history of myasthenia gravis. Median follow-up time was 7 years. 79% of patients were recurrence- and progression-free at 10-year follow-up (95% CI: 74-86%), and 81% of patients were alive at 10 years post-diagnosis (95% CI: 75-87%). Frequency of homozygous variants for either gene was not significantly different between thymoma cases and controls: homozygous BRM-741genotype (OR=1.0; 95%CI:0.6-1.8; P=0.95), homozygous BRM-1321 (OR=0.59; 95%CI:0.3-1.0; P=0.07) or double homozygous variants in both loci (OR=0.69; 95%CI:0.3-1.4; P=0.29). No association between BRM-741/BRM-1321 and OS and TTP was detected (For homozygous BRM-741, OS P=0.74, TTP P=0.93; for homozygous BRM-1321 OS P=0.39, TTP P=0.93). Consistently, there was also no association between double homozygous variants and OS and TTP (Double homozygous, OS P=0.64, TTP P=0.48). Heterozygous variants were also not associated with either risk or outcome.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Results of this study do not support use of BRM promoter polymorphisms as susceptibility or prognostic markers for thymoma. Molecular biologic mechanisms of risk and prognosis remain elusive in malignant thymoma.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-76 - The Impact of Concordance with a Lung Cancer Diagnosis Pathway Guideline on Treatment Access in Patients with Stage IV Lung Cancer (ID 12628)

      16:45 - 18:00  |  Author(s): Shaf Keshavjee

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer mortality with the majority of cases diagnosed at an advanced stage. Timely access to treatment is dependent on efficient and appropriate patient assessment and early referral for diagnostic workup. This study aims to assess the impact of referral concordance with a new Lung Cancer Diagnostic Pathway Guideline (LCDPG) on access to treatment in patients with stage IV lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a retrospective cohort study of patients with clinical stage IV lung cancer referred to the Diagnostic Assessment Program (DAP) at a Canadian tertiary cancer centre between November 1, 2015 and May 31, 2017. Patient referrals were defined as concordant or discordant based on Cancer Care Ontario LCDPG. The primary outcome; time to treatment from initial healthcare presentation; was compared between the concordant and discordant referrals.

      4c3880bb027f159e801041b1021e88e8 Result

      Two hundred patients were referred for clinical stage IV lung cancer during the study period. Of these referrals, 151 (75.5%) were assessed and referred in concordance with LCDP guidelines. Guideline concordant referrals were associated with reduced time to treatment from first healthcare presentation compared with guideline discordant referrals (55.3 vs 108.8 days, p<0.001). Time to diagnostic procedure (32.2 vs 86.7 days, p<0.001) and decision to treat (38.5 vs 93.8 days, p<0.001) was also reduced with guideline concordance. The most common reason for discordant assessment and referral was delayed or inadequate investigation of symptoms in a high risk patient (32.7% of discordant referrals).

      The mean time from referral to diagnostic procedure (19.4 [SD 16.0] days), decision to treat (23.3 [SD 17.1] days), and treatment initiation (39.7 [SD 26.3] days) did not significantly differ between concordant and discordant groups. Time from referral to decision to treat was within 28 days in 71.5% of patients. The mean number of hospital visits from referral to treatment was 4.9 (SD 3.5). Diagnosis was achieved with a single diagnostic test in the majority of patients (91%). The most common method of diagnosis was EBUS-TBNA (33.5%). The most common treatment modalities initiated were radiation (60.5%) followed by chemotherapy (43%) and targeted therapy (21.5%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Guideline concordant assessment and referral of patients with stage IV lung cancer results in reduced time to diagnosis and treatment. The utilization of a LCDPG for lung cancer provides a streamlined and efficient framework to facilitate early diagnosis and treatment. Future research and education should focus on improving factors leading to a delay in DAP referral.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    PC03 - Controversies in Management of Resectable Thymoma (ID 842)

    • Event: WCLC 2018
    • Type: Pro-Con Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 205 AC
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      PC03.04 - Debate on Standard Surgical Approaches - Minimally Invasive Thymectomy (ID 11610)

      15:45 - 15:55  |  Presenting Author(s): Shaf Keshavjee

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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