Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology

S. Arcangeli; B.A. Jereczek-Fossa; F. Alongi; C. Aristei; C. Becherini; L. Belgioia; M. Buglione; L. Caravatta; R.M. D'Angelillo; A.R. Filippi; M. Fiore; D. Genovesi; C. Greco; L. Livi; S.M. Magrini; G. Marvaso; R. Mazzola; I. Meattini; A. Merlotti; I. Palumbo; S. Pergolizzi; S. Ramella; U. Ricardi; E. Russi; M. Trovò; A. Sindoni; V. Valentini; R. Corvò

doi:10.1016/j.critrevonc.2018.11.006

Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology

S. Arcangeli, B.A. Jereczek-Fossa, F. Alongi, C. Aristei, C. Becherini, L. Belgioia, M. Buglione, L. Caravatta, R.M. D'Angelillo, A.R. Filippi, M. Fiore, D. Genovesi, C. Greco, L. Livi, S.M. Magrini, G. Marvaso, R. Mazzola, I. Meattini, A. Merlotti, I. PalumboS. Pergolizzi, S. Ramella, U. Ricardi, E. Russi, M. Trovò, A. Sindoni, V. Valentini, R. Corvò

Research output: Contribution to journal › Article › peer-review

Abstract

Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity. © 2018 Elsevier B.V.

Original language	English
Pages (from-to)	104-119
Number of pages	16
Journal	Crit. Rev. Oncol. Hematol.
Volume	134
DOIs	https://doi.org/10.1016/j.critrevonc.2018.11.006
Publication status	Published - 2019

Keywords

Radiotherapy
Systemic compounds
Toxicity
abiraterone
afatinib
antineoplastic agent
apalutamide
bevacizumab
cetuximab
cytotoxic T lymphocyte antigen 4 antagonist
dabrafenib
darolutamide
enzalutamide
erlotinib
everolimus
galeterone
gefitinib
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
orteronel
panitumumab
pertuzumab
programmed death 1 ligand 1 antagonist
programmed death 1 receptor antagonist
seviteronel
sonidegib
sorafenib
sunitinib
trastuzumab
unclassified drug
vemurafenib
vismodegib
radiosensitizing agent
cancer radiotherapy
cancer survival
clinical effectiveness
clinical outcome
clinical trial (topic)
drug effect
drug efficacy
drug response
human
quality of life
radiation dose
Review
solid malignant neoplasm
survival rate
treatment response
chemoradiotherapy
Italy
neoplasm
treatment outcome
Chemoradiotherapy
Humans
Neoplasms
Radiation-Sensitizing Agents
Treatment Outcome

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Arcangeli, S., Jereczek-Fossa, B. A., Alongi, F., Aristei, C., Becherini, C., Belgioia, L., Buglione, M., Caravatta, L., D'Angelillo, R. M., Filippi, A. R., Fiore, M., Genovesi, D., Greco, C., Livi, L., Magrini, S. M., Marvaso, G., Mazzola, R., Meattini, I., Merlotti, A., ... Corvò, R. (2019). Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology. Crit. Rev. Oncol. Hematol., 134, 104-119. https://doi.org/10.1016/j.critrevonc.2018.11.006

Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity : Critical Reviews in Oncology/Hematology. / Arcangeli, S.; Jereczek-Fossa, B.A.; Alongi, F. et al.

In: Crit. Rev. Oncol. Hematol., Vol. 134, 2019, p. 104-119.

Research output: Contribution to journal › Article › peer-review

Arcangeli, S, Jereczek-Fossa, BA, Alongi, F, Aristei, C, Becherini, C, Belgioia, L, Buglione, M, Caravatta, L, D'Angelillo, RM, Filippi, AR, Fiore, M, Genovesi, D, Greco, C, Livi, L, Magrini, SM, Marvaso, G, Mazzola, R, Meattini, I, Merlotti, A, Palumbo, I, Pergolizzi, S, Ramella, S, Ricardi, U, Russi, E, Trovò, M, Sindoni, A, Valentini, V & Corvò, R 2019, 'Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology', Crit. Rev. Oncol. Hematol., vol. 134, pp. 104-119. https://doi.org/10.1016/j.critrevonc.2018.11.006

Arcangeli S, Jereczek-Fossa BA, Alongi F, Aristei C, Becherini C, Belgioia L et al. Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology. Crit. Rev. Oncol. Hematol. 2019;134:104-119. doi: 10.1016/j.critrevonc.2018.11.006

@article{6bf341c30b6c430f87042e08a4085135,

title = "Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity: Critical Reviews in Oncology/Hematology",

abstract = "Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity. {\textcopyright} 2018 Elsevier B.V.",

keywords = "Radiotherapy, Systemic compounds, Toxicity, abiraterone, afatinib, antineoplastic agent, apalutamide, bevacizumab, cetuximab, cytotoxic T lymphocyte antigen 4 antagonist, dabrafenib, darolutamide, enzalutamide, erlotinib, everolimus, galeterone, gefitinib, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor, orteronel, panitumumab, pertuzumab, programmed death 1 ligand 1 antagonist, programmed death 1 receptor antagonist, seviteronel, sonidegib, sorafenib, sunitinib, trastuzumab, unclassified drug, vemurafenib, vismodegib, radiosensitizing agent, cancer radiotherapy, cancer survival, clinical effectiveness, clinical outcome, clinical trial (topic), drug effect, drug efficacy, drug response, human, quality of life, radiation dose, Review, solid malignant neoplasm, survival rate, treatment response, chemoradiotherapy, Italy, neoplasm, treatment outcome, Chemoradiotherapy, Humans, Neoplasms, Radiation-Sensitizing Agents, Treatment Outcome",

author = "S. Arcangeli and B.A. Jereczek-Fossa and F. Alongi and C. Aristei and C. Becherini and L. Belgioia and M. Buglione and L. Caravatta and R.M. D'Angelillo and A.R. Filippi and M. Fiore and D. Genovesi and C. Greco and L. Livi and S.M. Magrini and G. Marvaso and R. Mazzola and I. Meattini and A. Merlotti and I. Palumbo and S. Pergolizzi and S. Ramella and U. Ricardi and E. Russi and M. Trov{\`o} and A. Sindoni and V. Valentini and R. Corv{\`o}",

note = "Export Date: 25 February 2020 CODEN: CCRHE Correspondence Address: Arcangeli, S.; Department of Radiation Oncology, Policlinico S. Gerardo and University of Milan “Bicocca”Italy; email: stefano.arcangeli@yahoo.it Chemicals/CAS: abiraterone, 154229-19-3; afatinib, 439081-18-2, 850140-72-6, 850140-73-7; apalutamide, 956104-40-8; bevacizumab, 216974-75-3, 1438851-35-4; cetuximab, 205923-56-4; dabrafenib, 1195765-45-7, 1195768-06-9; darolutamide, 1297538-32-9; enzalutamide, 915087-33-1; erlotinib, 183319-69-9, 183321-74-6; everolimus, 159351-69-6; galeterone, 851983-85-2; gefitinib, 184475-35-2, 184475-55-6, 184475-56-7; orteronel, 566939-85-3; panitumumab, 339177-26-3; seviteronel, 1610537-15-9; sonidegib, 956697-53-3, 1218778-77-8; sorafenib, 284461-73-0; sunitinib, 341031-54-7, 557795-19-4; trastuzumab, 180288-69-1, 1446410-98-5; vemurafenib, 918504-65-1; vismodegib, 879085-55-9; Radiation-Sensitizing Agents Tradenames: arn 509; mdv 3100; odm 201; tak 700; tok 001; vt 464 References: Ahluwalia, M.S., Chao, S.T., Parsons, M.W., Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1-3 newly diagnosed brain metastases (2015) J. Neurooncol., 124 (3) Spetember), pp. 485-491; Ahmed, K.A., Stallworth, D.G., Kim, Y., Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy (2016) Ann. Oncol., 27, pp. 434-441; Ahn, P.H., Machtay, M., Anne, P.R., Phase i trial using induction ciplatin, docetaxel, 5-FU and erlotinib followed by cisplatin, bevacizumab and erlotinib with concurrent radiotherapy for advanced head and neck cancer (2016) Am J. Clin. Oncol., (July); Amici, J.M., Beylot-Barry, M., Locally advanced basal-cell carcinoma: Combined alternative treatments beyond surgery (2015) Ann. Chir. Plast. Esthet., 60, pp. 321-325; Ang, K.K., Zhang, Q., Rosenthal, D.I., Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522 (2014) J. Clin. Oncol., 32 (27)September), pp. 2940-2950; Anker, A., Ribas, A.H., Grossmann, X., Severe liver and skin toxicity after radiation and vemurafenib in metastatic melanoma (2013) J. Clin. Oncol., 31 (17)June), p. e283; Anker, C.J., Grossmann, K.F., Atkins, M.B., Avoiding severe toxicity from combined BRAF inhibitor and radiation treatment: consensus guidelines from the Eastern cooperative oncology group (ECOG) (2016) Int. J. Radiat. Oncol. Biol. Phys., 95 (2) June), pp. 632-646; http://www.pharmaceutical-technology.com/news/newsfda-grants-fast-track-status-innocrins, -; Antonia, S.J., Villegas, A., Daniel, D., Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer (2017) N Engl. J. Med., 377, pp. 1919-1929; Antonia, S.J., Villegas, A., Daniel, D., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC (2018) N Engl. J. Med.; Argiris, A., Heron, D.E., Smith, R.P., Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer (2010) J. Clin. Oncol., 28 (36)December), pp. 5294-5300; Arias de la Vega, F., Contreras, J., de Las Heras, M., Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase i trial (2012) Ann. Oncol., 23 (4) April), pp. 1005-1009; Avallone, A., Pecori, B., Bianco, F., Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the BRANCH trial (2015) Oncotarget, 6 (30) October), pp. 30394-30407; Barker, C.A., Postow, M.A., Khan, S.A., Concurrent RT and ipilimumab immunotherapy for patients with melanoma (2013) Cancer Immunol. Res., 1, pp. 92-98; Barney, B.M., Markovic, S.N., Laack, N.N., Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT) (2013) Int. J. Radiat. Oncol. Biol. Phys., 87 (1) September), pp. 73-80; Baroudjian, B., Boussemart, L., Routier, E., Dramatic response to radiotherapy combined with vemurafenib (2014) Is Vemurafenib Radiosensit.? Eur J. Dermatol., 24, pp. 265-267; Basset-S{\'e}guin, N., Hauschild, A., Kunstfeld, R., Vismodegib in patients with advanced basal cell carcinoma: primary analysis of STEVIE, an international, open-label trial (2017) Eur J. Cancer., 86 (November), pp. 334-348; Beer, T.M., Armstrong, A.J., Rathkopf, D., Enzalutamide in men with chemotherapy-na{\"i}ve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study (2017) Eur Urol., 71 (2) Febuary), pp. 151-154; Belkac{\'e}mi, Y., Gligorov, J., Ozsahin, M., Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study (2008) Ann. Oncol., 19, pp. 1110-1116; Blaszkowsky, L.S., Ryan, D.P., Szymonifka, J., Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer (2014) Ann. Oncol., 25 (1) January), pp. 121-126; Block, A.M., Alite, F., Diaz, A.Z., Combination trimodality therapy using vismodegib for basal cell carcinoma of the face (2015) Case Rep. Oncol. Med., 2015. , 827608; Blumenschein, G.R., Jr, Paulus, R., Curran, W.J., Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324 (2011) J. Clin. Oncol., 29 (17) June), pp. 2312-2318; Bonner, J.A., Harari, P.M., Giralt, J., Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck (2006) N Engl. J. Med., 354 (6)Febuary), pp. 567-578; Bourgier, C., Massard, C., Moldovan, C., Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent side-effect? (2011) Ann. Oncol., 2, pp. 485-486; Bradley, J.D., Paulus, R., Komaki, R., Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study (2015) Lancet Oncol., 16 (2) Febuary), pp. 187-199; Buglione, M., Maddalo, M., Corv{\`o}, R., Subgroup analysis according to human papillomavirus Status and tumor site of a randomized phase II trial comparing cetuximab and cisplatin combined with radiation therapy for locally advanced head and neck cancer (2017) Int. J. Radiat. Oncol. Biol Phys., 97 (3) March), pp. 462-472; Chadha, A.S., Skinner, H.D., Gunther, J.R., Phase i trial of consolidative radiotherapy with concurrent bevacizumab, erlotinib and capecitabine for unresectable pancreatic cancer (2016) PLoS One., 11 (6) June). , e0156910; Chang, A.L., Solomon, J.A., Hainsworth, J.D., Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib (2014) J. Am. Acad. Dermatol., 70 (Jan (1)), pp. 60-69; Chauffert, B., Feuvret, L., Bonnetain, F., Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF (2014) Ann. Oncol.; Chinnaiyan, P., Won, M., Wen, P.Y., A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG oncology RTOG 0913 (2018) Neuro Oncol., 20 (5) April), pp. 666-673; Chinnaiyan, P., Won, M., Wen, P.Y., RTOG 0913: a phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma (2013) Int. J. Radiat. Oncol. Biol. Phys., 86 (5) August), pp. 880-884; Chinot, O.L., Wick, W., Mason, W., Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma (2014) N Engl. J. Med., 370, pp. 709-722; Cho, E., Mostaghel, E.A., Russell, K.J., Liao, J.J., Konodi, M.A., Kurland, B.F., Marck, B.T., Montgomery, R.B., External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens (2015) Int. J. Radiat. Oncol. Biol. Phys., 92 (2)June), pp. 236-243; Chung, C., Dawson, L.A., Joshua, A.M., Brade, A.M., Radiation recall dermatitis triggered by multi-targeted tyrosine kinase inhibitors: sunitinib and sorafenib (2010) Anticancer Drugs., 21 (2) Febuary), pp. 206-209; Churilla, T.M., Chowdhry, V.K., Pan, D., Radiation-induced dermatitis with vemurafenib therapy (2013) Pract. Radiat. Oncol., 3, pp. e195-e198; Crane, C.H., Eng, C., Feig, B.W., Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer (2010) Int. J. Radiat. Oncol. Biol. Phys., 76 (3)March), pp. 824-830; Crosby, T., Hurt, C.N., Falk, S., Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial (2013) Lancet Oncol., 14 (7) June), pp. 627-637; Das, P., Eng, C., Rodriguez-Bigas, M.A., Preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib for rectal cancer: a phase 1 trial (2014) Int. J. Radiat. Oncol. Biol. Phys., 88 (2) Febuary), pp. 301-305; de Melo, A.C., Grazziotin-Reisner, R., Erlich, F., A phase i study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX i (2016) Cancer Chemother. Pharmacol., 78 (1), pp. 101-109; Dellas, K., H{\"o}hler, T., Reese, T., Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer (2013) Radiat. Oncol., 8 (April), p. 90; Deutsch, E., Le P{\'e}choux, C., Faivre, L., Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer (2015) Ann. Oncol., 26, pp. 1223-1229; Dipetrillo, T., Pricolo, V., Lagares-Garcia, J., Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer (2012) Int. J. Radiat. Oncol. Biol. Phys., 82 (1) January), pp. 124-129; Ducassou, A., David, I., Delannes, M., Radiosensitization induced by vemurafenib (2013) Cancer Radiother., 17, pp. 304-307; Duffy, A.G., Makarova-Rusher, O.V., Kleiner, D.E., A pilot study of immune checkpoint inhibition in combination with radiation therapy in patients with metastatic pancreatic cancer [abstract] (2017) J. Clin. Oncol., 35. , (Abstr nr e15786); Dummer, R., Guminski, A., Gutzmer, R., The 12-month analysis from basal cell carcinoma outcomes with LDE225 treatment (BOLT): a phase II, randomized, double blind study of sonidegib in patients with advanced basal cell carcinoma (2016) J. Am Acad. Dermatol., 75. , 113-125.e5; Dwedney, A., Cunningham, D., Tabernero, J., Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-c) (2012) J. Clin. Oncol., 30 (14) May), pp. 1620-1627; Ejlsmark, M.W., Kristiansen, C., Eriksen, J.C., Recall radiation myelitis after stereotactic radiation and dabrafenib in metastatic melanoma (2017) Acta Oncol., 56 (1) January), pp. 109-110; Fizazi, K., Massard, C., James, N.D., ODM-201, a new generation androgen receptor inhibitor for castration-resistant prostate cancer: preclinical and phase i data (2013) Proc. Am Soc. Clin. Oncol., 31. , abstr 65. 19; Formenti, S.C., Demaria, S., Combining RT and cancer immunotherapy: a paradigm shift (2013) J. Natl. Canc Inst., 105, pp. 256-265; Fornaro, L., Caparello, C., Vivaldi, C., Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: a systematic review (2014) World J. Gastroenterol., 20 (20)May), pp. 6081-6091; Forschner, A., Zips, D., Schraml, C., Radiation recall dermatitis and radiation pneumonitis during treatment with vemurafenib (2014) Melanoma Res., 24, pp. 512-516; Fu, P., He, Y.S., Huang, Q., Bevacizumab treatment for newly diagnosed glioblastoma: systematic review and meta-analysis of clinical trials (2016) Mol. Clin. Oncol., 4 (5) May), pp. 833-838; Fury, M.G., Lee, N.Y., Sherman, E., A phase i study of everolimus + weekly cisplatin + intensity modulated radiation therapy in head-and-neck cancer (2013) Int. J. Radiat. Oncol. Biol. Phys., 87 (3) November), pp. 479-486; Gasparini, G., Torino, F., Ueno, T., A phase II study of neoadjuvant bevacizumab plus capecitabine and concomitant radiotherapy in patients with locally advanced rectal cancer (2012) Angiogenesis., 15 (1) March), pp. 141-150; Geoffrois, L., Martin, L., De Raucourt, D., Induction chemotherapy followed By cetuximab radiotherapy Is not superior to concurrent chemoradiotherapy for head and neck carcinomas. Results of the GORTEC-02 phase III randomized trial (2018) J. Clin. Oncol., (July); Gilbert, M.R., Dignam, J.J., Armstrong, T.S., A randomized trial of bevacizumab for newly diagnosed glioblastoma (2014) N Engl. J. Med., 370, pp. 699-708; Giralt, J., Trigo, J., Nuyts, S., Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial (2015) Lancet Oncol., 16 (2) Febuary), pp. 221-232; Goldberg, S.B., Gettinger, S.N., Mahajan, A., Activity and safety of pembrolizumab in patients with metastatic Non-small cell lung cancer with untreated brain metastases (2015) J. Clin. Oncol., 33. , (Suppl; Abstr 8035); Golden, E.B., Demaria, S., Schiff, P.B., An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer (2013) Cancer Immunol. Res., 1, pp. 365-372; Govindan, R., Bogart, J., Stinchcombe, T., Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: cancer and leukemia group b trial 30407 (2011) J. Clin. Oncol., 29 (23) August), pp. 3120-3125; Halyard, M.Y., Pisansky, T., Dueck, A.C., Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG phase II trial N9831 (2009) J. Clin. Oncol., 27 (16) June), pp. 2638-2644; Hammel, P., Huguet, F., van Laethem, J.L., Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial (2016) JAMA., 315 (17) May), pp. 1844-1853; Hecht, M., Zimmer, L., Loquai, C., Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients (2015) Ann. Oncol., 26 (6), pp. 1238-1244; Helbling, D., Bodoky, G., Gautschi, O., Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07 (2013) Ann. Oncol., 24 (3) March), pp. 718-725; Herman, J.M., Fan, K.Y., Wild, A.T., Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer (2013) Int. J. Radiat. Oncol. Biol. Phys., 86 (4) July), pp. 678-685; Ho, A., Barker, C.A., Gucalp, A., Preliminary results from a single-Arm, phase II study assessing the efficacy of pembrolizumab plus radiotherapy in metastatic triple negative breast cancer (2017) J. Clin. Oncol., 35. , Abstract 95; Hofheinz, R.D., Horisberger, K., Woernle, C., Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer (2006) Int. J. Radiat. Oncol. Biol. Phys., 66 (5) December), pp. 1384-1390; Horton, J.K., Halle, J., Ferraro, M., Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial (2010) Int. J. Radiat. Oncol. Biol. Phys., 76, pp. 998-1004; Iacovelli, R., Palazzo, A., Mezi, S., Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials (2012) Acta Oncol., 51 (7) September), pp. 873-879; Ioannidis, G., Gkogkou, P., Charalampous, P., Radiation-recall dermatitis with the everolimus/exemestane combination ten years after adjuvant whole-breast radiotherapy (2014) Radiot Oncol., 112, pp. 449-450; Iyengar, P., Kavanagh, B.D., Wardak, Z., Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer (2014) J. Clin. Oncol., 32 (34) December), pp. 3824-3830; Jiang, Y., Mackley, H.B., Kimchi, E.T., Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer (2014) Cancer Chemother. Pharmacol., 74 (1) July), pp. 205-210; Kao, J., Packer, S., Vu, H.L., Phase I study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response (2009) Cancer, 115 (15) August), pp. 3571-3580; Kao, J., Chen, C.T., Tong, C.C., Concurrent sunitinib and stereotactic body radiotherapy for patients with oligometastases: final report of a prospective clinical trial (2014) Target. Oncol., 9 (2) June), pp. 145-153; Kao, J., Timmins, J., Ozao-Choy, J., Packer, S., Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis (2016) Oncol. Lett., 12 (3) September), pp. 2139-2144; Katz, D.A., Abrams, R.A., Sclamberg, J.S., Radiosensitizing effect of anti-HER2/neu agents: report of 2 cases and review of the literature (2015) Prac. Radiat. Oncol., 5, pp. e61-e65; Kennecke, H., Berry, S., Wong, R., Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial (2012) Eur. J. Cancer., 48 (1) January), pp. 37-45; Kiess, A.P., Wolchok, J.D., Barker, C.A., Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment (2015) Int. J. Radiat. Oncol. Biol. Phys., 92, pp. 368-375; Kwon, E.D., Drake, C.G., Scher, H.I., CA184-043 investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial (2014) Lancet Oncol., 15 (7) June), pp. 700-712; Lai, A., Tran, A., Nghiemphu, P.L., Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme (2011) J. Clin. Oncol. Off J. Am Soc. Clin. Oncol., 29, pp. 142-148; Landry, J.C., Feng, Y., Cohen, S.J., Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204 (2013) Cancer., 119 (8) April), pp. 1521-1527; Lee, S.M., Lewanski, C.R., Counsell, N., Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases (2014) J. Natl. Cancer Inst., 106 (7) July); Lefebvre, J.L., Pointreau, Y., Rolland, F., Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study (2013) J. Clin. Oncol., 31 (7) March), pp. 853-859. , Epub 2013 Jan 22. Erratum in: J Clin Oncol. 2013 May 1;31(13):1702; Leibowitz-Amit, R., Joshua, A.M., Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions (2012) Curr. Oncol., 19, pp. S22-31; Lin, J., Hoffman-Censits, J.H., Kelly, W.K., An exploratory study to investigate the immunomodulatory activity of radiation therapy in combination with pembrolizumab in patients with renal cell cancer (2017) J. Clin. Oncol., 35. , abstract 518; Lin, S.H., Lin, Y., Price, J., DETERRED: PD-L1 blockade to evaluate the safety of lung cancer therapy using carboplatin, paclitaxel, and radiation combined with MPDL3280A (atezolizumab) [abstract] (2017) J. Clin. Oncol., 35. , (Abstr nr 3064); Liniker, E., Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma (2016) OncoImmunology, 5 (9); Lledo, G., Huguet, F., Chibaudel, B., Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: the GERCOR phase II trial ERaFOX (2016) Eur. J. Cancer., 56 (March), pp. 115-121; Lockhart, A.C., Reed, C.E., Decker, P.A., Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051) (2014) Ann. Oncol., 25 (5) May), pp. 1039-1044; Lu, C.S., Liu, J.H., Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports (2017) Med. (Baltim.), (96), p. e5747; Ly, D., Bagshaw, H.P., Anker, C.J., Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment (2015) J. Neurosurg., 123, pp. 395-401; Ma, D.J., Galanis, E., Anderson, S.K., A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K (2015) Neuro Oncol., 17 (9) September), pp. 1261-1269; Machiels, J.P., Sempoux, C., Scalliet, P., Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer (2007) Ann. Oncol., 18 (4) April), pp. 738-744; Magrini, S.M., Buglione, M., Corv{\`o}, R., Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a randomized phase II trial (2016) J. Clin. Oncol., 34 (5) Febuary), pp. 427-435; Martinez, E., Martinez, M., Vinolas, N., Feasibility and tolerability of the addition of erlotinib to 3D thoracic radiotherapy (RT) in patients with unresectable NSCLC: a prospective randomized phase II study (2008) J. Clin. Oncol., 26. , abstr. 7563; Martins, R.G., Parvathaneni, U., Bauman, J.E., Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial (2013) J. Clin. Oncol., 31 (11)April), pp. 1415-1421; Marur, S., Li, S., Cmelak, A.J., Phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN cancer research group (2016) J. Clin. Oncol., (December). , JCO2016683300; Mathew, M., Tam, M., Ott, P.A., Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery (2013) Melanoma Res., 23, pp. 191-195; Mehta, M.P., Wang, D., Wang, F., Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study (2015) J. Neurooncol., 122 (2) April), pp. 409-417; Merten, R., Hecht, M., Haderlein, M., Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy (2014) Strahlenther. Onkol., 190 (12), pp. 1169-1172; Mes{\'i}a, R., Henke, M., Fortin, A., Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial (2015) Lancet Oncol., 16 (2) Febuary), pp. 208-220; Michaelson, M.D., Hu, C., Pham, H.T., Phase I/II trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for non cystectomy candidates with muscle invasive bladder cancer (trial NRG oncology RTOG 0524) (2017) Int. J. Radiat. Oncol. Biol. Phys., 97 (5):April), pp. 995-1001; Midgen, M.R., Guminski, A., Gutzmer, R., Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, doubleblind phase 2 trial (2015) Lancet Oncol., 16, pp. 716-728; Miura, Y., Suyama, K., Shimomura, A., Radiation-induced esophagitis exacerbated by everolimus (2013) Case Rep. Oncol., 6, pp. 320-324; Moilanen, A., Riikonen, R., Oksala, R., ODM-201—new generation antiandrogen with excellent antiandrogenic and antitumor activity in nonclinical models of CRPC (2013) Eur. J. Cancer, 49. , abstr 685; Narayan, V., Vapiwala, N., Mick, R., Phase 1 trial of everolimus and radiation therapy for salvage treatment of biochemical recurrence in prostate cancer patients following prostatectomy (2017) Int. J. Radiat. Oncol. Biol. Phys., 97 (2), pp. 355-361; Nishino, M., Giobbie-Hurder, A., Hatabu, H., Incidence of programmed cell death 1 Inhibitor–Related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis (2016) JAMA Oncol., 2 (12), pp. 1607-1616; Nogu{\'e}, M., Salud, A., Vicente, P., Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study (2011) Oncologist, 16 (5), pp. 614-620; Patel, K.R., Chowdhary, M., Switchenko, J.M., BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis (2016) Melanoma Res., 26 (4) August), pp. 387-394; Pesce, G.A., Klingbiel, D., Ribi, K., Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the swiss group for clinical cancer research (SAKK 70/03) (2012) Eur. J. Cancer, 48 (3) Febuary), pp. 377-384; Peuvrel, L., Ruellan, A.L., Thillays, F., Severe radiotherapy-induced extracutaneous toxicity under vemurafenib (2013) Eur. J. Dermatol, 23 (6), pp. 879-881; Pollom, E.L., Bui, T.T., Chang, A.L., Concurrent vismodegib and radiotherapy for recurrent, advanced basal cell carcinoma (2015) JAMA Dermatol., 151, pp. 998-1001; Raleigh, D.R., Algazi, A., Arron, S.T., Induction hedgehog pathway inhibition followed by combined-modality radiotherapy for basal cell carcinoma (2015) Br. J. Dermatol., 173, pp. 544-546; Ramella, S., Alberti, A.M., Cammilluzzi, E., Erlotinib and concurrent chemoradiation in pretreated NSCLC patients: radiobiological basis and clinical results (2013) Biomed. Res. Int., 2013. , 403869; Reiss, K.A., Herman, J.M., Zahurak, M., A phase i study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis (2015) Clin. Cancer Res., 21 (1)January), pp. 68-76; Rodon, J., Tawbi, H.A., Thomas, A.L., A phase i, multicenter, open-label, first-inhuman, dose-escalation study of the oral smoothened inhibitor sonidegib (LDE225) in patients with advanced solid tumors (2014) Clin. Cancer Res., 20, pp. 1900-1909; Ruhstaller, T., Pless, M., Dietrich, D., Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II trial (SAKK 75/06) (2011) J. Clin. Oncol., 29 (6) Febuary), pp. 626-631; Ruhstaller, T., Thuss-Patience, P., Hayoz, S., Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08) (2018) Ann. Oncol., 29 (6), June), pp. 1386-1393; Saad, American Urology Association Conference (2012), Abstract 682 (Oral presentation); Safran, H., Dipetrillo, T., Akerman, P., Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma (2007) Int. J. Radiat. Oncol. Biol. Phys., 67, pp. 405-409; Safran, H., Suntharalingam, M., Dipetrillo, T., Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity (2008) Int. J. Radiat. Oncol. Biol. Phys., 70 (2) Febuary), pp. 391-395; Salazar, R., Capdevila, J., Laquente, B., A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features (2015) BMC Cancer, 15 (Febuary), p. 60; Sandomenico, C., Costanzo, R., Carillio, G., Bevacizumab in non small cell lung cancer: development, current status and issues (2012) Curr. Med. Chem., 19, pp. 961-971; Sarkaria, J.N., Galanis, E., Wu, W., Combination of temsirolimus (CCI-779) with chemoradiation in newly diagnosed glioblastoma multiforme (GBM) (NCCTG trial N027D) is associated with increased infectious risks (2010) Clin. Cancer Res., 16 (22) November), pp. 5573-5580; Sarkaria, J.N., Galanis, E., Wu, W., North Central cancer treatment group phase i trial N057K of everolimus (RAD001) and temozolomide in combination with radiation therapy in patients with newly diagnosed glioblastoma multiforme (2011) Int. J. Radiat. Oncol. Biol. Phys., 81 (2) October), pp. 468-475; Satzger, I., Degen, A., Asper, H., Serious skin toxicity with the combination of BRAF inhibitors and radiotherapy (2013) J. Clin. Oncol., 31, pp. e220-e222; Scher, H.I., Fizazi, K., Saad, F., Increased survival with enzalutamide in prostate cancer after chemotherapy (2012) N Engl. J. Med., 367, pp. 1187-1197; Schulze, B., Meissner, M., Ghanaati, S., Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck (2016) Strahlenther. Onkol., 192 (Jan. (1)), pp. 25-31; Segal, N.H., Kemeny, N.E., Cercek, A., Non-randomized phase II study to assess the efficacy of pembrolizumab (pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients (2016) J. Clin. Oncol., p. 34. , (suppl; abstr 3539); Smith, M.R., Saad, F., Chowdhury, S., Apalutamide treatment and metastasis-free survival in prostate cancer (2018) N Engl. J. Med., 378 (15) April), pp. 1408-1418; Socinski, M.A., Stinchcombe, T.E., Moore, D.T., Incorporating bevacizumab and erlotinib in the combined-modality treatment of stage III non-small-cell lung cancer: results of a phase I/II trial (2012) J. Clin. Oncol., 30, pp. 3953-3959; Spigel, D.R., Hainsworth, J.D., Yardley, D.A., Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab (2010) J. Clin. Oncol., 28, pp. 43-48; Spigel, D.R., Bendell, J.C., McCleod, M., Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer (2012) Clin. Colorectal Cancer, 11 (1) March), pp. 45-52; Staehler, M., Haseke, N., Nuhn, P., Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma (2011) BJU Int., 108 (5) September), pp. 673-678; Staehler, M., Haseke, N., Stadler, T., Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer (2012) Urol Oncol., 30 (3) May-June), pp. 290-293; Stefan, D., Popotte, H., Stefan, A., Vemurafenib and concomitant stereotactic radiation for the treatment of melanoma with spinal metastases: a case report (2016) Reports Prac.Oncol. Radiother., 21, pp. 76-80; Sun, P.L., Li, B., YE, Q.F., Effect of neoadjuvant cetuximab, capecitabine and radiotherapy for locally advanced rectal cancer: results of a phase II study (2012) Int. J. Colorectal Dis., 27 (10) October), pp. 1325-1332; Suntharalingam, M., Winter, K., Ilson, D., Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the NRG oncology RTOG 0436 phase 3 randomized clinical trial (2017) JAMA Oncol., 3 (11) November), pp. 1520-1528; Tao, Y., Auperin, A., Sire, C., Improved outcome by adding concurrent chemotherapy to cetuximab and radiotherapy for locally advanced head and neck carcinomas: results of the GORTEC 2007-01 phase III randomized trial (2018) J. Clin. Oncol., (June). , JCO2017762518; Tazi, K., Hataway, A., Chiuzan, C., Shirai, K., Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery (2015) Cancer Med., 4, pp. 1-6; Tomblyn, M.B., Goldman, B.H., Thomas, C.R., Jr, Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414) (2012) J. Thorac. Oncol., 7 (5) May), pp. 906-912; Tong, C.C., Ko, E.C., Sung, M.W., Phase II trial of concurrent sunitinib and image-guided radiotherapy for oligometastases (2012) PLoS One, 7 (6), p. e36979; Trotti, A., Harris, J., Gillison, M., NRG-RTOG 1016: phase III trial comparing Radiation/Cetuximab to Radiation/Cisplatin in HPV-related cancer of the oropharynx (2018) Int. J. Radiat. Oncol. Biol. Phys., , Supplement; Valentini, V., De Paoli, A., Gambacorta, M.A., Infusional 5-fluorouracil and ZD1839 (gefitinib-iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase i and II trial (1839IL/0092) (2008) Int. J. Radiat. Oncol. Biol. Phys., 72 (3) November), pp. 644-649; Van den Heuvel, M.M., Uyterlinde, W., Vincent, A.D., Additional weekly cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: efficacy and safety outcomes of a randomized, multi-center phase II study investigating (2014) Radiother. Oncol., 110 (1) January), pp. 126-131; Velenik, V., Ocvirk, J., Music, M., Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study (2011) Radiat. Oncol., 6 (August), p. 105; Vivaldi, C., Buccianti, G., Musettini, F., TRUST: phase II trial of induction chemotherapy with FOLFOXIRI + bevacizumab followed by chemo-radiotherapy + bevacizumab and surgery in locally advanced rectal carcinoma (2016) Ann. Oncol., 27; Wang, Z., Zhu, X.X., Wu, X.H., Gefitinib combined with stereotactic radiosurgery in previously treated patients with advanced non-small cell lung cancer (2014) Am. J. Clin. Oncol., 37 (2) April), pp. 148-153; Welsh, J.W., Komaki, R., Amini, A., Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer (2013) J. Clin. Oncol., 31 (7) March), pp. 895-902; Willett, C.G., Duda, D.G., di Tomaso, E., Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study (2009) J. Clin. Oncol., 27 (18) June), pp. 3020-3026; William, N.L., Wuthrick, E.J., Kim, H., Phase i study of ipilimumab combine dwith whole brain radiation therapy Or radiosurgery for melanoma patients with brain metastases (2017) Int. J. Radiat. Oncol. Biol. Phys., 99 (1) September), pp. 22-30; Wirsching, H.G., Tabatabai, G., Roelcke, U., Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial (2018) Ann. Oncol., 29 (6)June), pp. 1423-1430; Wolf, A., Zia, S., Verma, R., Pavlick, A., Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases (2016) J. Neurooncol., 127 (3) May), pp. 607-615; Xu, T., Liu, Y., Dou, S., Weekly cetuximab concurrent with IMRT aggravated radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma: results of a randomized phase II study (2015) Oral Oncol., 51 (9) September), pp. 875-879; Yuasa, T., Kitsukawa, S., Sukegawa, G., Early onset recall pneumonitis during targeted therapy with sunitinib (2013) BMC Cancer, 2 (13 January), p. 3; Zhao, C., Lin, L., Liu, J., A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma (2016) Oncotarget., 7 (35) August), pp. 57310-57316; Zhu, M.L., Horbinski, C.M., Garzotto, M., Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer (2010) Cancer Res., 70, pp. 7992-8002; Zhuang, H., Yuan, Z., Wang, J., Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma (2013) Drug. Des. Devel Ther., 7 (October), pp. 1179-1186",

year = "2019",

doi = "10.1016/j.critrevonc.2018.11.006",

language = "English",

volume = "134",

pages = "104--119",

journal = "Crit. Rev. Oncol. Hematol.",

issn = "1879-0461",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Combination of novel systemic agents and radiotherapy for solid tumors – Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity

T2 - Critical Reviews in Oncology/Hematology

AU - Arcangeli, S.

AU - Jereczek-Fossa, B.A.

AU - Alongi, F.

AU - Aristei, C.

AU - Becherini, C.

AU - Belgioia, L.

AU - Buglione, M.

AU - Caravatta, L.

AU - D'Angelillo, R.M.

AU - Filippi, A.R.

AU - Fiore, M.

AU - Genovesi, D.

AU - Greco, C.

AU - Livi, L.

AU - Magrini, S.M.

AU - Marvaso, G.

AU - Mazzola, R.

AU - Meattini, I.

AU - Merlotti, A.

AU - Palumbo, I.

AU - Pergolizzi, S.

AU - Ramella, S.

AU - Ricardi, U.

AU - Russi, E.

AU - Trovò, M.

AU - Sindoni, A.

AU - Valentini, V.

AU - Corvò, R.

N1 - Export Date: 25 February 2020 CODEN: CCRHE Correspondence Address: Arcangeli, S.; Department of Radiation Oncology, Policlinico S. Gerardo and University of Milan “Bicocca”Italy; email: stefano.arcangeli@yahoo.it Chemicals/CAS: abiraterone, 154229-19-3; afatinib, 439081-18-2, 850140-72-6, 850140-73-7; apalutamide, 956104-40-8; bevacizumab, 216974-75-3, 1438851-35-4; cetuximab, 205923-56-4; dabrafenib, 1195765-45-7, 1195768-06-9; darolutamide, 1297538-32-9; enzalutamide, 915087-33-1; erlotinib, 183319-69-9, 183321-74-6; everolimus, 159351-69-6; galeterone, 851983-85-2; gefitinib, 184475-35-2, 184475-55-6, 184475-56-7; orteronel, 566939-85-3; panitumumab, 339177-26-3; seviteronel, 1610537-15-9; sonidegib, 956697-53-3, 1218778-77-8; sorafenib, 284461-73-0; sunitinib, 341031-54-7, 557795-19-4; trastuzumab, 180288-69-1, 1446410-98-5; vemurafenib, 918504-65-1; vismodegib, 879085-55-9; Radiation-Sensitizing Agents Tradenames: arn 509; mdv 3100; odm 201; tak 700; tok 001; vt 464 References: Ahluwalia, M.S., Chao, S.T., Parsons, M.W., Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1-3 newly diagnosed brain metastases (2015) J. Neurooncol., 124 (3) Spetember), pp. 485-491; Ahmed, K.A., Stallworth, D.G., Kim, Y., Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy (2016) Ann. Oncol., 27, pp. 434-441; Ahn, P.H., Machtay, M., Anne, P.R., Phase i trial using induction ciplatin, docetaxel, 5-FU and erlotinib followed by cisplatin, bevacizumab and erlotinib with concurrent radiotherapy for advanced head and neck cancer (2016) Am J. Clin. Oncol., (July); Amici, J.M., Beylot-Barry, M., Locally advanced basal-cell carcinoma: Combined alternative treatments beyond surgery (2015) Ann. Chir. Plast. Esthet., 60, pp. 321-325; Ang, K.K., Zhang, Q., Rosenthal, D.I., Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522 (2014) J. Clin. Oncol., 32 (27)September), pp. 2940-2950; Anker, A., Ribas, A.H., Grossmann, X., Severe liver and skin toxicity after radiation and vemurafenib in metastatic melanoma (2013) J. Clin. Oncol., 31 (17)June), p. e283; Anker, C.J., Grossmann, K.F., Atkins, M.B., Avoiding severe toxicity from combined BRAF inhibitor and radiation treatment: consensus guidelines from the Eastern cooperative oncology group (ECOG) (2016) Int. J. Radiat. Oncol. Biol. Phys., 95 (2) June), pp. 632-646; http://www.pharmaceutical-technology.com/news/newsfda-grants-fast-track-status-innocrins, -; Antonia, S.J., Villegas, A., Daniel, D., Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer (2017) N Engl. J. Med., 377, pp. 1919-1929; Antonia, S.J., Villegas, A., Daniel, D., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC (2018) N Engl. J. Med.; Argiris, A., Heron, D.E., Smith, R.P., Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer (2010) J. Clin. Oncol., 28 (36)December), pp. 5294-5300; Arias de la Vega, F., Contreras, J., de Las Heras, M., Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase i trial (2012) Ann. Oncol., 23 (4) April), pp. 1005-1009; Avallone, A., Pecori, B., Bianco, F., Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the BRANCH trial (2015) Oncotarget, 6 (30) October), pp. 30394-30407; Barker, C.A., Postow, M.A., Khan, S.A., Concurrent RT and ipilimumab immunotherapy for patients with melanoma (2013) Cancer Immunol. Res., 1, pp. 92-98; Barney, B.M., Markovic, S.N., Laack, N.N., Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT) (2013) Int. J. Radiat. Oncol. Biol. Phys., 87 (1) September), pp. 73-80; Baroudjian, B., Boussemart, L., Routier, E., Dramatic response to radiotherapy combined with vemurafenib (2014) Is Vemurafenib Radiosensit.? Eur J. Dermatol., 24, pp. 265-267; Basset-Séguin, N., Hauschild, A., Kunstfeld, R., Vismodegib in patients with advanced basal cell carcinoma: primary analysis of STEVIE, an international, open-label trial (2017) Eur J. Cancer., 86 (November), pp. 334-348; Beer, T.M., Armstrong, A.J., Rathkopf, D., Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study (2017) Eur Urol., 71 (2) Febuary), pp. 151-154; Belkacémi, Y., Gligorov, J., Ozsahin, M., Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study (2008) Ann. Oncol., 19, pp. 1110-1116; Blaszkowsky, L.S., Ryan, D.P., Szymonifka, J., Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer (2014) Ann. Oncol., 25 (1) January), pp. 121-126; Block, A.M., Alite, F., Diaz, A.Z., Combination trimodality therapy using vismodegib for basal cell carcinoma of the face (2015) Case Rep. Oncol. Med., 2015. , 827608; Blumenschein, G.R., Jr, Paulus, R., Curran, W.J., Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324 (2011) J. Clin. Oncol., 29 (17) June), pp. 2312-2318; Bonner, J.A., Harari, P.M., Giralt, J., Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck (2006) N Engl. J. Med., 354 (6)Febuary), pp. 567-578; Bourgier, C., Massard, C., Moldovan, C., Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent side-effect? (2011) Ann. Oncol., 2, pp. 485-486; Bradley, J.D., Paulus, R., Komaki, R., Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study (2015) Lancet Oncol., 16 (2) Febuary), pp. 187-199; Buglione, M., Maddalo, M., Corvò, R., Subgroup analysis according to human papillomavirus Status and tumor site of a randomized phase II trial comparing cetuximab and cisplatin combined with radiation therapy for locally advanced head and neck cancer (2017) Int. J. Radiat. Oncol. Biol Phys., 97 (3) March), pp. 462-472; Chadha, A.S., Skinner, H.D., Gunther, J.R., Phase i trial of consolidative radiotherapy with concurrent bevacizumab, erlotinib and capecitabine for unresectable pancreatic cancer (2016) PLoS One., 11 (6) June). , e0156910; Chang, A.L., Solomon, J.A., Hainsworth, J.D., Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib (2014) J. Am. Acad. Dermatol., 70 (Jan (1)), pp. 60-69; Chauffert, B., Feuvret, L., Bonnetain, F., Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF (2014) Ann. Oncol.; Chinnaiyan, P., Won, M., Wen, P.Y., A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG oncology RTOG 0913 (2018) Neuro Oncol., 20 (5) April), pp. 666-673; Chinnaiyan, P., Won, M., Wen, P.Y., RTOG 0913: a phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma (2013) Int. J. Radiat. Oncol. Biol. Phys., 86 (5) August), pp. 880-884; Chinot, O.L., Wick, W., Mason, W., Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma (2014) N Engl. J. Med., 370, pp. 709-722; Cho, E., Mostaghel, E.A., Russell, K.J., Liao, J.J., Konodi, M.A., Kurland, B.F., Marck, B.T., Montgomery, R.B., External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens (2015) Int. J. Radiat. Oncol. Biol. Phys., 92 (2)June), pp. 236-243; Chung, C., Dawson, L.A., Joshua, A.M., Brade, A.M., Radiation recall dermatitis triggered by multi-targeted tyrosine kinase inhibitors: sunitinib and sorafenib (2010) Anticancer Drugs., 21 (2) Febuary), pp. 206-209; Churilla, T.M., Chowdhry, V.K., Pan, D., Radiation-induced dermatitis with vemurafenib therapy (2013) Pract. Radiat. Oncol., 3, pp. e195-e198; Crane, C.H., Eng, C., Feig, B.W., Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer (2010) Int. J. Radiat. Oncol. Biol. Phys., 76 (3)March), pp. 824-830; Crosby, T., Hurt, C.N., Falk, S., Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial (2013) Lancet Oncol., 14 (7) June), pp. 627-637; Das, P., Eng, C., Rodriguez-Bigas, M.A., Preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib for rectal cancer: a phase 1 trial (2014) Int. J. Radiat. Oncol. Biol. Phys., 88 (2) Febuary), pp. 301-305; de Melo, A.C., Grazziotin-Reisner, R., Erlich, F., A phase i study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX i (2016) Cancer Chemother. Pharmacol., 78 (1), pp. 101-109; Dellas, K., Höhler, T., Reese, T., Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer (2013) Radiat. Oncol., 8 (April), p. 90; Deutsch, E., Le Péchoux, C., Faivre, L., Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer (2015) Ann. Oncol., 26, pp. 1223-1229; Dipetrillo, T., Pricolo, V., Lagares-Garcia, J., Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer (2012) Int. J. Radiat. Oncol. Biol. Phys., 82 (1) January), pp. 124-129; Ducassou, A., David, I., Delannes, M., Radiosensitization induced by vemurafenib (2013) Cancer Radiother., 17, pp. 304-307; Duffy, A.G., Makarova-Rusher, O.V., Kleiner, D.E., A pilot study of immune checkpoint inhibition in combination with radiation therapy in patients with metastatic pancreatic cancer [abstract] (2017) J. Clin. Oncol., 35. , (Abstr nr e15786); Dummer, R., Guminski, A., Gutzmer, R., The 12-month analysis from basal cell carcinoma outcomes with LDE225 treatment (BOLT): a phase II, randomized, double blind study of sonidegib in patients with advanced basal cell carcinoma (2016) J. Am Acad. Dermatol., 75. , 113-125.e5; Dwedney, A., Cunningham, D., Tabernero, J., Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-c) (2012) J. Clin. Oncol., 30 (14) May), pp. 1620-1627; Ejlsmark, M.W., Kristiansen, C., Eriksen, J.C., Recall radiation myelitis after stereotactic radiation and dabrafenib in metastatic melanoma (2017) Acta Oncol., 56 (1) January), pp. 109-110; Fizazi, K., Massard, C., James, N.D., ODM-201, a new generation androgen receptor inhibitor for castration-resistant prostate cancer: preclinical and phase i data (2013) Proc. Am Soc. Clin. Oncol., 31. , abstr 65. 19; Formenti, S.C., Demaria, S., Combining RT and cancer immunotherapy: a paradigm shift (2013) J. Natl. Canc Inst., 105, pp. 256-265; Fornaro, L., Caparello, C., Vivaldi, C., Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: a systematic review (2014) World J. Gastroenterol., 20 (20)May), pp. 6081-6091; Forschner, A., Zips, D., Schraml, C., Radiation recall dermatitis and radiation pneumonitis during treatment with vemurafenib (2014) Melanoma Res., 24, pp. 512-516; Fu, P., He, Y.S., Huang, Q., Bevacizumab treatment for newly diagnosed glioblastoma: systematic review and meta-analysis of clinical trials (2016) Mol. Clin. Oncol., 4 (5) May), pp. 833-838; Fury, M.G., Lee, N.Y., Sherman, E., A phase i study of everolimus + weekly cisplatin + intensity modulated radiation therapy in head-and-neck cancer (2013) Int. J. Radiat. Oncol. Biol. Phys., 87 (3) November), pp. 479-486; Gasparini, G., Torino, F., Ueno, T., A phase II study of neoadjuvant bevacizumab plus capecitabine and concomitant radiotherapy in patients with locally advanced rectal cancer (2012) Angiogenesis., 15 (1) March), pp. 141-150; Geoffrois, L., Martin, L., De Raucourt, D., Induction chemotherapy followed By cetuximab radiotherapy Is not superior to concurrent chemoradiotherapy for head and neck carcinomas. Results of the GORTEC-02 phase III randomized trial (2018) J. Clin. Oncol., (July); Gilbert, M.R., Dignam, J.J., Armstrong, T.S., A randomized trial of bevacizumab for newly diagnosed glioblastoma (2014) N Engl. J. Med., 370, pp. 699-708; Giralt, J., Trigo, J., Nuyts, S., Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial (2015) Lancet Oncol., 16 (2) Febuary), pp. 221-232; Goldberg, S.B., Gettinger, S.N., Mahajan, A., Activity and safety of pembrolizumab in patients with metastatic Non-small cell lung cancer with untreated brain metastases (2015) J. Clin. Oncol., 33. , (Suppl; Abstr 8035); Golden, E.B., Demaria, S., Schiff, P.B., An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer (2013) Cancer Immunol. Res., 1, pp. 365-372; Govindan, R., Bogart, J., Stinchcombe, T., Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: cancer and leukemia group b trial 30407 (2011) J. Clin. Oncol., 29 (23) August), pp. 3120-3125; Halyard, M.Y., Pisansky, T., Dueck, A.C., Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG phase II trial N9831 (2009) J. Clin. Oncol., 27 (16) June), pp. 2638-2644; Hammel, P., Huguet, F., van Laethem, J.L., Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial (2016) JAMA., 315 (17) May), pp. 1844-1853; Hecht, M., Zimmer, L., Loquai, C., Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients (2015) Ann. Oncol., 26 (6), pp. 1238-1244; Helbling, D., Bodoky, G., Gautschi, O., Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07 (2013) Ann. Oncol., 24 (3) March), pp. 718-725; Herman, J.M., Fan, K.Y., Wild, A.T., Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer (2013) Int. J. Radiat. Oncol. Biol. Phys., 86 (4) July), pp. 678-685; Ho, A., Barker, C.A., Gucalp, A., Preliminary results from a single-Arm, phase II study assessing the efficacy of pembrolizumab plus radiotherapy in metastatic triple negative breast cancer (2017) J. Clin. Oncol., 35. , Abstract 95; Hofheinz, R.D., Horisberger, K., Woernle, C., Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer (2006) Int. J. Radiat. Oncol. Biol. Phys., 66 (5) December), pp. 1384-1390; Horton, J.K., Halle, J., Ferraro, M., Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial (2010) Int. J. Radiat. Oncol. Biol. Phys., 76, pp. 998-1004; Iacovelli, R., Palazzo, A., Mezi, S., Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials (2012) Acta Oncol., 51 (7) September), pp. 873-879; Ioannidis, G., Gkogkou, P., Charalampous, P., Radiation-recall dermatitis with the everolimus/exemestane combination ten years after adjuvant whole-breast radiotherapy (2014) Radiot Oncol., 112, pp. 449-450; Iyengar, P., Kavanagh, B.D., Wardak, Z., Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer (2014) J. Clin. Oncol., 32 (34) December), pp. 3824-3830; Jiang, Y., Mackley, H.B., Kimchi, E.T., Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer (2014) Cancer Chemother. Pharmacol., 74 (1) July), pp. 205-210; Kao, J., Packer, S., Vu, H.L., Phase I study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response (2009) Cancer, 115 (15) August), pp. 3571-3580; Kao, J., Chen, C.T., Tong, C.C., Concurrent sunitinib and stereotactic body radiotherapy for patients with oligometastases: final report of a prospective clinical trial (2014) Target. Oncol., 9 (2) June), pp. 145-153; Kao, J., Timmins, J., Ozao-Choy, J., Packer, S., Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis (2016) Oncol. Lett., 12 (3) September), pp. 2139-2144; Katz, D.A., Abrams, R.A., Sclamberg, J.S., Radiosensitizing effect of anti-HER2/neu agents: report of 2 cases and review of the literature (2015) Prac. Radiat. Oncol., 5, pp. e61-e65; Kennecke, H., Berry, S., Wong, R., Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial (2012) Eur. J. Cancer., 48 (1) January), pp. 37-45; Kiess, A.P., Wolchok, J.D., Barker, C.A., Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment (2015) Int. J. Radiat. Oncol. Biol. Phys., 92, pp. 368-375; Kwon, E.D., Drake, C.G., Scher, H.I., CA184-043 investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial (2014) Lancet Oncol., 15 (7) June), pp. 700-712; Lai, A., Tran, A., Nghiemphu, P.L., Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme (2011) J. Clin. Oncol. Off J. Am Soc. Clin. Oncol., 29, pp. 142-148; Landry, J.C., Feng, Y., Cohen, S.J., Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204 (2013) Cancer., 119 (8) April), pp. 1521-1527; Lee, S.M., Lewanski, C.R., Counsell, N., Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases (2014) J. Natl. Cancer Inst., 106 (7) July); Lefebvre, J.L., Pointreau, Y., Rolland, F., Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study (2013) J. Clin. Oncol., 31 (7) March), pp. 853-859. , Epub 2013 Jan 22. Erratum in: J Clin Oncol. 2013 May 1;31(13):1702; Leibowitz-Amit, R., Joshua, A.M., Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions (2012) Curr. Oncol., 19, pp. S22-31; Lin, J., Hoffman-Censits, J.H., Kelly, W.K., An exploratory study to investigate the immunomodulatory activity of radiation therapy in combination with pembrolizumab in patients with renal cell cancer (2017) J. Clin. Oncol., 35. , abstract 518; Lin, S.H., Lin, Y., Price, J., DETERRED: PD-L1 blockade to evaluate the safety of lung cancer therapy using carboplatin, paclitaxel, and radiation combined with MPDL3280A (atezolizumab) [abstract] (2017) J. Clin. Oncol., 35. , (Abstr nr 3064); Liniker, E., Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma (2016) OncoImmunology, 5 (9); Lledo, G., Huguet, F., Chibaudel, B., Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: the GERCOR phase II trial ERaFOX (2016) Eur. J. Cancer., 56 (March), pp. 115-121; Lockhart, A.C., Reed, C.E., Decker, P.A., Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051) (2014) Ann. Oncol., 25 (5) May), pp. 1039-1044; Lu, C.S., Liu, J.H., Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports (2017) Med. (Baltim.), (96), p. e5747; Ly, D., Bagshaw, H.P., Anker, C.J., Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment (2015) J. Neurosurg., 123, pp. 395-401; Ma, D.J., Galanis, E., Anderson, S.K., A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K (2015) Neuro Oncol., 17 (9) September), pp. 1261-1269; Machiels, J.P., Sempoux, C., Scalliet, P., Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer (2007) Ann. Oncol., 18 (4) April), pp. 738-744; Magrini, S.M., Buglione, M., Corvò, R., Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a randomized phase II trial (2016) J. Clin. Oncol., 34 (5) Febuary), pp. 427-435; Martinez, E., Martinez, M., Vinolas, N., Feasibility and tolerability of the addition of erlotinib to 3D thoracic radiotherapy (RT) in patients with unresectable NSCLC: a prospective randomized phase II study (2008) J. Clin. Oncol., 26. , abstr. 7563; Martins, R.G., Parvathaneni, U., Bauman, J.E., Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial (2013) J. Clin. Oncol., 31 (11)April), pp. 1415-1421; Marur, S., Li, S., Cmelak, A.J., Phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN cancer research group (2016) J. Clin. Oncol., (December). , JCO2016683300; Mathew, M., Tam, M., Ott, P.A., Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery (2013) Melanoma Res., 23, pp. 191-195; Mehta, M.P., Wang, D., Wang, F., Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study (2015) J. Neurooncol., 122 (2) April), pp. 409-417; Merten, R., Hecht, M., Haderlein, M., Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy (2014) Strahlenther. Onkol., 190 (12), pp. 1169-1172; Mesía, R., Henke, M., Fortin, A., Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial (2015) Lancet Oncol., 16 (2) Febuary), pp. 208-220; Michaelson, M.D., Hu, C., Pham, H.T., Phase I/II trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for non cystectomy candidates with muscle invasive bladder cancer (trial NRG oncology RTOG 0524) (2017) Int. J. Radiat. Oncol. Biol. Phys., 97 (5):April), pp. 995-1001; Midgen, M.R., Guminski, A., Gutzmer, R., Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, doubleblind phase 2 trial (2015) Lancet Oncol., 16, pp. 716-728; Miura, Y., Suyama, K., Shimomura, A., Radiation-induced esophagitis exacerbated by everolimus (2013) Case Rep. Oncol., 6, pp. 320-324; Moilanen, A., Riikonen, R., Oksala, R., ODM-201—new generation antiandrogen with excellent antiandrogenic and antitumor activity in nonclinical models of CRPC (2013) Eur. J. Cancer, 49. , abstr 685; Narayan, V., Vapiwala, N., Mick, R., Phase 1 trial of everolimus and radiation therapy for salvage treatment of biochemical recurrence in prostate cancer patients following prostatectomy (2017) Int. J. Radiat. Oncol. Biol. Phys., 97 (2), pp. 355-361; Nishino, M., Giobbie-Hurder, A., Hatabu, H., Incidence of programmed cell death 1 Inhibitor–Related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis (2016) JAMA Oncol., 2 (12), pp. 1607-1616; Nogué, M., Salud, A., Vicente, P., Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study (2011) Oncologist, 16 (5), pp. 614-620; Patel, K.R., Chowdhary, M., Switchenko, J.M., BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis (2016) Melanoma Res., 26 (4) August), pp. 387-394; Pesce, G.A., Klingbiel, D., Ribi, K., Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the swiss group for clinical cancer research (SAKK 70/03) (2012) Eur. J. Cancer, 48 (3) Febuary), pp. 377-384; Peuvrel, L., Ruellan, A.L., Thillays, F., Severe radiotherapy-induced extracutaneous toxicity under vemurafenib (2013) Eur. J. Dermatol, 23 (6), pp. 879-881; Pollom, E.L., Bui, T.T., Chang, A.L., Concurrent vismodegib and radiotherapy for recurrent, advanced basal cell carcinoma (2015) JAMA Dermatol., 151, pp. 998-1001; Raleigh, D.R., Algazi, A., Arron, S.T., Induction hedgehog pathway inhibition followed by combined-modality radiotherapy for basal cell carcinoma (2015) Br. J. Dermatol., 173, pp. 544-546; Ramella, S., Alberti, A.M., Cammilluzzi, E., Erlotinib and concurrent chemoradiation in pretreated NSCLC patients: radiobiological basis and clinical results (2013) Biomed. Res. Int., 2013. , 403869; Reiss, K.A., Herman, J.M., Zahurak, M., A phase i study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis (2015) Clin. Cancer Res., 21 (1)January), pp. 68-76; Rodon, J., Tawbi, H.A., Thomas, A.L., A phase i, multicenter, open-label, first-inhuman, dose-escalation study of the oral smoothened inhibitor sonidegib (LDE225) in patients with advanced solid tumors (2014) Clin. Cancer Res., 20, pp. 1900-1909; Ruhstaller, T., Pless, M., Dietrich, D., Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II trial (SAKK 75/06) (2011) J. Clin. Oncol., 29 (6) Febuary), pp. 626-631; Ruhstaller, T., Thuss-Patience, P., Hayoz, S., Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08) (2018) Ann. Oncol., 29 (6), June), pp. 1386-1393; Saad, American Urology Association Conference (2012), Abstract 682 (Oral presentation); Safran, H., Dipetrillo, T., Akerman, P., Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma (2007) Int. J. Radiat. Oncol. Biol. Phys., 67, pp. 405-409; Safran, H., Suntharalingam, M., Dipetrillo, T., Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity (2008) Int. J. Radiat. Oncol. Biol. Phys., 70 (2) Febuary), pp. 391-395; Salazar, R., Capdevila, J., Laquente, B., A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features (2015) BMC Cancer, 15 (Febuary), p. 60; Sandomenico, C., Costanzo, R., Carillio, G., Bevacizumab in non small cell lung cancer: development, current status and issues (2012) Curr. Med. Chem., 19, pp. 961-971; Sarkaria, J.N., Galanis, E., Wu, W., Combination of temsirolimus (CCI-779) with chemoradiation in newly diagnosed glioblastoma multiforme (GBM) (NCCTG trial N027D) is associated with increased infectious risks (2010) Clin. Cancer Res., 16 (22) November), pp. 5573-5580; Sarkaria, J.N., Galanis, E., Wu, W., North Central cancer treatment group phase i trial N057K of everolimus (RAD001) and temozolomide in combination with radiation therapy in patients with newly diagnosed glioblastoma multiforme (2011) Int. J. Radiat. Oncol. Biol. Phys., 81 (2) October), pp. 468-475; Satzger, I., Degen, A., Asper, H., Serious skin toxicity with the combination of BRAF inhibitors and radiotherapy (2013) J. Clin. Oncol., 31, pp. e220-e222; Scher, H.I., Fizazi, K., Saad, F., Increased survival with enzalutamide in prostate cancer after chemotherapy (2012) N Engl. J. Med., 367, pp. 1187-1197; Schulze, B., Meissner, M., Ghanaati, S., Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck (2016) Strahlenther. Onkol., 192 (Jan. (1)), pp. 25-31; Segal, N.H., Kemeny, N.E., Cercek, A., Non-randomized phase II study to assess the efficacy of pembrolizumab (pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients (2016) J. Clin. Oncol., p. 34. , (suppl; abstr 3539); Smith, M.R., Saad, F., Chowdhury, S., Apalutamide treatment and metastasis-free survival in prostate cancer (2018) N Engl. J. Med., 378 (15) April), pp. 1408-1418; Socinski, M.A., Stinchcombe, T.E., Moore, D.T., Incorporating bevacizumab and erlotinib in the combined-modality treatment of stage III non-small-cell lung cancer: results of a phase I/II trial (2012) J. Clin. Oncol., 30, pp. 3953-3959; Spigel, D.R., Hainsworth, J.D., Yardley, D.A., Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab (2010) J. Clin. Oncol., 28, pp. 43-48; Spigel, D.R., Bendell, J.C., McCleod, M., Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer (2012) Clin. Colorectal Cancer, 11 (1) March), pp. 45-52; Staehler, M., Haseke, N., Nuhn, P., Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma (2011) BJU Int., 108 (5) September), pp. 673-678; Staehler, M., Haseke, N., Stadler, T., Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer (2012) Urol Oncol., 30 (3) May-June), pp. 290-293; Stefan, D., Popotte, H., Stefan, A., Vemurafenib and concomitant stereotactic radiation for the treatment of melanoma with spinal metastases: a case report (2016) Reports Prac.Oncol. Radiother., 21, pp. 76-80; Sun, P.L., Li, B., YE, Q.F., Effect of neoadjuvant cetuximab, capecitabine and radiotherapy for locally advanced rectal cancer: results of a phase II study (2012) Int. J. Colorectal Dis., 27 (10) October), pp. 1325-1332; Suntharalingam, M., Winter, K., Ilson, D., Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the NRG oncology RTOG 0436 phase 3 randomized clinical trial (2017) JAMA Oncol., 3 (11) November), pp. 1520-1528; Tao, Y., Auperin, A., Sire, C., Improved outcome by adding concurrent chemotherapy to cetuximab and radiotherapy for locally advanced head and neck carcinomas: results of the GORTEC 2007-01 phase III randomized trial (2018) J. Clin. Oncol., (June). , JCO2017762518; Tazi, K., Hataway, A., Chiuzan, C., Shirai, K., Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery (2015) Cancer Med., 4, pp. 1-6; Tomblyn, M.B., Goldman, B.H., Thomas, C.R., Jr, Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414) (2012) J. Thorac. Oncol., 7 (5) May), pp. 906-912; Tong, C.C., Ko, E.C., Sung, M.W., Phase II trial of concurrent sunitinib and image-guided radiotherapy for oligometastases (2012) PLoS One, 7 (6), p. e36979; Trotti, A., Harris, J., Gillison, M., NRG-RTOG 1016: phase III trial comparing Radiation/Cetuximab to Radiation/Cisplatin in HPV-related cancer of the oropharynx (2018) Int. J. Radiat. Oncol. Biol. Phys., , Supplement; Valentini, V., De Paoli, A., Gambacorta, M.A., Infusional 5-fluorouracil and ZD1839 (gefitinib-iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase i and II trial (1839IL/0092) (2008) Int. J. Radiat. Oncol. Biol. Phys., 72 (3) November), pp. 644-649; Van den Heuvel, M.M., Uyterlinde, W., Vincent, A.D., Additional weekly cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: efficacy and safety outcomes of a randomized, multi-center phase II study investigating (2014) Radiother. Oncol., 110 (1) January), pp. 126-131; Velenik, V., Ocvirk, J., Music, M., Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study (2011) Radiat. Oncol., 6 (August), p. 105; Vivaldi, C., Buccianti, G., Musettini, F., TRUST: phase II trial of induction chemotherapy with FOLFOXIRI + bevacizumab followed by chemo-radiotherapy + bevacizumab and surgery in locally advanced rectal carcinoma (2016) Ann. Oncol., 27; Wang, Z., Zhu, X.X., Wu, X.H., Gefitinib combined with stereotactic radiosurgery in previously treated patients with advanced non-small cell lung cancer (2014) Am. J. Clin. Oncol., 37 (2) April), pp. 148-153; Welsh, J.W., Komaki, R., Amini, A., Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer (2013) J. Clin. Oncol., 31 (7) March), pp. 895-902; Willett, C.G., Duda, D.G., di Tomaso, E., Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study (2009) J. Clin. Oncol., 27 (18) June), pp. 3020-3026; William, N.L., Wuthrick, E.J., Kim, H., Phase i study of ipilimumab combine dwith whole brain radiation therapy Or radiosurgery for melanoma patients with brain metastases (2017) Int. J. Radiat. Oncol. Biol. Phys., 99 (1) September), pp. 22-30; Wirsching, H.G., Tabatabai, G., Roelcke, U., Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial (2018) Ann. Oncol., 29 (6)June), pp. 1423-1430; Wolf, A., Zia, S., Verma, R., Pavlick, A., Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases (2016) J. Neurooncol., 127 (3) May), pp. 607-615; Xu, T., Liu, Y., Dou, S., Weekly cetuximab concurrent with IMRT aggravated radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma: results of a randomized phase II study (2015) Oral Oncol., 51 (9) September), pp. 875-879; Yuasa, T., Kitsukawa, S., Sukegawa, G., Early onset recall pneumonitis during targeted therapy with sunitinib (2013) BMC Cancer, 2 (13 January), p. 3; Zhao, C., Lin, L., Liu, J., A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma (2016) Oncotarget., 7 (35) August), pp. 57310-57316; Zhu, M.L., Horbinski, C.M., Garzotto, M., Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer (2010) Cancer Res., 70, pp. 7992-8002; Zhuang, H., Yuan, Z., Wang, J., Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma (2013) Drug. Des. Devel Ther., 7 (October), pp. 1179-1186

PY - 2019

Y1 - 2019

N2 - Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity. © 2018 Elsevier B.V.

AB - Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity. © 2018 Elsevier B.V.

KW - Radiotherapy

KW - Systemic compounds

KW - Toxicity

KW - abiraterone

KW - afatinib

KW - antineoplastic agent

KW - apalutamide

KW - bevacizumab

KW - cetuximab

KW - cytotoxic T lymphocyte antigen 4 antagonist

KW - dabrafenib

KW - darolutamide

KW - enzalutamide

KW - erlotinib

KW - everolimus

KW - galeterone

KW - gefitinib

KW - nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor

KW - orteronel

KW - panitumumab

KW - pertuzumab

KW - programmed death 1 ligand 1 antagonist

KW - programmed death 1 receptor antagonist

KW - seviteronel

KW - sonidegib

KW - sorafenib

KW - sunitinib

KW - trastuzumab

KW - unclassified drug

KW - vemurafenib

KW - vismodegib

KW - radiosensitizing agent

KW - cancer radiotherapy

KW - cancer survival

KW - clinical effectiveness

KW - clinical outcome

KW - clinical trial (topic)

KW - drug effect

KW - drug efficacy

KW - drug response

KW - human

KW - quality of life

KW - radiation dose

KW - Review

KW - solid malignant neoplasm

KW - survival rate

KW - treatment response

KW - chemoradiotherapy

KW - Italy

KW - neoplasm

KW - treatment outcome

KW - Chemoradiotherapy

KW - Humans

KW - Neoplasms

KW - Radiation-Sensitizing Agents

KW - Treatment Outcome

U2 - 10.1016/j.critrevonc.2018.11.006

DO - 10.1016/j.critrevonc.2018.11.006

M3 - Article

SN - 1879-0461

VL - 134

SP - 104

EP - 119

JO - Crit. Rev. Oncol. Hematol.

JF - Crit. Rev. Oncol. Hematol.

ER -