23 results on '"Deborah Blythe Doroshow"'
Search Results
2. Abstract P1-12-02: The tolerance of CREATE-X capecitabine dosing in a United States patient population
- Author
-
Alaina Justine Kessler, Natalie S. Berger, Hsin-Hui Huang, Deborah Blythe Doroshow, and Paula Klein
- Subjects
Cancer Research ,Oncology - Abstract
Background: Capecitabine was shown to prolong overall survival in patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy based on the CREATE-X study. The starting dose of capecitabine in CREATE-X was 1250 mg/m2 twice per day on days 1-14 every 3 weeks whereas the United States (US) standard dosing of capecitabine is 1000 mg/m2. Fluoropyrimidine toxicity is higher in the US compared to East Asia. The goal of this study was to evaluate the tolerance of capecitabine at an urban clinic in the US consisting of predominantly non-Asian patients. . Methods: We performed a retrospective chart review of patients with TNBC with residual disease after neoadjuvant chemotherapy who were prescribed capecitabine from June 1, 2017 through June 1, 2021. Exclusion criteria included patients who received capecitabine concurrently with radiation. All statistical analyses were conducted using R software, version 4.1.0. Results: There were 64 patients who met criteria with an average age of 54 (SD 10) years. Of these patients, 13 (20.3%) were Hispanic/Latino; 26 (40.6%) white, 17 (26.6%) African American, and 4 (6.3%) Asian. There were 28 patients (43.8%) prescribed the CREATE-X capecitabine dosing of 1250 mg/m2, 26 (40.6%) prescribed the US standard dosing of 1000 mg/m2, and 10 (15.6%) prescribed a different dosing regimen. Characteristics of patients prescribed capecitabine 1250 mg/m2 and 1000 mg/m2 are in Table 1. Of the 28 patients prescribed 1250mg/m2 dosing, 8 (28.6%) completed 8 cycles, all requiring dose reductions; 7 (25.0%) discontinued due to intolerance. Of the 283 patients in the CREATE-X study treated with 8 cycles of 1250 mg/m2, 107 (37.8%) completed capecitabine treatment with the planned dose compared to no patients in our cohort. Of the 26 patients prescribed 1000 mg/m2, 9 (34.6%) completed 8 cycles with 3 patients requiring dose reductions; 6 (23.1%) discontinued due to intolerance. The most common adverse events were hand-foot syndrome (HFS) in 48 patients (75.0%), nausea in 24 (37.5%), fatigue in 23 (35.9%), and diarrhea in 22 (34.4%). Adverse events based on starting dose of capecitabine can be found in Table 1. The logistic regression was fitted to test the effect of the starting dose of capecitabine on the incidence of dose change after adjusting for the co-variates. The higher starting dose has higher odds (OR 9.065, 95% CI 2.558, 38.190) to change the capecitabine dose at the significant level of 0.05 (Table 2). Conclusions: No patients in our cohort tolerated 8 cycles of the CREATE-X dosing of 1250 mg/m2 compared to 37.8% of the study population. Of the patients who completed 8 cycles of the US standard dosing of capecitabine 1000 mg/m2, 66.7% of patients completed the planned dose. This dose was not studied in CREATE-X. Trials in metastatic disease comparing these two doses demonstrated similar efficacy with less toxicity. Further studies are warranted in this curative intent population. Table 1.Characteristics by Starting Dose of CapecitabineCapecitabine DoseCharacteristics1250 mg/m2(N = 28)1000 mg/m2(N = 26)Age – yrsMedian (IQR)53.5 [34.0, 65.0]50.0 [30.0, 68.0]Ethnicity – no (%)Hispanic5 (17.9)6 (23.1)Not Hispanic23 (82.1)20 (76.9)Race – no (%)White15 (53.6)9 (34.6)Black/AA5 (17.9)8 (30.8)Asian1 (3.6)1 (3.8)Other7 (25.0)8 (30.8)Clinical Stage – no (%)16 (21.5)1 (3.8)217 (60.7)9 (34.6)35 (17.8)15 (57.7)Unknown0 (0)1 (3.8)Adverse Event – no (%)HFS22 (78.6)19 (73.1)Diarrhea9 (32.1)10 (38.5)Fatigue8 (28.6)11 (42.3)Mucositis1 (3.6)1 (3.8) Table 2.Odds Ratio95% CIVariableORLCLUCLp-valueCapecitabine Dose1250 mg/m29.0652.55838.1900.0001000 mg/m2RefAge (yr)> 656.4210.477163.8950.158< 65RefEthnicityHispanic1.4490.15515.4070.744Non-HispanicRefRaceAsian1.2010.02857.1560.992Black/AA1.0450.2095.522Other1.3870.15712.926WhiteRefChemoCarbo1.6800.4396.6790.447No carboRefHFSYes0.9200.1964.1540.913NoRef Citation Format: Alaina Justine Kessler, Natalie S. Berger, Hsin-Hui Huang, Deborah Blythe Doroshow, Paula Klein. The tolerance of CREATE-X capecitabine dosing in a United States patient population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-02.
- Published
- 2022
3. Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations)
- Author
-
Khanh T. Do, Brunella Felicetti, Geoffrey I. Shapiro, Haider Mahdi, Davendra Sohal, Jeffrey Sklar, Joseph Paul Eder, Deborah Blythe Doroshow, Vickie L. Keedy, Navid Hafez, Manuel Avedissian, Juliane Jürgensmeier, Patricia LoRusso, Emma Dean, Peter G. Mortimer, and Colin Glover
- Subjects
Adult ,Male ,Cancer Research ,Indoles ,DNA damage ,Poly ADP ribose polymerase ,Morpholines ,Ataxia Telangiectasia Mutated Proteins ,Poly(ADP-ribose) Polymerase Inhibitors ,Piperazines ,Olaparib ,chemistry.chemical_compound ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Precision Medicine ,Protein Kinase Inhibitors ,Polymerase ,Aged ,Sulfonamides ,biology ,BRCA1 Protein ,ORIGINAL REPORTS ,Middle Aged ,Pyrimidines ,Oncology ,chemistry ,biology.protein ,Cancer research ,Phthalazines ,Female ,Homologous recombination ,DNA Damage - Abstract
PURPOSE Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising therapy in cancers with homologous recombination repair deficiency. However, efficacy is limited by both intrinsic and acquired resistance. The Olaparib Combinations basket trial explored olaparib alone and in combination with other homologous recombination–directed targeted therapies. Here, we report the results of the arm in which olaparib was combined with the orally bioavailable ataxia telangiectasia and RAD3-related inhibitor ceralasertib in patients with relapsed or refractory cancers harboring DNA damage response and repair alterations, including patients with BRCA-mutated PARP inhibitor–resistant high-grade serous ovarian cancer (HGSOC). PATIENTS AND METHODS Germline and somatic mutations had to be deleterious by COSMIC or ClinVar for eligibility. Olaparib was administered at 300 mg twice daily and ceralasertib at 160 mg daily on days 1-7 in 28-day cycles until progression or unacceptable toxicities. Primary end points were confirmed complete response (CR) or partial response (PR) rates and clinical benefit rate (CBR; CR + PR + stable disease [SD] at 16 weeks). RESULTS Twenty-five patients were enrolled, with median four prior therapies. Five patients required dose reductions for myelosuppression. Overall response rate was 8.3% and CBR was 62.5% among the entire cohort. Two of five patients with tumor harboring ATM mutation achieved CR or SD ongoing at 24+ months, respectively (CBR 40%). Of seven patients with PARP inhibitor–resistant HGSOC, one achieved PR (–90%) and five had SD ranging 16-72 weeks (CBR 86%). CONCLUSION Olaparib with ceralasertib demonstrated preliminary activity in ATM-mutated tumors and in PARP inhibitor–resistant BRCA1/2–mutated HGSOC. These data warrant additional studies to further confirm activity in these settings.
- Published
- 2021
4. Financial toxicity in patients with advanced solid malignancies participating in early-phase clinical trials
- Author
-
Julia Blanter, Michael Werner, Melanie Wain Kier, Olivia Hapanowicz, Muhieddine Itani, Maham Ahmad, Mandy DeMerchant, Joseph Paul Eder, Matt D. Galsky, Ashley Hammad, Paula King, Michael Lachowicz, Natalie Lucas, Thomas Urban Marron, Gary Shelton, Kathy Wu, Suzanne Xu, Patricia LoRusso, Erin Wysong Hofstatter, and Deborah Blythe Doroshow
- Subjects
Cancer Research ,Oncology - Abstract
267 Background: Financial toxicity (FT) adversely influences patient quality of life and is a barrier to clinical trial enrollment. Early phase clinical trials (EPTs) primarily recruit patients with advanced malignancies who have received all standard therapy regimens and may thus have high levels of FT. We sought to assess baseline FT and its association with clinicodemographic factors in patients participating in early phase clinical trials. Methods: We conducted a study to assess baseline FT in English-speaking patients (pts) with advanced metastatic solid tumors who were participating in EPTs at the Yale Cancer Center (Yale) and the Tisch Cancer Institute at Mount Sinai (Sinai). Pts were consented after EPT consent and prior to day 1 of study treatment. Pts completed a clinical and demographic questionnaire as well as the 11-item validated Comprehensive Score for Financial Toxicity (COST) FT instrument. Primary endpoints included baseline FT and association with clinicodemographic variables. Statistical analysis was performed using two-sided T-tests and Pearson correlations for numeric data and Fisher’s Exact Test for categorical data. Multivariate analysis was performed using a linear regression model. Results: 138 pts enrolled in this study, of whom 132 completed the COST instrument (Yale, N = 84; Sinai, N = 48). Median age was 62 and 49.2% were male. 71.2% patients self-identified as White and 15.2% as Black; 7.2% identified as Hispanic. 32.6% reported an annual income of < $50,000. Insurance providers included private insurers (50%), Medicare (31.8%), Medicaid (10.6%), and Medicaid with Medicare supplemental (3.8%). 56.8% reported monthly out of pocket medical expenses of $100 or more. Median FT score was 22.5 out of a maximum score of 44 (mean 21.5). FT scores ≥ 22.5 in pts were associated with age < 65 (OR = 2.229, P = 0.04), being the household money manager (OR = 2.98, P = 0.02), and being the primary wage earner (OR = 3.12, P = 0.004). FT scores < 22.5 in pts was associated with retirement (OR = 0.15, P = 3.67e-05). In multivariate analysis, retirement was associated with FT score < 22.5 (OR = 0.18, P = 0.02). There was no statistically significant difference in FT scores between Yale and Sinai pts. However, Sinai pts were more racially diverse (p = 3.05e-05), had lower household income (P = 0.01), out of pocket expenses (P = 0.01), ED visits (P = 0.0075), and dependents (P = 0.004) and were less likely to have private insurance (P = 0.004). Conclusions: Pts with advanced cancers consenting to EPTs report significant baseline FT. Our study encompasses a diverse population from two large urban academic centers. Baseline FT was higher among pts < 65 years of age, primary wage earners, and those who managed household finances independently. Retirement was a protective factor, which may be explained by the life savings often required to retire. Ongoing work will compare baseline and 2 month FT in this patient population.
- Published
- 2022
5. The Inpatient Immunotherapy Outcomes study: A multicenter retrospective study of patients treated with immune checkpoint inhibitors in the inpatient setting
- Author
-
Fauzia Riaz, Huili Zhu, Wei Cheng, Samantha Brongiel, Elena Baldwin, Melanie Wain Kier, Jacob Zaemes, Caleb Hearn, Osama Abdelghany, Ravi Bharat Parikh, Joshua E. Reuss, Elizabeth Horn Prsic, and Deborah Blythe Doroshow
- Subjects
Cancer Research ,Oncology - Abstract
300 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients (pts) with cancer. However, median time to response is 2-6 months and many pts derive no benefit from ICIs. Pts are often admitted to the hospital with complications of advanced disease or its treatment, and many have prognoses limited to months. Several recent studies have demonstrated a limited benefit of anticancer therapy at end of life. ICIs are also associated with significant financial toxicity for both pts and the health care system. The role of ICI therapy in the inpatient (IP) setting is unclear. To begin to address this gap in knowledge, we conducted the Inpatient Immunotherapy Outcomes Study (IIOS) to describe characteristics and outcomes of pts who received IP ICIs. Methods: IIOS is a multicenter, retrospective study of pts treated with PD-(L)1 and CTLA-4 inhibitors during IP hospitalization between 2012-2021 at 4 large academic institutions: Mount Sinai Hospital, Yale-New Haven Hospital, University of Pennsylvania, and Georgetown University Hospital. Manual data collection was performed using each institution’s EMR and was approved by each institution’s IRB. Descriptive statistics were used to characterize the population and demonstrate pt outcomes. Results: A total of 159 pts received IPI ICI. Median age was 61 years. 54.7% of pts were white and 17.6% were Black; 12.6% were Hispanic. Thoracic/head and neck malignancies were most common (26.4%), followed by gastrointestinal (19.5%) and hematologic malignancies (17.6%). Most pts (73%) initiated ICIs in the IP setting while 27% continued an outpatient ICI regimen. 129 pts (81.1%) had stage IV solid malignancies at the time of ICI initiation in any setting; median prior lines of systemic therapy was 1 (range, 0-11). The most commonly administered IP ICI was pembrolizumab (49.1%) followed by nivolumab (34.0%), with ICIs administered with non-curative intent in 91.8% of pts. In 44.7% of pts, the ICI given did not have an FDA approval for that cancer type and stage at the time of administration. PD-L1 expression was available on tumors from 60 pts, 32 (53.3%) of whom had expression of 50% or higher. 112 pts (70.4%) had no documented clinical or imaging-based response to ICI therapy. Discharge disposition included home (47.2%), IP death (27%), rehabilitation centers (15.1%), and hospice (10.1%). Median days between first IP ICI dose and death was 47 (95% CI, 33-68). Conclusions: This is the largest multi-institutional effort to understand pt outcomes following IP ICI administration. Preliminary data, as outlined above, is concerning for poor clinical outcomes which should give clinicians pause when considering IP ICI use. Further analysis is ongoing to determine predictors of overall survival and discharge to home.
- Published
- 2022
6. A phase 1b/2 trial of dupilumab given in conjunction with PD-(L)1 blockade in the treatment of relapsed/refractory metastatic NSCLC
- Author
-
Bailey Gleason Fitzgerald, Thomas Urban Marron, Nicole Hall, Daniel O'Grady, Nelson LaMarche, Clotilde Hennequin, Samarth Hegde, Barbara Maier, Jessica Le Berichel, Udit Chadda, Mary Beth Beasley, David F Yankelevitz, Jorge E. Gomez, Deborah Blythe Doroshow, Rajwanth Veluswamy, Nicholas Cole Rohs, Christian Diego Rolfo, Fred R. Hirsch, and Miriam Merad
- Subjects
Cancer Research ,Oncology - Abstract
TPS9139 Background: Although tumor microenvironments may contain chronic inflammatory cells, this milieu can lead to immune evasion and may contribute to resistance to immunotherapy. Dendritic cells are one of the most potent cross presenters of tumor antigen, and their function is crucial to tumor-directed adaptive immune responses. In the KP mouse model of lung adenocarcinoma (KrasG12D; Tp53-/-), we recently identified interleukin-4 (IL-4)-driven suppression of tumor-antigen charged dendritic cells, which was similarly seen in human lung cancer lesions (Maier, B., et al., A conserved dendritic-cell regulatory program limits antitumour immunity. Nature, 2020.580[7802]:257-262). In the mouse model IL-4 blockade resulted in an increase in IL-12, IFNg and TNF in CD8+ T cells and decreased tumor burden, and further antitumor activity was seen when combined with PD-L1 blockade. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit which disrupts signaling through receptors for both IL-4 and IL-13; it is FDA approved for patients with multiple atopic conditions, in whom series adverse effects are rare. Based on this pre-clinical data, we hypothesize that the addition of dupilumab to anti PD-(L)1 therapy will be well tolerated, and will rescue the anti-tumor effect of immune checkpoint blockade. Methods: This is a phase Ib/II trial. Patients with relapsed/refractory NSCLC who have received prior anti PD-(L)1 treatment are eligible for enrollment. In a phase Ib safety run-in, six patients will be enrolled in a modified set-dose 3+3 design. If no more than 1 DLT is observed during this phase, the trial will proceed to phase II. Phase II will enroll a further 15 patients in a minimax design with early stopping for futility to a maximum total of 21 patients. Patients will undergo pre-treatment biopsies and peripheral blood sampling prior to receiving 3 doses of dupilumab, administered every three weeks, in conjunction with continuing standard-of-care anti-PD-(L)1 therapy. Patients will undergo repeat biopsies 4 weeks after starting therapy. After completion of dupilumab (at 9 weeks) patients will undergo repeat staging. The primary endpoint of phase 1b is safety as measured by frequency and severity of adverse effects. The primary endpoint of phase II is overall response rate as assessed using RECIST 1.1 criteria at the time of post-dupilumab imaging. Exploratory endpoints include analysis of peripheral blood by CyTOF and O-link, and tissue biopsies will be analyzed by multiplex-IHC and bulk-RNA-sequencing. T cell receptor sequencing will be performed on tumor and matched peripheral blood samples, and circulating tumor DNA will be assessed at multiple time points. Phase 1b is currently enrolling as planned. Clinical trial information: NCT05013450.
- Published
- 2022
7. PD-L1 as a biomarker of response to immune-checkpoint inhibitors
- Author
-
Deborah Blythe, Doroshow, Sheena, Bhalla, Mary Beth, Beasley, Lynette M, Sholl, Keith M, Kerr, Sacha, Gnjatic, Ignacio I, Wistuba, David L, Rimm, Ming Sound, Tsao, and Fred R, Hirsch
- Subjects
Treatment Outcome ,Biopsy ,Neoplasms ,Biomarkers, Tumor ,Humans ,Immune Checkpoint Inhibitors ,Immunohistochemistry ,B7-H1 Antigen ,Biomarkers, Pharmacological ,Specimen Handling - Abstract
Immune-checkpoint inhibitors targeting PD-1 or PD-L1 have already substantially improved the outcomes of patients with many types of cancer, although only 20-40% of patients derive benefit from these new therapies. PD-L1, quantified using immunohistochemistry assays, is currently the most widely validated, used and accepted biomarker to guide the selection of patients to receive anti-PD-1 or anti-PD-L1 antibodies. However, many challenges remain in the clinical use of these assays, including the necessity of using different companion diagnostic assays for specific agents, high levels of inter-assay variability in terms of both performance and cut-off points, and a lack of prospective comparisons of how PD-L1
- Published
- 2021
8. Trastuzumab emtansine: determining its role in management of HER2+ breast cancer
- Author
-
Deborah Blythe Doroshow and Patricia LoRusso
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Antibody-drug conjugate ,Immunoconjugates ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Ado-Trastuzumab Emtansine ,Antibodies, Monoclonal, Humanized ,Lapatinib ,Maytansinoid ,Disease-Free Survival ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,Humans ,Maytansine ,030212 general & internal medicine ,skin and connective tissue diseases ,neoplasms ,Cell Proliferation ,Clinical Trials as Topic ,business.industry ,General Medicine ,medicine.disease ,chemistry ,Trastuzumab emtansine ,030220 oncology & carcinogenesis ,Female ,Pertuzumab ,business ,Adjuvant ,medicine.drug - Abstract
Trastuzumab emtansine is an antibody–drug conjugate comprised of the anti-HER2 monoclonal antibody trastuzumab linked to DM1 (emtansine), a potent cytotoxic maytansinoid derivative, by a stable linker. This structure results in improved tumor-directed cytotoxicity in HER2+ breast cancer with reduced systemic toxicities, particularly the cardiac toxicities associated with single agent trastuzumab. Phase III trials have demonstrated improved progression-free and overall survival in heavily pretreated patients with advanced HER2+ breast cancer, with an acceptable toxicity profile. However, its role in first-line treatment is less clear. Ongoing studies continue to evaluate its role in neoadjuvant and adjuvant management of HER2+ breast cancer.
- Published
- 2018
9. Phase 1 and phase 2a, first-in-human (FIH) study, of DRP-104, a broad glutamine antagonist, in adult patients with advanced solid tumors
- Author
-
Melissa Lynne Johnson, Matthias Scheffler, S. Patel, Sunil Sharma, Francois Lafleur, Aaron Lisberg, M. K. Gibson, Vamsidhar Velcheti, Tanguy Y. Seiwert, Margaret Dugan, and Deborah Blythe Doroshow
- Subjects
Cancer Research ,Glutaminolysis ,Adult patients ,business.industry ,Antagonist ,Cancer ,First in human ,medicine.disease ,Clinical trial ,Glutamine ,Oncology ,Cancer cell ,Cancer research ,medicine ,business - Abstract
TPS3149 Background: Dependence of cancer cells on glutamine has made glutaminolysis an attractive therapeutic target in cancer. Prior clinical trials evaluating glutamine analogues for the treatment of cancer were abandoned due to lack of efficacy and/or tolerability. DON (6-Diazo-5-oxo-L-norleucine) is an irreversible inhibitor of several enzymes that utilize glutamine as a metabolic substrate. In addition to direct anti-tumor efficacy, inhibition of glutamine metabolism in the tumor microenvironment has been shown to improve T-cell activation and tumor infiltration, increasing anti-tumor immune responses. As such, combining DON with an immune checkpoint inhibitor (ICI), has strong preclinical rationale. The investigational product DRP-104 (sirpiglenastat) is an inactive prodrug of DON designed to limit systemic DON exposure while targeting glutamine dependence in tumor cells. Methods: A phase 1/2a, FIH, multi-center, non-randomized, multi-cohort, open-label study of DRP-104 is currently open to accrual for patients with advanced solid tumors. This study will be conducted in 4 parts: A) Dose Escalation of IV and subQ DRP-104 (Run-In phase followed by modified Continual Reassessment Method) to define MTD/RP2D. Primary objective of dose escalation is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of DRP-104 as a single agent; B) Dose Expansion of IV and subQ DRP-104 for safety assessment while primary objective is to select and recommend phase 2 DRP-104 route of administration; C) Phase 2a at recommended MTD/RP2D of selected route of DRP-104 in 2 patient cohorts: patients with locally advanced/metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation and patients with unresectable or metastatic SCCHN, in order to assess the safety, tolerability and preliminary antitumor activity of DRP-104 as a single agent; D) Phase 2a at recommended MTD/RP2D of selected route of DRP-104 in combination with atezolizumab in adult patients with advanced solid tumors previously treated with an ICI, in order to assess the safety, tolerability and preliminary antitumor activity of DRP-104 in combination with atezolizumab; DRP-104 IV is infused TIW over 1 hour infusion for 2 consecutive weeks followed by 1 week off. DRP-104 subQ is administered BIW weekly. Study is currently open with 6 IV patients (Run-In Phase completed and at Dose Level 4) and 3 subQ patients at Dose Level 1 at time of submission. Clinical trial information: NCT04471415.
- Published
- 2021
10. Thrombotic complications with SARS-CoV-2 infection in patients with cancer on high-risk therapies: Data from the COVID-19 and Cancer Consortium (CCC19)
- Author
-
Surbhi Shah, Peter Paul Yu, Shuchi Gulati, Clara Hwang, Rachel P. Rosovsky, Imo J. Akpan, Ziad Bakouny, Chih-Yuan Hsu, Julie Fu, Aakash Desai, Deborah Blythe Doroshow, Rana R. McKay, Vaibhav Kumar, Dimpy P. Shah, Petros Grivas, Amit Kulkarni, Jennifer Girard, Jeremy L. Warner, Rebecca L. Zon, and Jean M. Connors
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Cancer ,equipment and supplies ,medicine.disease ,Internal medicine ,medicine ,In patient ,cardiovascular diseases ,business ,Thrombotic complication - Abstract
e18788 Background: Patients (pts) with cancer have a high risk of venous thromboembolic (VTE) complications, further enhanced by anti-cancer treatments, specifically hormonal therapies, targeted therapies (VEGF inhibitors, other TKIs) and immune checkpoint inhibitors (ICIs). We hypothesized that high-risk therapies would predispose pts with cancer and COVID-19 to higher risk of VTE complications. Methods: CCC19 is the largest international registry (NCT04354701) recording outcomes of pts with cancer and COVID-19. The registry was queried for hospitalized pts who developed VTE and received systemic cancer treatment in the year prior to COVID-19. Incidence of VTE was analyzed as the primary endpoint; 30-day any cause mortality & need for ICU admission at baseline were secondary endpoints in pts with and without VTE respectively. Pts were stratified by treatment type and time from last treatment dose
- Published
- 2021
11. Phase I study of BJ-001, a tumor-targeting interleukin-15 fusion protein, in patients with solid tumor
- Author
-
Deborah Blythe Doroshow, Haizhou Zhang, Pankaj C. Patel, Haeseong Park, Ki Y. Chung, Leijun Hu, Keiko Nakai, Teresa A. Coleman, Raghad Muhsin Abdul-Karim, Jorge Chaves, and John Qiang Wang
- Subjects
Cancer Research ,Tumor targeting ,Oncology ,business.industry ,Interleukin 15 ,Cancer research ,Medicine ,In patient ,Solid tumor ,business ,Fusion protein ,Phase i study - Abstract
e14545 Background: BJ-001 is the first tumor-targeting Interleukin-15 (IL-15) fusion protein, composed of an integrin-binding Arg-Gly-Asp (RGD)-4C motif, linked with a human IgG1 Fc, and then a modified sushi domain of human IL-15Rα unit and a human IL-15. Tumor-targeting is achieved with RGD-4C motif which binds to αvβ3, αvβ5, and αvβ6 integrins, commonly overexpressed in solid tumors. The molecule has shown an ability to activate Natural Killer (NK) and T cells in vitro and in pre-clinical in vivo studies. Methods: This first in-human (FIH) study has 2 phases: Phase 1a and Phase 1b. Phase 1a consists of 3 parts. In all 3 parts patients receive escalating doses of BJ-001 as a once weekly subcutaneous injection for 4 weeks in 6-week cycles. Part 1 utilizes an accelerated dose escalation design with single patient cohort for the first 3 dose levels. Part 2 uses a 3+3 dose escalation design. Part 3 uses a 3+3 dose escalation of BJ-001 but in combination with a fixed-dose PD-(L)1 inhibitor. Dose escalation will proceed based on clinical safety and tolerability data observed during the Dose Limiting Toxicity (DLT) period, i.e., Cycle 1 Days 1 through 28 for Part 1 and Cycle 1 Days 1 through 42 for Parts 2 and 3. Adult patients (ECOG PS ≤ 2) with locally advanced or metastatic solid tumors refractory to or intolerant of all existing therapies are eligible for Phase 1a. Phase 1b will enroll cohorts of adult patients with selected solid tumors known to have high levels of integrin expression at the Maximum Tolerated Dose or Recommended Phase 2 Dose of BJ-001 in combination with a PD-(L)1 inhibitor, as identified in Phase 1a, Part 3. Results: As of Jan 31, 2021, 9 patients have received BJ-001 dosing as a single agent at 0.21 µg/kg (n = 1), 0.9 µg/kg (n = 1), 3 µg/kg (n = 1), 6 µg/kg (n = 3), or 10 µg/kg (n = 3) in Phase 1a Parts 1 and 2, wherein 7 patients, including 1 patient in the 10 µg/kg cohort, have completed the DLT period. Among these 7 patients, 2 (1 in 3 µg/kg and 1 in 6 µg/kg cohorts) have stable disease and are still receiving BJ-001 treatment beyond Cycle 1. The longest duration in the study, to date, is approximately 4 cycles (over 5 months). Treatment Emergent Adverse Events (TRAEs) include injection site reactions (6/7, Grade 1-2), anorexia (2/7, Grade 1-2), cytokine release syndrome (1/7, Grade 1, resolved in 1 day), and temporal wasting (1/7, Grade 1). The AEs did not result in dose interruption or dose level adjustment. No DLTs observed to date. With escalating doses, a trend of increased post-dose NK cell counts observed, whereas Regulatory T cell (Treg) counts remained stable. Conclusions: To date, BJ-001 is well tolerated up to 6 µg/kg. The safety evaluation for 10 µg/kg is ongoing. The observed NK and Treg cell profiles are consistent with known IL-15 biology. Clinical trial information: NCT04294576.
- Published
- 2021
12. BET inhibitors: a novel epigenetic approach
- Author
-
Deborah Blythe Doroshow, Joseph Paul Eder, and Patricia LoRusso
- Subjects
0301 basic medicine ,Drug ,medicine.drug_class ,media_common.quotation_subject ,Genes, myc ,Antineoplastic Agents ,chemical and pharmacologic phenomena ,Biology ,DNA methyltransferase ,B7-H1 Antigen ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Epigenetics ,media_common ,Histone deacetylase inhibitor ,Proteins ,Drug Synergism ,hemic and immune systems ,Hematology ,Cell cycle ,Bromodomain ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Demethylase ,Histone deacetylase - Abstract
Epigenetics has been defined as 'the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.' Currently, several classes of anticancer drugs function at the epigenetic level, including inhibitors of DNA methyltransferase, histone deacetylase (HDAC), lysine-specific demethylase 1, zeste homolog 2, and bromodomain and extra-terminal motif (BET) proteins.BET proteins have multiple functions, including the initiation and elongation of transcription and cell cycle regulation. In recent years, inhibitors of BET proteins have been developed as anticancer agents. These inhibitors exhibit selectivity for tumor cells by preferentially binding to superenhancers, noncoding regions of DNA critical for the transcription of genes that determine a cell's identity. Preclinical research on BET inhibitors has identified them as a potential means of targeting MYC.Early clinical trials with BET inhibitors have had mixed results, with few responses in both hematologic and solid tumors that tend to be short-lived. Toxicities have included severe, thrombocytopenia, fatigue, nausea, vomiting, and diarrhea; GI side-effects, fatigue, and low-grade dysgeusia have limited compliance. However, preclinical data suggest that BET inhibitors may have a promising future in combination with other agents. They appear to be able to overcome resistance to targeted agents and have strong synergy with immune checkpoint inhibitors as well as with multiple epigenetic agents, particularly HDAC inhibitors. In many instances, BET and HDAC inhibitors were synergistic at reduced doses, suggesting a potential means of avoiding the overlapping toxicities of the two drug classes.BET inhibitors provide a novel approach to epigenetic anticancer therapy. However, to date they appear to have limited efficacy as single agents. A focus on BET inhibitors in combination with other drugs such as targeted and/or as other epigenetic agents is warranted, due to limited monotherapy activity, including pharmacodynamic correlatives differential activity amongst select drug combinations.
- Published
- 2017
13. Emotionally Disturbed
- Author
-
Deborah Blythe Doroshow
- Published
- 2019
14. New Directions in the Historiography of Psychiatry
- Author
-
Deborah Blythe Doroshow, Matthew Gambino, and Mical Raz
- Subjects
Adult ,Hospitals, Psychiatric ,Male ,Mental Health Services ,History ,Context (language use) ,Criminology ,Intellectual history ,Economic Justice ,History, 21st Century ,Politics ,Social Justice ,medicine ,Humans ,Sociology ,Psychiatry ,Cultural history ,Health Policy ,Historiography ,History, 20th Century ,Middle Aged ,Mental illness ,medicine.disease ,Mental health ,United States ,Geriatrics and Gerontology - Abstract
Gerald Grob's work in the history of psychiatry over the course of almost fifty years created a model for how historians might successfully situate mental health in its social and political context, and how inseparable it was from this context. Over the last twenty years, the field has grown tremendously. Historians have incorporated categories of analysis like gender and race, methodologies like cultural history and intellectual history, and sought to continue Grob's quest to understand American mental health history as a critical component of American history writ large. In this piece, we suggest several potential areas for future study. Building on Grob's work on the asylum, we focus on the continued need to explore the texture of lived experience for both practitioners and those experiencing mental illness, both within and beyond the institution. In an era when the politics of deinstitutionalization continue to shape the modern mental health enterprise, we suggest that further examination of the consequences of deinstitutionalization is both inherently rich and relevant to contemporary mental health practice. Finally, we discuss opportunities for historians to engage with policymaking and social justice, pointing to incarceration and juvenile justice as two especially relevant areas for further study.
- Published
- 2018
15. Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes
- Author
-
Deborah Blythe Doroshow, Ignacio Melero, Katerina Politi, David L. Rimm, Katherine Hastings, Kurt A. Schalper, Miguel F. Sanmamed, Lieping Chen, and Roy S. Herbst
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Inflammation ,B7-H1 Antigen ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Carcinoma ,Humans ,Immunologic Factors ,In patient ,Lung cancer ,Chemotherapy ,Clinical Trials as Topic ,business.industry ,Immunotherapy ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Non small cell ,medicine.symptom ,business - Abstract
Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non–small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.
- Published
- 2018
16. Abstract A080: Olaparib and the ATR inhibitor AZD6738 in relapsed, refractory cancer patients with homologous recombination (HR) repair mutations – OLAPCO
- Author
-
Khanh T. Do, Manuel Avedissian, Joseph Paul Eder, Patricia LoRusso, Navid Hafez, Vicki L. Keedy, Geoffrey I. Shapiro, Colin Glover, Haider Mahdi, Peter G. Mortimer, Davendra Sohal, Juliane M. Juergensmeier, and Deborah Blythe Doroshow
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Performance status ,business.industry ,Anemia ,Cancer ,medicine.disease ,Discontinuation ,Olaparib ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,chemistry ,Prostate ,030220 oncology & carcinogenesis ,Internal medicine ,PARP inhibitor ,Toxicity ,Medicine ,business - Abstract
Introduction: Olaparib is a PARP inhibitor (PARPi) that provides significant clinical benefit in several BRCA-mutant cancers, including ovarian, breast, pancreas and prostate. The benefit is reduced considerably in patients with multiple prior lines of therapy and olaparib resistance has no specific treatment. PARP inhibition results in replication stress (RS) due to unrepaired single strand DNA breaks (SSB) and PARP trapping in BRCA- and other HR repair-deficient tumors. ATR has critical roles in the cellular response to SSB and RS. This makes ATR inhibitors an attractive partner with olaparib, since ATR inhibition has the potential to reverse the two major mechanisms of PARP inhibitor resistance, including restored HR or stabilization of stalled replication forks. The OLAPCO trial (NCT02576444 clinicaltrials.gov) investigated. the combination of olaparib and AZD6738, an inhibitor of ATR, in relapsed, refractory cancer patients with tumors harboring HR repair mutations and in patients with BRCA-mutated PARPi pre-treated/resistant high-grade serous ovarian cancer (HGSOC). Methods: Patients with treatment-refractory, relapsed cancer were enrolled at 4 participating centers. Germline and somatic mutations had to be deleterious by COSMIC or ClinVar for eligibility. Performance status and organ function requirements were standard for early phase trials. Olaparib was given at 300 mg bid daily and AZD6738 at 160 mg daily days 1-7 in a 28-day cycle. Patients were treated until progression. Objective response was assessed by RECIST1.1 and toxicity was assessed by CTCAE4.0. Endpoints were confirmed complete [CR] or partial [PR] response rate and clinical benefit (CB) rate (response [PR] and stable disease [SD] for > 16 weeks). Results: We enrolled 24 patients; 17 (71%) females; median age 59 (36-78) years. Patients were heavily pretreated, with a median of 4 (0-10) prior regimens. Myelosuppression, especially anemia and thrombocytopenia, was the most frequent toxicity but no patient required discontinuation. Two patients required olaparib reductions for anemia. At the time of data cut-off, 20 patients are evaluable for response assessment. One of 5 patients with ATM mutations had a CR, 2 patients have CB ongoing at 12+ months. Of 7 patients with HGSOC resistant to platinum and PARP inhibitors (1-3 prior agents), 1 achieved a PR ( -90%), 3 had a best response of SD with regression < 30% (1 ongoing at 1 year) and 3 patients had progression (PD) as best response (Table 1). No other mutation or cancer type demonstrated objective response. Conclusions: The combination of olaparib and the ATR inhibitor AZD6738 demonstrated preliminary activity in patients with tumors harboring ATM mutations and in PARPi-resistant BRCA1/2-mutated HGSOC. Activity in ATM loss with an ATR inhibitor is consistent with the expected synthetic lethality of these interwoven DNA repair pathways. The encouraging data in HGSOC patients who have already progressed on a PARP inhibitor warrants additional study to further define the potential of this regimen to reverse PARPi resistance in BRCA-mutated HGSOC and other relevant solid tumors. The durability of responses in both groups (4 >1 year) is promising. Table 1MutationATMBRCA prostate pancreasBRCA Prior PARPi HGSOCCHEK2MUS81PALB2IDH and SDHD #5471142 CR1 PR0 1 SD > 4 mos213 11 PD 33112 Inevaluable110 11 Citation Format: Joseph Paul Eder, Davendra Sohal, Haider Mahdi, Khanh Do, Vicki Keedy, Navid Hafez, Deborah Doroshow, Manuel Avedissian, Peter Mortimer, Colin Glover, Patricia LoRusso, Juliane M Juergensmeier, Geoffrey I Shapiro. Olaparib and the ATR inhibitor AZD6738 in relapsed, refractory cancer patients with homologous recombination (HR) repair mutations – OLAPCO [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A080. doi:10.1158/1535-7163.TARG-19-A080
- Published
- 2019
17. Treatment of Advanced Non-Small Cell Lung Cancer in 2018
- Author
-
Deborah Blythe Doroshow and Roy S. Herbst
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,MEDLINE ,Medical Oncology ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Carcinoma ,Humans ,Molecular Targeted Therapy ,Lung cancer ,Protein Kinase Inhibitors ,Clinical Trials as Topic ,business.industry ,Disease progression ,Cell Cycle Checkpoints ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Disease Progression ,Non small cell ,business - Published
- 2018
18. Residential Treatment and the Invention of the Emotionally Disturbed Child in Twentieth-Century America
- Author
-
Deborah Blythe Doroshow
- Subjects
History ,medicine.medical_specialty ,Adolescent ,Medicine (miscellaneous) ,Poison control ,Suicide prevention ,Occupational safety and health ,03 medical and health sciences ,0302 clinical medicine ,Injury prevention ,medicine ,Humans ,0601 history and archaeology ,Affective Symptoms ,Psychiatry ,Child ,Residential Treatment ,General Nursing ,Social work ,business.industry ,Human factors and ergonomics ,06 humanities and the arts ,General Medicine ,History, 20th Century ,Mental health ,United States ,030227 psychiatry ,060105 history of science, technology & medicine ,Law ,Child, Preschool ,business ,Medical literature - Abstract
In the 1930s, children who were violent, depressed, psychotic, or suicidal would likely have been labeled delinquent and sent to a custodial training school for punitive treatment. But starting in the 1940s, a new group of institutions embarked on a new experiment to salvage and treat severely deviant children. In the process, psychiatrists, psychologists, and social workers at these residential treatment centers (RTCs) made visible, and indeed invented, a new patient population. This article uses medical literature, popular media, and archival sources from several RTCs to argue that staff members created what they called the "emotionally disturbed" child. While historians have described the identification of the mildly "troublesome" child in child guidance clinics, I demonstrate how a much more severely ill child was identified and defined in the process of creating residential treatment and child mental health as a professional enterprise.
- Published
- 2016
19. An Alarming Solution: Bedwetting, Medicine, and Behavioral Conditioning in Mid‐Twentieth‐Century America
- Author
-
Deborah Blythe Doroshow
- Subjects
History ,Psychoanalysis ,Bedwetting alarm ,media_common.quotation_subject ,Child Rearing ,Optimism ,History and Philosophy of Science ,Behavior Therapy ,Enuresis ,Behaviorism ,Earth and Planetary Sciences (miscellaneous) ,medicine ,Humans ,Sociology ,media_common ,Child rearing ,Multitude ,Historical Article ,History, 20th Century ,United States ,Epistemology ,Equipment failure ,Child, Preschool ,Equipment Failure ,medicine.symptom ,Nocturnal Enuresis - Abstract
This article explores the history of the bedwetting alarm, invented in 1938 by two psychologists to cure enuresis, or bedwetting, using the principles of classical conditioning. Infused with the optimism of behaviorism, the bedwetting alarm unexpectedly proved difficult to implement in practice, bearing a multitude of unanticipated complications that hindered its widespread acceptance. Introduced as a medical and psychological technology, in practice the alarm was also a child‐rearing device, encouraging the kind of behavioristic attitudes that had prompted its initial development, while simultaneously promoting the child‐centered approach that would become dominant in the early 1950s. The life story of the bedwetting alarm muddies the traditional account of how child‐rearing theories progressed in tidy succession, suggesting both that behavioristic approaches did not die out in the 1930s and that elements of permissive child‐rearing were being considered earlier than we traditionally assume.
- Published
- 2010
20. Hypothyroidism to predict for long term survival in patients with fosbretabulin treated anaplastic thyroid carcinoma
- Author
-
Hari Anant Deshpande, Aarti K. Bhatia, Deborah Blythe Doroshow, and Scot C. Remick
- Subjects
Oncology ,Combretastatin ,Cancer Research ,Poor prognosis ,medicine.medical_specialty ,Systemic disease ,Fosbretabulin ,business.industry ,medicine.disease ,Anaplastic thyroid carcinoma ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Long term survival ,medicine ,In patient ,Anaplastic thyroid cancer ,business - Abstract
e18108Background: Anaplastic thyroid cancer (ATC) is considered a systemic disease at the time of diagnosis and has a poor prognosis. A long-term survivor (Case #1) treated with combretastatin (fos...
- Published
- 2018
21. Performing a Cure for Schizophrenia: Insulin Coma Therapy on the Wards
- Author
-
Deborah Blythe Doroshow
- Subjects
Hospitals, Psychiatric ,History ,medicine.medical_specialty ,Staffing ,Psychiatric history ,parasitic diseases ,medicine ,Humans ,Insulin ,Psychiatric Somatic Therapies ,Psychiatry ,business.industry ,History, 20th Century ,Mental illness ,medicine.disease ,Somatic psychology ,Treatment Outcome ,Schizophrenia ,Insulin Coma ,Personal experience ,Geriatrics and Gerontology ,Biological psychiatry ,business ,Discipline - Abstract
Most historians of psychiatry regard insulin coma therapy (ICT) either as an embarrassing stumble on the path to modern biological psychiatry or as one member of a long line of somatic therapies used to treat mental illness in the mid-twentieth century. This article explores the ICT era, roughly 1933-60, as a key moment in the development of American psychiatry. Developed only ten years after insulin had been embraced as a "miracle drug" for the treatment of diabetes, ICT was perceived by psychiatrists as a means of bringing their field closer to mainstream medicine, particularly to neurology. In addition, the story of ICT reveals how a treatment never quite proven on paper was unquestionably efficacious in the local world in which it was performed. An institutionally-based treatment, ICT was administered in a specific area of the mental hospital deemed the insulin unit, a room with its own staff, practices, and attitudes toward mental illness. There, psychiatrists often experienced wondrous recoveries of individual, formerly intractable patients. These intense personal experiences allowed psychiatrists to feel truly efficacious, enabling them to reinvent themselves as medical doctors rather than behavioral and disciplinary supervisors. The confidence they derived from this capacity, along with the operating room-like setting of the insulin unit, the unit's specialized staffing and group bond, and the availability of both risk-assessment tests and a medley of treatments that countered side effects and complications, allowed ICT to be understood as an efficacious treatment for schizophrenia within the local world in which it was administered.
- Published
- 2006
22. Matthew Smith, An Alternative History of Hyperactivity: Food Additives and the Feingold Diet
- Author
-
Deborah Blythe Doroshow
- Subjects
Gerontology ,History ,food.ingredient ,food ,Traditional medicine ,Food additive ,medicine ,Medicine (miscellaneous) ,Feingold diet ,medicine.disease ,Psychology - Published
- 2012
23. The Progressive Past of Residential Treatment of Emotionally Disturbed Children
- Author
-
Deborah Blythe Doroshow
- Subjects
Gerontology ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Psychological intervention ,Poison control ,History of medicine ,Suicide prevention ,Occupational safety and health ,Haven ,Pediatrics, Perinatology and Child Health ,Injury prevention ,Medicine ,Girl ,business ,Psychiatry ,media_common - Abstract
In January 1949, 9-year-old Betty stepped through the doors of the Cincinnati Child Guidance Home. For the next 2 years, the Home would attempt to treat her severe emotional and behavioral problems in an experimental approach called residential treatment. After 4 years of child welfare and child guidance interventions, the Home was a last resort. Betty's home life was a mess. When she was 3, her “promiscuous” mother had deserted the family, and her father, an alcoholic, was gone most of the time. The house was so messy that the family was evicted over and over.1 Two foster homes later, Betty arrived at a local child guidance clinic, where the staff noted her “extreme stubbornness, destructive behavior, vomiting, soiling, and diurnal and nocturnal enuresis.”1 Betty's third foster mother, Mrs F, resented having to care for this “defective” child. She regularly beat Betty, who had blank staring spells and skipped school. Fed up with this behavior, Mrs F begged the child guidance clinic to admit the girl to a psychiatric hospital.1 Looking back, we might imagine that Betty would have been sent away to a state mental hospital or a punitive custodial institution for delinquent girls. Twenty years earlier, this might have been the case,2 but, in fact, Betty had a very different experience than what we might expect. The Cincinnati Child Guidance Home, where … Address correspondence to Deborah Blythe Doroshow, MA, MPhil, Section of the History of Medicine, Yale University, 333 Cedar St, Sterling Hall of Medicine, L-132, New Haven, CT 06520. E-mail: deborah.doroshow{at}yale.edu
- Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.