Bio

Bio

Dr. Das specializes in the treatment of thoracic malignancies. She sees and treats patients both at the Stanford Cancer Center and at the Palo Alto VA Hospital. She is Chief of Oncology at the Palo Alto VA and also leads the VA thoracic tumor board on a biweekly basis. She has a strong interest in clinical research, serving as a principal investigator for multiple clinical and translational studies at the Palo Alto VA, and also as a co-investigator on all of the lung cancer trials at Stanford. In her free time, she enjoys spending time with her family, traveling, and running.

Clinical Focus

  • Thoracic Oncology
  • Medical Oncology

Academic Appointments

Administrative Appointments

  • Chief, Oncology, VA Palo Alto Health Care System (2015 - Present)
  • Associate Program Director, Oncology Fellowship, Stanford University (2015 - Present)

Boards, Advisory Committees, Professional Organizations

  • Member, International Association for the Study of Lung Cancer (IASLC) (2009 - Present)
  • Member, American Society of Clinical Oncology (ASCO) (2008 - Present)

Professional Education

  • Fellowship: Stanford University Hematology and Oncology Fellowship (2001) CA
  • Board Certification: American Board of Internal Medicine, Medical Oncology (2011)
  • Residency: Stanford University Hospital -Clinical Excellence Research Center (2007) CA
  • Internship: Stanford University Hospital -Clinical Excellence Research Center (2005) CA
  • Medical Education: University of Massachusetts Medical Center (2004) MA

Contact

  • Stanford Cancer Center 875 Blake Wilbur Dr MC 6560 Stanford, CA 94305
    • Tel: (650) 498-6000
    Fax: (650) 725-9113

Links

Research & Scholarship

Clinical Trials

  • MAGE A10????T for Advanced NSCLC Recruiting

    This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE A10????T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response or clinical benefit ?4 weeks after the first T-cell infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.

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  • Pembrolizumab in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer Recruiting

    This phase II trial studies how well pembrolizumab works in treating patients with non-squamous non-small cell lung cancer which has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

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  • A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors Not Recruiting

    This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Phase 1/2 Study to Evaluate MEDI4736 Not Recruiting

    This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced solid tumors followed by an expansion phase in patients with advanced solid tumors. An exploration cohort has been added to determine the safety using Q4W dosing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, 650-724-1388.

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  • A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges Not Recruiting

    This was a phase II, multi-center, open-label, five-arm study in which the efficacy and safety of oral ceritinib treatment was assessed in patients with NSCLC metastatic to the brain and/or to leptomeninges harboring a confirmed ALK rearrangement, using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above was not locally available, a test to confirm ALK rearrangement was performed by a Novartis designated central laboratory. Patients waited for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib.

    Stanford is currently not accepting patients for this trial. For more information, please contact Richard A Quick, 650-724-1388.

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  • A Study of Atezolizumab in Participants With Programmed Death - Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer Not Recruiting

    This multicenter, single-arm study will evaluate the efficacy and safety of Atezolizumab in participants with PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Participants will receive Atezolizumab 1200 milligrams (mg) intravenously every 3 weeks as long as participants are experiencing clinical benefit as assessed by the investigator, that is , in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, 650-736-4112.

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  • An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026) Not Recruiting

    The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy

    Stanford is currently not accepting patients for this trial. For more information, please contact Smriti Rai, 650-723-0270.

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  • Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer Not Recruiting

    This randomized phase I/II trial studies the side effects and best dose of veliparib when given together with or without cisplatin and etoposide and to see how well they work in treating patients with extensive stage small cell lung cancer or large cell neuroendocrine non-small cell lung cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cisplatin and etoposide with or without veliparib may work better in treating patients with extensive stage small cell lung cancer or metastatic large cell neuroendocrine non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, 650-721-6977.

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  • Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer Not Recruiting

    This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with chemoradiation therapy works in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Katie Brown, 650-723-1423.

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  • Expanded Treatment Protocol With LDK378 in ALK(+) NSCLC Not Recruiting

    Novartis-sponsored, open-label, multi-center, interventional ETP to provide LDK378 to patients with ALK (+)NSCLC, who have been pre-treated with an ALK inhibitor; except in countries where ALK inhibitors are not approved or available. The protocol will further evaluate the safety of LDK378 in patients with ALK(+) NSCLC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, 650-724-1388.

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  • Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor Not Recruiting

    This phase I trial studies the side effects and best dose of necitumumab when given together with osimertinib in treating patients with EGFR-mutant non-small cell lung cancer that is stage IV or has come back (recurrent) and who have progressed on a previous EGFR tyrosine kinase inhibitor. Immunotherapy with monoclonal antibodies, such as necitumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving necitumumab with osimertinib may be a better treatment for EGFR-mutant non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sukhmani K. Padda, 650-498-7061.

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  • PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients Not Recruiting

    The primary purpose of this study is to establish the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of PDR001 when administered in combination with platinum-doublet chemotherapy and other immunooncology agent(s) in treatment naive patients with PD-L1 unselected, advanced NSCLC, and to estimate the preliminary anti-tumor activity in this patient population.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer Not Recruiting

    This is the first human study to use X-396 (ensartinib), a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). Once the recommended Phase 2 dose has been determined, an expansion phase will assess the preliminary anti-tumor activity of X-396 in ALK-positive non-small cell lung cancer. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the efficacy of X-396.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melanie San Pedro-Salcedo, 650-724-1388.

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  • Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer Not Recruiting

    This phase 2 trial evaluates how well pegylated irinotecan (NKTR-102) works in treating patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), or breast cancer (mBC) that has spread to the brain and does not respond to treatment. Pegylated irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sophie Bertrand, 650-723-4467.

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  • Safety and Efficacy Study of Abraxane as Maintenance Treatment After Abraxane Plus Carboplatin in 1st Line Stage IIIB / IV Squamous Cell Non-small Cell Lung Cancer Not Recruiting

    Maintenance treatment of advanced stage squamous cell NSCLC. Phase III, randomized, open-label, multi-center study of nab-paclitaxel with best supportive care (BSC) or BSC alone as maintenance treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin as induction in subjects with stage IIIB/IV squamous cell NSCLC. Subjects who discontinued treatment from the maintenance part for any reason other than withdrawal of consent, lost to follow-up, or death, were entered into a Follow-up period that had a visit 28 days after progression or discontinuation. Those who entered Follow-up without progression continued with follow-up scans according to standard of care (SOC) until documentation of progression of disease. Additionally, subjects were followed for OS by phone approximately every 90 days for a minimum of 18 months, for up to approximately 5 years after the last subject was randomized.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer Not Recruiting

    AC0010MA is a new, irreversible, Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor. Aim at local advanced or metastatic non-small cell lung cancer patients with EGFR mutation or T790M drug-resistant mutation. The molecular mechanism: by irreversible combining the EGFR-RTKs ATP binding site of cell, selectively suppress the activities of EGFR tyrosine kinase phosphorylation, block the signal transduction pathway of EGFR and inhibit the function of ras/raf/MAPK downstream, thus block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010MA Maleate Capsules has three characters: 1. Irreversible binding to EGFR; 2. Effectively suppresses the tumor cell with EGFR mutant while has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Screening Protocol for Tumor Antigen Expression Profiling and HLA Typing for Eligibility Determination Not Recruiting

    This screening study is intended for men and women at least 18 years of age who have advanced solid or hematologic malignancy. The study will assess a subject's human leukocyte antigen (HLA) subtype and tumor antigen expression profile. Based on the results, it will be determined if a subject is eligible to be considered for Adaptimmune sponsored clinical trials testing the safety and efficacy of genetically changed T cells targeting specific tumor antigens. No treatment intervention will occur as part of this screening study. Upon enrollment, subjects will be required to provide a blood sample for HLA subtype analysis. If the results of the analysis match the HLA-A subtypes noted in the inclusion criteria and do not express the HLA subtypes that are exclusionary for the available interventional clinical trial(s), then the subject will be required to provide either an archival tumor specimen or fresh tumor tissue biopsy. The tumor specimen will be screened at a central laboratory for the expression (protein or gene) of multiple antigens which may include, but are not limited to NY-ESO-1 and/or LAGE-1a and MAGE A10. Based upon the results of these diagnostic analyses, if eligible, subjects will be referred to an appropriate available interventional clinical trial(s) at the discretion of the Investigator. Following screening, tumor samples will be retained by Adaptimmune for the purpose of developing and validating in vitro diagnostic (IVD) assay(s) for antigen expression profiling which is required for regulatory approval of a new therapeutic product indication.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients With Lung Cancer [IMpower010] Not Recruiting

    This is a Phase III, global, multicenter, open-label, randomized study to compare the efficacy and safety of 16 cycles (1 cycle duration=21 days) of atezolizumab (MPDL3280A) treatment compared with best supportive care (BSC) in participants with Stage IB-Stage IIIA non-small cell lung cancer (NSCLC) following resection and adjuvant chemotherapy, as measured by disease-free survival (DFS) as assessed by the investigator and overall survival (OS). Participants, after completing up to 4 cycles of adjuvant cisplatin-based chemotherapy, will be randomized in a 1:1 ratio to receive atezolizumab for 16 cycles or BSC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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Publications

All Publications

  • Giant Magnetoresistive Nanosensor Analysis of Circulating Tumor DNA Epidermal Growth Factor Receptor Mutations for Diagnosis and Therapy Response Monitoring. Clinical chemistry Nesvet, J. C., Antilla, K. A., Pancirer, D. S., Lozano, A. X., Preiss, J. S., Ma, W., Fu, A., Park, S. M., Gambhir, S. S., Fan, A. C., Neal, J. W., Padda, S. K., Das, M., Li, T., Wakelee, H. A., Wang, S. X. 2021

    Abstract

    Liquid biopsy circulating tumor DNA (ctDNA) mutational analysis holds great promises for precision medicine targeted therapy and more effective cancer management. However, its wide adoption is hampered by high cost and long turnaround time of sequencing assays, or by inadequate analytical sensitivity of existing portable nucleic acid tests to mutant allelic fraction in ctDNA.We developed a ctDNA Epidermal Growth Factor Receptor (EGFR) mutational assay using giant magnetoresistive (GMR) nanosensors. This assay was validated in 36 plasma samples of non-small cell lung cancer patients with known EGFR mutations. We assessed therapy response through follow-up blood draws, determined concordance between the GMR assay and radiographic response, and ascertained progression-free survival of patients.The GMR assay achieved analytical sensitivities of 0.01% mutant allelic fraction. In clinical samples, the assay had 87.5% sensitivity (95% CI = 64.0-97.8%) for Exon19 deletion and 90% sensitivity (95% CI = 69.9-98.2%) for L858R mutation with 100% specificity; our assay detected T790M resistance with 96.3% specificity (95% CI = 81.7-99.8%) with 100% sensitivity. After 2?weeks of therapy, 10 patients showed disappearance of ctDNA by GMR (predicted responders), whereas 3 patients did not (predicted nonresponders). These predictions were 100% concordant with radiographic response. Kaplan-Meier analysis showed responders had significantly (P?

    View details for DOI 10.1093/clinchem/hvaa307

    View details for PubMedID 33393992

  • Systemic Therapy of Extensive Stage Small Cell Lung Cancer in the Era of Immunotherapy. Current treatment options in oncology Ragavan, M., Das, M. 2020; 21 (8): 64

    Abstract

    OPINION STATEMENT: In March 2019, the FDA approved the use of the anti-programmed death ligand 1 (PD-L1) antibody atezolizumab, as a first-line treatment option in combination with platinum-etoposide (PE) for patients with extensive stage small cell lung cancer (ED SCLC) based upon the results of the IMpower133 trial. More recently, the FDA approved the anti-PD-L1 antibody durvalumab in March 2020 , also in the frontline setting for SCLC based upon the results of the CASPIAN trial. Both these trials demonstrated a small, but significant overall survival (OS) benefit with the addition of a PD-L1 antibody to standard chemotherapy in the treatment of ED SCLC, thereby altering the treatment paradigm for this aggressive disease. Previously, the FDA had approved the anti-PD1 antibodies nivolumab and pembrolizumab as single-agent third-line treatment options based upon encouraging phase 1/2 data in patients with relapsed SCLC who had not received prior immunotherapy (IO). Despite these recent advances, the overall benefit of IO in SCLC remains somewhat disappointing in comparison with the results seen in non-small cell lung cancer (NSCLC). To date, no reliable biomarkers exist to predict responsiveness to IO in SCLC, and the utility of second- or third-line immunotherapy is questionable in patients who have received IO as part of first-line treatment. There has also been minimal success in identifying targetable mutations in SCLC. Novel approaches include combination approaches with IO, including PARP inhibitors and CDK inhibitors. Few ongoing trials, however, have enrolled patients who have received frontline immunotherapy given the only recent change in standard of care. Consequently, the results of current trials evaluating second- and third-line therapies need to be interpreted and translated into clinical practice with caution. The most significant challenge in SCLC remains the identification of molecular targets for which drugs can be developed that can improve survival over the current standard of care.

    View details for DOI 10.1007/s11864-020-00762-8

    View details for PubMedID 32601742

  • The Project Baseline Health Study: a step towards a broader mission to map human health NPJ DIGITAL MEDICINE Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84

    Abstract

    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for Web of Science ID 000538242900001

    View details for PubMedID 32550652

    View details for PubMedCentralID PMC7275087

  • Advances in the Treatment of Stage III Non-Small Cell Lung Cancer. Clinics in chest medicine Myall, N. J., Das, M. 2020; 41 (2): 211?22

    Abstract

    Treatment of stage III non-small cell lung cancer (NSCLC) traditionally has involved combinations of chemotherapy, radiation, and surgical resection. Although the multimodality approach remains standard, only a fraction of patients with stage III lung cancer can undergo complete resection, and long-term prognosis remains poor. The PACIFIC trial generated significant enthusiasm when it demonstrated that the programmed death ligand-1 inhibitor, durvalumab, improved survival in patients with unresectable stage III NSCLC after completion of definitive concurrent chemoradiation. This article reviews the indications for traditional therapies in stage III NSCLC and highlights ongoing advances that have led to the incorporation of novel therapeutic agents.

    View details for DOI 10.1016/j.ccm.2020.02.008

    View details for PubMedID 32402357

  • KEAP1/NFE2L2 mutations to predict local recurrence after radiotherapy but not surgery in localized non-small cell lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D. S., Yoo, C., Kurtz, D., Owen, S., Backhus, L., Berry, M. F., Shrager, J. B., Ramchandran, K., Padda, S., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020

    View details for Web of Science ID 000560368303348

  • A mid-chemoradiation dynamic risk model integrating tumor features and ctDNA analysis for lung cancer outcome prediction. Moding, E. J., Esfahani, M., Nabet, B., Liu, Y., Chabon, J. J., He, J., Qiao, Y., Xu, T., Yao, L., Gandhi, S., Liao, Z. X., Das, M., Ramchandran, K., Padda, S., Neal, J. W., Wakelee, H. A., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020

    View details for Web of Science ID 000560368303378

  • Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell Nabet, B. Y., Esfahani, M. S., Moding, E. J., Hamilton, E. G., Chabon, J. J., Rizvi, H., Steen, C. B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Almanza, D., Stehr, H., Gojenola, L., Bonilla, R. F., Jin, M. C., Jeon, Y. J., Tseng, D., Liu, C., Merghoub, T., Neal, J. W., Wakelee, H. A., Padda, S. K., Ramchandran, K. J., Das, M., Plodkowski, A. J., Yoo, C., Chen, E. L., Ko, R. B., Newman, A. M., Hellmann, M. D., Alizadeh, A. A., Diehn, M. 2020

    Abstract

    Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

    View details for DOI 10.1016/j.cell.2020.09.001

    View details for PubMedID 33007267

  • A PHASE IIA STUDY REPOSITIONING DESIPRAMINE IN SMALL CELL LUNG CANCER AND OTHER HIGH-GRADE NEUROENDOCRINE TUMORS. Cancer treatment and research communications Riess, J. W., Jahchan, N. S., Das, M., Zach Koontz, M., Kunz, P. L., Wakelee, H. A., Schatzberg, A., Sage, J., Neal, J. W. 2020; 23: 100174

    Abstract

    A bioinformatics approach identified antitumor effects of tricyclic antidepressants (TCAs) in small cell lung cancer (SCLC) and other high-grade neuroendocrine carcinomas (grade 3 neuroendocrine carcinomas) (G3NEC) that was subsequently validated in preclinical models with a putative mechanism of action via inhibition of neuroendocrine signaling pathways. This study was undertaken to reposition the candidate TCA desipramine in a clinical trial in SCLC and G3NEC.In this prospective, phase IIa intrapatient dose escalation clinical trial, patients were required to have failed at least one prior chemotherapy for metastatic SCLC or G3NEC. Treatment with desipramine began at 75 mg nightly with escalation in increments of 75 mg weekly to a maximum of 450 mg daily.Six patients were enrolled, 3 with SCLC, and 3 with G3NEC (lung, rectal, and pancreas). Tolerability of desipramine was worse than predicted. Of the 6 patients enrolled: 1 patient achieved 300 mg daily, 2 patients reached 150 mg daily, 1 patient reached 75 mg daily, and 2 patients were unable to tolerate any stable dose. Reasons for discontinuation included drug-related grade 3 colon pseudo-obstruction, unrelated GI bleed, and grade 1-2 neurocognitive adverse events. Median clinical or radiographic progression free survival was 1.2 months (range 0.2-3.3) and median overall survival from study entry was 2.7 months (range 1.3-5.6).No clinical or radiographic benefit was observed using desipramine to treat SCLC and G3NEC, so this trial was terminated. Intolerable low and medium grade neurocognitive side effects led to intermittent treatment and early discontinuation in most patients; given this limitation, doses achieved may be inadequate compared to the preclinical studies.A bioinformatics approach previously identified a potential antitumor effect of tricyclic antidepressants (TCAs) in small cell lung cancer (SCLC) and other high-grade neuroendocrine carcinomas (grade 3 neuroendocrine carcinoma) (G3NEC), which was validated in preclinical models. In this prospective, phase IIa clinical trial, patients were required to have failed at least one prior chemotherapy for metastatic SCLC or G3NEC (Ki-67 ? 20% or ? 20 mitoses/10 HPF). Treatment with desipramine began at 75 mg nightly with escalation by 75 mg weekly to a maximum dose of 450 mg daily. Six patients were enrolled on this clinical trial, 3 with SCLC, and 3 with G3NEC (lung, rectal, and pancreatic). Tolerability of desipramine was worse than predicted. In the 6 patients enrolled: 1 patient achieved 300 mg daily, 2 patients reached 150 mg daily, 1 patient reached 75 mg daily, and 2 patients were unable to tolerate any stable dose. Reasons for discontinuation included drug-related grade 3 colon pseudo-obstruction, unrelated GI bleed, and grade 1-2 drug related dizziness, confusion, and somnolence. Though numbers are small, median clinical or radiographic progression free survival was 1.2 months (range 0.2-3.3) and median overall survival from study entry was 2.7 months (range 1.3-5.6). Although preclinical evidence was promising, no clinical or radiographic benefit was observed using desipramine to treat SCLC and G3NEC, so this trial was terminated.

    View details for DOI 10.1016/j.ctarc.2020.100174

    View details for PubMedID 32413603

  • KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer discovery Binkley, M. S., Jeon, Y. J., Nesselbush, M., Moding, E. J., Nabet, B. Y., Almanza, D., Kunder, C., Stehr, H., Yoo, C. H., Rhee, S., Xiang, M., Chabon, J. J., Hamilton, E., Kurtz, D. M., Gojenola, L., Owen, S. G., Ko, R. B., Shin, J. H., Maxim, P. G., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. 2020

    Abstract

    Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in KEAP1/NFE2L2 mutation tumors, indicating they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1 mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations.

    View details for DOI 10.1158/2159-8290.CD-20-0282

    View details for PubMedID 33071215

  • Feasibility and design of a cloud-based digital platform in patients with advanced cancer. Roy, M., Hall, E., Velazquez, B., Shah, S., Fardeen, T., Cunanan, K., San Pedro-Salcedo, M., Wakelee, H. A., Neal, J. W., Padda, S., Das, M., Fan, A. C., Srinivas, S., Fisher, G. A., Haraldsdottir, S., Johnson, T., Chu, G., McMillan, A., Ramchandran, K. AMER SOC CLINICAL ONCOLOGY. 2019

    View details for DOI 10.1200/JCO.2019.37.27_suppl.211

    View details for Web of Science ID 000518223100208

  • Circulating Tumor DNA Changes During Chemoradiation for Lung Cancer Predict Patient Outcomes Moding, E. J., Nabet, B. Y., Liu, Y., Chabon, J. J., Chaudhuri, A. A., Hui, A. B., Binkley, M. S., He, J., Qiao, Y., Xu, T., Yao, L., Gandhi, S., Liao, Z., Das, M., Ramchandran, K. J., Padda, S., Neal, W., Wakelee, H. A., Gensheimer, M. F., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2019: S113

    View details for DOI 10.1016/j.ijrobp.2019.06.610

    View details for Web of Science ID 000485671502643

  • Impact of KEAP1/NFE2L2/CUL3 mutations on duration of response to EGFR tyrosine kinase inhibitors in EGFR mutated non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) Hellyer, J. A., Stehr, H., Das, M., Padda, S. K., Ramchandran, K., Neal, J. W., Diehn, M., Wakelee, H. A. 2019; 134: 42?45

    Abstract

    For patients with Epidermal Growth Factor Receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), frontline EGFR-tyrosine kinase inhibitor (TKI) therapy compared to chemotherapy improves outcomes. However, resistance to these agents uniformly develops. Recently, mutations in the KEAP1-NFE2L2 pathway have been implicated as a potential mechanism of acquired EGFR TKI resistance.We examined all patients with metastatic NSCLC with mutations in both EGFR and KEAP1/NFE2L2/CUL3 identified on next generation sequencing from 2015 - 2018. These patients were compared to a NSCLC control cohort with mutations in EGFR and wild type in KEAP1/NFE2L2/CUL3 matched on the basis of sex, smoking status, age and race. Time to treatment failure on EGFR TKI therapy and overall survival were examined.Among 228 EGFR mutant NSCLCs, 17 (7%) also carried mutations in KEAP1, NFE2L2, or CUL3. The most common co-mutation in both the KEAP1/NFE2L2/CUL3 mutant and wild-type cohort was TP53. Patients with KEAP1/NFE2L2/CUL3 mutations had a shorter median time to treatment failure on EGFR TKI (4.7 months) compared with the wild-type matched cohort (13.0 months), p= 0.0014. There was no difference in overall survival.For NSCLC patients with mutations in EGFR, co-mutations in KEAP1/NFE2L2/CUL3 are associated with significantly decreased time to treatment failure. Our results suggest that these mutations represent a mechanism of intrinsic resistance to TKI treatment.

    View details for DOI 10.1016/j.lungcan.2019.05.002

    View details for PubMedID 31319993

  • Role of KEAP1/NFE2L2 mutations in the chemotherapeutic response of non-small cell lung cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research Jeong, Y., Hellyer, J. A., Stehr, H., Hoang, N. T., Niu, X., Das, M., Padda, S. K., Ramchandran, K., Neal, J. W., Wakelee, H. A., Diehn, M. 2019

    Abstract

    Activation of NFE2L2 has been linked to chemoresistance in cell line models. Recently, somatic mutations which activate NFE2L2, including mutations in NFE2L2,KEAP1, or CUL3,have been found to be associated with poor outcomes in patients with non-small cell lung cancer (NSCLC). However, the impact of these mutations on chemoresistance remains incompletely explored.We investigated the effect of Keap1 deletion on chemoresistance in cell lines from Trp53-based mouse models of lung squamous cell carcinoma (LSCC) and lung adenocarcinoma (LUAD). Separately, we identified 51 stage IV NSCLC patients with KEAP1, NFE2L2, or CUL3mutations and a matched cohort of 52 wildtype patients. Time to treatment failure after front line platinum doublet chemotherapy and overall survival was compared between the two groups.Deletion of Keap1 in Trp53-null murine LUAD and LSCC resulted in increased clonogenic survival upon treatment with diverse cytotoxic chemotherapies. In NSCLC patients, median time to treatment failure (TTF) after first line chemotherapy for the KEAP1/NFE2L2/CUL3-mutant cohort was 2.8 months compared to 8.3 months in the control group (p < 0.0001) Median overall survival (OS) was 11.2 months in the KEAP1/NFE2L2/CUL3-mutant group and 36.8 months in the control group (p = 0.006). Conclusions: Keap1 deletion confers chemoresistance in murine lung cancer cells. Patients with metastatic NSCLC with mutations in KEAP1, NFE2L2, or CUL3 have shorter time to treatment failure and overall survival after first line platinum doublet chemotherapy compared with matched controls. Novel approaches for improving outcomes in this subset of NSCLC patients are therefore needed.

    View details for DOI 10.1158/1078-0432.CCR-19-1237

    View details for PubMedID 31548347

  • Invasive nodal evaluation prior to stereotactic ablative radiation for non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) Harris, J. P., Nwachukwu, C., Qian, Y., Pollom, E., Loo, B. W., Das, M., Diehn, M. 2018; 124: 76?85

    Abstract

    INTRODUCTION: Invasive nodal evaluation (INE) is used to improve staging for early stage non-small cell lung cancer (NSCLC), including when stereotactic ablative radiation (SABR) is used. Consensus guidelines from the NCCN recommend performing INE for patients with T2N0 tumors and considering INE for those with T1N0 tumors. We reasoned that if INE results in significant stage migration in the form of substantially fewer patients with occult nodal involvement, then patients treated with SABR who do not undergo INE should have worse overall survival (OS).METHODS: Patients diagnosed 2004-2014 with stage T1-2N0M0 NSCLC and treated with SABR were identified from the National Cancer Database. Factors associated with INE were determined using mixed effects logistic regression. We tested for an association between INE and OS for patients diagnosed 2004-2013 using mixed effects proportional hazards regression methods.RESULTS: 24,603 SABR patients were identified. 6% of the 19,322 patients with T1 tumors and 9% of the 5281 patients with T2 tumors had INE. Median OS was 2.8 years for the no-INE group and 2.7 years for the INE group (log-rank P=0.69). No significant association was observed between the use of INE and OS in the univariate analysis (HR 1.02, 95% CI 0.94-1.11) or the multivariate analysis (HR 0.94, 95% CI 0.86-1.02). These findings were confirmed using propensity score matched and instrumental variable analysis. On subgroup analysis, INE was associated with a non-significant trend for improved OS in patients with T2 tumors (HR 0.87, 95% CI 0.76-1.00) but not T1 tumors (HR 0.98, 95% CI 0.88-1.09).CONCLUSIONS: Despite current NCCN recommendations, the rate of INE was low for patients with stage T1 or T2 tumors. While omitting INE represents a compromise in the completeness of nodal evaluation, we found that it was not associated with a detriment in overall survival.

    View details for PubMedID 30268484

  • A safety, tolerability, and pharmacokinetic analysis of two phase I studies of multitargeted small molecule tyrosine kinase inhibitor XL647 with an intermittent and continuous dosing schedule in patients with advanced solid malignancies. Cancer chemotherapy and pharmacology Das, M., Padda, S. K., Frymoyer, A., Molina, J., Adjei, A., Lensing, J. L., Miles, D., Sikic, B. I., Wakelee, H. A. 2018

    Abstract

    PURPOSE: To evaluate the safety, tolerability, and pharmacokinetics of XL647 and determine the maximum tolerated dose (MTD) of oral XL647 once-daily using intermittent or continuous dosing schedules.METHODS: Patients with advanced solid malignancies were enrolled in successive cohorts to receive escalating dose levels of oral once-daily XL647 using two different dosing schedules: 5 consecutive days of every 14-day cycle (study XL647-001) or continuously over 28-day cycles (study XL647-002). PK sampling was performed to determine Cmax, and AUC. Patients remained on study until progressive disease or unacceptable AEs.RESULTS: In XL647-001, 42 individuals were enrolled across 9 dose levels. The most frequently occurring drug-related AEs were diarrhea, nausea, rash, and fatigue. Expansion of the 4.68mg/kg cohort to 6 patients occurred without further dose-limiting toxicities (DLTs) and this was considered the MTD. In XL647-002, 31 patients were enrolled across 5 dose levels. A DLT of grade 3 pneumonitis occurred in 1/6 patients at 300mg, which was declared the MTD. The most common AEs included grade 1/2 rash, diarrhea, fatigue, dysgeusia, and QTc prolongation. Levels of pharmacodynamic plasma markers were not consistently changed after XL647 and no conclusions could be drawn with this limited data set.CONCLUSIONS: For oral XL647, the MTD was 4.68mg/kg or 350mg fixed dose when administered once-daily for 5 consecutive days of every 14-day cycle and was 300mg when administered once-daily continuously. XL647 was well tolerated at doses up to the MTD.

    View details for PubMedID 30030583

  • Circulating Tumor DNA Quantitation for Early Response Assessment of Immune Checkpoint Inhibitors for Metastatic Non-Small Cell Lung Cancer Chaudhuri, A. A., Nabet, B. Y., Merriott, D. J., Jin, M., Chen, E. L., Chabon, J. J., Newman, A. M., Stehr, H., Say, C., Carter, J. N., Walters, S., Becker, H., Das, M., Padda, S. K., Loo, B. W., Wakelee, H. A., Neal, J. W., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2018: E1?E2

    View details for Web of Science ID 000432447200003

  • Circulating Tumor DNA Quantitation for Early Response Assessment of Immune Checkpoint Inhibitors for Lung Cancer Merriott, D. J., Chaudhuri, A. A., Jin, M., Chabon, J. J., Newman, A., Stehr, H., Say, C., Carter, J. N., Walters, S., Becker, H. R., Das, M., Padda, S., Loo, B. W., Wakelee, H. A., Neal, J. W., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2017: S20?S21

    View details for DOI 10.1016/j.ijrobp.2017.06.061

    View details for Web of Science ID 000411559106127

  • Patterns of Care and Health Disparities for Patients With Stage I Non-small Cell Lung Cancer in the US Harris, J. P., Nwachukwu, C. R., Loo, B. W., Das, M., Diehn, M. ELSEVIER SCIENCE INC. 2017: E399

    View details for DOI 10.1016/j.ijrobp.2017.06.1556

    View details for Web of Science ID 000411559103118

  • Diagnosis and Treatment of Adenocarcinomas and Squamous Cell Carcinomas of the Lung. Journal of the advanced practitioner in oncology Das, M., Tisch, A. H. 2017; 8 (3): 267?72

    Abstract

    Following years in which there were only modest gains in treatment options for non-small cell lung cancer, recognition of targetable mutations and immunogenicity of lung cancer now impact treatment decisions.

    View details for PubMedID 29928550

  • ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies. Journal of thoracic oncology Chuang, J. C., Stehr, H., Liang, Y., Das, M., Huang, J., Diehn, M., Wakelee, H. A., Neal, J. W. 2017

    Abstract

    Erb-b2 receptor tyrosine kinase 2 gene (ERBB2) (also called HER2) has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers in which amplification of this gene confers sensitivity to treatment with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-directed agents. More recently, somatic mutations in ERBB2 have been reported in 1% to 2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies.Here we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2-targeted therapies.Four of the nine patients had response to targeted therapies, with durations of response ranging from 3 to 10 months. We identified a de novo phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and ERBB2 copy number gain as potential resistance mechanisms.We showed patients with ERBB2-mutated lung adenocarcinoma can respond to targeted therapies, and we identified potential resistance mechanisms upon progression to targeted therapies.

    View details for DOI 10.1016/j.jtho.2017.01.023

    View details for PubMedID 28167203

  • Dovitinib and erlotinib in patients with metastatic non-small cell lung cancer: A drug-drug interaction LUNG CANCER Das, M., Padda, S. K., Frymoyer, A., Zhou, L., Riess, J. W., Neal, J. W., Wakelee, H. A. 2015; 89 (3): 280-286

    Abstract

    Erlotinib is a FDA approved small molecule inhibitor of epidermal growth factor receptor and dovitinib is a novel small molecule inhibitor of fibroblast growth factor and vascular endothelial growth factor receptor. This phase 1 trial was conducted to characterize the safety and determine the maximum tolerated dose of erlotinib plus dovitinib in patients with previously treated metastatic non-small cell lung cancer.Escalating dose cohorts of daily erlotinib and dovitinib dosed 5 days on/2 days off, starting after a 2-week lead-in of erlotinib alone, were planned. A potential pharmacokinetic interaction was hypothesized as dovitinib induces CYP1A1/1A2. Only cohort 1 (150mg erlotinib+300mg dovitinib) and cohort -1 (150mg erlotinib+200mg dovitinib) enrolled. Plasma concentrations of erlotinib were measured pre- and post-dovitinib exposure.Two of three patients in cohort 1 had a DLT (grade 3 transaminitis and grade 3 syncope). Two of 6 patients in cohort -1 had a DLT (grade 3 pulmonary embolism and grade 3 fatigue); thus, the study was terminated. Erlotinib exposure (average Cmax 2308±698ng/ml and AUC 0-24 41,030±15,577 ng×h/ml) approximated previous reports in the six patients with pharmacokinetic analysis. However, erlotinib Cmax and AUC0-24 decreased significantly by 93% (p=0.02) and 97% (p<0.01), respectively, during dovitinib co-administration.This small study demonstrated considerable toxicity and a significant pharmacokinetic interaction with a marked decrease in erlotinib exposure in the presence of dovitinib, likely mediated through CYP1A1/1A2 induction. Given the toxicity and the pharmacokinetic interaction, further investigation with this drug combination will not be pursued.

    View details for DOI 10.1016/j.lungcan.2015.06.011

    View details for Web of Science ID 000360513200010

  • Angiogenesis and lung cancer: ramucirumab prolongs survival in 2(nd)-line metastatic NSCLC. Translational lung cancer research Das, M., Wakelee, H. 2014; 3 (6): 397-399

    Abstract

    In the REVEL trial, ramucirumab, a monoclonal antibody to VEGFR-2, improved overall survival in combination with docetaxel compared to docetaxel alone in the second-line setting of non-small cell lung cancer (NSCLC). Along with bevacizumab and nintedanib, ramucirumab is the third anti-angiogenic agent that has yielded positive overall survival results in a phase III trial of patients with advanced NSCLC. Given the lack of effective therapies in the relapsed setting and the disappointing results of many other VEGF-targeted agents in lung cancer, the results from REVEL are encouraging. One of the major remaining hurdles is the identification of reliable predictive biomarkers in order to predict which patients are most likely to benefit from anti-angiogenic therapies. Despite the positive results seen in REVEL, the exact role of ramucirumab in the treatment paradigm of lung cancer remains to be seen given the modest survival benefit of 1.4 months and the lack of predictive biomarkers at this time.

    View details for DOI 10.3978/j.issn.2218-6751.2014.09.05

    View details for PubMedID 25806332

  • A multicenter randomized phase II trial of erlotinib with and without hydroxychloroquine (HCQ) in TKI-naive patients (pts) with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) Neal, J. W., Wakelee, H. A., Feliciano, J., Goldberg, S. B., Morgensztern, D., Das, M., Heist, R., Lennes, I., Muzikansky, A., Edelman, M. J., Gettinger, S. N., Sequist, L. V. AMER SOC CLINICAL ONCOLOGY. 2014

    View details for Web of Science ID 000358613204150

  • Anti-angiogenic Agents in Metastatic NSCLC LUNG CANCER,4TH EDITION Das, M., Wakelee, H., Roth, J. A., Hong, W. K., Komaki, R. U., Tsao, A. S., Chang, J. Y., Blackmon, S. H. 2014: 527?40

    View details for Web of Science ID 000354798900035

  • VIETNAMESE NON-SMALL CELL LUNG CANCER PATIENTS IN CALIFORNIA: MOLECULAR PROFILES AND CLINICAL CHARACTERISTICS Nguyen, K. H., Das, M., Ramchandran, K., Shrager, J., Merritt, R. E., Hoang, C., Burt, B., Tisch, A., Pagtama, J., Zehnder, J., Berry, G., Wakelee, H. A., Anh-Hoa Nguyen, Neal, J. W. LIPPINCOTT WILLIAMS & WILKINS. 2013: S208?S209

    View details for Web of Science ID 000339624901009

  • PALLIATIVE CARE AND ANTI-CANCER CARE INTEGRATION: DESCRIPTION OF THREE MODELS OF CARE DELIVERY AT A TERTIARY MEDICAL CENTER Ramchandran, K. J., Fronk, J., Trieu, S., Wakelee, H. A., Das, M., Neal, J. W., Harman, S., Dwyer, P., Bosch, J., Shaw, H., Safari, S., Oden, R., Morrison, T., Blayney, D. LIPPINCOTT WILLIAMS & WILKINS. 2013: S1324

    View details for Web of Science ID 000339624906208

  • A Case Series of Lengthy Progression-Free Survival With Pemetrexed-Containing Therapy in Metastatic Non-Small-Cell Lung Cancer Patients Harboring ROS1 Gene Rearrangements. Clinical lung cancer Riess, J. W., Padda, S. K., Bangs, C. D., Das, M., Neal, J. W., Adrouny, A. R., Cherry, A., Wakelee, H. A. 2013; 14 (5): 592-595

    View details for DOI 10.1016/j.cllc.2013.04.008

    View details for PubMedID 23810364

  • A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab JOURNAL OF THORACIC ONCOLOGY Riess, J. W., Nagpal, S., Das, M., Neal, J. W., Kim, J. W., Wakelee, H. A. 2013; 8 (2): E17-E18

    View details for DOI 10.1097/JTO.0b013e31827690da

    View details for Web of Science ID 000316204900003

    View details for PubMedID 23328555

    View details for PubMedCentralID PMC3552378

  • Angiogenesis inhibitors. Journal of thoracic oncology Das, M., Wakelee, H. 2012; 7 (16): S397-8

    View details for DOI 10.1097/JTO.0b013e31826df227

    View details for PubMedID 23160332

  • Anti-angiogenic agents in Non-Small-Cell Lung Cancer (NSCLC): a perspective on the MONET1 (Motesanib NSCLC Efficacy and Tolerability) study JOURNAL OF THORACIC DISEASE Das, M., Wakelee, H. 2012; 4 (6): 558-561

    View details for DOI 10.3978/j.issn.2072-1439.2012.10.02

    View details for Web of Science ID 000314790400004

    View details for PubMedID 23205278

    View details for PubMedCentralID PMC3506785

  • BIOMARKERS FOR ANTI-ANGIOGENIC THERAPY Das, M., Wakelee, H. ELSEVIER SCIENCE INC. 2012: S442?S443

    View details for Web of Science ID 000428093300114

  • ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy. Lung cancer Das, M., Riess, J. W., Frankel, P., Schwartz, E., Bennis, R., Hsieh, H. B., Liu, X., Ly, J. C., Zhou, L., Nieva, J. J., Wakelee, H. A., Bruce, R. H. 2012; 77 (2): 421-426

    Abstract

    To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC).ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ?2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation.PFS decreased with increasing ERCC1 expression (p<0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p<0.02) in a Kaplan-Meier analysis using ERCC expression level of 1 as a cutoff (range 0-30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25-14.1, p<0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p<0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging.Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy.

    View details for DOI 10.1016/j.lungcan.2012.04.005

    View details for PubMedID 22555222

  • Angiogenesis Inhibitors JOURNAL OF THORACIC ONCOLOGY Das, M., Wakelee, H. 2011; 6 (11): S1801-S1802

    View details for DOI 10.1097/01.JTO.0000407564.91781.ab

    View details for PubMedID 22005536

  • Results from a Single Institution Phase II Trial of Concurrent Docetaxel/Carboplatin/Radiotherapy Followed by Surgical Resection and Consolidation Docetaxel/Carboplatin in Stage III Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Das, M., Donington, J. S., Murphy, J., Kozak, M., Eclov, N., Whyte, R. I., Hoang, C. D., Zhou, L., Le, Q., Loo, B. W., Wakelee, H. 2011; 12 (5): 280-285

    Abstract

    The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity.We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m(2) and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m(2) and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support.All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none.This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.

    View details for DOI 10.1016/j.cllc.2011.06.003

    View details for PubMedID 21752720

  • Stage IIIB and IV NSCLC: Primary Therapy LUNG CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT Das, M., Wakelee, H., Kernstine, K., Reckamp, K. 2011: 183?95

    View details for Web of Science ID 000283895900015

  • Vascular Disrupting Agents JOURNAL OF THORACIC ONCOLOGY Das, M., Wakelee, H. 2010; 5 (12): S482-S483

    View details for PubMedID 21102249

  • Alternatives to Surgery for Early Stage Non-Small Cell Lung Cancer-Ready for Prime Time? CURRENT TREATMENT OPTIONS IN ONCOLOGY Das, M., Abdelmaksoud, M. H., Loo, B. W., Kothary, N. 2010; 11 (1-2): 24-35

    Abstract

    Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC), with lobectomy being the most oncologically sound resection. Medically inoperable patients and high-risk surgical candidates require effective alternatives to surgery; even operable patients may opt for less invasive options if they are proven to achieve similar outcomes to surgery. Minimally invasive local treatment modalities including dose-intensified conformal radiation therapy, most notably stereotactic ablative radiotherapy (SABR; also known as stereotactic body radiation therapy), and thermal ablation methods such as radiofrequency ablation (RFA) and microwave ablation (MWA) are emerging as promising treatment options whose roles in the treatment of early stage lung cancer are being defined. Early clinical experience and a rapidly growing body of prospective clinical trials, primarily in medically inoperable patients, are demonstrating encouraging effectiveness and safety outcomes in some cases approaching historical results with surgery. Given the very poor prognosis of the medically inoperable patient population, these alternatives to surgery, particularly SABR, are starting to be considered appropriate first-line therapy in properly selected patients, and prospective cooperative group trials to evaluate and optimize RFA and SABR in specific patient subsets are being conducted. For operable patients, prospective multi-center and cooperative groups trials of SABR are ongoing or completed, and international randomized trials of SABR vs. surgery have been initiated. Thus, promising alternatives to surgery for early stage NSCLC are ready for prime time evaluation in the setting of clinical trials, and participation in ongoing trials for both operable and medically inoperable patients is strongly encouraged.

    View details for DOI 10.1007/s11864-010-0119-z

    View details for PubMedID 20577833

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