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Pilar Laguna



Name  Laguna Pes

First names  Maria del Pilar

Born  5 January 1956

Place of birth: Barcelona (Spain)

Work adressIstanbul Medipol University

TEM Avrupa Otoyolu Göztepe Çıkışı No: 1 Bağcılar

34214 İstanbul, Turkey

Telephone at work+90 537 604 1778



1973–1979      Autonomous University, Barcelona

                        Studies of Medicine

1979–1982      Hospital del Sagrado CorazónBarcelona

                        Doctor in training at the department of Urology

1982–1988      Hospital del Sagrado CorazónBarcelona

                        Medical Staff of Urology

1989–1995      Fundación Puigvert Barcelona

                        Medical Staff of Urology

1989–1995      Autonomous University Barcelona

                        Docent Activity

1995–2000      Hospital Gral La Mancha Centro, Alcazar de San Juan

                        Chairperson at the department of Urology

2000–2002      UMC St. Radboud Nijmegen

                         Medical Staff at the department of Urology

2002 - present  Academic Medical Center Amsterdam

                         Medical Staff at the department of Urology

2015                 Professor in Surgical Urological Oncology
                         Academic Medical Center Amsterdam

2018                 Professor in Urology

                          Istanbul Medipol University, Istanbul, Turkey



March 2003 University of Las Palmas de Gran Canaria, Las Palmas Grade of European Doctor in Medicine “Cum Laude”.

Thesis Doctoral: ”La sigmoidoplastia distal destubulizada (Neovejiga Canaria): una nueva sustitución vesical. Estudio clinico y funcional.”


‘’The distal detubulized sigmoidoplasty: a new bladder

         substitution, clinical and functional study’’



1. Dr C.A. Mochtar: prognostic factors for clinical progression after treatment of BPH (April 4th 2006).

2. Dr S. Gravas: TUMT treatment of BPH: from evidence based guidelines to clinical practice (April 20th 2007).

3. Dr M.M. van Dijk: Balancing clinical outcomes and quality of life aspects in the treatment of LUTS/BPH (January 22nd 2010).

4. Dr I. Kümmerlin: Renal tumours in the Netherlands- a decade of pathology and a plea for biopsy (November 11th 2010).

5. Dr G.P. Haber: Adaptation of Emerging Technologies to Urologic Oncology Applications (November 16th 2010).

6. Dr P. Beemster: Defining the position of cryoablation in the therapeutic armamentarium of small renal masses (January 11th 2012).

7. Dr K. Barwari: Renal tumor ablation:beyond limitations of biopsy and follow-up (December 18th 2012).

8. Dr L.P.W.Witte: Muscarinic Receptors in the Lower Urinary Tract (May 26th 2015).

9. Dr W. vd Bos: Focal therapy in prostate cancer (May 26th 2016).

10. Dr. M.N. Hew: Reflections on the current knowledge of epidemiology, treatment and prognosis for renal cell carcinoma (December 23rd 2016).



1. Dr P. Wagstaff: New techniques in the diagnosis and treatment of renal masses (May 26th  2016).

2. Dr. E. van der Toom: Circulating and Disseminated Tumor Cells in Patients with High-Risk and Metastatic Genitourinary Cancers (May 25th 2018).



§ Member of the “Asociación Española de Urologia”, since 1981.

§ Member of the “Societat Catalana d´Urologia”, since 1992 . Member of the Board from 1994 to 1996.

§ Member of the “Societé Internationale d´Urologie”, since 1994.

§ Full Member of the “European Association of Urology “, since 1995.

§ Member of the “Asociación Castellano-Manchega de Urologia”, since its constitution in 1998 until 2000.

§ Member of the “Comite Clinico de Enfermedades Infecciosas” of the Hospital Gral. La Mancha Centro, since 1995 until 2000.

§ Member and Secretary of the “CEIC del Hospital Gral. La Mancha- Centro”, since April 1996 until 2000.

§ Member of the “CME Committee” of the European Board of Urology, since 1997 until 2000. And treasurer of the Committee from November 1998 until 2000.

§ Member of the “Uro-Oncological Committee “ of the HCO European Association of Urology since its constitution, 1998. Chairperson of the Testis Cancer subgroup until 2006.

§ Member of the Spanish Group for Oncological Study (“CUETO”) since 1998 until 2000.

§ Coordinator of International Projects of the Hospital General La Mancha-Centro since 1997until 2000.

§ Member of the Capitulo Español in the Societé Internationale  D”Urologie since 1995.

§ Member of the Editorial Committee of Annales  d´Urologie (Paris), since 1996 until its disparition in 2002.

§ Member of the Editorial Committe of Archivos Españoles de Urologia, since 1998.

§ Member of the Editorial Committe of Urologia Integrada y de Investigacion, since 1999.

§ Member of the Jury of the XXII edition of the Award Perez Castro (1999-2000).

§ Member of the Board of the Media Office EAU, since 2001 until 2008.

§ Member of the American Urological Association( AUA) since 2005.

§ Member of de Endourological Society since 2000.

§ Member of the Board of the ESUT (EAU Section of Urotechnology) since 2007 and chairperson ablative working party EAU

§ Member of the Editorial Board of European Urology since 2007

§ Member of the Editorial board of Journal of Endourology since 2007 and section editor reviewer Journal of Endourology

§ Associate editor Central European Journal

§ BKO-certificate



§ J.J.M.C.H. de la Rosette, M.P. Laguna, P.J. Zondervan: Laparoscopic and Percutaneous Cryoablation of Small Renal Masses. In Ahmed, K. et al. The management of small renal masses. Springer International Publishing AG, 2018. ISBN 978-3-319-65656-4



§ Award of Endourology of the Asociation Française d´Urologie for the best poster: “Uretrotomie endoscopique vs uretrotomie plus laser”. Authors: M.P. Laguna Pes, J. Vicente Rodriguez, J. Salvador, J. Caffaratti. Congres Français d´Urologie. Paris, 1989.

§ Award: Video Archivos de Urologia. “Prótesis prostática en espiral”. Authors: J. Vicente Rodriguez, J. Salvador, M.P. Laguna Pes. 1991.

§ Award of the Asociación Española de Urologia for the best poster. “Pseudotumores de la via urinaria alta”. Authors: O. Laucirica, J. Iglesias, M.P. Laguna Pes, H. Villavicencio Marvrich. Congreso Nacional de Urologia. Lanzarote, 1991.

§ Award best poster of the Congres Français d´Urologie. “Prostatotomie bilateral vs Prostatotomie unilateral”. Authors: M.P. Laguna Pes, F. Sanchez-Martin, J.Martinez-Hurtado, J.Palou, J. Vicente Rodriguez. Paris 1993.

§ Award Abbott Urologia. “Induce la Hormonoterapia neoadyuvante cambios morfologicos en el cancer  prostatico localmente avanzado?”. Authors: H. Villavicencio Marvrich, F. Algaba, M.P. Laguna Pes, X. Ponce de León. 1993.

§ Award Video Urology 1992

§ Grant of the FIS (Fondo de Investigaciones Sanitarias ). Project : “Estudio del valor pronóstico de los factores de coagulación en el cancer prostático”. 1993.

§ Grant of  Junta de Comunidades de Castilla-La Mancha.Project :“Estudio del cociente PSAL/PSAT en el diagnostico precoz del cancer de prostata”. 1996.

§ Grant of the HOPE Program (Insalud). Centre Hospitalier Universitaire de Bordeaux (France). 1999.

§ Accesit to the prize of the EAU “Ponce de Leon” to the best thesis in urodynamics. Grupo espaňol de Incontinencia y urologia funtional . 2004.  

§ 2015 Principal Investigator




1. M.J. Scheltema, K.J. Tay, A.W. Postema, D.M. de Bruin, J. Feller, J.J. Futterer, A.K. George, R.T. Gupta, F. Kahmann, C. Kastner, M.P. Laguna Pes, S. Natarajan, S. Rais-Bahrami, A.R. Rastinehad, T.M. de Reijke, G. Salomon, N. Stone, R. van Velthoven, R. Villani, A. Villers, J. Walz, T.J. Polascik, J.J.M.C.H. de la Rosette. Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project. World J Urol.2017 ;35(5):695-701.

2. G. Gakis, T. Schubert , M. Alemozaffar, J. Bellmunt, B.H. Bochner, S.A. Boorjian, S. Daneshmand, W.C. Huang, T. Kondo, B.R. Konety, M.P. Laguna Pes, S.F. Matin, A.O. Siefker-Radtke, S.F. Shariat, A. Stenzl. Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of localized high-risk disease. World J Urol. 2017 Mar;35(3):327-335.

3. M.T. Bus, D.M. de Bruin, G.M. Kamphuis, P.J. Zondervan, M.P. Laguna Pes, Th.M. de Reijke, T.G. van Leeuwen, J.J.M.C.H. de la Rosette. Current position of diagnostics and surgical treatment for upper tract urothelial carcinoma. Minerva Urol Nefrol. 2017 Apr;69(2):159-165.

4. M. Buijs, K.P. van Lienden, P.G. Wagstaff , M.J. Scheltema, D.M. de Bruin, P.J. Zondervan, O.M. van Delden, T.G. van Leeuwen, J.J.M.C.H. de la Rosette, M.P. Laguna Pes. Irreversible Electroporation for the Ablation of Renal Cell Carcinoma: A Prospective, Human, In Vivo Study Protocol (IDEAL Phase 2b). JMIR Res Protoc. 2017 Feb 16;6(2):e21

5. A. Ingels, M. Hew, F. Algaba, O.J. de Boer, R.J. van Moorselaar, S. Horenblas, P. Zondervan, J.J.M.C.H. de la Rosette, M.P. Laguna Pes. Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study. World J Urol. 2017 Jan;35(1):81-87.

6. J. Baard, J.E. Freund, J.J.M.C.H. de la Rosette, M.P. Laguna Pes. New technologies for upper tract urothelial carcinoma management. Curr Opin Urol. 2017 Mar;27(2):170-175.

7. M.P. Laguna Pes Re: Clinically Localized Type 1 and 2 Papillary Renal Cell Carcinomas Have Similar Survival Outcomes following Surgery. J Urol. 2017 Jan;197(1):50-51.

8. M. Smeenge, F. Tranquart, C.K. Mannaerts, Th. M. de Reijke, M.J. van de Vijver, M.P. Laguna Pes, S. Pochon, J.J.M.C.H. de la Rosette, H. Wijkstra. First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study. Invest Radiol. 2017 Jul;52(7):419-427.


9. J. Baard, D.M de Bruin, P.J Zondervan, G. Kamphuis, J.J.M.C.H. de la Rosette, M.P. Laguna Pes. Diagnostic dilemmas in patients with upper tract urothelial carcinoma. Nature Review;  Urol. 2017 Mar;14(3):181-191.


10. M.P. Laguna Pes. Re: Population-Based Assessment of Cancer-Specific Mortality after

Local Tumour Ablation or Observation for Kidney Cancer: A Competing Risks

Analysis. J Urol. 2017 Feb;197(2):314-315.


11. D.A. Wollin, A.D. Joyce, M. Gupta, M.Y. Wong, M.P. Laguna Pes, S. Gravas, J. Gutierrez, L. Cormio, K. Wang, G.M. Preminger. Antibiotic use and the prevention and management of infectious complications in stone disease. World J Urol. 2017 Feb 3.


12. M.P. Laguna Pes. Re: Cost-Effectiveness of Management Options for Small Renal Mass: A Systematic Review. J Urol. 2017 Mar;197(3 Pt 1):602-603.

13. E.I.M.L. Liem, J. Baard, E.C.C. Cauberg, M.T.J. Bus, D.M. de Bruin, M.P. Laguna Pes, J.J.M.C.H. de la Rosette, Th.M. de Reijke. Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette-Guérin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer. Med Oncol. 2017 Sep 2;34(10):172.

14. M.J. Scheltema, A.W. Postema, D.M. de Bruin, M. Buijs, M.R. Engelbrecht, M.P. Laguna Pes, H. Wijkstra, Th.M. de Reijke, J.J.M.C.H. de la Rosette. Irreversible electroporation for the treatment of localized prostate cancer: a summary of imaging findings and treatment feedback. Diagn Interv Radiol. 2017 Sep-Oct;23(5):365-370.

15. M.P. Laguna Pes. Re: Irreversible Electroporation of Small Renal Masses: Suboptimal  Oncologic Efficacy in an Early Series. J Urol. 2017 Sep;198(3):481-482.

16. M.P. Laguna Pes. Re: Management of Small Renal Masses: American Society of Clinical Oncology Clinical Practice Guideline. J Urol. 2017 Sep;198(3):480-482.

17. M.P. Laguna Pes. Re: Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations. J Urol. 2017 Jul;198(1):36-37.

18. M.P. Laguna Pes. Re: Robot-Assisted vs Open Adrenalectomy: Evaluation of Cost-Effectiveness and Peri-Operative Outcome. J Urol. 2017 Jun;197(6):1438.

19. M.P. Laguna Pes. Re: Oncologic Outcomes of Kidney-Sparing Surgery versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-Muscle Invasive Bladder Cancer Guidelines Panel. J Urol. 2017 Jun;197(6):1437-1438.

20. R.R. Pessoa, R. Autorino, M.P. Laguna Pes, W.R. Molina, D. Gustafson, L. Nogueira, da Silva, P.N. Werahera , F.J. Kim. Laparoscopic Versus Percutaneous Cryoablation of Small Renal Mass: Systematic Review and Cumulative Analysis of Comparative Studies. Clin Genitourin Cancer. 2017;15(5):513-519.

21. M.P. Laguna. Re: First-Line Sunitinib versus Pazopanib in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma. Database Consortium. J Urol. 2017 Mar;197(3 Pt 1):603.

22. M.P. Laguna. Re: Urinary Collecting System Invasion is Associated with Poor Survival in Patients with Clear-Cell Renal Cell Carcinoma. J Urol. 2017 Nov;198(5):976-978.

23. M.P. Laguna. Re: Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness. J Urol. 2017 Nov;198(5):977-978.

24. M.P. Laguna. Re: Partial Nephrectomy versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-Analysis of Comparative Studies. J Urol. 2017 Dec;198(6):1204-1206.

25. M.P. Laguna. Re: Efficacy of Systemic Chemotherapy plus Radical Nephroureterectomy for Metastatic Upper Tract Urothelial Carcinoma. J Urol. 2017 Dec;198(6):1205-1206.

26. M.P. Laguna. Re: Mortality, Morbidity and Healthcare Expenditures after Local Tumour Ablation or Partial Nephrectomy for T1A Kidney Cancer. J Urol. 2017 Aug;198(2):252-254

27. M.P. Laguna. Re: Findings and Impact of Early Imaging after Partial Nephrectomy. J Urol. 2017 Aug;198(2):253-254.

28. M.P. Laguna. Re: End-Stage Renal Disease after Renal Surgery in Patients with Normal Preoperative Kidney Function: Balancing Surgical Strategy and Individual Disorders at Baseline. J Urol. 2017 May;197(5):1214-1215.

29. M.P. Laguna. Re: Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. J Urol. 2017 May;197(5):1215.



30. M.P. Laguna. Re: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. J Urol. 2018 Jan;199(1):23-25.

31. M.P. Laguna. Re: Surgical Histopathology for Suspected Oncocytoma on Renal Mass Biopsy: A Systematic Review and Meta-Analysis. J Urol. 2018 Jan;199(1):24-25.

32. M.P. Laguna. Re: The Impact of Quality Variations on Patients Undergoing Surgery for Renal Cell Carcinoma: A National Cancer Database Study. J Urol. 2018 Feb;199(2):338-339.

33. M.P. Laguna. Re: When to Perform Preoperative Chest Computed Tomography for Renal Cancer Staging. J Urol. 2018 Feb;199(2):339.

34. M. Buijs,P.G.K. Wagstaff,D.M. de Bruin, P.J. Zondervan, C.D. Savci-Heijink,O.M. van Delden,T.G. van Leeuwen,R.J.A. van Moorselaar, J.J.M.C.H. de la Rosette, M.P. Laguna Pes. An In-vivo Prospective Study of the Diagnostic Yield and Accuracy of Optical Biopsy Compared with Conventional Renal Mass Biopsy for the Diagnosis of Renal Cell Carcinoma: The Interim Analysis. Eur Urol Focus. 2017 Oct 24. pii: S2405-4569(17)30239-0. doi: 10.1016/j.euf.2017.10.002. [Epub ahead of print] PubMed PMID: 29079496.

35. M.T.J. Bus,P. Cernohorsky,D.M. de Bruin,S.L. Meijer,G.J. Streekstra,D.J. Faber, G.M. Kamphuis, P.J. Zondervan,M. van Herk,M.P. Laguna Pes,M.J. Grundeken,M.J. Brandt , T.M. de Reijke, J.J.M.C.H. de la Rosette, T.G. van Leeuwen. Ex-vivo study in nephroureterectomy specimens defining the role of 3-D upper urinary tract visualization using optical coherence tomography and endoluminal ultrasound. J Med Imaging (Bellingham). 2018 Jan;5(1):017001.

36. J.L Boormans, J. Mayor de Castro, L. Marconi, Y. Yuan, M.P. Laguna Pes, C. Bokemeyer, N. Nicolai, F. Algaba, J. Oldenburg, P. Albers. Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel. Eur Urol. 2017 Nov 20. pii:S0302-2838(17)30826-6. doi: 10.1016/j.eururo.2017.09.025. [Epub ahead of print]

37. A.Basiri, J.J. de la Rosette, S. Tabatabaei, H.H. Woo, M.P. Laguna, H. Shemshaki.Comparison of retropubic, laparoscopic and robotic radical prostatectomy: who is the winner? World J Urol. 2018 Apr;36(4):609-621.

38. M.P. Laguna. Re: Stereotactic Ablative Body Radiotherapy for Inoperable Primary Kidney Cancer: A Prospective Clinical Trial. J Urol. 2018 Jun;199(6):1393-1394.

39. M.P. Laguna. Re: Randomized Phase III Trial of Adjuvant Pazopanib versus Placebo after Nephrectomy in Patients with Localized or Locally Advanced Renal Cell Carcinoma. J Urol. 2018 Jun;199(6):1393-1394.

40. M.P. Laguna. Re: Stereotactic Ablative Body Radiotherapy for Inoperable Primary Kidney Cancer: A Prospective Clinical Trial. J Urol. 2018 Jun;199(6):1393-1394.

41. M.P. Laguna. Re: Randomized Phase III Trial of Adjuvant Pazopanib versus Placebo after Nephrectomy in Patients with Localized or Locally Advanced Renal Cell Carcinoma. J Urol. 2018 Jun;199(6):1393-1394.

42. M.P. Laguna. Re: Recommendations for the Management of Rare Kidney Cancers. J Urol. 2018 May;199(5):1109.

43. M.P. Laguna. Re: Intravenous Mannitol versus Placebo during Partial Nephrectomy in Patients with Normal Kidney Function: A Double-Blind, Clinically-Integrated, Randomized Trial. J Urol. 2018 May;199(5):1108-1109.

44. M.P. Laguna. Re: Defining the Role of Intraoperative Transesophageal Echocardiography during Radical Nephrectomy with Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma. J Urol. 2018 Apr;199(4):890.

45. M.P. Laguna. Re: Impact of Diagnostic Ureteroscopy on Intravesical Recurrence in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Cancer: A Systematic Review and Meta-Analysis. J Urol. 2018 Apr;199(4):889-890.

46. E.I. Liem, J.E. Freund, J. Baard, D.M. de Bruin,M.P. Laguna Pes,C.D. Savci-Heijink,T.G. van Leeuwen,T.M. de Reijke,J.J. de la Rosette. Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies. JMIR Res Protoc. 2018 Feb7;7(2):e34.

47. M.P. Laguna. Re: Pathological Heterogeneity in Sporadic Synchronous RenalTumors: Is the Histological Concordance Predictable? J Urol. 2018 Oct;200(4):694-695.

48. M.P. Laguna. Re: Incidence of T3a Up-Staging and Survival after Partial Nephrectomy: Size-Stratified Rates and Implications for Prognosis. J Urol. 2018 Oct;200(4):695.

49. L. Sandbergen, S. Guven, M.P. Laguna. Can ablation win against partial nephrectomy and become first line therapy in cT1a renal tumours? Curr Opin Urol. 2019 Jan;29(1):70-77.

50. M.P. Laguna. Re: A Multigene Signature Based on Cell Cycle Proliferation Improves Prediction of Mortality within 5 Yr of Radical Nephrectomy for Renal Cell Carcinoma. J Urol. 2018 Nov;200(5):941-942.

51. M.P. Laguna. Re: Patients' Preferences for Adjuvant Sorafenib after Resection of Renal Cell Carcinoma in the SORCE Trial: What Makes it Worthwhile? J Urol. 2018 Sep;200(3): 494-496.

52. M.P. Laguna. Re: Perioperative Morbidity of Lymph Node Dissection for Renal Cell Carcinoma: A Propensity Score-Based Analysis. J Urol. 2018 Sep;200(3):495-496.

53. T. Deng, Y. Chen, B. Liu, M.P. Laguna, JJMCH de la Rosette, X Duan, W Wu, G. Zeng. Systematic review and cumulative analysis of the managements for proximal impacted ureteral stones. World J Urol. 2018 Nov 14. doi: 10.1007/s00345-018-2561-7. [Epub ahead of print].


54. M.P. Laguna. Re: The Role of Lymph Node Dissection in the Management of Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. J Urol. 2019 Jan;201(1):26-27.

55. M.P. Laguna. Re: Oncologic Outcomes of Patients with Positive Surgical Margin after Partial Nephrectomy: A 25-Year Single Institution Experience. J Urol. 2019 Jan; 201(1) :27-28

56. M.P. Laguna. Re: Outcomes of Pathologic Stage T3a Renal Cell Carcinoma Up-Staged from Small Renal Tumor: . J Urol. 2019 Feb;201(2):224-225

57. M.P. Laguna. Re: Molecular Subtypes of Clear-Cell Renal Cell Carcinoma Are Prognostic for Outcome after Complete Metastasectomy. J Urol. 2019 Jan 15. Doi 10.1097/ JU.0000000000000099. [Epub ahead of print]

58. A. Bex, P. Mulders, M. Jewett, J. Wagstaff, J.V. van Thienen, C.U. Blank, R. van Velthoven, M. del Pilar Laguna, L. Wood, H.H.E. van Melick,  M.J.Aarts, J.B. Lattouf, T. Powles, I.J. de Jong, S. Rottey, B. Tombal, S. Marreaud, S. Collette, L. Collette, J. Haanen J. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2018 Dec 13. doi: 10.1001 / jamaoncol .2018.5543. [Epub ahead of print]

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