Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma: review of current clinical trials

1Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424. doi: 10.3322/caac.21492BrayFFerlayJSoerjomataramISiegelRLTorreLAJemalA.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countriesCA Cancer J Clin20186839442410.3322/caac.21492Open DOISearch in Google Scholar

2Petersen JF, Timmermans AJ, van Dijk BAC, Overbeek LIH, Smit LA, Hilgers FJM, et al. Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands. Eur Arch Oto-Rhino-Laryngology 2018; 275: 181-9. doi: 10.1007/s00405-017-4766-6PetersenJFTimmermansAJvan DijkBACOverbeekLIHSmitLAHilgersFJMet alTrends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the NetherlandsEur Arch Oto-Rhino-Laryngology2018275181910.1007/s00405-017-4766-6Open DOISearch in Google Scholar

3Goor KM, Peeters AJGE, Mahieu HF, Langendijk JA, Leemans CR, Verdonckde Leeuw IM, et al. Cordectomy by CO2 laser or radiotherapy for small T1a glottic carcinomas: Costs, local control, survival, quality of life, and voice quality. Head Neck 2007; 29: 128-36. doi: 10.1002/hed.20500GoorKMPeetersAJGEMahieuHFLangendijkJALeemansCRVerdonckdeLeeuw IMet alCordectomy by CO2 laser or radiotherapy for small T1a glottic carcinomas: Costs, local control, survival, quality of life, and voice qualityHead Neck2007291283610.1002/hed.20500Open DOISearch in Google Scholar

4Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet 2008; 371: 1695-709. doi: 10.1016/S0140-6736(08)60728-XArgirisAKaramouzisMVRabenDFerrisRLHead and neck cancerLancet2008371169570910.1016/S0140-6736(08)60728-XOpen DOISearch in Google Scholar

5Corry J, Smee R, Ferlito A, Suárez C, Rapidis AD, Strojan P, et al. Management of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we? Eur Arch Oto-Rhino-Laryngology 2015; 273: 2877-94. doi: 10.1007/s00405-015-3771-xCorryJSmeeRFerlitoASuárezCRapidisADStrojanPet alManagement of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we?Eur Arch Oto-Rhino-Laryngology201527328779410.1007/s00405-015-3771-xOpen DOISearch in Google Scholar

6Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363: 24-35. doi: 10.1056/NEJMoa0912217AngKKHarrisJWheelerRWeberRRosenthalDINguyen-TânPFet alHuman papillomavirus and survival of patients with oropharyngeal cancerN Engl J Med2010363243510.1056/NEJMoa0912217Open DOISearch in Google Scholar

7Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011; 331: 1565-70. doi: 10.1126/science.1203486SchreiberRDOldLJSmythMJCancer immunoediting: integrating immunity’s roles in cancer suppression and promotionScience201133115657010.1126/science.1203486Open DOISearch in Google Scholar

8Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 2019; 394: 1915-28. doi: 10.1016/S0140-6736(19)32591-7BurtnessBHarringtonKJGreilRSoulièresDTaharaMde CastroGet alPembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 studyLancet201939419152810.1016/S0140-6736(19)32591-7Open DOISearch in Google Scholar

9Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016; 375: 1856-67. doi: 10.1056/NEJMoa1602252FerrisRLBlumenscheinGFayetteJGuigayJColevasADLicitraLet alNivolumab for recurrent squamous-cell carcinoma of the head and neckN Engl J Med201637518566710.1056/NEJMoa1602252556429227718784Open DOISearch in Google Scholar

10Saba NF, Blumenschein G, Guigay J, Licitra L, Fayette J, Harrington KJ, et al. Nivolumab versus investigator’s choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by age. Oral Oncol 2019; 96: 7-14. doi: 10.1016/j.oraloncology.2019.06.017SabaNFBlumenscheinGGuigayJLicitraLFayetteJHarringtonKJet alNivolumab versus investigator’s choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by ageOral Oncol20199671410.1016/j.oraloncology.2019.06.017772382031422216Open DOISearch in Google Scholar

11Hanna GJ, Adkins DR, Zolkind P, Uppaluri R. Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma. Oral Oncol 2017; 73: 65-9. doi: 10.1016/j.oraloncology.2017.08.008HannaGJAdkinsDRZolkindPUppaluriRRationale for neoadjuvant immunotherapy in head and neck squamous cell carcinomaOral Oncol20177365910.1016/j.oraloncology.2017.08.008Open DOISearch in Google Scholar

12Harrington KJ, Ferris RL, Blumenschein G, Colevas AD, Fayette J, Licitra L, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol 2017; 18: 1104-15. doi: 10.1016/S1470-2045(17)30421-7HarringtonKJFerrisRLBlumenscheinGColevasADFayetteJLicitraLet alNivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trialLancet Oncol20171811041510.1016/S1470-2045(17)30421-7Open DOISearch in Google Scholar

13Monjazeb AM, Schalper KA, Villarroel-Espindola F, Nguyen A, Shiao SL, Young K. Effects of radiation on the tumor microenvironment. Semin Radiat Oncol 2020; 30: 145-57. doi: 10.1016/j.semradonc.2019.12.004MonjazebAMSchalperKAVillarroel-EspindolaFNguyenAShiaoSLYoungKEffects of radiation on the tumor microenvironmentSemin Radiat Oncol2020301455710.1016/j.semradonc.2019.12.004876496832381294Open DOISearch in Google Scholar

14Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 2009; 114: 589-95. doi: 10.1182/blood-2009-02-206870LeeYAuhSLWangYBurnetteBWangYMengYet alTherapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatmentBlood20091145899510.1182/blood-2009-02-206870271347219349616Open DOISearch in Google Scholar

15Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014; 124: 687-95. doi: 10.1172/JCI67313DengLLiangHBurnetteBBeckettMDargaTWeichselbaumRRet alIrradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in miceJ Clin Invest20141246879510.1172/JCI67313390460124382348Open DOISearch in Google Scholar

16Sha CM, Lehrer EJ, Hwang C, Trifiletti DM, Mackley HB, Drabick JJ, et al. Toxicity in combination immune checkpoint inhibitor and radiation therapy: a systematic review and meta-analysis. Radiother Oncol 2020; 151: 141-8.; doi: 10.1016/j.radonc.2020.07.035ShaCMLehrerEJHwangCTrifilettiDMMackleyHBDrabickJJet alToxicity in combination immune checkpoint inhibitor and radiation therapy: a systematic review and meta-analysisRadiother Oncol2020151141810.1016/j.radonc.2020.07.03532717359Open DOISearch in Google Scholar

17Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, et al. A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Int J Radiat Oncol 2016; 96: 578-88. doi: 10.1016/j.ijrobp.2016.07.005HinikerSMReddySAMaeckerHTSubrahmanyamPBRosenberg-HassonYSwetterSMet alA prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanomaInt J Radiat Oncol2016965788810.1016/j.ijrobp.2016.07.005507716627681753Open DOISearch in Google Scholar

18Sundahl N, De Wolf K, Kruse V, Meireson A, Reynders D, Goetghebeur E, et al. Phase 1 dose escalation trial of ipilimumab and stereotactic body radiation therapy in metastatic melanoma. Int J Radiat Oncol 2018; 100: 906-15. doi: 10.1016/j.ijrobp.2017.11.029SundahlNDe WolfKKruseVMeiresonAReyndersDGoetghebeurEet alPhase 1 dose escalation trial of ipilimumab and stereotactic body radiation therapy in metastatic melanomaInt J Radiat Oncol20181009061510.1016/j.ijrobp.2017.11.02929485070Open DOISearch in Google Scholar

19Campbell AM, Cai WL, Burkhardt D, Gettinger SN, Goldberg SB, Amodio M, et al. Final results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC). Int J Radiat Oncol 2019; 105: S36-7. doi: 10.1016/j.ijrobp.2019.06.453CampbellAMCaiWLBurkhardtDGettingerSNGoldbergSBAmodioMet alFinal results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC)Int J Radiat Oncol2019105S36710.1016/j.ijrobp.2019.06.453Open DOISearch in Google Scholar

20Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJ V., et al. Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non–small cell lung cancer. JAMA Oncol 2019; 5: 1276. doi: 10.1001/jamaoncol.2019.1478TheelenWSMEPeulenHMULalezariFvan derNoort Vde VriesJFAertsJGJ V.et alEffect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non–small cell lung cancerJAMA Oncol20195127610.1001/jamaoncol.2019.1478662481431294749Open DOISearch in Google Scholar

21Patel JD, Bestvina CM, Karrison T, Jelinek MJ, Juloori A, Pointer K, et al. Randomized phase I trial to evaluate Concurrent or Sequential Ipilimumab, Nivolumab, and stereotactic body Radiotherapy in patients with stage IV non-small cell lung cancer (COSINR Study). [abstract]. J Clin Oncol 2020; 38(15 Suppl): 9616. doi: 10.1200/JCO.2020.38.15_suppl.9616PatelJDBestvinaCMKarrisonTJelinekMJJulooriAPointerKet alRandomized phase I trial to evaluate Concurrent or Sequential Ipilimumab, Nivolumab, and stereotactic body Radiotherapy in patients with stage IV non-small cell lung cancer (COSINR Study). [abstract]J Clin Oncol20203815 Suppl961610.1200/JCO.2020.38.15_suppl.9616Open DOISearch in Google Scholar

22Ferris RL, Licitra L, Fayette J, Even C, Blumenschein G, Harrington KJ, et al. Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior cetuximab use. Clin Cancer Res 2019; 25: 5221-30. doi: 10.1158/1078-0432.CCR-18-3944FerrisRLLicitraLFayetteJEvenCBlumenscheinGHarringtonKJet alNivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior cetuximab useClin Cancer Res20192552213010.1158/1078-0432.CCR-18-3944Open DOISearch in Google Scholar

23Cohen EEW, Soulières D, Le Tourneau C, Dinis JJ, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019; 393: 156-67. doi: 10.1016/S0140-6736(18)31999-8CohenEEWSoulièresDLe TourneauCDinisJJLicitraLAhnMJet alPembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 studyLancet20193931566710.1016/S0140-6736(18)31999-8Open DOISearch in Google Scholar

24Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017; 168: 707-23. doi: 10.1016/j.cell.2017.01.017SharmaPHu-LieskovanSWargoJARibasAPrimary, adaptive, and acquired resistance to cancer immunotherapyCell20171687072310.1016/j.cell.2017.01.017539169228187290Open DOISearch in Google Scholar

25Jensen PE. Recent advances in antigen processing and presentation. Nat Immunol 2007; 8: 1041-8. doi: 10.1038/ni1516JensenPERecent advances in antigen processing and presentationNat Immunol200781041810.1038/ni151617878914Open DOISearch in Google Scholar

26Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 2017; 9: 34. doi: 10.1186/s13073-017-0424-2ChalmersZRConnellyCFFabrizioDGayLAliSMEnnisRet alAnalysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burdenGenome Med201793410.1186/s13073-017-0424-2539571928420421Open DOISearch in Google Scholar

27Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science 2015; 348: 69-74. doi: 10.1126/science.aaa4971SchumacherTNSchreiberRDNeoantigens in cancer immunotherapyScience2015348697410.1126/science.aaa497125838375Open DOISearch in Google Scholar

28López-Albaitero A, Nayak J V., Ogino T, Machandia A, Gooding W, DeLeo AB, et al. Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J Immunol 2006; 176: 3402-9. doi: 10.4049/jimmunol.176.6.3402López-AlbaiteroANayakJ V.OginoTMachandiaAGoodingWDeLeoABet alRole of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTLJ Immunol20061763402910.4049/jimmunol.176.6.340216517708Open DOISearch in Google Scholar

29Meissner M, Reichert TE, Kunkel M, Gooding W, Whiteside TL, Ferrone S, et al. Defects in the human leukocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin Cancer Res 2005; 11: 2552-60. doi: 10.1158/1078-0432.CCR-04-2146MeissnerMReichertTEKunkelMGoodingWWhitesideTLFerroneSet alDefects in the human leukocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: association with clinical outcomeClin Cancer Res20051125526010.1158/1078-0432.CCR-04-214615814633Open DOISearch in Google Scholar

30Concha-Benavente F, Srivastava R, Ferrone S, Ferris RL. Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells. Oral Oncol 2016; 58: 52-8. doi: 10.1016/j.oraloncology.2016.05.008Concha-BenaventeFSrivastavaRFerroneSFerrisRLImmunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cellsOral Oncol20165852810.1016/j.oraloncology.2016.05.008526451827264839Open DOISearch in Google Scholar

31Hoglund P, Sundback J, Olsson-Alheim MY, Johansson M, Salcedo M, Ohien C, et al. Host MHC class I gene control of NK-cell specificity in the mouse. Immunol Rev 1997; 155: 11-28. doi: 10.1111/j.1600-065X.1997.tb00936.xHoglundPSundbackJOlsson-AlheimMYJohanssonMSalcedoMOhienCet alHost MHC class I gene control of NK-cell specificity in the mouseImmunol Rev1997155112810.1111/j.1600-065X.1997.tb00936.xOpen DOISearch in Google Scholar

32Grandis JR, Falkner DM, Melhem MF, Gooding WE, Drenning SD, Morel PA. Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clin Cancer Res 2000; 6: 2794-802. PMID: 10914726GrandisJRFalknerDMMelhemMFGoodingWEDrenningSDMorelPAHuman leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequencesClin Cancer Res200062794802PMID: 10914726Search in Google Scholar

33Ferris RL, Hunt JL, Ferrone S. Human leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significance. Immunol Res 2005; 33: 113-34. doi: 10.1385/IR:33:2:113FerrisRLHuntJLFerroneSHuman leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significanceImmunol Res2005331133410.1385/IR:33:2:113Open DOISearch in Google Scholar

34Pollack BP, Sapkota B, Cartee T V. Epidermal growth factor receptor inhibition augments the expression of MHC class I and II genes. Clin Cancer Res 2011; 17: 4400-13. doi: 10.1158/1078-0432.CCR-10-3283PollackBPSapkotaBCarteeT VEpidermal growth factor receptor inhibition augments the expression of MHC class I and II genesClin Cancer Res20111744001310.1158/1078-0432.CCR-10-328321586626Open DOISearch in Google Scholar

35Chowell D, Morris LGT, Grigg CM, Weber JK, Samstein RM, Makarov V, et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 2018; 359: 582-7. doi: 10.1126/science.aao4572ChowellDMorrisLGTGriggCMWeberJKSamsteinRMMakarovVet alPatient HLA class I genotype influences cancer response to checkpoint blockade immunotherapyScience2018359582710.1126/science.aao4572605747129217585Open DOISearch in Google Scholar

36Chen P-L, Roh W, Reuben A, Cooper ZA, Spencer CN, Prieto PA, et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov 2016; 6: 827-37. doi: 10.1158/2159-8290.CD-15-1545ChenP-LRohWReubenACooperZASpencerCNPrietoPAet alAnalysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockadeCancer Discov201668273710.1158/2159-8290.CD-15-1545508298427301722Open DOISearch in Google Scholar

37Patel SA, Minn AJ. Combination cancer therapy with immune checkpoint blockade: mechanisms and strategies. Immunity 2018; 48: 417-33. doi: 10.1016/j.immuni.2018.03.007PatelSAMinnAJCombination cancer therapy with immune checkpoint blockade: mechanisms and strategiesImmunity2018484173310.1016/j.immuni.2018.03.007694819129562193Open DOISearch in Google Scholar

38Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 140: 798-804. doi: 10.1016/j.cell.2010.02.015ZitvogelLKeppOKroemerGDecoding cell death signals in inflammation and immunityCell201014079880410.1016/j.cell.2010.02.01520303871Open DOISearch in Google Scholar

39Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31: 51-72. doi: 10.1146/annurev-immunol-032712-100008KroemerGGalluzziLKeppOZitvogelLImmunogenic cell death in cancer therapyAnnu Rev Immunol201331517210.1146/annurev-immunol-032712-10000823157435Open DOISearch in Google Scholar

40Sánchez-Paulete AR, Teijeira A, Cueto FJ, Garasa S, Pérez-Gracia JL, Sánchez-Arráez A, et al. Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy. Ann Oncol 2017; 28: xii44-55. doi: 10.1093/annonc/mdx237Sánchez-PauleteARTeijeiraACuetoFJGarasaSPérez-GraciaJLSánchez-ArráezAet alAntigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapyAnn Oncol201728xii44–5510.1093/annonc/mdx23728945841Open DOISearch in Google Scholar

41Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol 2015; 15: 405-14. doi: 10.1038/nri3845ZitvogelLGalluzziLKeppOSmythMJKroemerGType I interferons in anticancer immunityNat Rev Immunol2015154051410.1038/nri384526027717Open DOISearch in Google Scholar

42Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 2013; 154: 47-60. doi: 10.1016/j.cell.2013.06.007HatchEMFischerAHDeerinckTJHetzerMWCatastrophic nuclear envelope collapse in cancer cell micronucleiCell2013154476010.1016/j.cell.2013.06.007374977823827674Open DOISearch in Google Scholar

43Duan S, Thomas PG. Balancing immune protection and immune pathology by CD8+ T-cell responses to influenza infection. Front Immunol 2016; 7: doi: 10.3389/fimmu.2016.00025DuanSThomasPGBalancing immune protection and immune pathology by CD8+ T-cell responses to influenza infectionFront Immunol2016710.3389/fimmu.2016.00025474279426904022Open DOISearch in Google Scholar

44Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 mmunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192: 1027-34. doi: 10.1084/jem.192.7.1027FreemanGJLongAJIwaiYBourqueKChernovaTNishimuraHet alEngagement of the PD-1 mmunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activationJ Exp Med200019210273410.1084/jem.192.7.1027219331111015443Open DOISearch in Google Scholar

45Bardhan K, Anagnostou T, Boussiotis VA. The PD1:PD-L1/2 pathway from discovery to clinical implementation. Front Immunol 2016; 7: 550. doi: 10.3389/fimmu.2016.00550BardhanKAnagnostouTBoussiotisVAThe PD1:PD-L1/2 pathway from discovery to clinical implementationFront Immunol2016755010.3389/fimmu.2016.00550514952328018338Open DOISearch in Google Scholar

46Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515: 568-71. doi: 10.1038/nature13954TumehPCHarviewCLYearleyJHShintakuIPTaylorEJMRobertLet alPD-1 blockade induces responses by inhibiting adaptive immune resistanceNature20145155687110.1038/nature13954424641825428505Open DOISearch in Google Scholar

47Golden EB, Frances D, Pellicciotta I, Demaria S, Helen Barcellos-Hoff M, Formenti SC, et al. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 2014; 3: e28518. doi: 10.4161/onci.28518GoldenEBFrancesDPellicciottaIDemariaSHelenBarcellos-Hoff MFormentiSCet alRadiation fosters dose-dependent and chemotherapy-induced immunogenic cell deathOncoimmunology20143e2851810.4161/onci.28518410615125071979Open DOISearch in Google Scholar

48Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517: 576-82. doi: 10.1038/nature14129LawrenceMSSougnezCLichtensteinLCibulskisKLanderEGabrielSBet alComprehensive genomic characterization of head and neck squamous cell carcinomasNature20155175768210.1038/nature14129431140525631445Open DOISearch in Google Scholar

49Durante M, Formenti SC. Radiation-induced chromosomal aberrations and immunotherapy: micronuclei, cytosolic DNA, and interferon-production pathway. Front Oncol 2018; 8: 192. doi: 10.3389/fonc.2018.00192DuranteMFormentiSCRadiation-induced chromosomal aberrations and immunotherapy: micronuclei, cytosolic DNA, and interferon-production pathwayFront Oncol2018819210.3389/fonc.2018.00192599241929911071Open DOISearch in Google Scholar

50Vanpouille-Box C, Demaria S, Formenti SC, Galluzzi L. Cytosolic DNA Sensing in organismal tumor control. Cancer Cell 2018; 34: 361-78. doi: 10.1016/j.ccell.2018.05.013Vanpouille-BoxCDemariaSFormentiSCGalluzziLCytosolic DNA Sensing in organismal tumor controlCancer Cell2018343617810.1016/j.ccell.2018.05.01330216189Open DOISearch in Google Scholar

51Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, K.Wansley E, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 2006; 203: 1259-71. doi: 10.1084/jem.20052494ReitsEAHodgeJWHerbertsCAGroothuisTAChakrabortyMK.WansleyEet alRadiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapyJ Exp Med200620312597110.1084/jem.20052494321272716636135Open DOISearch in Google Scholar

52Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015; 520: 373-7. doi: 10.1038/nature14292Twyman-SaintVictor CRechAJMaityARenganRPaukenKEStelekatiEet alRadiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancerNature2015520373710.1038/nature14292Open DOISearch in Google Scholar

53Han J, Duan J, Bai H, Wang Y, Wan R, Wang X, et al. TCR repertoire diversity of peripheral PD-1 + CD8 + T cells predicts clinical outcomes after immunotherapy in patients with non–small cell lung cancer. Cancer Immunol Res 2020; 8: 146-54. doi: 10.1158/2326-6066.CIR-19-0398HanJDuanJBaiHWangYWanRWangXet alTCR repertoire diversity of peripheral PD-1 + CD8 + T cells predicts clinical outcomes after immunotherapy in patients with non–small cell lung cancerCancer Immunol Res202081465410.1158/2326-6066.CIR-19-0398Open DOISearch in Google Scholar

54Khan S, de Giuli R, Schmidtke G, Bruns M, Buchmeier M, van den Broek M, et al. Cutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein. J Immunol 2001; 167: 4801-4. doi: 10.4049/jimmunol.167.9.4801KhanSde GiuliRSchmidtkeGBrunsMBuchmeierMvan denBroek Met alCutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral proteinJ Immunol20011674801410.4049/jimmunol.167.9.4801Open DOISearch in Google Scholar

55Weichselbaum RR, Hallahan D, Fuks Z, Kufe D. Radiation induction of immediate early genes: Effectors of the radiation-stress response. Int J Radiat Oncol 1994; 30: 229-34. doi: 10.1016/0360-3016(94)90539-8WeichselbaumRRHallahanDFuksZKufeDRadiation induction of immediate early genes: Effectors of the radiation-stress responseInt J Radiat Oncol1994302293410.1016/0360-3016(94)90539-8Open DOISearch in Google Scholar

56Lan J, Li R, Yin LM, Deng L, Gui J, Chen BQ, et al. Targeting myeloid-derived suppressor cells and programmed death ligand 1 confers therapeutic advantage of ablative hypofractionated radiation therapy compared with conventional fractionated radiation therapy. Int J Radiat Oncol Biol Phys 2018; 101: 74-87. doi: 10.1016/j.ijrobp.2018.01.071LanJLiRYinLMDengLGuiJChenBQet alTargeting myeloid-derived suppressor cells and programmed death ligand 1 confers therapeutic advantage of ablative hypofractionated radiation therapy compared with conventional fractionated radiation therapyInt J Radiat Oncol Biol Phys2018101748710.1016/j.ijrobp.2018.01.07129619980Open DOISearch in Google Scholar

57Matsumura S, Wang B, Kawashima N, Braunstein S, Badura M, Cameron TO, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol 2008; 181: 3099-107. doi: 10.4049/jimmunol.181.5.3099MatsumuraSWangBKawashimaNBraunsteinSBaduraMCameronTOet alRadiation-induced CXCL16 release by breast cancer cells attracts effector T cellsJ Immunol2008181309910710.4049/jimmunol.181.5.3099258710118713980Open DOISearch in Google Scholar

58Chakraborty M, Abrams SI, Camphausen K, Liu K, Scott T, Coleman CN, et al. Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol 2003; 170: 6338-47. doi: 10.4049/jimmunol.170.12.6338ChakrabortyMAbramsSICamphausenKLiuKScottTColemanCNet alIrradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapyJ Immunol200317063384710.4049/jimmunol.170.12.633812794167Open DOISearch in Google Scholar

59Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 2004; 64: 4328-37. doi: 10.1158/0008-5472.CAN-04-0073ChakrabortyMAbramsSIColemanCNCamphausenKSchlomJHodgeJWExternal beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killingCancer Res20046443283710.1158/0008-5472.CAN-04-007315205348Open DOISearch in Google Scholar

60Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, et al. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 2013; 24: 589-602. doi: 10.1016/j.ccr.2013.09.014KlugFPrakashHHuberPESeibelTBenderNHalamaNet alLow-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapyCancer Cell20132458960210.1016/j.ccr.2013.09.01424209604Open DOISearch in Google Scholar

61Savage T, Pandey S, Guha C. Postablation modulation after single high-dose radiation therapy improves tumor control via enhanced immunomodulation. Clin Cancer Res 2020; 26: 910-21. doi: 10.1158/1078-0432.CCR-18-3518SavageTPandeySGuhaCPostablation modulation after single high-dose radiation therapy improves tumor control via enhanced immunomodulationClin Cancer Res2020269102110.1158/1078-0432.CCR-18-351831757878Open DOISearch in Google Scholar

62Hallahan D, Kuchibhotla J, Wyble C. Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer Res 1996; 56: 5150-5. PMID: 8912850HallahanDKuchibhotlaJWybleCCell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endotheliumCancer Res19965651505PMID: 8912850Search in Google Scholar

63Tran L, Allen CT, Xiao R, Moore E, Davis R, Park SJ, et al. Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res 2017; 5: 1141-51. doi: 10.1158/2326-6066.CIR-17-0235TranLAllenCTXiaoRMooreEDavisRParkSJet alCisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinomaCancer Immunol Res2017511415110.1158/2326-6066.CIR-17-0235571228129097421Open DOISearch in Google Scholar

64Luo R, Firat E, Gaedicke S, Guffart E, Watanabe T, Niedermann G. Cisplatin facilitates radiation-induced abscopal effects in conjunction with PD-1 checkpoint blockade through CXCR3/CXCL10-mediated T-cell recruitment. Clin Cancer Res 2019; 25: 7243-55. doi: 10.1158/1078-0432.CCR-19-1344LuoRFiratEGaedickeSGuffartEWatanabeTNiedermannGCisplatin facilitates radiation-induced abscopal effects in conjunction with PD-1 checkpoint blockade through CXCR3/CXCL10-mediated T-cell recruitmentClin Cancer Res20192572435510.1158/1078-0432.CCR-19-134431506388Open DOISearch in Google Scholar

65Teijeira Á, Garasa S, Gato M, Alfaro C, Migueliz I, Cirella A, et al. CXCR1 and CXCR2 Chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 2020; 52: 856-71.e8. doi: 10.1016/j.immuni.2020.03.001TeijeiraÁGarasaSGatoMAlfaroCMiguelizICirellaAet alCXCR1 and CXCR2 Chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicityImmunity2020528567110.1016/j.immuni.2020.03.00132289253Open DOISearch in Google Scholar

66Shinde-Jadhav S, Mansure JJ, Rayes R, Ayoub M, Spicer J, Kassouf W. Abstract 3743: Neutrophil extracellular traps and their implication with radioresistance in muscle invasive bladder cancer. [abstract]. In: Proceedings AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Cancer Res 2019; 79(13 Suppl): 3743. doi: 10.1158/1538-7445.AM2019-3743Shinde-JadhavSMansureJJRayesRAyoubMSpicerJKassoufWAbstract 3743: Neutrophil extracellular traps and their implication with radioresistance in muscle invasive bladder cancer[abstract]. In: Proceedings AACR Annual Meeting2019March 29-April 3, 2019; Atlanta, GA. Cancer Res 20197913 Suppl374310.1158/1538-7445.AM2019-3743Open DOISearch in Google Scholar

67Deaglio S, Robson SC. Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity. Adv Pharmacol; 2011; 61: 301-32. doi: 10.1016/B978-0-12-385526-8.00010-2DeaglioSRobsonSCEctonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunityAdv Pharmacol;2011613013210.1016/B978-0-12-385526-8.00010-2587977321586363Open DOISearch in Google Scholar

68Ohta A, Kini R, Ohta A, Subramanian M, Madasu M, Sitkovsky M. The development and immunosuppressive functions of CD4+ CD25+ FoxP3+ regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol 2012; 3: 190. doi: 10.3389/fimmu.2012.00190OhtaAKiniROhtaASubramanianMMadasuMSitkovskyMThe development and immunosuppressive functions of CD4+ CD25+ FoxP3+ regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathwayFront Immunol2012319010.3389/fimmu.2012.00190338964922783261Open DOISearch in Google Scholar

69Palmer TM, Trevethick MA. Suppression of inflammatory and immune responses by the A 2A adenosine receptor: an introduction. Br J Pharmacol 2008; 153: S27-34. doi: 10.1038/sj.bjp.0707524PalmerTMTrevethickMASuppression of inflammatory and immune responses by the A 2A adenosine receptor: an introductionBr J Pharmacol2008153S273410.1038/sj.bjp.0707524226803818026131Open DOISearch in Google Scholar

70Cekic C, Day YJ, Sag D, Linden J. Myeloid expression of adenosine a2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Res 2014; 74: 7250-9. doi: 10.1158/0008-5472.CAN-13-3583CekicCDayYJSagDLindenJMyeloid expression of adenosine a2A receptor suppresses T and NK cell responses in the solid tumor microenvironmentCancer Res2014747250910.1158/0008-5472.CAN-13-3583445978225377469Open DOISearch in Google Scholar

71Liang H, Deng L, Hou Y, Meng X, Huang X, Rao E, et al. Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. Nat Commun 2017; 8: 1736. doi: 10.1038/s41467-017-01566-5LiangHDengLHouYMengXHuangXRaoEet alHost STING-dependent MDSC mobilization drives extrinsic radiation resistanceNat Commun20178173610.1038/s41467-017-01566-5570101929170400Open DOISearch in Google Scholar

72Bakhoum SF, Ngo B, Laughney AM, Cavallo J-A, Murphy CJ, Ly P, et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 2018; 553: 467-72. doi: 10.1038/nature25432BakhoumSFNgoBLaughneyAMCavalloJ-AMurphyCJLyPet alChromosomal instability drives metastasis through a cytosolic DNA responseNature20185534677210.1038/nature25432578546429342134Open DOISearch in Google Scholar

73Lemos H, Mohamed E, Huang L, Ou R, Pacholczyk G, Arbab AS, et al. STING promotes the growth of tumors characterized by low antigenicity via IDO activation. Cancer Res 2016; 76: 2076-81. doi: 10.1158/0008-5472.CAN-15-1456LemosHMohamedEHuangLOuRPacholczykGArbabASet alSTING promotes the growth of tumors characterized by low antigenicity via IDO activationCancer Res20167620768110.1158/0008-5472.CAN-15-1456Open DOISearch in Google Scholar

74Monjazeb AM, Kent MS, Grossenbacher SK, Mall C, Zamora AE, Mirsoian A, et al. Blocking indolamine-2,3-dioxygenase rebound immune suppression boosts antitumor effects of radio-immunotherapy in murine models and spontaneous canine malignancies. Clin Cancer Res 2016; 22: 4328-40. doi: 10.1158/1078-0432.CCR-15-3026MonjazebAMKentMSGrossenbacherSKMallCZamoraAEMirsoianAet alBlocking indolamine-2,3-dioxygenase rebound immune suppression boosts antitumor effects of radio-immunotherapy in murine models and spontaneous canine malignanciesClin Cancer Res20162243284010.1158/1078-0432.CCR-15-3026Open DOISearch in Google Scholar

75Jacquelot N, Yamazaki T, Roberti MP, Duong CPM, Andrews MC, Verlingue L, et al. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res 2019; 29: 846-61. doi: 10.1038/s41422-019-0224-xJacquelotNYamazakiTRobertiMPDuongCPMAndrewsMCVerlingueLet alSustained Type I interferon signaling as a mechanism of resistance to PD-1 blockadeCell Res2019298466110.1038/s41422-019-0224-xOpen DOISearch in Google Scholar

76Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors. Cancer Cell 2004; 5: 429-41. doi: 10.1016/S1535-6108(04)00115-1MoellerBJCaoYLiCYDewhirstMWRadiation activates HIF-1 to regulate vascular radiosensitivity in tumorsCancer Cell200454294110.1016/S1535-6108(04)00115-1Open DOISearch in Google Scholar

77Corzo CA, Condamine T, Lu L, Cotter MJ, Youn J-I, Cheng P, et al. HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 2010; 207: 2439-53. doi: 10.1084/jem.20100587CorzoCACondamineTLuLCotterMJYounJ-IChengPet alHIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironmentJ Exp Med201020724395310.1084/jem.20100587296458420876310Open DOISearch in Google Scholar

78Suzuki H, Onishi H, Wada J, Yamasaki A, Tanaka H, Nakano K, et al. VEGFR2 is selectively expressed by FOXP3high CD4+ Treg. Eur J Immunol 2009; 40: 197-203. doi: 10.1002/eji.200939887SuzukiHOnishiHWadaJYamasakiATanakaHNakanoKet alVEGFR2 is selectively expressed by FOXP3high CD4+ TregEur J Immunol20094019720310.1002/eji.20093988719902430Open DOISearch in Google Scholar

79Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998; 92: 4150-66. doi: 10.1182/blood.v92.11.4150.423k45_4150_4166GabrilovichDIshidaTOyamaTRanSKravtsovVNadafSet alVascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivoBlood19989241506610.1182/blood.v92.11.4150.423k45_4150_4166Open DOISearch in Google Scholar

80Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, et al. Expression of vascular endothelial growth factor in ovarian cancer inhibits tumor immunity through the accumulation of myeloid-derived suppressor cells. Clin Cancer Res 2017; 23: 587-99. doi: 10.1158/1078-0432.CCR-16-0387HorikawaNAbikoKMatsumuraNHamanishiJBabaTYamaguchiKet alExpression of vascular endothelial growth factor in ovarian cancer inhibits tumor immunity through the accumulation of myeloid-derived suppressor cellsClin Cancer Res2017235879910.1158/1078-0432.CCR-16-038727401249Open DOISearch in Google Scholar

81National Comprehensive Cancer Network (NCCN). Head and Neck Cancers, Version 2.2020. (cited 2020 Jul 20). Available at: https://www.nccn.orgNational Comprehensive Cancer Network (NCCN). Head and Neck Cancers, Version 2.2020(cited 2020 Jul 20). Available athttps://www.nccn.orgSearch in Google Scholar

82Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 2013; 38: 729-41. doi: 10.1016/j.immuni.2013.03.003MaYAdjemianSMattarolloSRYamazakiTAymericLYangHet alAnticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cellsImmunity2013387294110.1016/j.immuni.2013.03.00323562161Open DOISearch in Google Scholar

83Crittenden MR, Zebertavage L, Kramer G, Bambina S, Friedman D, Troesch V, et al. Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity. Sci Rep 2018; 8: 1-15. doi: 10.1038/s41598-018-25482-wCrittendenMRZebertavageLKramerGBambinaSFriedmanDTroeschVet alTumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunitySci Rep2018811510.1038/s41598-018-25482-w593447329725089Open DOISearch in Google Scholar

84Markovsky E, Budhu S, Samstein RM, Li H, Russell J, Zhang Z, et al. An anti-tumor immune response is evoked by partial-volume single-dose radiation in 2 murine models. Int J Radiat Oncol 2019; 103: 697-708. doi: 10.1016/j.ijrobp.2018.10.009MarkovskyEBudhuSSamsteinRMLiHRussellJZhangZet alAn anti-tumor immune response is evoked by partial-volume single-dose radiation in 2 murine modelsInt J Radiat Oncol201910369770810.1016/j.ijrobp.2018.10.009676441630342090Open DOISearch in Google Scholar

85Takeshima T, Chamoto K, Wakita D, Ohkuri T, Togashi Y, Shirato H, et al. Local radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: its potentiation by combination with TH1 cell therapy. Cancer Res 2010; 70: 2697-706. doi: 10.1158/0008-5472.CAN-09-2982TakeshimaTChamotoKWakitaDOhkuriTTogashiYShiratoHet alLocal radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: its potentiation by combination with TH1 cell therapyCancer Res201070269770610.1158/0008-5472.CAN-09-298220215523Open DOISearch in Google Scholar

86Marciscano AE, Ghasemzadeh A, Nirschl TR, Theodros D, Kochel CM, Francica BJ, et al. Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy. Clin Cancer Res 2018; 24: 5058-71. doi: 10.1158/1078-0432.CCR-17-3427MarciscanoAEGhasemzadehANirschlTRTheodrosDKochelCMFrancicaBJet alElective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapyClin Cancer Res20182450587110.1158/1078-0432.CCR-17-3427653297629898992Open DOISearch in Google Scholar

87Botticelli A, Mezi S, Pomati G, Sciattella P, Cerbelli B, Roberto M, et al. The impact of locoregional treatment on response to nivolumab in advanced platinum refractory head and neck cancer: The need trial. Vaccines 2020; 8: 191. doi: 10.3390/vaccines8020191BotticelliAMeziSPomatiGSciattellaPCerbelliBRobertoMet alThe impact of locoregional treatment on response to nivolumab in advanced platinum refractory head and neck cancer: The need trialVaccines2020819110.3390/vaccines8020191734976832326034Open DOISearch in Google Scholar

88Zandberg DP, Ferris RL. Window studies in squamous cell carcinoma of the head and neck: values and limits. Curr Treat Options Oncol 2018; 19: 68. doi: 10.1007/s11864-018-0587-0ZandbergDPFerrisRLWindow studies in squamous cell carcinoma of the head and neck: values and limitsCurr Treat Options Oncol2018196810.1007/s11864-018-0587-0656467630367283Open DOISearch in Google Scholar

89Leidner R, Bell RB, Young K, Curti B, Couey M, Patel A, et al. Abstract CT182: Neoadjuvant immuno-radiotherapy (NIRT) in head and neck cancer: Phase I/Ib study of combined PD-1/SBRT prior to surgical resection. [abstract]. In: Proceedings AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Cancer Res 2019; 79(13 Suppl): CT182. doi: 10.1158/1538-7445.AM2019-CT182LeidnerRBellRBYoungKCurtiBCoueyMPatelAet alAbstract CT182: Neoadjuvant immuno-radiotherapy (NIRT) in head and neck cancer: Phase I/Ib study of combined PD-1/SBRT prior to surgical resection[abstract]. In: Proceedings AACR Annual Meeting2019March 29-April32019; Atlanta, GA. Cancer Res 2019; 79(13 Suppl): CT18210.1158/1538-7445.AM2019-CT182Open DOISearch in Google Scholar

90Saâda-Bouzid E, Defaucheux C, Karabajakian A, Coloma VP, Servois V, Paoletti X, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol 2017; 28: 1605-11. doi: 10.1093/annonc/mdx178Saâda-BouzidEDefaucheuxCKarabajakianAColomaVPServoisVPaolettiXet alHyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinomaAnn Oncol20172816051110.1093/annonc/mdx17828419181Open DOISearch in Google Scholar

91Bell RB, Leidner R, Young KH, Curti B, Couey M, Patel A, et al. Cohort expansion study of neoadjvuant immunoradiotherapy in locoregionally advanced HPV+ and HPV- head and neck squamous cell carcinoma. Int J Radiat Oncol 2020; 106: 1225-6. doi: 10.1016/j.ijrobp.2020.02.013BellRBLeidnerRYoungKHCurtiBCoueyMPatelAet alCohort expansion study of neoadjvuant immunoradiotherapy in locoregionally advanced HPV+ and HPV- head and neck squamous cell carcinomaInt J Radiat Oncol20201061225610.1016/j.ijrobp.2020.02.013Open DOISearch in Google Scholar

92Chin R. Stereotactic body radiation therapy and Durvalumab with or without Tremelimumab before surgery in treating participants with human papillomavirus positive oropharyngeal squamous cell cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03618134ChinRStereotactic body radiation therapy and Durvalumab with or without Tremelimumab before surgery in treating participants with human papillomavirus positive oropharyngeal squamous cell cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03618134Search in Google Scholar

93Economopoulou P, Kotsantis I, Psyrri A. The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches. ESMO Open 2017; 1: e000122. doi: 10.1136/esmoopen-2016-000122EconomopoulouPKotsantisIPsyrriAThe promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approachesESMO Open20171e00012210.1136/esmoopen-2016-000122554897428848660Open DOISearch in Google Scholar

94Barbari C, Fontaine T, Parajuli P, Lamichhane N, Jakubski S, Lamichhane P, et al. Immunotherapies and combination strategies for immuno-oncology. Int J Mol Sci 2020; 21: 5009. doi: 10.3390/ijms21145009BarbariCFontaineTParajuliPLamichhaneNJakubskiSLamichhanePet alImmunotherapies and combination strategies for immuno-oncologyInt J Mol Sci202021500910.3390/ijms21145009740404132679922Open DOISearch in Google Scholar

95Diehl A, Yarchoan M, Hopkins A, Jaffee E, Grossman SA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors. Oncotarget 2017; 8: 114268-80. doi: 10.18632/oncotarget.23217DiehlAYarchoanMHopkinsAJaffeeEGrossmanSARelationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitorsOncotarget201781142688010.18632/oncotarget.23217576840229371985Open DOISearch in Google Scholar

96Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res 2014; 74: 5458-68. doi: 10.1158/0008-5472.CAN-14-1258DovediSJAdlardALLipowska-BhallaGMcKennaCJonesSCheadleEJet alAcquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockadeCancer Res20147454586810.1158/0008-5472.CAN-14-125825274032Open DOISearch in Google Scholar

97Chen D, Patel RR, Verma V, Ramapriyan R, Barsoumian HB, Cortez MA, et al. Interaction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapy. Radiother Oncol 2020 Avg 13; [Ahead of print.] doi: 10.1016/j.radonc.2020.05.051ChenDPatelRRVermaVRamapriyanRBarsoumianHBCortezMAet alInteraction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapyRadiother Oncol202013[Ahead of print.]10.1016/j.radonc.2020.05.05132525003Open DOISearch in Google Scholar

98Ho WJ, Yarchoan M, Hopkins A, Mehra R, Grossman S, Kang H. Association between pretreatment lymphocyte count and response to PD1 inhibitors in head and neck squamous cell carcinomas. J Immunother Cancer 2018; 6: 84. doi: 10.1186/s40425-018-0395-xHoWJYarchoanMHopkinsAMehraRGrossmanSKangHAssociation between pretreatment lymphocyte count and response to PD1 inhibitors in head and neck squamous cell carcinomasJ Immunother Cancer201868410.1186/s40425-018-0395-x611794430170629Open DOISearch in Google Scholar

99Kaanders JHAM, van den Bosch S, Dijkema T, Al-Mamgani A, Raaijmakers CPJ, Vogel W V. Advances in cancer imaging require renewed radiotherapy dose and target volume concepts. Radiother Oncol 2020; 148: 140-2. doi: 10.1016/j.radonc.2020.04.016KaandersJHAMvanden Bosch SDijkemaTAl-MamganiARaaijmakersCPJVogelW VAdvances in cancer imaging require renewed radiotherapy dose and target volume conceptsRadiother Oncol2020148140210.1016/j.radonc.2020.04.01632361663Open DOISearch in Google Scholar

100Grapin M, Richard C, Limagne E, Boidot R, Morgand V, Bertaut A, et al. Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combination. J Immunother Cancer 2019; 7: 1-12. doi: 10.1186/s40425-019-0634-9GrapinMRichardCLimagneEBoidotRMorgandVBertautAet alOptimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combinationJ Immunother Cancer2019711210.1186/s40425-019-0634-9659352531238970Open DOISearch in Google Scholar

101Filatenkov A, Baker J, Mueller AMS, Kenkel J, Ahn GO, Dutt S, et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res 2015; 21: 3727-39. doi: 10.1158/1078-0432.CCR-14-2824FilatenkovABakerJMuellerAMSKenkelJAhnGODuttSet alAblative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissionsClin Cancer Res20152137273910.1158/1078-0432.CCR-14-2824453784425869387Open DOISearch in Google Scholar

102Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre J-L, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350: 1945-52. doi: 10.1056/NEJMoa032641BernierJDomengeCOzsahinMMatuszewskaKLefèbvreJ-LGreinerRHet alPostoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancerN Engl J Med200435019455210.1056/NEJMoa03264115128894Open DOISearch in Google Scholar

103Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349: 2091-8. doi: 10.1056/NEJMoa031317ForastiereAAGoepfertHMaorMPajakTFWeberRMorrisonWet alConcurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancerN Engl J Med20033492091810.1056/NEJMoa03131714645636Open DOISearch in Google Scholar

104Yoon S-Y, Han JJ, Baek SK, Kim HJ, Maeng CH. Pembrolizumab-induced severe oral mucositis in a patient with squamous cell carcinoma of the lung: a case study. Lung Cancer 2020; 147: 21-5. doi: 10.1016/j.lungcan.2020.06.033YoonS-YHanJJBaekSKKimHJMaengCHPembrolizumab-induced severe oral mucositis in a patient with squamous cell carcinoma of the lung: a case studyLung Cancer202014721510.1016/j.lungcan.2020.06.03332652370Open DOISearch in Google Scholar

105García-Foncillas J, Sunakawa Y, Aderka D, Wainberg Z, Ronga P, Witzler P, et al. Distinguishing features of Cetuximab and Panitumumab in colorectal cancer and other solid tumors. Front Oncol 2019; 9: 849. doi:10.3389/fonc.2019.00849García-FoncillasJSunakawaYAderkaDWainbergZRongaPWitzlerPet alDistinguishing features of Cetuximab and Panitumumab in colorectal cancer and other solid tumorsFront Oncol2019984910.3389/fonc.2019.00849676361931616627Open DOISearch in Google Scholar

106Ferris RL, Lenz H-J, Trotta AM, García-Foncillas J, Schulten J, Audhuy F, et al. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. Cancer Treat Rev 2018; 63: 48-60. doi: 10.1016/j.ctrv.2017.11.008FerrisRLLenzH-JTrottaAMGarcía-FoncillasJSchultenJAudhuyFet alRationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulationCancer Treat Rev201863486010.1016/j.ctrv.2017.11.008750516429223828Open DOISearch in Google Scholar

107Sacco AG, Chen R, Ghosh D, Worden F, Wong DJ, Adkins D, et al. An open-label, non-randomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): updated results of cohort 1 analysis. Int J Radiat Oncol 2020; 106: 1121-2. doi: 10.1016/j.ijrobp.2019.11.376SaccoAGChenRGhoshDWordenFWongDJAdkinsDet alAn open-label, non-randomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): updated results of cohort 1 analysisInt J Radiat Oncol20201061121210.1016/j.ijrobp.2019.11.376Open DOISearch in Google Scholar

108Lin Y-C, Uen W-C, Hao S-P, Hsiao C-Y, Lai H-C. Triple combination treatment of cetuximab, chemotherapy, and anti-PD1 check-point inhibitor for recurrent and/or metastatic head and neck squamous cell carcinoma: a single institute experience. J Clin Oncol 2018; 36: e18001. doi: 10.1200/JCO.2018.36.15_suppl.e18001LinY-CUenW-CHaoS-PHsiaoC-YLaiH-CTriple combination treatment of cetuximab, chemotherapy, and anti-PD1 check-point inhibitor for recurrent and/or metastatic head and neck squamous cell carcinoma: a single institute experienceJ Clin Oncol201836e1800110.1200/JCO.2018.36.15_suppl.e18001Open DOISearch in Google Scholar

109EMD Serono and Pfizer provide update on phase III JAVELIN Head and Neck 100 Study. (cited 2020 Jul 15). Available at: https://www.pfizer.com/news/press-release/press-release-detail/emd_serono_and_pfizer_provide_update_on_phase_iii_javelin_head_and_neck_100_studyEMD Serono and Pfizer provide update on phase III JAVELIN Head and Neck 100 Study. (cited 2020 Jul 15)Available athttps://www.pfizer.com/news/press-release/press-release-detail/emd_serono_and_pfizer_provide_update_on_phase_iii_javelin_head_and_neck_100_studySearch in Google Scholar

110Yu Y, Lee NY. JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Futur Oncol 2019; 15: 687-94. doi: 10.2217/fon-2018-0405YuYLeeNYJAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancerFutur Oncol2019156879410.2217/fon-2018-040530461306Open DOISearch in Google Scholar

111Tao Y, Auperin A, Sun XS, Sire C, Martin L, Bera G, et al. Avelumabcetuximab-radiotherapy (RT) versus standards of care (SoC) in locally advanced squamous cell carcinoma of the head and neck (SCCHN): safety phase of the randomized trial GORTEC 2017-01 (REACH). J Clin Oncol 2018; 36: 6076. doi: 10.1200/jco.2018.36.15_suppl.6076TaoYAuperinASunXSSireCMartinLBeraGet alAvelumabcetuximab-radiotherapy (RT) versus standards of care (SoC) in locally advanced squamous cell carcinoma of the head and neck (SCCHN): safety phase of the randomized trial GORTEC 2017-01 (REACH)J Clin Oncol201836607610.1200/jco.2018.36.15_suppl.6076Open DOISearch in Google Scholar

112Tao Y, Auperin A, Sun XS, Sire C, Martin L, Bera G, et al. Avelumabcetuximab-radiotherapy versus standards of care in locally advanced squamous cell carcinoma of the head and neck: safety phase of the randomized phase III trial GORTEC 2017-01 REACH. (cited 2020 Jul 15). Available at: https://www.gortec.net/images/publi/ESMO2019_REACH_POSTER_Discussion.pdfTaoYAuperinASunXSSireCMartinLBeraGet alAvelumabcetuximab-radiotherapy versus standards of care in locally advanced squamous cell carcinoma of the head and neck: safety phase of the randomized phase III trial GORTEC 2017-01 REACH(cited 2020 Jul 15). Available athttps://www.gortec.net/images/publi/ESMO2019_REACH_POSTER_Discussion.pdf10.1200/JCO.2018.36.15_suppl.6076Search in Google Scholar

113Mell LK, Torres-Saavedra PA, Wong SJ, Chang S, Kish JA, Minn A, et al. Safety of radiotherapy with concurrent and adjuvant MEDI4736 (durvalumab) in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin: NRG-HN004. J Clin Oncol 2019; 37: 6065. doi: 10.1200/JCO.2019.37.15_suppl.6065MellLKTorres-SaavedraPAWongSJChangSKishJAMinnAet alSafety of radiotherapy with concurrent and adjuvant MEDI4736 (durvalumab) in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin: NRG-HN004J Clin Oncol201937606510.1200/JCO.2019.37.15_suppl.6065Open DOISearch in Google Scholar

114Sun XS, Sire C, Tao Y, Martin L, Alfonsi M, Prevost JB, et al. A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): first results of the GORTEC 2015-01 “PembroRad” trial. J Clin Oncol 2018; 36: 6018. doi: 10.1200/jco.2018.36.15_suppl.6018SunXSSireCTaoYMartinLAlfonsiMPrevostJBet alA phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): first results of the GORTEC 2015-01 “PembroRad” trialJ Clin Oncol201836601810.1200/jco.2018.36.15_suppl.6018Open DOISearch in Google Scholar

115Klinghammer KF, Gauler TC, Stromberger C, Kofla G, de Wit M, Gollrad J, et al. DURTRERAD: a phase II open-label study evaluating feasibility and efficacy of durvalumab (D) and durvalumab and tremelimumab (DT) in combination with radiotherapy (RT) in non-resectable locally advanced HPV-negative HNSCC – results of the preplanned feasibi. J Clin Oncol 2020; 38: 6574. doi: 10.1200/JCO.2020.38.15_suppl.6574KlinghammerKFGaulerTCStrombergerCKoflaGde WitMGollradJet alDURTRERAD: a phase II open-label study evaluating feasibility and efficacy of durvalumab (D) and durvalumab and tremelimumab (DT) in combination with radiotherapy (RT) in non-resectable locally advanced HPV-negative HNSCC – results of the preplanned feasibiJ Clin Oncol202038657410.1200/JCO.2020.38.15_suppl.6574Open DOISearch in Google Scholar

116Weiss J, Sheth S, Deal AM, Grilley Olson JE, Patel S, Hackman TG, et al. Concurrent definitive immunoradiotherapy for patients with stage III–IV head and neck cancer and cisplatin contraindication. Clin Cancer Res 2020; 26: 4260-7. doi: 10.1158/1078-0432.CCR-20-0230WeissJShethSDealAMGrilleyOlson JEPatelSHackmanTGet alConcurrent definitive immunoradiotherapy for patients with stage III–IV head and neck cancer and cisplatin contraindicationClin Cancer Res2020264260710.1158/1078-0432.CCR-20-0230796811432371539Open DOISearch in Google Scholar

117Powell SF, Gold KA, Gitau MM, Sumey CJ, Lohr MM, McGraw SC, et al. Safety and efficacy of pembrolizumab with chemoradiotherapy in locally advanced head and neck squamous cell carcinoma: a phase IB study. J Clin Oncol 2020; 38: 2427-37. doi: 10.1200/JCO.19.03156PowellSFGoldKAGitauMMSumeyCJLohrMMMcGrawSCet alSafety and efficacy of pembrolizumab with chemoradiotherapy in locally advanced head and neck squamous cell carcinoma: a phase IB studyJ Clin Oncol20203824273710.1200/JCO.19.03156736576632479189Open DOISearch in Google Scholar

118Gillison M, Ferris RL, Zhang Q, Colevas AD, Mell LK, Kirsch C, et al. Safety evaluation of nivolumab concomitant with platinum-based chemoradiation therapy for intermediate and high-risk local-regionally advanced head and neck squamous cell carcinoma: RTOG foundation 3504. Int J Radiat Oncol 2018; 100: 1307-8. doi: 10.1016/j.ijrobp.2017.12.022GillisonMFerrisRLZhangQColevasADMellLKKirschCet alSafety evaluation of nivolumab concomitant with platinum-based chemoradiation therapy for intermediate and high-risk local-regionally advanced head and neck squamous cell carcinoma: RTOG foundation 3504Int J Radiat Oncol20181001307810.1016/j.ijrobp.2017.12.022Open DOISearch in Google Scholar

119Ferris RL, Gillison ML, Harris J, Colevas AD, Mell LK, Kong C, et al. Safety evaluation of nivolumab (Nivo) concomitant with cetuximab-radiotherapy for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG 3504. J Clin Oncol 2018; 36: 6010. doi: 10.1200/JCO.2018.36.15_suppl.6010FerrisRLGillisonMLHarrisJColevasADMellLKKongCet alSafety evaluation of nivolumab (Nivo) concomitant with cetuximab-radiotherapy for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG 3504J Clin Oncol201836601010.1200/JCO.2018.36.15_suppl.6010Open DOISearch in Google Scholar

120Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, et al. Safety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504. J Clin Oncol 2019; 37: 6073. doi: 10.1200/jco.2019.37.15_suppl.6073GillisonMLFerrisRLHarrisJColevasADMellLKKongCet alSafety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504J Clin Oncol201937607310.1200/jco.2019.37.15_suppl.6073Open DOISearch in Google Scholar

121Johnson JM, Bar Ad V, Lorber E, Poller D, Luginbuhl A, Curry JM, et al. Safety of nivolumab and ipilimumab in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). J Clin Oncol 2019; 37: 6070. doi: 10.1200/JCO.2019.37.15_suppl.6070JohnsonJMBarAd VLorberEPollerDLuginbuhlACurryJMet alSafety of nivolumab and ipilimumab in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN)J Clin Oncol201937607010.1200/JCO.2019.37.15_suppl.6070Open DOISearch in Google Scholar

122Elbers JBW, Al-Mamgani A, Tesseslaar MET, van den Brekel MWM, Lange CAH, van der Wal JE, et al. Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: results from a phase-I trial. Radiother Oncol 2020; 142: 79-84. doi: 10.1016/j.radonc.2019.08.007ElbersJBWAl-MamganiATesseslaarMETvan denBrekel MWMLangeCAHvan derWal JEet alImmuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: results from a phase-I trialRadiother Oncol2020142798410.1016/j.radonc.2019.08.00731563412Open DOISearch in Google Scholar

123Hecht M, Gostian A-O, Eckstein M, Rutzner S, von der Grün J, Illmer T, et al. Single cycle induction treatment with cisplatin/docetaxel plus durvalumab/ tremelimumab in stage III-IVB head and neck squamous cell cancer (CheckRad-CD8 trial). Ann Oncol 2019; 30: v456-7. doi: 10.1093/annonc/mdz252.016HechtMGostianA-OEcksteinMRutznerSvon derGrün JIllmerTet alSingle cycle induction treatment with cisplatin/docetaxel plus durvalumab/ tremelimumab in stage III-IVB head and neck squamous cell cancer (CheckRad-CD8 trial)Ann Oncol201930v456710.1093/annonc/mdz252.016Open DOISearch in Google Scholar

124Machiels J-P, Tao Y, Burtness B, Tahara M, Licitra L, Rischin D, et al. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Futur Oncol 2020; 16: 1235-43. doi: 10.2217/fon-2020-0184MachielsJ-PTaoYBurtnessBTaharaMLicitraLRischinDet alPembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412Futur Oncol20201612354310.2217/fon-2020-018432490686Open DOISearch in Google Scholar

125Nivolumab or nivolumab plus cisplatin, in combination with radiotherapy in patients with cisplatin-ineligible or eligible locally advanced squamous cell head and neck cancer. (cited 2020 Jul 15). Available at: https://clinical-trials.gov/ct2/show/NCT03349710Nivolumab or nivolumab plus cisplatin, in combination with radiotherapy in patients with cisplatin-ineligible or eligible locally advanced squamous cell head and neck cancer(cited 2020 Jul 15). Available athttps://clinical-trials.gov/ct2/show/NCT03349710Search in Google Scholar

126Yom SS. De-intensified radiation therapy with chemotherapy (cisplatin) or immunotherapy (nivolumab) in treating patients with early-stage, HPV-positive, non-smoking associated oropharyngeal cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03952585YomSSDe-intensified radiation therapy with chemotherapy (cisplatin) or immunotherapy (nivolumab) in treating patients with early-stage, HPV-positive, non-smoking associated oropharyngeal cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03952585Search in Google Scholar

127Ferris RL. HPV-16 Vaccination and pembrolizumab plus cisplatin for “intermediate risk” HPV-16-associated head and neck squamous cell carcinoma. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT04369937FerrisRLHPV-16 Vaccination and pembrolizumab plus cisplatin for “intermediate risk” HPV-16-associated head and neck squamous cell carcinoma(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT04369937Search in Google Scholar

128Massarelli E, William W, Johnson F, Kies M, Ferrarotto R, Guo M, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer. JAMA Oncol 2019; 5: 67. doi: 10.1001/jamaoncol.2018.4051MassarelliEWilliamWJohnsonFKiesMFerrarottoRGuoMet alCombining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancerJAMA Oncol201956710.1001/jamaoncol.2018.4051643976830267032Open DOISearch in Google Scholar

129Trial evaluating the tolerance and safety of durvalumab - RT combination for treatment in SCCHN (REWRITe). (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03726775Trial evaluating the tolerance and safety of durvalumab - RT combination for treatment in SCCHN (REWRITe)(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03726775Search in Google Scholar

130Clump D. Pembrolizumab in combination with cisplatin and intensity modulated radiotherapy (IMRT) in head and neck cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT02777385ClumpDPembrolizumab in combination with cisplatin and intensity modulated radiotherapy (IMRT) in head and neck cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT02777385Search in Google Scholar

131Takiar V. A study of chemoradiation plus pembrolizumab for locally advanced laryngeal squamous cell carcinoma. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT02759575TakiarVA study of chemoradiation plus pembrolizumab for locally advanced laryngeal squamous cell carcinoma(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT02759575Search in Google Scholar

132El-Sherify MS. Concomitant immune check point inhibitor with radio-chemotherapy in head and neck cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03532737El-SherifyMS.Concomitant immune check point inhibitor with radio-chemotherapy in head and neck cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03532737Search in Google Scholar

133Mell L. Chemoradiation vs immunotherapy and radiation for head and neck cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2 show/NCT03383094MellLChemoradiation vs immunotherapy and radiation for head and neck cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03383094Search in Google Scholar

134Harrington K. Pembrolizumab combined with chemoradiotherapy in squamous cell carcinoma of the head and neck (PEACH). (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT02819752HarringtonKPembrolizumab combined with chemoradiotherapy in squamous cell carcinoma of the head and neck (PEACH)(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT02819752Search in Google Scholar

135Haddad R. Induction TPN followed by nivolumab with radiation in locoregionally advanced laryngeal and hypopharyngeal cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03894891HaddadRInduction TPN followed by nivolumab with radiation in locoregionally advanced laryngeal and hypopharyngeal cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03894891Search in Google Scholar

136Mierzwa M. Radiotherapy, carboplatin/paclitaxel and nivolumab for high risk HPV-related head and neck cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03829722MierzwaMRadiotherapy, carboplatin/paclitaxel and nivolumab for high risk HPV-related head and neck cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03829722Search in Google Scholar

137Gillison ML. Ipilimumab, nivolumab, and radiation therapy in treating patients with HPV positive advanced oropharyngeal squamous cell carcinoma. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03799445GillisonMLIpilimumab, nivolumab, and radiation therapy in treating patients with HPV positive advanced oropharyngeal squamous cell carcinoma(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03799445Search in Google Scholar

138Tao Y, Auperin A, Sun XS, Sire C, Martin L, Bera G, et al. Avelumabcetuximab-radiotherapy versus standards of care in locally advanced squamous cell carcinoma of the head and neck: safety phase of the randomized phase III trial GORTEC 2017-01 REACH. (cited 2020 Jul 15). Available at: https://gortec.net/images/publi/ESMO2019_REACH_POSTER_Discussion.pdfTaoYAuperinASunXSSireCMartinLBeraGet alAvelumabcetuximab-radiotherapy versus standards of care in locally advanced squamous cell carcinoma of the head and neck: safety phase of the randomized phase III trial GORTEC 2017-01 REACH(cited 2020 Jul 15). Available athttps://gortec.net/images/publi/ESMO2019_REACH_POSTER_Discussion.pdf10.1200/JCO.2018.36.15_suppl.6076Search in Google Scholar

139Bonomo P, Desideri I, Loi M, Mangoni M, Sottili M, Marrazzo L, et al. Anti PD-L1 durvalumab combined with cetuximab and radiotherapy in locally advanced squamous cell carcinoma of the head and neck: a phase I/II study (DUCRO). Clin Transl Radiat Oncol 2018; 9: 42-7. doi: 10.1016/j. ctro.2018.01.005BonomoPDesideriILoiMMangoniMSottiliMMarrazzoLet alAnti PD-L1 durvalumab combined with cetuximab and radiotherapy in locally advanced squamous cell carcinoma of the head and neck: a phase I/II study (DUCRO)Clin Transl Radiat Oncol2018942710.1016/j.ctro.2018.01.005586268429594250Open DOISearch in Google Scholar

140Cisplatin or immunotgerapy in association with definitive radiotherapy in HPV-related oropharyngEal squamous cell carcinoma: a randomized phase II trial. (CITHARE). (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03623646Cisplatin or immunotgerapy in association with definitive radiotherapy in HPV-related oropharyngEal squamous cell carcinoma: a randomized phase II trial. (CITHARE)(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03623646Search in Google Scholar

141Li Y. A study of concomitant camrelizumab with chemoradiation for locally advanced head and neck cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT04405154LiYA study of concomitant camrelizumab with chemoradiation for locally advanced head and neck cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT04405154Search in Google Scholar

142Wise-Draper TM, Old MO, Worden FP, O’Brien PE, Cohen EEW, Dunlap N, et al. Phase II multi-site investigation of neoadjuvant pembrolizumab and adjuvant concurrent radiation and pembrolizumab with or without cisplatin in resected head and neck squamous cell carcinoma. J Clin Oncol 2018; 36: 6017. doi: 10.1200/JCO.2018.36.15_suppl.6017Wise-DraperTMOldMOWordenFPO’BrienPECohenEEWDunlapNet alPhase II multi-site investigation of neoadjuvant pembrolizumab and adjuvant concurrent radiation and pembrolizumab with or without cisplatin in resected head and neck squamous cell carcinomaJ Clin Oncol201836601710.1200/JCO.2018.36.15_suppl.6017Open DOISearch in Google Scholar

143Bauman JE, Harris J, Uppaluri R, Yao M, Ferris RL, Chen J, et al. NRG-HN003: Phase I and expansion cohort study of adjuvant cisplatin, intensity-modulated radiation therapy (IMRT), and MK-3475 (pembrolizumab) in high-risk head and neck squamous cell carcinoma (HNSCC). J Clin Oncol 2019; 37: 6023. doi: 10.1200/JCO.2019.37.15_suppl.6023BaumanJEHarrisJUppaluriRYaoMFerrisRLChenJet alNRG-HN003: Phase I and expansion cohort study of adjuvant cisplatin, intensity-modulated radiation therapy (IMRT), and MK-3475 (pembrolizumab) in high-risk head and neck squamous cell carcinoma (HNSCC)J Clin Oncol201937602310.1200/JCO.2019.37.15_suppl.6023Open DOISearch in Google Scholar

144Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. KEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinoma. J Clin Oncol 2019; 37: TPS6090. doi: 10.1200/JCO.2019.37.15_suppl.TPS6090UppaluriRLeeNYWestraWCohenEEWHaddadRITemamSet alKEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinomaJ Clin Oncol201937TPS609010.1200/JCO.2019.37.15_suppl.TPS6090Open DOISearch in Google Scholar

145Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. KEYNOTE-689: phase 3 study of neoadjuvant and adjuvant pembrolizumab combined with standard of care in patients with resectable, locally advanced head and neck squamous cell carcinoma. (cited 2020 Jul 15). Available at: http://uppalurilab.dana-farber.org/uploads/1/2/9/7/129766176/uppaluri_kn689_asco_2019_poster_presented.pdfUppaluriRLeeNYWestraWCohenEEWHaddadRITemamSet alKEYNOTE-689: phase 3 study of neoadjuvant and adjuvant pembrolizumab combined with standard of care in patients with resectable, locally advanced head and neck squamous cell carcinoma(cited 2020 Jul 15). Available athttp://uppalurilab.dana-farber.org/uploads/1/2/9/7/129766176/uppaluri_kn689_asco_2019_poster_presented.pdf10.1200/JCO.2019.37.15_suppl.TPS6090Search in Google Scholar

146A trial evaluating the addition of nivolumab to cisplatin-RT for treatment of cancers of the head and neck (NIVOPOSTOP). (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03576417A trial evaluating the addition of nivolumab to cisplatin-RT for treatment of cancers of the head and neck (NIVOPOSTOP)(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03576417Search in Google Scholar

147Maintenance immune check-point inhibitor following post-operative chemo-radiation in subjects with HPV-negative HNSCC (ADHERE). (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03673735Maintenance immune check-point inhibitor following post-operative chemo-radiation in subjects with HPV-negative HNSCC (ADHERE)(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03673735Search in Google Scholar

148Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350: 1937-44. doi: 10.1056/NEJMoa032646CooperJSPajakTFForastiereAAJacobsJCampbellBHSaxmanSBet alPostoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neckN Engl J Med200435019374410.1056/NEJMoa03264615128893Open DOISearch in Google Scholar

149Dietz A. Postoperative aRCH with cisplatin versus aRCH with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma. (cited 2020 Jul 14). Available at: https://clinicaltrials.gov/ct2/show/NCT03480672DietzAPostoperative aRCH with cisplatin versus aRCH with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma(cited 2020 Jul 14). Available athttps://clinicaltrials.gov/ct2/show/NCT03480672Search in Google Scholar

150Ferris R. Adjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer. (cited 2020 Jul 15). Available at: https://clinicaltrials.gov/ct2/show/NCT03715946FerrisRAdjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer(cited 2020 Jul 15). Available athttps://clinicaltrials.gov/ct2/show/NCT03715946Search in Google Scholar

151Weiss J. Durvalumab with radiotherapy for adjuvant treatment of intermediate risk SCCHN. (cited 2020 Jul 16). Available at: https://clinicaltrials.gov/ct2/show/NCT03529422WeissJDurvalumab with radiotherapy for adjuvant treatment of intermediate risk SCCHN(cited 2020 Jul 16). Available athttps://clinicaltrials.gov/ct2/show/NCT03529422Search in Google Scholar

152Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 2018; 379: 2342-50. doi: 10.1056/NEJMoa1809697AntoniaSJVillegasADanielDVicenteDMurakamiSHuiRet alOverall survival with durvalumab after chemoradiotherapy in stage III NSCLCN Engl J Med201837923425010.1056/NEJMoa180969730280658Open DOISearch in Google Scholar

153Weber JS, Mandalà M, Del Vecchio M, Gogas H, Arance AM, Cowey CL, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: updated results from a phase III trial (CheckMate 238). J Clin Oncol 2018; 36: 9502. doi: 10.1200/ JCO.2018.36.15_suppl.9502WeberJSMandalàMDelVecchio MGogasHAranceAMCoweyCLet alAdjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: updated results from a phase III trial (CheckMate 238)J Clin Oncol201836950210.1200/JCO.2018.36.15_suppl.9502Open DOISearch in Google Scholar

154Eggermont AMM, Chiarion-Sileni V, Grob J-J, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial. Eur J Cancer 2019; 119: 1-10. doi: 10.1016/j.ejca.2019.07.001EggermontAMMChiarion-SileniVGrobJ-JDummerRWolchokJDSchmidtHet alAdjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trialEur J Cancer201911911010.1016/j.ejca.2019.07.00131400634Open DOISearch in Google Scholar

155Steuer CE, Behera M, Ernani V, Higgins KA, Saba NF, Shin DM, et al. Comparison of concurrent use of thoracic radiation with either carboplatin-paclitaxel or cisplatin-etoposide for patients with stage III non–small-cell lung cancer. JAMA Oncol 2017; 3: 1120. doi: 10.1001/jamaoncol.2016.4280SteuerCEBeheraMErnaniVHigginsKASabaNFShinDMet alComparison of concurrent use of thoracic radiation with either carboplatin-paclitaxel or cisplatin-etoposide for patients with stage III non–small-cell lung cancerJAMA Oncol20173112010.1001/jamaoncol.2016.428027978552Open DOISearch in Google Scholar

156Duprez F, Berwouts D, De Neve W, Bonte K, Boterberg T, Deron P, et al. Distant metastases in head and neck cancer. Head Neck 2017; 39: 1733-43. doi: 10.1002/hed.24687DuprezFBerwoutsDDe NeveWBonteKBoterbergTDeronPet alDistant metastases in head and neck cancerHead Neck20173917334310.1002/hed.2468728650113Open DOISearch in Google Scholar

157Wang H, Mustafa A, Liu S, Liu J, Lv D, Yang H, et al. Immune checkpoint inhibitor toxicity in head and neck cancer: from identification to management. Front Pharmacol 2019; 10: doi: 10.3389/fphar.2019.01254WangHMustafaALiuSLiuJLvDYangHet alImmune checkpoint inhibitor toxicity in head and neck cancer: from identification to managementFront Pharmacol20191010.3389/fphar.2019.01254681943431708780Open DOISearch in Google Scholar

158Santana-Davila R, Rodriguez CP. Immunotherapy for head and neck cancer in the era of exponentially increasing health care expenditure. Oncologist 2018; 23: 147-9. doi: 10.1634/theoncologist.2017-0527Santana-DavilaRRodriguezCP.Immunotherapy for head and neck cancer in the era of exponentially increasing health care expenditureOncologist201823147910.1634/theoncologist.2017-0527581375629192017Open DOISearch in Google Scholar

159Gavrielatou N, Doumas S, Economopoulou P, Foukas PG, Psyrri A. Biomarkers for immunotherapy response in head and neck cancer. Cancer Treat Rev 2020; 84: 101977. doi: 10.1016/j.ctrv.2020.101977GavrielatouNDoumasSEconomopoulouPFoukasPGPsyrriABiomarkers for immunotherapy response in head and neck cancerCancer Treat Rev20208410197710.1016/j.ctrv.2020.10197732018128Open DOISearch in Google Scholar