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4. The Evolving Management of Peritoneal Surface Malignancies

Author

Stewart, John H., IV, Blazer, Dan G., III, Calderon, Maria Jose Godoy, Carter, Taylor M., Eckhoff, Austin, Al Efishat, Mohammad A., Fernando, Deemantha G., Foster, Jason M., Hayes-Jordan, Andrea, Johnston, Fabian M., Lautz, Timothy B., Levine, Edward A., Maduekwe, Ugwuji N., Mangieri, Christopher W., Moaven, Omeed, Mogal, Harveshp, Shen, Perry, and Votanopoulos, Konstantinos I.

Published
2021
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5. The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Author

Alyami, Mohammad S., André, Thierry, Barrios-Sanchez, Pedro, Baumgartner, Joel M., Bhatt, Aditi, Ben-Yaacov, Almog, Bertulli, Rosella, Braess, Jan, Burger, Jacobus W.A., Cascales-Campos, Pedro, Cashin, Peter, Cecil, P, Tom, Ceelen, Wim P., Creemers, Geert-Jan, Cortes-Guiral, Delia, Dayal, Sanjeev, De Simone, Michele, Di Bartolomeo, Maria, Dube, Pierre, Flatmark, Kjersti, Foster, Jason M., Goere, Diane, Gonzales-Bayon, Luis, Heriot, Alexander, Hewett, Peter J., Hsieh, Mao-Chih, Hubner, Martin, Kok, NielsF.M., Larsen, Stein G., Lehmann, Kuno, Li, Yan, Loggie, Brian W., Lutton, Nicholas, Ly, Jasen, Lynch, Craig, Lyra, Marcos, Mehta, Sanket, Mohamed, Faheez, Morris, David L., Nissan, Aviram, Nowacki, Maciej S., Pande, Pankaj K., Park, Eun Jung, Peron, Julien, Perry, David J., Pietrantonio, Filippo, Piso, Pompiliu, Pocard, Marc, Quadros, Claudio, Rajan, Firoz, Rau, Beate, Reymond, Marc A., Thuss-Patience, Peter, Sardi, Armando, Sideris, Lucas, Sinn, Marianne, Sokmen, Selman, Somashekhar, Sampige P., Spiliotis, John D., Sugarbaker, Paul H., Syk, Ingvar, Tentes, Antonios A., Teo, MelissaC.C., Turaga, Kiran K., Valle, Mario, Verwaal, Victor J., Wilson, Malcom S., Yarema, Roman R., Yonemura, Yutaka, Yu, Yang, Lurvink, R.J., Villeneuve, L., Govaerts, K., de Hingh, I.H.J.T., Moran, B.J., Deraco, M., Van der Speeten, K., Glehen, O., Kepenekian, V., and Kusamura, S.

Published
2021
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6. Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment

Author

Barrios-Sanchez, Pedro, Baumgartner, Joel M., Ben-Yaacov, Almog, Bertulli, Rosella, Cashin, Peter, Cecil, Tom, Dayal, Sanjeev, De Simone, Michele, Foster, Jason M., Goere, Diane, Lehmann, Kuno, Li, Yan, Loggie, Brian W., Mohamed, Faheez, Morris, David L., Nissan, Aviram, Piso, Pompiliu, Pocard, Marc, Rau, Beate, Reymond, Marc A., Sideris, Lucas, Spiliotis, John D., Sugarbaker, Paul H., Verwaal, Victor J., Wilson, Malcom S., Yonemura, Yutaka, Yu, Yang, Govaerts, K., Lurvink, R.J., De Hingh, I.H.J.T., Van der Speeten, K., Villeneuve, L., Kusamura, S., Kepenekian, V., Deraco, M., Glehen, O., and Moran, B.J.

Published
2021
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7. Peritoneal mesothelioma: PSOGI/EURACAN clinical practice guidelines for diagnosis, treatment and follow-up

Author

Barrios-Sanchez, Pedro, Baumgartner, Joel M., Ben-Yaacov, Almog, Bertulli, Rosella, Cashin, Peter, Cecil, Tom, Dayal, Sanjeev, De Simone, Michele, Foster, Jason M., Goere, Diane, Lehmann, Kuno, Li, Yan, Loggie, Brian W., Mohamed, Faheez, Morris, David L., Nissan, Aviram, Piso, Pompiliu, Pocard, Marc, Rau, Beate, Reymond, Marc A., Sideris, Lucas, Spiliotis, John D., Sugarbaker, Paul H., Verwaal, Victor J., Wilson, Malcom S., Yonemura, Yutaka, Yu, Yang, Kusamura, S., Kepenekian, V., Villeneuve, L., Lurvink, R.J., Govaerts, K., De Hingh, I.H.J.T., Moran, B.J., Van der Speeten, K., Deraco, M., and Glehen, O.

Published
2021
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9. Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis

Author

Kaushik, Garima, Seshacharyulu, Parthasarathy, Rauth, Sanchita, Nallasamy, Palanisamy, Rachagani, Satyanarayana, Nimmakayala, Rama Krishna, Vengoji, Raghupathy, Mallya, Kavita, Chirravuri-Venkata, Ramakanth, Singh, Amar B., Foster, Jason M., Ly, Quan P., Smith, Lynette M., Lele, Subodh M., Malafa, Mokenge P., Jain, Maneesh, Ponnusamy, Moorthy P., and Batra, Surinder K.

Published
2021
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12. Exploring barriers and promoters of CRC screening use among agricultural operators: a pilot study of an application of concept mapping.

Author

Beseler, Cheryl, Jungyoon Kim, Subramanian, Roma, Harris, Susan, Funkenbusch, Karen, Yoder, Aaron M., Robinson, Tamara, Foster, Jason M., and Watanabe-Galloway, Shinobu

Abstract

Introduction: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US. Methods: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted. Results: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, and lack of awareness of the need to be screened. Some gender differences regarding barriers were observed, such as women were more concerned about the cost of screening while men were far more concerned about the embarrassment associated with CRC screening. Conclusion: These findings will be crucial to developing educational materials to increase knowledge of risk factors for CRC and of CRC screening in the agricultural population. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Red cabbage juice-mediated gut microbiota modulation improves intestinal epithelial homeostasis and ameliorates colitis

Author

Jean Wilson, Emily, primary, Sirpu Natesh, Nagabhishek, additional, Ghadermazi, Parsa, additional, Pothuraju, Ramesh, additional, Shanmugam, Marudhupandiyan, additional, Prajapati, Dipakkumar R., additional, Pandey, Sanjit, additional, Kaifi, Jussuf T., additional, Dodam, John R., additional, Bryan, Jeffrey, additional, Lorson, Christian L., additional, Watrelot, Aude A., additional, Foster, Jason M., additional, Mansel, Thomas J., additional, Joshua Chan, Siu Hung, additional, Batra, Surinder K., additional, Subbiah, Jeyamkondan, additional, and Rachagani, Satyanarayana, additional

Published
2023
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14. Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

Author

Foster, Jason M, Radhakrishna, Uppala, Govindarajan, Venkatesh, Carreau, Joseph H, Gatalica, Zoran, Sharma, Poonam, Nath, Swapan K, and Loggie, Brian W

Abstract

Abstract Background There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma. Methods Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib. Results Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months. Conclusions The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.

Published
2010

16. Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

Author

Jean Wilson, Emily, Sirpu Natesh, Nagabhishek, Ghadermazi, Parsa, Pothuraju, Ramesh, Prajapati, Dipakkumar R., Pandey, Sanjit, Kaifi, Jussuf T., Dodam, John R., Bryan, Jeffrey N., Lorson, Christian L., Watrelot, Aude A., Foster, Jason M., Mansell, Thomas J., Joshua Chan, Siu Hung, Batra, Surinder K., Subbiah, Jeyamkondan, and Rachagani, Satyanarayana

Subjects
GUT microbiome, INFLAMMATORY bowel diseases, COLITIS, SHORT-chain fatty acids, HOMEOSTASIS
Abstract

Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ's protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition was analyzed via shotgun metagenomics. RCJ treatment significantly improved body weight (p ≤ 0.001), survival in mice (p < 0.001) and reduced disease activity index (DAI) scores. Further, RCJ improved colonic barrier integrity by enhancing the expression of protective colonic mucins (p < 0.001) and tight junction proteins (p ≤ 0.01) in RCJ + DSS-treated mice compared to the DSS group. Shotgun metagenomic analysis revealed an enrichment of short-chain fatty acids (SCFAs)-producing bacteria (p < 0.05), leading to increased Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) activation (p ≤ 0.001). This, in turn, resulted in repression of the nuclear factor κB (NFκB) signaling pathway, causing decreased production of inflammatory cytokines and chemokines. Our study demonstrates colitis remission in a DSS-induced mouse model, showcasing RCJ as a potential modulator for gut microbiota and metabolites, with promising implications for IBD prevention and treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Elevated PAF1-RAD52 axis confers chemoresistance to human cancers

Author

Rauth, Sanchita, primary, Ganguly, Koelina, additional, Atri, Pranita, additional, Parte, Seema, additional, Nimmakayala, Rama Krishna, additional, Varadharaj, Venkatesh, additional, Nallasamy, Palanisamy, additional, Vengoji, Raghupathy, additional, Ogunleye, Ayoola O., additional, Lakshmanan, Imayavaramban, additional, Chirravuri, Ramakanth, additional, Bessho, Mika, additional, Cox, Jesse L., additional, Foster, Jason M., additional, Talmon, Geoffrey A., additional, Bessho, Tadayoshi, additional, Ganti, Apar Kishor, additional, Batra, Surinder K., additional, and Ponnusamy, Moorthy P., additional

Published
2023
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18. Small molecule inhibitor against onco-mucins disrupts Src/FosL1 axis to enhance gemcitabine efficacy in pancreatic ductal adenocarcinoma

Author

Zhang, Chunmeng, primary, Atri, Pranita, additional, Nallasamy, Palanisamy, additional, Parte, Seema, additional, Rauth, Sanchita, additional, Nimmakayala, Rama Krishna, additional, Marimuthu, Saravanakumar, additional, Chirravuri-Venkata, Ramakanth, additional, Bhatia, Rakesh, additional, Halder, Sushanta, additional, Shah, Ashu, additional, Cox, Jesse L., additional, Smith, Lynette, additional, Kumar, Sushil, additional, Foster, Jason M., additional, Kukreja, Rakesh C., additional, Seshacharyulu, Parthasarathy, additional, Ponnusamy, Moorthy P., additional, and Batra, Surinder K., additional

Published
2022
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26. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future.

Author

Foster, Jason M., Zhang, Chunmeng, Rehman, Shahyan, Sharma, Prateek, and Alexander, H. Richard

Subjects
HYPERTHERMIC intraperitoneal chemotherapy, ADENOSINE diphosphate ribose, OVARIAN cancer, FRUSTRATION, PERITONEAL cancer, DRUG development, CYTOREDUCTIVE surgery
Abstract

Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy—specifically hyperthermic intraperitoneal chemotherapy—with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development. [ABSTRACT FROM AUTHOR]

Published
2023
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27. In brief

Author

Stewart IV, John H., Blazer III, Dan G., Calderon, Maria Jose Godoy, Carter, Taylor M., Eckhoff, Austin, Al Efishat, Mohammad A., Fernando, Deemantha G., Foster, Jason M., Hayes-Jordan, Andrea, Johnston, Fabian, Lautz, Timothy B., Levine, Edward A., Maduekwe, Ugwuji N., Mangieri, Christopher W., Moaven, Omeed, Mogal, Harveshp, Shen, Perry, and Votanopoulos, Konstantinos I.

Published
2021
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29. Appendiceal Tumours and Pseudomyxoma Peritonei: Literature Review with PSOGI/EURACAN Clinical Practice Guidelines for Diagnosis and Treatment

Author

Govaerts, K, Lurvink, R J, de Hingh, I H J T, Van der Speeten, K, Villeneuve, L, Kusamura, S, Kepenekian, V, Deraco, M, Glehen, O, Moran, B J, Barrios-Sanchez, Pedro, Baumgartner, Joel M, Ben-Yaacov, Almog, Bertulli, Rosella, Cashin, Peter, Cecil, Tom, Dayal, Sanjeev, De Simone, Michele, Foster, Jason M, Goere, Diane, Lehmann, Kuno, Li, Yan, Loggie, Brian W, Mohamed, Faheez, Morris, David L, Nissan, Aviram, Piso, Pompiliu, Pocard, Marc, Rau, Beate, Reymond, Marc A, et al, University of Zurich, and Govaerts, K

Subjects
Oncology, 610 Medicine & health, 2730 Oncology, Surgery, General Medicine, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2021

30. Peritoneal Mesothelioma: PSOGI/EURACAN Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up

Author

Kusamura, S, Kepenekian, V, Villeneuve, L, Lurvink, R J, Govaerts, K, De Hingh, I H J T, Moran, B J, Van der Speeten, K, Deraco, M, Glehen, O, Barrios-Sanchez, Pedro, Baumgartner, Joel M, Ben-Yaacov, Almog, Bertulli, Rosella, Cashin, Peter, Cecil, Tom, Dayal, Sanjeev, De Simone, Michele, Foster, Jason M, Goere, Diane, Lehmann, Kuno, Li, Yan, Loggie, Brian W, Mohamed, Faheez, Morris, David L, Nissan, Aviram, Piso, Pompiliu, Pocard, Marc, Rau, Beate, Reymond, Marc A, et al, University of Zurich, and Deraco, M

Subjects
Oncology, 610 Medicine & health, 2730 Oncology, Surgery, General Medicine, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2021

32. Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Author

Zhang, Chunmeng, primary, Plambeck, Benjamin D., additional, Craig, Margaret E., additional, Tu, Alexander, additional, Mikus, Ryan J, additional, Shostrom, Valerie, additional, McDermott, Sean P., additional, Igbinigie, Ikponmwosa, additional, Brown, Krista, additional, Cushman‐Vokoun, Allison, additional, and Foster, Jason M., additional

Published
2021
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36. Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment

Author

Govaerts, K., primary, Lurvink, R.J., additional, De Hingh, I.H.J.T., additional, Van der Speeten, K., additional, Villeneuve, L., additional, Kusamura, S., additional, Kepenekian, V., additional, Deraco, M., additional, Glehen, O., additional, Moran, B.J., additional, Barrios-Sanchez, Pedro, additional, Baumgartner, Joel M., additional, Ben-Yaacov, Almog, additional, Bertulli, Rosella, additional, Cashin, Peter, additional, Cecil, Tom, additional, Dayal, Sanjeev, additional, De Simone, Michele, additional, Foster, Jason M., additional, Goere, Diane, additional, Lehmann, Kuno, additional, Li, Yan, additional, Loggie, Brian W., additional, Mohamed, Faheez, additional, Morris, David L., additional, Nissan, Aviram, additional, Piso, Pompiliu, additional, Pocard, Marc, additional, Rau, Beate, additional, Reymond, Marc A., additional, Sideris, Lucas, additional, Spiliotis, John D., additional, Sugarbaker, Paul H., additional, Verwaal, Victor J., additional, Wilson, Malcom S., additional, Yonemura, Yutaka, additional, and Yu, Yang, additional

Published
2021
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37. The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Author

Lurvink, R.J., primary, Villeneuve, L., additional, Govaerts, K., additional, de Hingh, I.H.J.T., additional, Moran, B.J., additional, Deraco, M., additional, Van der Speeten, K., additional, Glehen, O., additional, Kepenekian, V., additional, Kusamura, S., additional, Alyami, Mohammad S., additional, André, Thierry, additional, Barrios-Sanchez, Pedro, additional, Baumgartner, Joel M., additional, Bhatt, Aditi, additional, Ben-Yaacov, Almog, additional, Bertulli, Rosella, additional, Braess, Jan, additional, Burger, Jacobus W.A., additional, Cascales-Campos, Pedro, additional, Cashin, Peter, additional, Cecil, P, Tom, additional, Ceelen, Wim P., additional, Creemers, Geert-Jan, additional, Cortes-Guiral, Delia, additional, Dayal, Sanjeev, additional, De Simone, Michele, additional, Di Bartolomeo, Maria, additional, Dube, Pierre, additional, Flatmark, Kjersti, additional, Foster, Jason M., additional, Goere, Diane, additional, Gonzales-Bayon, Luis, additional, Heriot, Alexander, additional, Hewett, Peter J., additional, Hsieh, Mao-Chih, additional, Hubner, Martin, additional, Kok, NielsF.M., additional, Larsen, Stein G., additional, Lehmann, Kuno, additional, Li, Yan, additional, Loggie, Brian W., additional, Lutton, Nicholas, additional, Ly, Jasen, additional, Lynch, Craig, additional, Lyra, Marcos, additional, Mehta, Sanket, additional, Mohamed, Faheez, additional, Morris, David L., additional, Nissan, Aviram, additional, Nowacki, Maciej S., additional, Pande, Pankaj K., additional, Park, Eun Jung, additional, Peron, Julien, additional, Perry, David J., additional, Pietrantonio, Filippo, additional, Piso, Pompiliu, additional, Pocard, Marc, additional, Quadros, Claudio, additional, Rajan, Firoz, additional, Rau, Beate, additional, Reymond, Marc A., additional, Thuss-Patience, Peter, additional, Sardi, Armando, additional, Sideris, Lucas, additional, Sinn, Marianne, additional, Sokmen, Selman, additional, Somashekhar, Sampige P., additional, Spiliotis, John D., additional, Sugarbaker, Paul H., additional, Syk, Ingvar, additional, Tentes, Antonios A., additional, Teo, MelissaC.C., additional, Turaga, Kiran K., additional, Valle, Mario, additional, Verwaal, Victor J., additional, Wilson, Malcom S., additional, Yarema, Roman R., additional, Yonemura, Yutaka, additional, and Yu, Yang, additional

Published
2021
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38. Peritoneal mesothelioma: PSOGI/EURACAN clinical practice guidelines for diagnosis, treatment and follow-up

Author

Kusamura, S., primary, Kepenekian, V., additional, Villeneuve, L., additional, Lurvink, R.J., additional, Govaerts, K., additional, De Hingh, I.H.J.T., additional, Moran, B.J., additional, Van der Speeten, K., additional, Deraco, M., additional, Glehen, O., additional, Barrios-Sanchez, Pedro, additional, Baumgartner, Joel M., additional, Ben-Yaacov, Almog, additional, Bertulli, Rosella, additional, Cashin, Peter, additional, Cecil, Tom, additional, Dayal, Sanjeev, additional, De Simone, Michele, additional, Foster, Jason M., additional, Goere, Diane, additional, Lehmann, Kuno, additional, Li, Yan, additional, Loggie, Brian W., additional, Mohamed, Faheez, additional, Morris, David L., additional, Nissan, Aviram, additional, Piso, Pompiliu, additional, Pocard, Marc, additional, Rau, Beate, additional, Reymond, Marc A., additional, Sideris, Lucas, additional, Spiliotis, John D., additional, Sugarbaker, Paul H., additional, Verwaal, Victor J., additional, Wilson, Malcom S., additional, Yonemura, Yutaka, additional, and Yu, Yang, additional

Published
2021
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39. Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis

Author

Kaushik, Garima, primary, Seshacharyulu, Parthasarathy, additional, Rauth, Sanchita, additional, Nallasamy, Palanisamy, additional, Rachagani, Satyanarayana, additional, Nimmakayala, Rama Krishna, additional, Vengoji, Raghupathy, additional, Mallya, Kavita, additional, Chirravuri-Venkata, Ramakanth, additional, Singh, Amar B., additional, Foster, Jason M., additional, Ly, Quan P., additional, Smith, Lynette M., additional, Lele, Subodh M., additional, Malafa, Mokenge P., additional, Jain, Maneesh, additional, Ponnusamy, Moorthy P., additional, and Batra, Surinder K., additional

Published
2020
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50. Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

Author

Gatalica Zoran, Carreau Joseph H, Govindarajan Venkatesh, Radhakrishna Uppala, Foster Jason M, Sharma Poonam, Nath Swapan K, and Loggie Brian W

Subjects
Surgery, RD1-811, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma. Methods Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib. Results Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months. Conclusions The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.

Published
2010
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