Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial.
Methods
The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress.
Results
The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial.
Conclusions
Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.
FilippiARAlongiFCiammellaPDe BariBFrancoPLiviLA strategy for young members within national radiation oncology societies: the Italian experience (AIRO Giovani group). Rep Pract Oncol Radiother2012;17 (5)259–261
2.
FrancoPCiammellaPPeruzzo CornettoAThe STYRO 2011 project: a survey on perceived quality of training among young Italian radiation oncologists. Med Oncol2013;30 (4)729
3.
De BariBChiesaSFilippiAR; AIRO (Italian Association of Radiation Oncology) and the AIRO Palliative Care Group. The INTER-ROMA project—a survey among Italian radiation oncologists on their approach to the treatment of bone metastases. Tumori2011;97 (2)177–184
4.
AlongiFDe BariBFrancoP; AIRO Young and AIRO Prostate cancer Working Group. The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): a survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer. Radiol Med (Torino)2013;118 (4)660–678
5.
De BariBAlongiFFrancoP; AIRO Young and AIRO Prostate cancer Working Group. The “PROCAINA (PROstate CAncer INdication Attitudes) Project” (Part II)—a survey among Italian radiation oncologists on radical radiotherapy in prostate cancer. Radiol Med (Torino)2013;118 (7)1220–1239
6.
CiammellaPDe BariBFiorentinoA; AIRO Giovani (Italian Association of Radiation Oncology-Young Members Working Group). The “BUONGIORNO” project: burnout syndrome among young Italian radiation oncologists. Cancer Invest2013;31 (8)522–528
7.
De BariBFrancoPCiammellaP; AIRO Giovani Italian Association of Radiation Oncology-Young Members Working Group. The PEDRO (Pocketable Electronic Devices in Radiation Oncology) project: how clinical practice is changing among young radiation oncologists. Tumori2014;100 (6)e236–e242
8.
De BariBFrancoPNiyaziM; AIRO Giovani (Italian Association of Radiation Oncology-Young Members Working Group), of yDEGRO (Young German Society of Radiation Oncology), of SYROG (Spanish Young Radiation Oncology Group), of SEOR (Spanish Society of Radiation Oncology), of SPRO (Portuguese Society of Radiotherapy and Oncology-Young Members Working Group), SPRO Jovem), and of FYO (The Danish Association of Young Oncologists). The Pocketable Electronic Devices in radiation Oncology (PEDRO) Project: how the use of tools in medical decision making is changing? Technol Cancer Res Treat2016;15 (2)365–376
9.
De BariBFiorentinoAGretoDProstate cancer as a paradigm of multidisciplinary approach? Highlights from the Italian young radiation oncologist meeting. Tumori2013;99 (6)637–649
10.
FrancoPDe BariBCiammellaPThe role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highligh ts from the 7th Meeting of AIRO – Young Members Working Group (AIRO Giovani). Tumori2014;100214e–229e
11.
RamnathNDillingTJHarrisLJTreatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest2013;1435 Supple314S–e340S
12.
EberhardtWEDe RuysscherDWederW; Panel Members. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol2015;26 (8)1573–1588
13.
De LeynPDoomsCKuzdzalJPreoperative mediastinal lymph node staging for non-small cell lung cancer: 2014 update of the 2007 ESTS guidelines. Transl Lung Cancer Res2014;3 (4)225–233
14.
ArriagadaRAuperinABurdettS; NSCLC Meta-analyses Collaborative Group. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet2010;375 (9722)1267–1277
15.
PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet1998;352 (9124)257–263
16.
RobinsonCGPatelAPBradleyJDPostoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base. J Clin Oncol2015;33 (8)870–876
17.
HancockJGRosenJEAntonicelliAImpact of adjuvant treatment for microscopic residual disease after non-small cell lung cancer surgery. Ann Thorac Surg2015;99 (2)406–413
18.
WindJSmitEJSenanSEerenbergJPResidual disease at the bronchial stump after curative resection for lung cancer. Eur J Cardiothorac Surg2007;32 (1)29–34
19.
RiquetMAchourKFoucaultCLe Pimpec BarthesFDujonACazesAMicroscopic residual disease after resection for lung cancer: a multifaceted but poor factor of prognosis. Ann Thorac Surg2010;89 (3)870–875
20.
AlbainKSSwannRSRuschVWRadiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet2009;374 (9687)379–386
21.
KoshyMGoloubevaOSuntharalingamMImpact of neoadjuvant radiation on survival in stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys2011;79 (5)1388–1394
22.
ThomasMRübeCHoffknechtP; German Lung Cancer Cooperative Group. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol2008;9 (7)636–648
23.
GirardNMornexFDouillardJYIs neoadjuvant chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung cancer? Mature results of the randomized IFCT-0101 phase II trial. Lung Cancer2010;69 (1)86–93
24.
KatakamiNTadaHMitsudomiTA phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903). Cancer2012;118 (24)6126–6135
25.
SherDJFidlerMJLiptayMJKoshyMComparative effectiveness of neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery for patients with stage IIIA non-small cell lung cancer. Lung Cancer2015;88 (3)267–274
26.
AupérinALe PéchouxCRollandEMeta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol2010;28 (13)2181–2190
27.
BelderbosJUitterhoeveLvan ZandwijkN; EORTC LCG and RT Group. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer2007;43 (1)114–121
28.
BezjakATeminSFranklinGDefinitive and Adjuvant Radiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol2015;33 (18)2100–2105
29.
AupérinALe PéchouxCPignonJP; Meta-Analysis of Cisplatin/carboplatin based Concomitant Chemotherapy in non-small cell Lung Cancer (MAC3-LC) Group. Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients. Ann Oncol2006;17 (3)473–483
30.
HannaNNeubauerMYiannoutsosC; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol2008;26 (35)5755–5760
31.
PerezCAStanleyKRubinPA prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung. Preliminary report by the Radiation Therapy Oncology Group. Cancer1980;45 (11)2744–2753
32.
BradleyJDPaulusRKomakiRStandard-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. Lancet Oncol2015;16 (2)187–199
33.
BonnerJAMcGinnisWLStellaPJThe possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma: results of a North Central Cancer Treatment Group Phase III Study. Cancer1998;82 (6)1037–1048
34.
CoxJDAzarniaNByhardtRWShinKHEmamiBPajakTFA randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with Radiation Therapy Oncology Group stage III non-small-cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11. J Clin Oncol1990;8 (9)1543–1555
35.
BaumannMHerrmannTKochR; CHARTWEL-Bronchus studygroup. Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Radiother Oncol2011;100 (1)76–85
36.
SaundersMDischeSBarrettAHarveyAGriffithsGParmarM(on behalf of the CHART steering committee). Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. Radiother Oncol1999;52 (2)137–148
37.
SlawsonRGSalazarOMPoussin-RosilloHAminPPStrohlRSewchandWOnce-a-week vs conventional daily radiation treatment for lung cancer: final report. Int J Radiat Oncol Biol Phys1988;15 (1)61–68
38.
BelderbosJSHeemsbergenWDDe JaegerKBaasPLebesqueJVFinal results of a Phase I/II dose escalation trial in non-small-cell lung cancer using three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys2006;66 (1)126–134
39.
ChangJYIntensity-modulated radiotherapy, not 3 dimensional conformal, is the preferred technique for treating locally advanced lung cancer. Semin Radiat Oncol2015;25 (2)110–116
40.
GovindanRBogartJStinchcombeTRandomized 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. J Clin Oncol2011;29 (23)3120–3125
41.
van den HeuvelMMUyterlindeWVincentADAdditional 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. Radiother Oncol2014;110 (1)126–131
42.
WangJXiaTYWangYJProspective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer. Int J Radiat Oncol Biol Phys2011;81 (3)e59–e65
43.
OkamotoITakahashiTOkamotoHSingle-agent gefitinib with concurrent radiotherapy for locally advanced non-small cell lung cancer harboring mutations of the epidermal growth factor receptor. Lung Cancer2011;72 (2)199–204
44.
StinchcombeTEMorrisDELeeCBInduction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer. J Thorac Oncol2008;3 (3)250–257
45.
ReadyNJännePABogartJ; Cancer, Leukemia Group B, Chicago, IL. Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial. J Thorac Oncol2010;5 (9)1382–1390
46.
KellyKChanskyKGasparLEPhase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol2008;26 (15)2450–2456
47.
KomakiRAllenPKWeiXAdding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys2015;92 (2)317–324
48.
HerbstRSPragerDHermannR; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol2005;23 (25)5892–5899
49.
PaezJGJännePALeeJCEGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science2004;304 (5676)1497–1500
50.
HuberRMReckMThomasMCurrent status of and future strategies for multimodality treatment of unresectable stage III nonsmall cell lung cancer. Eur Respir J2013;42 (4)1119–1133
51.
SpigelDRHainsworthJDYardleyDATracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol2010;28 (1)43–48
52.
ButtsCSocinskiMAMitchellPLSTART trial team. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol2014;1559–68
53.
LynchTJBondarenkoILuftAIpilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol2012302046–2054
54.
GaronEBRizviNAHuiRPembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med2015;212018–2028
55.
BorghaeiHPaz-AresLHornLNivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med2015;3731627–1639
56.
BrahmerJReckampKLBassPNivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med2015;373123–135
57.
SobinLGospodarowiczMWittekindCTNM Classification of Malignant Tumors, 7th ed. Wiley-Blackwell, Oxford2009
58.
CrewKDNeugutAIEpidemiology of upper gastrointestinal malignancies. Semin Oncol2004;31450–464
59.
LeersJMDemeesterSRChanNClinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus. J Thorac Cardiovasc Surg2009;138594–602
60.
RiceTWRuschVWIshwaranHBlackstoneEHWorldwide Esophageal Cancer C. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer. 116 3763–3773
61.
CelliniFMorgantiAGMatteoDi FMMattiucciGCValentiniVClinical management of gastroesophageal junction tumors: past and recent evidences for the role of radiotherapy in the multidisciplinary approach. Radiat Oncol2014;945
62.
NCCN Guidelines - Esophageal and Esophagogastric Cancers (excluding proximal 5 cm stomach). NCCN Clinical Practice Guideline in Oncology - Available at: http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf, (Version 2.2013). Accessed November 16, 2015.
63.
BurmeisterBHRole of radiotherapy in the pre-operative management of carcinoma of the esophagus. World J Gastrointest Oncol2015;71–5
64.
WalshTNNoonanNHollywoodDKellyAKeelingNHennessyTPA comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med1996;335462–467
65.
UrbaSGOrringerMBTurrisiAIannettoniMForastiereAStrawdermanMRandomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol2001;19305–313
66.
BurmeisterBHSmithersBMGebskiVSurgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol2005;6659–668
67.
TepperJKrasnaMJNiedzwieckiDPhase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol2008;261086–1092
68.
Van HagenPHulshofMCVan LanschotJJPreoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med2012;3662074–2084
69.
ShapiroJvan LanschotJJHulshofMCNeoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomized controlled trial. Lancet Oncol2015;161090–1098
70.
ArnottSJDuncanWGignouxMPreoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group). Int J Radiat Oncol Biol Phys1998;41579–583
71.
GreerSEGoodneyPPSuttonJEBirkmeyerJDNeoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis. Surgery2005;137172–177
72.
UrschelJDVasanHA meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg2003;185538–543
73.
FioricaFDi BonaDSchepisFPreoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut2004;53925–930
74.
JinHLZhuHLingTSZhangHJShiRHNeoadjuvant chemoradiotherapy for resectable esophageal carcinoma: a meta-analysis. World J Gastroenterol2009;155983–5991
75.
SjoquistKMBurmeisterBHSmithersBMSurvival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol2011;12681–692
76.
WangDBZhangXHanHLXuYJSunDQShiZLNeoadjuvant chemoradiotherapy could improve survival outcomes for esophageal carcinoma: a meta-analysis. Dig Dis Sci2012;573226–3233
77.
DengJWangCXiangMLiuFLiuYZhaoKMeta-analysis of postoperative efficacy in patients receiving chemoradiotherapy followed by surgery for resectable esophageal carcinoma. Diagnostic pathology2014;9151
78.
BurmeisterBHThomasJMBurmeisterEAIs concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus?A randomised phase II trial. Eur J Cancer2011;47354–360
79.
StahlMWalzMKStuschkeMPhase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol2009;27851–856
80.
RonellenfitschUSchwarzbachMHofheinzRPreoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer2013;493149–3158
81.
CooperJSGuoMDHerskovicAChemoradiotherapy of locally advanced esophageal cancer. JAMA1999;2811623–1627
82.
CrehangeGMaingonPPeignauxKPhase III trial of protracted compared with split-course chemoradiation for esophageal carcinoma: Federation Francophone de Cancerologies Digestive 9102. J Clin Oncol2007;254895–4901
83.
MinskyBDPajakTFGinsbergRJINT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined modality therapy for esophageal cancer: high-dose versus standard dose radiation therapy. J Clin Oncol2002;201167–1174
84.
GasparLEWinterKKochaWIA phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report. Cancer2000;88988–95
85.
HoningJSmitJKMuijsCTA comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. Ann Oncol2014;25638–643
86.
ConroyTGalaisMPRaoulJLDefinitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol2014;15305–14
87.
AjaniJAWinterKKomakiRPhase II randomized trial of two non-operative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol2008;264551–4556
88.
American Society of Clinical Oncology, Pfister DG, Laurie SA, Weinstein GS, et al. American Society of Clinical Oncology Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer. J Clin Oncol2006;243693–3704
89.
RussiEGSanguinetiGChiesaFIs there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable?A survey of head and neck surgical/radiation oncologists. Acta Otorhinolaryngol Ital2013;33.311–319
90.
RemacleMHantzakosAEckelHEndoscopic supraglottic laryngectomy: a proposal for a classification by the working committee on nomenclature, European Laryngological Society. Eur Arch Otorhinolaryngol2009;266993–998
91.
RemacleMEckelHEAntonelliAEndoscopic cordectomy. A proposal for a classifcation by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol2000;257227–231
92.
MendenhallWMWerningJWHinermanRWManagement of T1-T2 glottic carcinomas. Cancer2004;1001786–1792
93.
PotenzaIFrancoPMorettoFExclusive radiotherapy for early-stage glottic cancer: a single-institution retrospective analysis with a focus on voice quality. Anticancer Res2015;354155–4160
94.
RussiEGCorvo’RMerlottiASwallowing dysfunction in head and neck cancer patents treated by radiotherapy: review and recommendations of the supportive task group of the Italian Association of Radiation Oncology. Cancer Treat Rev2012;381033–1049
95.
Sanchez-CuadradoICastroABernaldezRDel PalacioAGavilanJOncologic outcomes after supracricoid partial laryngectomy. Otolaryngol Head Neck Surg2011;144910–914
96.
DenaroNRussiEGLefebvreJLMerlanoMCA systematic review of current and emerging approaches in the field of larynx preservation. Radiother Oncol2014;11016–24
97.
Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study. N Engl J Med1991;3241685–1690
98.
LefebvreJLAndryGChevalierDLaryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol2012;232708–2714
99.
ForastiereAAZhangQWeberRSLong-term results of the RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol2012;31845–852
100.
LefebvreJLRollandFTesselaarMPhase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Nat Cancer Inst2009;101142–152
101.
PointreauYGaraudPChapetSRandomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst2009;101498–506
102.
PosnerMRHershockDMBlajmanCRCisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med2007;3571705–1715
103.
LefebvreJLPointreauYRollandFInduction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol2013;31853–859
104.
NumicoGFrancoPCristofanoAIs the combination of cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence. Crit Rev Oncol Hematol2013;85112–120
105.
FrancoPPotenzaISchenaMInduction chemotherapy and sequential concomitant chemo-radiation in locally advanced head and neck cancers: how induction phase intensity and treatment breaks may impact on clinical outcomes. Anticancer Res2015;356247–6254
106.
MerlottiAAlterioDVigna-TagliantiRTechnical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology – head and neck working group. Radiat Oncol2014;9264
107.
GebskiVBurmeisterBSmithersBMSurvival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol2007226–234
