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1. Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study

Author

Ercan, Ayse Bahar, Aronson, Melyssa, Fernandez, Nicholas R, Chang, Yuan, Levine, Adrian, Liu, Zhihui Amy, Negm, Logine, Edwards, Melissa, Bianchi, Vanessa, Stengs, Lucie, Chung, Jiil, Al-Battashi, Abeer, Reschke, Agnes, Lion, Alex, Ahmad, Alia, Lassaletta, Alvaro, Reddy, Alyssa T, Al-Darraji, Amir F, Shah, Amish C, Van Damme, An, Bendel, Anne, Rashid, Aqeela, Margol, Ashley S, Kelly, Bethany L, Pencheva, Bojana, Heald, Brandie, Lemieux-Anglin, Brianna, Crooks, Bruce, Koschmann, Carl, Gilpin, Catherine, Porter, Christopher C, Gass, David, Samuel, David, Ziegler, David S, Blumenthal, Deborah T, Kuo, Dennis John, Hamideh, Dima, Basel, Donald, Khuong-Quang, Dong-Anh, Stearns, Duncan, Opocher, Enrico, Carceller, Fernando, Baris Feldman, Hagit, Toledano, Helen, Winer, Ira, Scheers, Isabelle, Fedorakova, Ivana, Su, Jack M, Vengoechea, Jaime, Sterba, Jaroslav, Knipstein, Jeffrey, Hansford, Jordan R, Gonzales-Santos, Julieta Rita, Bhatia, Kanika, Bielamowicz, Kevin J, Minhas, Khurram, Nichols, Kim E, Cole, Kristina A, Penney, Lynette, Hjort, Magnus Aasved, Sabel, Magnus, Gil-da-Costa, Maria Joao, Murray, Matthew J, Miller, Matthew, Blundell, Maude L, Massimino, Maura, Al-Hussaini, Maysa, Al-Jadiry, Mazin F, Comito, Melanie A, Osborn, Michael, Link, Michael P, Zapotocky, Michal, Ghalibafian, Mithra, Shaheen, Najma, Mushtaq, Naureen, Waespe, Nicolas, Hijiya, Nobuko, Fuentes-Bolanos, Noemi, Ahmad, Olfat, Chamdine, Omar, Roy, Paromita, Pichurin, Pavel N, Nyman, Per, Pearlman, Rachel, Auer, Rebecca C, Sukumaran, Reghu K, Kebudi, Rejin, Dvir, Rina, Raphael, Robert, Elhasid, Ronit, McGee, Rose B, Chami, Rose, Noss, Ryan, Tanaka, Ryuma, Raskin, Salmo, Sen, Santanu, Lindhorst, Scott, Perreault, Sebastien, Caspi, Shani, Riaz, Shazia, Constantini, Shlomi, Albert, Sophie, Chaleff, Stanley, Bielack, Stefan, Chiaravalli, Stefano, Cramer, Stuart Louis, Roy, Sumita, Cahn, Suzanne, Penna, Suzanne, Hamid, Syed Ahmer, Ghafoor, Tariq, Imam, Uzma, Larouche, Valerie, Magimairajan Issai, Vanan, Foulkes, William D, Lee, Yi Yen, Nathan, Paul C, Maruvka, Yosef E, Greer, Mary-Louise C, Durno, Carol, Shlien, Adam, Ertl-Wagner, Birgit, Villani, Anita, Malkin, David, Hawkins, Cynthia, Bouffet, Eric, Das, Anirban, and Tabori, Uri

Published
2024
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2. Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency

Author

Das, Anirban, Sudhaman, Sumedha, Morgenstern, Daniel, Coblentz, Ailish, Chung, Jiil, Stone, Simone C, Alsafwani, Noor, Liu, Zhihui Amy, Karsaneh, Ola Abu Al, Soleimani, Shirin, Ladany, Hagay, Chen, David, Zatzman, Matthew, Cabric, Vanja, Nobre, Liana, Bianchi, Vanessa, Edwards, Melissa, Sambira Nahum, Lauren C, Ercan, Ayse B, Nabbi, Arash, Constantini, Shlomi, Dvir, Rina, Yalon-Oren, Michal, Campino, Gadi Abebe, Caspi, Shani, Larouche, Valerie, Reddy, Alyssa, Osborn, Michael, Mason, Gary, Lindhorst, Scott, Bronsema, Annika, Magimairajan, Vanan, Opocher, Enrico, De Mola, Rebecca Loret, Sabel, Magnus, Frojd, Charlotta, Sumerauer, David, Samuel, David, Cole, Kristina, Chiaravalli, Stefano, Massimino, Maura, Tomboc, Patrick, Ziegler, David S, George, Ben, Van Damme, An, Hijiya, Nobuko, Gass, David, McGee, Rose B, Mordechai, Oz, Bowers, Daniel C, Laetsch, Theodore W, Lossos, Alexander, Blumenthal, Deborah T, Sarosiek, Tomasz, Yen, Lee Yi, Knipstein, Jeffrey, Bendel, Anne, Hoffman, Lindsey M, Luna-Fineman, Sandra, Zimmermann, Stefanie, Scheers, Isabelle, Nichols, Kim E, Zapotocky, Michal, Hansford, Jordan R, Maris, John M, Dirks, Peter, Taylor, Michael D, Kulkarni, Abhaya V, Shroff, Manohar, Tsang, Derek S, Villani, Anita, Xu, Wei, Aronson, Melyssa, Durno, Carol, Shlien, Adam, Malkin, David, Getz, Gad, Maruvka, Yosef E, Ohashi, Pamela S, Hawkins, Cynthia, Pugh, Trevor J, Bouffet, Eric, and Tabori, Uri

Subjects
Rare Diseases, Pediatric, Cancer, Neurosciences, Pediatric Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, B7-H1 Antigen, Biomarkers, Tumor, Child, DNA Repair, DNA Replication, Female, Germ-Line Mutation, Humans, Immune Checkpoint Inhibitors, Male, Neoplasms, Prospective Studies, Retrospective Studies, Survival Analysis, Tumor Microenvironment, Young Adult, Medical and Health Sciences, Immunology
Abstract

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Published
2022

3. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G, Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N, Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T, Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D, Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R, Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C, Link, Michael P, De Mola, Rebecca Loret, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L, MagimairajanIssai, Vanan, Maher, Ossama M, Massimino, Maura, McGee, Rose B, Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E, Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, and Ziegler, David S

Subjects
Cancer, Brain Disorders, Clinical Research, Digestive Diseases, Prevention, Brain Cancer, Rare Diseases, Adolescent, Adult, Brain Neoplasms, Child, Child, Preschool, Colorectal Neoplasms, DNA Mismatch Repair, DNA Repair Enzymes, Early Detection of Cancer, Female, Follow-Up Studies, Humans, Male, Neoplastic Syndromes, Hereditary, Population Surveillance, Prognosis, Prospective Studies, Survival Rate, United States, Young Adult, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeConstitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.Patients and methodsData were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.ResultsA total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years.ConclusionSurveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

4. Mapping the coverage of attributes in validated instruments that evaluate primary healthcare from the patient perspective

Author

Lévesque Jean-Frédéric, Haggerty Jeannie, Beninguissé Gervais, Burge Frederick, Gass David, Beaulieu Marie-Dominique, Pineault Raynald, Santor Darcy, and Beaulieu Christine

Subjects
Primary healthcare, Quality of healthcare, Qualitative analysis, Measurement instruments, Medicine (General), R5-920
Abstract

Abstract Background Primary healthcare in developed countries is undergoing important reforms, and these require evaluation strategies to assess how well the population's expectations are being met. Although numerous instruments are available to evaluate primary healthcare (PHC) from the patient perspective, they do not all measure the same range of constructs. To analyze the extent to which important PHC attributes are covered in validated instruments measuring quality of care from the patient perspective. Method We systematically identified validated instruments from the literature and by consulting experts. Using a Delphi consensus-building process, Canadian PHC experts identified and operationally defined 24 important PHC attributes. One team member mapped instrument subscales to these operational definitions; this mapping was then independently validated by members of the research team and conflicts were resolved by the PHC experts. Results Of the 24 operational definitions, 13 were evaluated as being best measured by patients, 10 by providers, three by administrative databases and one by chart audits (some being best measured by more than one source). Our search retained 17 measurement tools containing 118 subscales. After eliminating redundancies, we mapped 13 unique measurement tools to the PHC attributes. Accessibility, relational continuity, interpersonal communication, management continuity, respectfulness and technical quality of clinical care were the attributes widely covered by available instruments. Advocacy, management of clinical information, comprehensiveness of services, cultural sensitivity, family-centred care, whole-person care and equity were poorly covered. Conclusions Validated instruments to evaluate PHC quality from the patient perspective leave many important attributes of PHC uncovered. A complete assessment of PHC quality will require adjusting existing tools and/or developing new instruments.

Published
2012
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5. Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature

Author

Martin-Misener Ruth, Fleming Mark, Murphy Andrea L, Sketris Ingrid S, MacCara Mary, and Gass David

Subjects
Nursing, RT1-120
Abstract

Abstract Background Keeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners. Methods Nurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS. Results Twenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources. Conclusion The use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes.

Published
2006
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6. Supplementary Figures S1-S5 from Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti–PD-1 Monotherapy: A Report from the International RRD Consortium

Author

Das, Anirban, primary, Fernandez, Nicholas R., primary, Levine, Adrian, primary, Bianchi, Vanessa, primary, Stengs, Lucie K., primary, Chung, Jiil, primary, Negm, Logine, primary, Dimayacyac, Jose Rafael, primary, Chang, Yuan, primary, Nobre, Liana, primary, Ercan, Ayse B., primary, Sanchez-Ramirez, Santiago, primary, Sudhaman, Sumedha, primary, Edwards, Melissa, primary, Larouche, Valerie, primary, Samuel, David, primary, Van Damme, An, primary, Gass, David, primary, Ziegler, David S., primary, Bielack, Stefan S., primary, Koschmann, Carl, primary, Zelcer, Shayna, primary, Yalon-Oren, Michal, primary, Campino, Gadi Abede, primary, Sarosiek, Tomasz, primary, Nichols, Kim E., primary, Loret De Mola, Rebecca, primary, Bielamowicz, Kevin, primary, Sabel, Magnus, primary, Frojd, Charlotta A., primary, Wood, Matthew D., primary, Glover, Jason M., primary, Lee, Yi-Yen, primary, Vanan, Magimairajan, primary, Adamski, Jenny K., primary, Perreault, Sebastien, primary, Chamdine, Omar, primary, Hjort, Magnus Aasved, primary, Zapotocky, Michal, primary, Carceller, Fernando, primary, Wright, Erin, primary, Fedorakova, Ivana, primary, Lossos, Alexander, primary, Tanaka, Ryuma, primary, Osborn, Michael, primary, Blumenthal, Deborah T., primary, Aronson, Melyssa, primary, Bartels, Ute, primary, Huang, Annie, primary, Ramaswamy, Vijay, primary, Malkin, David, primary, Shlien, Adam, primary, Villani, Anita, primary, Dirks, Peter B., primary, Pugh, Trevor J., primary, Getz, Gad, primary, Maruvka, Yosef E., primary, Tsang, Derek S., primary, Ertl-Wagner, Birgit, primary, Hawkins, Cynthia, primary, Bouffet, Eric, primary, Morgenstern, Daniel A., primary, and Tabori, Uri, primary

Published
2024
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7. Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti–PD-1 Monotherapy: A Report from the International RRD Consortium

Author

Das, Anirban, primary, Fernandez, Nicholas R., additional, Levine, Adrian, additional, Bianchi, Vanessa, additional, Stengs, Lucie K., additional, Chung, Jiil, additional, Negm, Logine, additional, Dimayacyac, Jose Rafael, additional, Chang, Yuan, additional, Nobre, Liana, additional, Ercan, Ayse B., additional, Sanchez-Ramirez, Santiago, additional, Sudhaman, Sumedha, additional, Edwards, Melissa, additional, Larouche, Valerie, additional, Samuel, David, additional, Van Damme, An, additional, Gass, David, additional, Ziegler, David S., additional, Bielack, Stefan S., additional, Koschmann, Carl, additional, Zelcer, Shayna, additional, Yalon-Oren, Michal, additional, Campino, Gadi Abede, additional, Sarosiek, Tomasz, additional, Nichols, Kim E., additional, Loret De Mola, Rebecca, additional, Bielamowicz, Kevin, additional, Sabel, Magnus, additional, Frojd, Charlotta A., additional, Wood, Matthew D., additional, Glover, Jason M., additional, Lee, Yi-Yen, additional, Vanan, Magimairajan, additional, Adamski, Jenny K., additional, Perreault, Sebastien, additional, Chamdine, Omar, additional, Hjort, Magnus Aasved, additional, Zapotocky, Michal, additional, Carceller, Fernando, additional, Wright, Erin, additional, Fedorakova, Ivana, additional, Lossos, Alexander, additional, Tanaka, Ryuma, additional, Osborn, Michael, additional, Blumenthal, Deborah T., additional, Aronson, Melyssa, additional, Bartels, Ute, additional, Huang, Annie, additional, Ramaswamy, Vijay, additional, Malkin, David, additional, Shlien, Adam, additional, Villani, Anita, additional, Dirks, Peter B., additional, Pugh, Trevor J., additional, Getz, Gad, additional, Maruvka, Yosef E., additional, Tsang, Derek S., additional, Ertl-Wagner, Birgit, additional, Hawkins, Cynthia, additional, Bouffet, Eric, additional, Morgenstern, Daniel A., additional, and Tabori, Uri, additional

Published
2024
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10. The Clinical and Biological Landscape of Constitutional Mismatch Repair Deficiency: An IRRDC Study

Author

Ercan, Ayse Bahar, primary, Aronson, Melyssa, additional, Fernandez, Nicholas R., additional, Chang, Yuan, additional, Levine, Adrian, additional, Liu, Amy Zhihui, additional, Negm, Logine, additional, Edwards, Melissa, additional, Bianchi, Vanessa, additional, Stengs, Lucie, additional, Chung, Brian, additional, Al-Battashi, Abeer, additional, Reschke, Agnes, additional, Lion, Alex, additional, Ahmad, Alia, additional, Lassaletta, Alvaro, additional, Reddy, Alyssa, additional, Al-Darraji, Amir Fadhil, additional, Shah, Amish C., additional, Van Damme, An, additional, Bendel, Anne E., additional, Rashid, Aqeela, additional, Margol, Ashley S., additional, Kelly, Bethany L., additional, Pencheva, Bojana, additional, Heald, Brandie, additional, Anglin, Brianna Lemieux, additional, Crooks, Bruce, additional, Koschmann, Carl, additional, Gilpin, Catherine, additional, Porter, Christopher C., additional, Gass, David, additional, Samuel, David, additional, Ziegler, David S., additional, Blumenthal, Deborah T., additional, Kuo, Dennis John, additional, Hamideh, Dima, additional, Basel, Donald, additional, Khuong Quang, Dong Anh, additional, Stearns, Duncan, additional, Opocher, Enrico, additional, Carcellar, Fernando, additional, Feldman, Hagit Baris, additional, Toledano, Helen, additional, Winer, Ira S., additional, Scheers, Isabelle, additional, Fedorakova, Ivana, additional, Su, Jack M., additional, Barrios, Jaime Vengoechea, additional, Sterba, Jaroslav, additional, Knipstein, Jeffrey, additional, Hansford, Jordan R., additional, Gonzales-Santos, Julieta Rita, additional, Bhatia, Kanika, additional, Bielamowicz, Kevin J., additional, Minhas, Khurram, additional, Nichols, Kim E., additional, Cole, Kristina A., additional, Penney, Lynette, additional, Hjort, Magnus Aasved, additional, Sabel, Magnus, additional, Gil-da-Costa, Maria Joao, additional, Murray, Matthew J., additional, Miller, Matthew, additional, Blundell, Maude, additional, Massimino, Maura, additional, Al-Hussaini, Maysa, additional, Al-Jadiry, Mazin Faisal, additional, Comito, Melanie A., additional, Osborn, Michael, additional, Link, Michael P., additional, Zapotocky, Michal, additional, Ghalibafian, Mithra, additional, Shaheen, Najma, additional, Mushtaq, Naureen, additional, Waespe, Nicolas, additional, Hijiya, Nobuko, additional, Fuentes Bolanos, Noemi, additional, Ahmad, Olfat, additional, Chamdine, Omar, additional, Roy, Paromita, additional, Pichurin, Pavel N., additional, Nymen, Per, additional, Pearlman, Rachel, additional, Auer, Rebecca C., additional, Sukumaran, Reghu K., additional, Kebudi, Rejin, additional, Dvir, Rina, additional, Raphael, Robert, additional, Elhasid, Ronit, additional, McGee, Rose B., additional, Chami, Rose, additional, Noss, Ryan, additional, Tanaka, Ryuma, additional, Raskin, Salmo, additional, Sen, Santanu, additional, Lindhorst, Scott, additional, Perreault, Sebastian, additional, Caspi, Shani, additional, Riaz, Shazia, additional, Constantini, Shlomi, additional, Albert, Sophie, additional, Chaleff, Stanley, additional, Bielack, Stefan S., additional, Chiaravalli, Stefano, additional, Cramer, Stuart Louis, additional, Roy, Sumita, additional, Cahn, Suzanne, additional, Penna, Suzanne, additional, Hamid, Syed Ahmer, additional, Ghafoor, Tariq, additional, Imam, Uzma, additional, Larouche, Valerie, additional, MagimairajanIssai, Vanan, additional, Foulkes, William, additional, Lee, Yi Yen, additional, Maruvka, Yosef E., additional, Greer, Mary-Louise C., additional, Durno, Carol, additional, Shlien, Adam, additional, Ertl-Wagner, Birgit, additional, Villani, Anita, additional, Malkin, David, additional, Hawkins, Cynthia, additional, Bouffet, Eric, additional, Das, Anirban, additional, and Tabori, Uri, additional

Published
2023
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11. EPCT-06. Phase I study of ribociclib and everolimus post-radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG): Updated report from the COllaborative Network for NEuro-Oncology Clinical Trials (CONNECT)

Author

Lazow, Margot A, primary, DeWire, Mariko, additional, Campagne, Olivia, additional, Leach, James L, additional, Fuller, Christine, additional, Kumar, Shiva Senthil, additional, Stanek, Joseph, additional, de Blank, Peter, additional, Hummel, Trent R, additional, Pillay-Smiley, Natasha, additional, Salloum, Ralph, additional, Stevenson, Charles B, additional, Baxter, Patricia, additional, Gass, David, additional, Goldman, Stewart, additional, Leary, Sarah E S, additional, Carle, Adam, additional, Lane, Adam, additional, Drissi, Rachid, additional, Stewart, Clinton, additional, and Fouladi, Maryam, additional

Published
2022
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12. IMMU-13. Dual CTLA4/ PD-1 blockade improves survival for replication-repair deficient high-grade gliomas failing single agent PD-1 inhibition: An IRRDC study

Author

Das, Anirban, primary, Morgenstern, Daniel, additional, Bianchi, Vanessa, additional, Sudhaman, Sumedha, additional, Edwards, Melissa, additional, Stengs, Lucie, additional, Larouche, Valerie, additional, Samuel, David, additional, Van Damme, An, additional, Gass, David, additional, Ziegler, David, additional, Bielack, Stefan, additional, Zelcer, Shayna, additional, Yalon, Michal, additional, Constantini, Shlomi, additional, Sarosiek, Tomasz, additional, Libionka, Witold, additional, Nichols, Kim, additional, De Mola, Rebecca Loret, additional, Bielamowicz, Kevin, additional, Sabel, Magnus, additional, Frojd, Charlotta, additional, Wood, Matthew D, additional, Migueis, Joana Cristiano Sous, additional, Abongwa, Chenue, additional, Yen, Lee Yi, additional, Stearns, Duncan, additional, Opocher, Enrico, additional, Bhatia, Kanika, additional, Sen, Santanu, additional, Cantero, Eduardo Quiroga, additional, Paez, Palma Solano, additional, Crooks, Bruce, additional, Magimairajan, Vanan, additional, Reddy, Alyssa, additional, Adamski, Jenny, additional, Mason, Gary, additional, Lindhorst, Scott, additional, Aronson, Melyssa, additional, Ertl-Wagner, Birgit, additional, Hawkins, Cynthia, additional, Bouffet, Eric, additional, and Tabori, Uri, additional

Published
2022
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13. Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Das, Anirban, Sudhaman, Sumedha, Morgenstern, Daniel, Coblentz, Ailish, Chung, Jiil, Stone, Simone C., Alsafwani, Noor, Liu, Zhihui Amy, Karsaneh, Ola Abu Al, Soleimani, Shirin, Ladany, Hagay, Chen, David, Zatzman, Matthew, Cabric, Vanja, Nobre, Liana, Bianchi, Vanessa, Edwards, Melissa, Sambira Nahum, Lauren C, Ercan, Ayse B., Nabbi, Arash, Constantini, Shlomi, Dvir, Rina, Yalon-Oren, Michal, Campino, Gadi Abebe, Caspi, Shani, Larouche, Valerie, Reddy, Alyssa, Osborn, Michael, Mason, Gary, Lindhorst, Scott, Bronsema, Annika, Magimairajan, Vanan, Opocher, Enrico, De Mola, Rebecca Loret, Sabel, Magnus, Frojd, Charlotta, Sumerauer, David, Samuel, David, Cole, Kristina, Chiaravalli, Stefano, Massimino, Maura, Tomboc, Patrick, Ziegler, David S., George, Ben, Van Damme, An, Hijiya, Nobuko, Gass, David, McGee, Rose B., Mordechai, Oz, Bowers, Daniel C., Laetsch, Theodore W., Lossos, Alexander, Blumenthal, Deborah T., Sarosiek, Tomasz, Yen, Lee Yi, Knipstein, Jeffrey, Bendel, Anne, Hoffman, Lindsey M., Luna-Fineman, Sandra, Zimmermann, Stefanie, Scheers, Isabelle, Nichols, Kim E., Zapotocky, Michal, Hansford, Jordan R., Maris, John M., Dirks, Peter, Taylor, Michael D., Kulkarni, Abhaya V., Shroff, Manohar, Tsang, Derek S., Villani, Anita, Xu, Wei, Aronson, Melyssa, Durno, Carol, Shlien, Adam, Malkin, David, Getz, Gad, Maruvka, Yosef E., Ohashi, Pamela S., Hawkins, Cynthia, Pugh, Trevor J., Bouffet, Eric, Tabori, Uri, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Das, Anirban, Sudhaman, Sumedha, Morgenstern, Daniel, Coblentz, Ailish, Chung, Jiil, Stone, Simone C., Alsafwani, Noor, Liu, Zhihui Amy, Karsaneh, Ola Abu Al, Soleimani, Shirin, Ladany, Hagay, Chen, David, Zatzman, Matthew, Cabric, Vanja, Nobre, Liana, Bianchi, Vanessa, Edwards, Melissa, Sambira Nahum, Lauren C, Ercan, Ayse B., Nabbi, Arash, Constantini, Shlomi, Dvir, Rina, Yalon-Oren, Michal, Campino, Gadi Abebe, Caspi, Shani, Larouche, Valerie, Reddy, Alyssa, Osborn, Michael, Mason, Gary, Lindhorst, Scott, Bronsema, Annika, Magimairajan, Vanan, Opocher, Enrico, De Mola, Rebecca Loret, Sabel, Magnus, Frojd, Charlotta, Sumerauer, David, Samuel, David, Cole, Kristina, Chiaravalli, Stefano, Massimino, Maura, Tomboc, Patrick, Ziegler, David S., George, Ben, Van Damme, An, Hijiya, Nobuko, Gass, David, McGee, Rose B., Mordechai, Oz, Bowers, Daniel C., Laetsch, Theodore W., Lossos, Alexander, Blumenthal, Deborah T., Sarosiek, Tomasz, Yen, Lee Yi, Knipstein, Jeffrey, Bendel, Anne, Hoffman, Lindsey M., Luna-Fineman, Sandra, Zimmermann, Stefanie, Scheers, Isabelle, Nichols, Kim E., Zapotocky, Michal, Hansford, Jordan R., Maris, John M., Dirks, Peter, Taylor, Michael D., Kulkarni, Abhaya V., Shroff, Manohar, Tsang, Derek S., Villani, Anita, Xu, Wei, Aronson, Melyssa, Durno, Carol, Shlien, Adam, Malkin, David, Getz, Gad, Maruvka, Yosef E., Ohashi, Pamela S., Hawkins, Cynthia, Pugh, Trevor J., Bouffet, Eric, and Tabori, Uri

Abstract

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Published
2022

15. Phase I study of ribociclib and everolimus in children with newly diagnosed DIPG and high-grade glioma: A CONNECT pediatric neuro-oncology consortium report

Author

DeWire, Mariko, primary, Lazow, Margot, additional, Campagne, Olivia, additional, Leach, James, additional, Fuller, Christine, additional, Senthil Kumar, Shiva, additional, Stanek, Joseph, additional, de Blank, Peter, additional, Hummel, Trent R, additional, Pillay-Smiley, Natasha, additional, Salloum, Ralph, additional, Stevenson, Charles B, additional, Baxter, Patricia, additional, Gass, David, additional, Goldman, Stewart, additional, Leary, Sarah E S, additional, Carle, Adam, additional, Mikael, Leonie, additional, Crabtree, Dorothy, additional, Chaney, Brooklyn, additional, Lane, Adam, additional, Drissi, Rachid, additional, Stewart, Clinton F, additional, and Fouladi, Maryam, additional

Published
2022
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16. Contributors

Author

Al-Ghafry, Maha, Alme, Charlotte, Alobeid, Bachir, Arnold, Staci D., Askew, Megan, Beauchemin, Melissa P., Bhatia, Monica, Bombacie, Michelle, Bonilla, Mary Ann, Brittenham, Gary M., Broglie, Larisa, Chen, Jing, Connolly, Eileen, Constantino, Caitlin, Davis, Laurie, Debelenko, Larisa, Dela Cruz, Filemon S., El-Mallawany, Nader Kim, Ender, Katie, Fallon, Erica M., Foca, Marc D., Gallitto, Matthew, Gampel, Bradley, Gartrell, Robyn D., Garvin, James, Jr, Gass, David, George, Gabriella E., Glade Bender, Julia, Glasser, Chana L., Graham, Rudi-Ann, Granowetter, Linda, Green, Nancy S., Gulati, Nitya, Hijiya, Nobuko, Hochberg, Jess, Joffe, Lenat, Kadenhe-Chiweshe, Angela V., Kahn, Justine M., Kaicker, Shipra, Kaur, Dominder, Kelly, Kara M., Kinnaman, Michael D., Kochhar, Manpreet, Krajewski, Jennifer, Kurtz, Justin L., Ladas, Elena J., Levine, Jennifer, Lee, Margaret T., Lieb, Kristin, Madubata, Chinwe, Mansukhani, Mahesh M., Marks, Lianna J., McGuinn, Catherine, Menell, Jill S., Myers, Regina, Minns, Hanna E., Moisander Joyce, Hanna, Neunert, Cindy, Oberg, Jennifer, Orjuela, Manuela, Parrott, Andrew Myles, Pavisic, Jovana, Phillips, Lia N., Ramirez, Evelyn M., Ricci, Angela, Rosenzweig, Jaclyn D., Satwani, Prakash, Silverman, Andrew M., Steinberg, Dara M., Sheth, Sujit, Sulis, Maria Luisa, Szalontay, Luca, Tang, Amy, Tomb, Meghan F., Varkey, Joyce, Webster Carrion, Andrea, Weiner, Michael, Weisberg, Stuart P., Wu, Cheng-Chia, Yamashiro, Darrell J., and Zacharoulis, Stergios

Published
2024
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17. Characteristics of patients ≥10 years of age with diffuse intrinsic pontine glioma: a report from the International DIPG/DMG Registry

Author

Erker, Craig, primary, Lane, Adam, additional, Chaney, Brooklyn, additional, Leary, Sarah, additional, Minturn, Jane E, additional, Bartels, Ute, additional, Packer, Roger J, additional, Dorris, Kathleen, additional, Gottardo, Nicholas G, additional, Warren, Katherine E, additional, Broniscer, Alberto, additional, Kieran, Mark W, additional, Zhu, Xiaoting, additional, White, Peter, additional, Dexheimer, Phillip J, additional, Black, Katie, additional, Asher, Anthony, additional, DeWire, Mariko, additional, Hansford, Jordan R, additional, Gururangan, Sridharan, additional, Nazarian, Javad, additional, Ziegler, David S, additional, Sandler, Eric, additional, Bartlett, Allison, additional, Goldman, Stewart, additional, Shih, Chie-Schin, additional, Hassall, Tim, additional, Dholaria, Hetal, additional, Bandopadhayay, Pratiti, additional, Samson, Yvan, additional, Monje, Michelle, additional, Fisher, Paul G, additional, Dodgshun, Andrew, additional, Parkin, Sarah, additional, Chintagumpala, Murali, additional, Tsui, Karen, additional, Gass, David, additional, Larouche, Valerie, additional, Broxson, Emmett, additional, Garcia Lombardi, Mercedes, additional, Wang, Stacie Shiqi, additional, Ma, Jie, additional, Hawkins, Cynthia, additional, Hamideh, Dima, additional, Wagner, Lars, additional, Koschmann, Carl, additional, Fuller, Christine, additional, Drissi, Rachid, additional, Jones, Blaise V, additional, Leach, James, additional, and Fouladi, Maryam, additional

Published
2021
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18. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G., Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N., Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T., Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D., Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R., Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C., Link, Michael P., Loret De Mola, Rebecca, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L., MagimairajanIssai, Vanan, Maher, Ossama M., Massimino, Maura, McGee, Rose B., Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E., Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, Ziegler, David S., Zimmermann, Stefanie, Hawkins, Cynthia, Malkin, David, Bouffet, Eric, Villani, Anita, Tabori, Uri, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G., Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N., Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T., Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D., Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R., Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C., Link, Michael P., Loret De Mola, Rebecca, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L., MagimairajanIssai, Vanan, Maher, Ossama M., Massimino, Maura, McGee, Rose B., Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E., Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, Ziegler, David S., Zimmermann, Stefanie, Hawkins, Cynthia, Malkin, David, Bouffet, Eric, Villani, Anita, and Tabori, Uri

Abstract

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. Patients and methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. Results: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. Conclusion: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

19. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G., Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N., Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T., Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D., Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R., Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C., Link, Michael P., Loret De Mola, Rebecca, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L., MagimairajanIssai, Vanan, Maher, Ossama M., Massimino, Maura, McGee, Rose B., Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E., Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, Ziegler, David S., Zimmermann, Stefanie, Hawkins, Cynthia, Malkin, David, Bouffet, Eric, Villani, Anita, Tabori, Uri, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G., Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N., Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T., Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D., Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R., Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C., Link, Michael P., Loret De Mola, Rebecca, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L., MagimairajanIssai, Vanan, Maher, Ossama M., Massimino, Maura, McGee, Rose B., Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E., Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, Ziegler, David S., Zimmermann, Stefanie, Hawkins, Cynthia, Malkin, David, Bouffet, Eric, Villani, Anita, and Tabori, Uri

Abstract

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. Patients and methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. Results: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. Conclusion: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

21. Mutation and Microsatellite Burden Predict Response to PD-1 Inhibition in Children with Germline DNA Replication Repair Deficiency

Author

Tabori, Uri, primary, Morgenstern, Daniel, additional, Sudhaman, Sumedha, additional, Das, Anirban, additional, Coblentz, Ailish, additional, Chung, Jiil, additional, Stone, Simone, additional, Alsafwani, Noor, additional, Cabric, Vanja, additional, Nobre, Liana, additional, Bianchi, Vanessa, additional, Edwards, Melissa, additional, Sambira, Lauren, additional, Constantini, Shlomi, additional, Dvir, Rina, additional, Yalon, Michal, additional, Campino, Gadi, additional, Caspi, Shani, additional, Larouche, Valerie, additional, Reddy, Alyssa, additional, Osborn, Michael, additional, Mason, Gary, additional, Lindhorst, Scott, additional, Bronsema, Annika, additional, Magimairajan, Vanan, additional, Opocher, Enrico, additional, De Mola, Rebecca, additional, Sabel, Magnus, additional, Frojd, Charlotta, additional, Sumerauer, David, additional, Samuel, David, additional, Cole, Kristina, additional, Chiaravalli, Stefano, additional, Massimino, Maura, additional, Tomboc, Patrick, additional, Ziegler, David, additional, George, Ben, additional, Damme, An Van, additional, Hijaya, Nobuko, additional, Gass, David, additional, McGee, Rose, additional, Mordechai, Oz, additional, Bowers, Daniel, additional, Laetsch, Ted, additional, Lossos, Alexander, additional, Blumenthal, Deborah, additional, Sarosiek, Tomasz, additional, Yen, Lee, additional, Knipstein, Jeffrey, additional, Bendel, Anne, additional, Hoffman, Lindsey, additional, Luna-Fineman, Sandra, additional, Zimmermann, Stefanie, additional, Scheers, Isabelle, additional, Nichols, Kim, additional, Zapotocky, Michal, additional, Hansford, Jordan, additional, Maris, John, additional, Dirks, Peter, additional, Taylor, Michael, additional, Kulkarni, Abhaya, additional, Shroff, Manohar, additional, Tsang, Derek, additional, Malkin, David, additional, Villani, Anita, additional, Aronson, Melyssa, additional, Durno, Carol, additional, Shlien, Adam, additional, Getz, Gad, additional, Maruvka, Yosef, additional, Ohashi, Pamela, additional, Hawkins, Cynthia, additional, Pugh, Trevor, additional, and Bouffet, Eric, additional

Published
2021
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22. IMMU-18. FAVORABLE OUTCOME IN REPLICATION REPAIR DEFICIENT HYPERMUTANT BRAIN TUMORS TO IMMUNE CHECKPOINT INHIBITION: AN INTERNATIONAL RRD CONSORTIUM REGISTRY STUDY

Author

Bouffet, Eric, primary, Sudhaman, Sumedha, additional, Chung, Jiil, additional, Kelly, Jacalyn, additional, Coblentz, Ailish, additional, Edwards, Melissa, additional, Lipman, Tatiana, additional, Zhang, Cindy, additional, Ercan, Ayse Bahar, additional, Sambira, Lauren, additional, Bendel, Anne, additional, Bielack, Stefan, additional, Koustenis, Elisabeth, additional, Blumenthal, Deborah, additional, Bowers, Daniel, additional, Broniscer, Alberto, additional, Bronsema, Annika, additional, Carroll, Sara, additional, Chiaravalli, Stefano, additional, Cole, Kristina, additional, Constantini, Shlomi, additional, De Mola, Rebecca Loret, additional, Dunn, Gavin, additional, Fröjd, Charlotta, additional, Gass, David, additional, Gauvain, Karen, additional, George, Ben, additional, Hijiya, Nobuko, additional, Hoffman, Lindsey, additional, Knipstein, Jeffrey, additional, Laetsch, Ted, additional, Larouche, Valérie, additional, Lassaletta, Alvaro, additional, Lindhorst, Scott, additional, Lossos, Alexander, additional, Luna-Fineman, Sandra, additional, Magimairajan, Vanan, additional, Mason, Gary, additional, Mason, Warren, additional, Massimino, Maura, additional, Mordechai, Oz, additional, Opocher, Enrico, additional, Oren, Michal, additional, Osborn, Michael, additional, Reddy, Alyssa, additional, Remke, Mark, additional, Roy, Sumita, additional, Sabel, Magnus, additional, Samuel, David, additional, Schneider, Kami, additional, Sen, Santanu, additional, Stearns, Duncan, additional, Sumerauer, David, additional, Thomas, Gregory, additional, Tomboc, Patrick, additional, Van Damme, An, additional, Wierman, Margaret, additional, Winer, Ira, additional, Yen, Lee Yi, additional, Zapotocky, Michal, additional, Ziegler, David, additional, Zimmermann, Stefanie, additional, Dvir, Rina, additional, Rechavi, Gidi, additional, Durno, Carol, additional, Aronson, Melyssa, additional, Taylor, Michael, additional, Dirks, Peter, additional, Pugh, Trevor, additional, Shlien, Adam, additional, Hawkins, Cynthia, additional, Morgenstern, Daniel, additional, and Tabori, Uri, additional

Published
2020
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23. DIPG-74. RE-IRRADIATION OF DIPG: DATA FROM THE INTERNATIONAL DIPG REGISTRY

Author

Lafay-Cousin, Lucie, primary, Lane, Adam, additional, Schafer, Austin, additional, Saab, Raya, additional, Cheng, Sylvia, additional, Bandopadhayay, Pratiti, additional, Zaghloul, Mohamed, additional, El-Ayadi, Motasem, additional, Dorris, Kathleen, additional, Packer, Roger, additional, Kilburn, Lindsey, additional, Minturn, Jane, additional, Dodgshun, Andrew, additional, Parkin, Sara, additional, Lombardi, Mercedes Garcia, additional, Cohen, Kenneth, additional, Gass, David, additional, Goldman, Stewart, additional, Sandler, Eric, additional, Warren, Katherine, additional, Greiner, Robert, additional, Gottardo, Nicholas, additional, Dholaria, Hetal, additional, Hassall, Tim, additional, Coven, Scott, additional, Hansford, Jordan, additional, Samson, Yvan, additional, Leary, Sarah, additional, Bartels, Ute, additional, Bouffet, Eric, additional, Ma, Jie, additional, Tinkle, Christopher, additional, Monje-Deisseroth, Michelle, additional, Fisher, Paul, additional, Tsui, Karen, additional, Ziegler, David, additional, Chintagumpala, Murali, additional, Gururangan, Sridharan, additional, Wagner, Lars, additional, Koschmann, Carl, additional, DeWire-Schottmiller, Mariko, additional, Leach, James, additional, Jones, Blaise, additional, Fuller, Christine, additional, Drissi, Rachid, additional, Chaney, Brooklyn, additional, Black, Katie, additional, Fouladi, Maryam, additional, and Strother, Douglas, additional

Published
2020
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24. EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

Author

DeWire, Mariko, primary, Leach, James, additional, Fuller, Christine, additional, de Blank, Peter, additional, Hummel, Trent, additional, Pillay-Smiley, Natasha, additional, Salloum, Ralph, additional, Stevenson, Charles, additional, Drissi, Rachid, additional, Kumar, Shiva Senthil, additional, Baxter, Patricia, additional, Gass, David, additional, Goldman, Stewart, additional, Leary, Sarah, additional, Lane, Adam, additional, Campagne, Olivia, additional, Stewart, Clinton, additional, and Fouladi, Maryam, additional

Published
2020
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25. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy

Author

Dietrich, Jorg, Lacagnina, Michelle, Gass, David, Richfield, Eric, Mayer-Proschel, Margot, Noble, Mark, Torres, Carlos, and Proschel, Christoph

Abstract

Vanishing white matter disease (VWM) is a heritable leukodystrophy linked to mutations in translation initiation factor 2B (eIF2B). Although the clinical course of this disease has been relatively well described, the cellular consequences of EIF2B mutations on neural cells are unknown. Here we have established cell cultures from the brain of an individual with VWM carrying mutations in subunit 5 of eIF2B (encoded by EIF2B5). Despite the extensive demyelination apparent in this VWM patient, normal-appearing oligodendrocytes were readily generated in vitro. In contrast, few GFAP-expressing (GFAP[sup.+]) astrocytes were present in primary cultures, induction of astrocytes was severely compromised, and the few astrocytes generated showed abnormal morphologies and antigenic phenotypes. Lesions in vivo also lacked GFAP[sup.+] astrocytes. RNAi targeting of EIF2B5 severely compromised the induction of GFAP[sup.+] cells from normal human glial progenitors. This raises the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM leukodystrophy., Author(s): Jorg Dietrich [1]; Michelle Lacagnina [1]; David Gass [1]; Eric Richfield [2, 3]; Margot Mayer-Proschel [1]; Mark Noble [1]; Carlos Torres [4]; Christoph Proschel (corresponding author) [1] Despite rapid [...]

Published
2005
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26. A tribute to Chief Justice Ruth McGregor.

Author

O'Connor, Sandra Day, Berg, Timothy, Brisman, Avi, Burke, Tim, Ellerin, Betty Weinberg, Gass, David, Martone, Frederick J., Merritt, Deborah Jones, and Savel, Mary Beth

Subjects
Chief justices -- Testimonials, Arizona. Supreme Court -- Officials and employees
Published
2010

28. Property damage is an emotional experience.

Author

Jennings, Marianne M. and Gass, David

Subjects
Mental distress (Law) -- Analysis, Offenses against property -- Psychological aspects, Construction industry -- Cases
Published
1994

31. IMMU-20. IMMUNE AND TUMOR BIOMARKERS OF OUTCOME IN REPLICATION REPAIR DEFICIENT BRAIN TUMORS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: UPDATES FROM THE INTERNATIONAL REPLICATION REPAIR DEFICIENCY CONSORTIUM

Author

Bouffet, Eric, primary, Sudhaman, Sumedha, additional, Chung, Jiil, additional, Campbell, Brittany, additional, Kelly, Jacalyn, additional, Coblentz, Ailish, additional, Edwards, Melissa, additional, Lipman, Tatiana, additional, Zhang, Cindy, additional, Ercan, Ayse Bahar, additional, Sambira, Lauren, additional, Bendel, Anne, additional, Bielack, Stefan, additional, Koustenis, Elisabeth, additional, Blumenthal, Deborah, additional, Bowers, Daniel, additional, Nichols, Kim, additional, Bronsema, Annika, additional, Carroll, Sara, additional, Chiaravalli, Stefano, additional, Cole, Kristina, additional, Constantini, Shlomi, additional, De Mola, Rebecca Loret, additional, Dunn, Gavin, additional, Fröjd, Charlotta, additional, Gass, David, additional, Gauvain, Karen, additional, George, Ben, additional, Hijiya, Nobuko, additional, Hoffman, Lindsey, additional, Knipstein, Jeffrey, additional, Laetsch, Ted, additional, Larouche, Valérie, additional, Lassaletta, Alvaro, additional, Lindhorst, Scott, additional, Lossos, Alexander, additional, Luna-Fineman, Sandra, additional, Magimairajan, Vanan, additional, Mason, Gary, additional, Mason, Warren, additional, Massimino, Maura, additional, Mordechai, Oz, additional, Opocher, Enrico, additional, Oren, Michal, additional, Osborn, Michael, additional, Reddy, Alyssa, additional, Remke, Mark, additional, Roy, Sumita, additional, Sabel, Magnus, additional, Samuel, David, additional, Schneider, Kami, additional, Sen, Santanu, additional, Stearns, Duncan, additional, Sumerauer, David, additional, Thomas, Gregory, additional, Tomboc, Patrick, additional, Damme, An Van, additional, Wierman, Margaret, additional, Winer, Ira, additional, Yen, Lee Yi, additional, Zapotocky, Michal, additional, Ziegler, David, additional, Zimmermann, Stefanie, additional, Dvir, Rina, additional, Rechavi, Gidi, additional, Durno, Carol, additional, Aronson, Melyssa, additional, Taylor, Michael, additional, Dirks, Peter, additional, Pugh, Trevor, additional, Shlien, Adam, additional, Hawkins, Cynthia, additional, Morgenstern, Daniel, additional, and Tabori, Uri, additional

Published
2019
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40. Accessibility from the Patient Perspective: Comparison of Primary Healthcare Evaluation Instruments

Author

Haggerty, Jeannie L., Lévesque, Jean-Frédéric, Santor, Darcy A., Burge, Frederick, Beaulieu, Christine, Bouharaoui, Fatima, Beaulieu, Marie-Dominique, Pineault, Raynald, and Gass, David

Subjects
Research Paper
Abstract

The operational definition of first-contact accessibility is "the ease with which a person can obtain needed care (including advice and support) from the practitioner of choice within a time frame appropriate to the urgency of the problem"; accommodation is "the way healthcare resources are organized to accommodate a wide range of patients' abilities to contact healthcare providers and reach healthcare services, that is to say telephone services, flexible appointment systems, hours of operation, and walk-in periods."To compare how well accessibility is measured in validated subscales that evaluate primary healthcare from the patient's perspective.645 adults with at least one healthcare contact in the previous 12 months responded to six instruments that evaluate primary healthcare with four subscales that measure accessibility: the Primary Care Assessment Survey (PCAS), the Primary Care Assessment Tool - Short Form (PCAT-S, two subscales) and the first version of the EUROPEP (EUROPEP-I). Scores were normalized to a 0-to-10 scale for descriptive comparison. Exploratory and confirmatory (structural equation modelling) factor analysis examined fit to operational definition, and item response theory analysis examined item performance on common constructs.The subscales demonstrate similar psychometric measures to those reported by developers. The PCAT-S First-Contact Utilization subscale does not fit the accessibility construct. The remaining three subscales load reasonably onto a single factor, presumed to be accessibility, but the best-fitting model has two factors: "timeliness of obtaining needed care" (PCAT-S First-Contact Access, some EUROPEP-I items) and "how resources are organized to accommodate clients" (PCAS Organizational Access and most of EUROPEP-I organization of care). Items in the PCAS and PCAT-S subscales have good discriminability.Only three of the four subscales measure accessibility; all are appropriate for use in Canada. The PCAT-S First-Contact Access subscale is the best measure for first-contact accessibility, and PCAS Organizational Accessibility has good metric properties and measures for accommodation.

Published
2011

45. Understanding circumscribed interests in individuals with autism-spectrum disorders and how they relate to families.

Author

Gass, David S.J. and Gass, David S.J.

Abstract

Autism-spectrum disorders (ASDs) are a group of neurodevelopmental disorders that are becoming increasingly more prevalent. A diagnostic criterion for autism is the presence of restricted, repetitive behaviours (RRBs), one of which is the intense fascinations for virtually any topic: circumscribed interests (CIs). CIs have the potential to be used for motivational purposes. This study employed semi-structured interviews using Interpretative Phenomenological Analysis (IPA) with individuals with ASDs and their parents. In total, 11 families participated in this study, comprising 33 individuals (16 parents and 17 individuals with ASDs). This study found five themes: He's Very Unique; They Don't Realize that Not Everyone Lives and Thinks the Same Thing All the Time; We Couldn't even Pronounce the Names of These Dinosaurs, and Jason was Telling Us; You Can't Change Them, You Can Only Love Them; and So I Can Do My Job at the Same Time and Observe the Weather at the Same Time.

Published
2013

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