Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma Prospective evaluation of patient-reported quality-of-life outcomes following SBRT ± cetuximab for locally-recurrent, previously-irradiated head and neck cancer. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. Dose escalation of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma: a prospective randomised study. Recurrent head and neck cancer: retreatment of previously irradiated areas with combined chemotherapy and radiation therapy-results of a prospective study. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head-and-neck cancer: a feasibility study. Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split‐course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies Reirradiation alternating with docetaxel and cisplatin in inoperable recurrence of head-and-neck cancer: a prospective phase I/II trial. A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. A phase II study of primary reirradiation in squamous cell carcinoma of head and neck. Re-irradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease. Results of postoperative reirradiation for recurrent or second primary head and neck carcinoma Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. Phase 1 trial of combined chemotherapy and reirradiation for recurrent unresectable head and neck cancer. Pilot study of postoperative reirradiation, chemotherapy, and amifostine after surgical salvage for recurrent head-and-neck cancer. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. Platinum-based chemotherapy plus cetuximab in head and neck cancer. Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent. Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients. Salvage re-irradiation for recurrent head and neck cancer. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Prospective trial of high-dose reirradiation using daily image guidance with intensity-modulated radiotherapy for recurrent and second primary head-and-neck cancer. Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer. Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy.
PURPOSE Locoregional recurrence is the dominant form of treatment failure in head and neck ( H&N ) cancer . The epidermal growth factor receptor ( EGFR ) is frequently amplified in this disease ( < or=80 % ) and can lead to activation of phosphatidylinositol-3-kinase ( PI3 K ) , both directly and indirectly through Ras . We have shown previously that radioresistance could be conferred via the Ras-PI3 K pathway . Here we investigate the contribution of EGFR to this pathway and its impact on treatment outcome . EXPERIMENTAL DESIGN In a series of 38 H&N cancer patients , overexpression of EGFR by immunohistochemical staining was assessed . PI3 K signaling was evaluated by staining for phosphorylated Akt ( P-Akt ) , a downstream target of PI3 K . Both EGFR and P-Akt were then related to outcome . Radiation survival was determined in the SQ20B cell line , a radioresistant squamous cell line derived from a recurrent laryngeal cancer , after pharmacological blockade of EGFR with Iressa , of Ras by the FTI L744,832 , or of PI3 K by LY294002 . RESULTS A significant association was found between P-Akt staining and local control in the patient series . Two-year local control was 100 % for patients staining 0 - 1 + for P-Akt as compared with 70.6 % for patients staining 2 - 3 + ( P = 0.04 ) . In our series of 38 H&N cancers , 30 ( 78.9 % ) of the specimens were strongly ( 3 + ) positive for EGFR , whereas 25 ( 65.8 % ) were moderately to strongly ( 2 - 3 + ) positive for P-Akt . Pharmacologically inhibiting EGFR , Ras , and PI3 K led to radiosensitization of SQ20B cells . CONCLUSIONS Evaluation of PI3 K activation by Akt phosphorylation might be a prognostic marker for response to therapy , and PI3 K could be a useful target for therapy . These results also suggest that signaling from EGFR to PI3 K can lead to radioresistance BACKGROUND Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible . Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions . Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer ( RTOG/EORTC ) criteria . RESULTS Seventy-nine of the 86 patients enrolled were analyzable . The worst acute toxicity was grade 4 in 17.7 % and grade 5 in 7.6 % . Grade 3 and 4 late toxicities were found in 19.4 % and 3.0 % , respectively . The estimated cumulative incidence of grade 3 to 4 late effects occurring at > 1 year was 9.4 % ( 95 % confidence interval [ CI ] : 0 , 19.7 ) at 2 and 5 years . The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1 % ( 95 % CI : 0 , 9.3 ) . The estimated 2- and 5-year survival rates were 15.2 % ( 95 % CI : 7.3 , 23.1 ) and 3.8 % ( 95 % CI : 0.8 , 8.0 ) , respectively . Patients who entered the study at > 1 year from initial radiotherapy ( RT ) had better survival than did those who were < 1 year from prior RT ( median survival , 9.8 months vs 5.8 months ; p = .036 ) . No correlation was detected between dose received and overall survival . Three patients were alive at 5 years . CONCLUSION This is the first prospect i ve multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN . The approach is feasible with acceptable acute and late effects . The results serve as a benchmark for ongoing RTOG trials The purpose of this study was to analyze the tolerance and efficacy of full dose reirradiation combined with chemotherapy in patients with head and neck carcinoma ( HNC ) with a high risk of recurrence after salvage surgery PURPOSE Stereotactic body radiotherapy ( SBRT ) has emerged as a promising salvage strategy for unresectable , previously-irradiated recurrent squamous cell carcinomas of the head and neck ( rSCCHN ) . Here-in , we report the first prospect i ve evaluation of patient-reported quality -of-life ( PR-QoL ) following re-irradiation with SBRT±cetuximab for rSCCHN . MATERIAL S AND METHODS From November 2004 to May 2011 , 150 patients with unresectable , rSCCHN in a previously-irradiated field receiving > 40 Gy were treated  with SBRT to 40 - 50 Gy in 5 fractions ± concurrent cetuximab . PR-QoL was prospect ively acquired using the University of Washington Quality -of-Life Revised ( UW-QoL-R ) . RESULTS Overall PR-QoL , health-related PR-QoL , and select domains commonly affected by re-irradiation progressively increase following an initial 1-month decline with statistically significant improvements noted in swallowing ( p=0.025 ) , speech ( p=0.017 ) , saliva ( p=0.041 ) , activity ( p=0.032 ) and recreation ( p=0.039 ) . CONCLUSIONS Especially for patients surviving > 1-year , improved tumor control associated with SBRT re-irradiation may ameliorate decreased PR-QoL result ing from rSCCHN . These improvements in PR-QoL transcend all measured domains in a vali date d PR-QoL assessment tool independent of age , use of cetuximab , tumor volume , and interval since prior irradiation BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab  ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 . PURPOSE Recurrent squamous cell carcinoma of the head and neck ( SCCHN ) or new second primary tumor ( SPT ) in a previous radiation field , if not curable by surgery or radiation , is almost always fatal . Chemotherapy alone yields a median survival time ( MST ) of no more than 10 months and 1-year overall survival ( OS ) of 35 % at best . Concurrent reirradiation and chemotherapy is an alternative strategy . PATIENTS AND METHODS Eligibility for Radiation Therapy Oncology Group ( RTOG ) protocol 9911 stipulated recurrent SCCHN or SPT in a previous radiation field . Patients received twice-daily radiation ( 1.5 Gy per fraction bid x 5 days every 2 weeks x4 ) , plus cisplatin 15 mg/m2 intravenously ( IV ) daily x 5 and paclitaxel 20 mg/m2 IV daily x 5 every 2 weeks x4 . Granulocyte colony-stimulated factor was administered days 6 through 13 of each 2-week cycle . RESULTS One hundred five patients were enrolled from March 2000 through June 2003 ; 23 % had SPT . Oropharynx ( 40 % ) and oral cavity ( 27 % ) were the predominant primary sites . Median prior radiation dose was 65.4 Gy . Seventy-four percent of patients completed chemotherapy . Grade 4 or worse acute toxicity occurred in 28 % , grade 4 or worse acute hematologic toxicity in 21 % . Eight treatment-related deaths ( 8 % ) occurred : five in the acute setting , three late ( including two carotid hemorrhages ) . MST was 12.1 months , with estimated 1- and 2-year OS rates of 50.2 % and 25.9 % . CONCLUSION Despite a high incidence of grade 5 toxicity , 1- and 2-year OS rates for split-course bid radiation therapy and concurrent cisplatin/paclitaxel exceed results generally seen with chemotherapy alone AIMS To investigate prospect ively the feasibility and efficacy of dose escalation using three-dimensional conformal radiotherapy ( 3D-CRT ) boost technique for locally recurrent nasopharyngeal carcinoma ( NPC ) in a r and omised study . MATERIAL S AND METHODS Thirty-six patients with locally recurrent NPC ( > 6 months interval from previous radical radiotherapy , no cervical lymph-node involvement and no distant metastasis ) were enrolled . Treatment included conventional external-beam radiotherapy to 54 Gy , followed by a 3D-CRT boost to the gross tumour region . Patients were r and omised to three boost dose levels : 16 Gy , 20 Gy and 24 Gy for groups I , II and III , respectively , with 12 patients in each group . All boost doses were delivered in 4-Gy fractions and 3 fractions per week . Median follow-up was 27 months ( range 14 - 44 months ) . RESULTS Three-year , local-recurrence-free survival rate was significantly higher ( 72 % ) for the high-dose group III than for groups I and II ( 37 % and 28 % , respectively , P = 0.047 ) . No significant difference was found in the 3-year overall survival rate among the three groups ( 72 % , 59 % and 82 % for groups I , II and III , respectively ) . Three-year distant metastases rates were 17 % , 0 % and 18 % , respectively . Skull-base invasion ( P = 0.017 ) and pathology ( P = 0.0006 ) correlated with overall survival . Treatment was well tolerated and no significant difference was observed among the three groups in acute and late toxicities ( grade III toxicity is minimal : 17 % , 17 % , 0 % of oral mucositis and 25 % , 17 % , 17 % of nasopharyngeal mucositis in groups I , II , III , respectively , and 8 % leukocytopenia only in group II ; no grade IV toxicity occurred in any of the groups except for a fatal bleeding in group III ) . CONCLUSIONS Re-irradiation with high-dose 3D-CRT boost technique results in high local control rate and acceptable toxicity in patients with recurrent NPC . Dose escalation to the boost volume to 78 Gy ( 54 Gy + 24 Gy boost ) results in improved recurrence-free survival compared with lower doses PURPOSE To prospect ively test the effectiveness of combined chemotherapy and radiation therapy for recurrent head and neck cancer . MATERIAL S AND METHODS In 32 patients ,  external-beam radiation therapy ( 2 Gy/d )  was administered as a 5-day course with simultaneous hydroxyurea ( 1.5 g/d orally ) and 5-fluorouracil ( 300 mg/m(2)/d bolus ) , followed by 9 days of rest . This cycle was repeated until a cumulative soft-tissue radiation dose of 110 Gy ( including prior radiation therapy ) was reached . RESULTS At a median follow-up of 18 months , three patients were alive , and 29 had died . The overall 1-year survival rate was 39 % . The overall response rate was 41 % ( 13 patients ) . Acute toxicity was low . According to World Health Organization and Radiation Therapy Oncology Group criteria , there were three cases of grade 3 mucositis or dermatitis and three cases of grade 3 or 4 neutropenia . Three patients had grade 3 late effects : one oral trismus , one jugular venous thrombosis , and one cerebral stroke . CONCLUSION The combination of simultaneous 5-fluorouracil and hydroxyurea infusion and local reirradiation is feasible for retreatment of recurrent head and neck tumors . This regimen provides short-term tumor control in most patients and long-term control in a few patients PURPOSE Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months , the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head- and -neck carcinomas . With a minimum of 10 years of follow-up potentially now available for all patients , these results are up date d here to examine long-term outcomes . METHODS AND MATERIAL S A total of 410 analyzable patients who had high-risk resected head- and -neck cancers were prospect ively r and omized to receive either radiation therapy ( RT : 60 Gy in 6 weeks ) or identical RT plus cisplatin , 100 mg/m(2)i.v . on days 1 , 22 , and 43 ( RT + CT ) . RESULTS At 10 years , the local-regional failure rates were 28.8 % vs 22.3 % ( P=.10 ) , disease-free survival was 19.1 % vs 20.1 % ( P=.25 ) , and overall survival was 27.0 % vs 29.1 % ( P=.31 ) for patients treated by RT vs RT + CT , respectively . In the unplanned subset analysis limited to patients who had microscopically involved resection margins and /or extracapsular spread of disease , local-regional failure occurred in 33.1 % vs 21.0 % ( P=.02 ) , disease-free survival was 12.3 % vs 18.4 % ( P=.05 ) , and overall survival was 19.6 % vs 27.1 % ( P=.07 ) , respectively . CONCLUSION At a median follow-up of 9.4 years for surviving patients , no significant differences in outcome were observed in the analysis of all r and omized eligible patients . However , analysis of the subgroup of patients who had either microscopically involved resection margins and /or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy . The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer , we compared the efficacy and toxicity of cisplatin ( CP ) and fluorouracil ( 5-FU ) , alone and in combination in a phase III trial . PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were r and omized to one of three treatments :  CP ( 100 mg/m2 ) and 5-FU ( 1 g/m2 x 4 ) , CP , or 5-FU every 3 weeks . RESULTS The overall response rate to the combination ( 32 % ) was superior to that of CP ( 17 % ) or 5-FU ( 13 % ) ( P = .035 ) . Response was associated with good performance status ( PS ) but not with primary site , site of recurrence , histology , prior irradiation , or relative dose intensity . Median time to progression was less than 2.5 months , and there was no significant difference in median survival ( 5.7 months ) among the groups . By multivariate analysis , patients with better PS and poorly differentiated tumors had superior survival . Hematologic toxicity and alopecia were worse in the combination arm . CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents , survival did not improve PURPOSE Normal tissues tolerance limits the use of reirradiation for recurrent head- and -neck cancers ( HNC ) .  Stereotactic body radiotherapy ( SBRT ) could offer precise irradiation while sparing healthy tissues . Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC . METHODS AND MATERIAL S Patients with inoperable recurrent , or new primary tumor , in a previously irradiated area were included . Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85 % isodose line covering 95 % of the planning target volume . Patients with squamous cell carcinoma received concomitant cetuximab . RESULTS Between June 2007 and January 2010 , 40 patients were prospect ively treated for 43 lesions . Median age was 60 and median tumor size was 29 mm . Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin . Median follow-up was 25.6 months with 34 patients evaluable for tumor response . Median overall survival was 13.6 months and response rate was 79.4 % ( 15 complete and 12 partial responses ) . Grade 3 toxicity occurred in 4 patients . CONCLUSION These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC . Treatment is feasible and , with appropriate care to limiting critical structure , acute toxicities are acceptable . A prospect i ve multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment . One option for select patients is to undergo reirradiation with concurrent chemotherapy . The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospect i ve reirradiation and chemotherapy studies PURPOSE Inoperable locoregional recurrences of head- and -neck cancer in a previously irradiated volume represent a therapeutic dilemma . Chemotherapy alone has no curative potential , whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients . Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy . Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy . The latter may provide a particular advantage for recurrent , potentially radiation resistant tumors . The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested . PATIENTS AND METHODS Twenty-seven patients ( Karnofsky performance status score > /=70 % ) with histologically proven recurrent squamous cell cancer that occurred > /= 6 months in a previously irradiated area ( > /= 60 Gy ) were considered unresectable and unsuitable for brachytherapy .  Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m(2 ) d1 and cisplatin 15 mg/m(2 ) d2 - 5 , q d22 , and involved field radiotherapy 2.0 Gy every day d8 - 12 , d15 - 19 , d29 - 33 , and d36 - 40 ( 40.0 Gy total dose ) . Dose reduction of docetaxel to 50 mg/m(2 ) was necessary , because of hematologic toxicity in the first 12 patients . RESULTS Alternating chemoreirradiation was applied as planned in 12 of 27 patients , with reirradiation completed per protocol in 81 % . Overall , patients received 83 % of the intended dose of docetaxel and 73 % of cisplatin .  Third-degree common toxicity criteria mucositis occurred in 15 % , leukopenia of > /= third degree by common toxicity criteria in 37 % , and 3 early deaths were observed . Median time to follow-up , time to local progression , median survival , and 3-year survival rates were 42 months , 10 months , 10 months , and 18 % , respectively . CONCLUSIONS Alternating chemoreirradiation in recurrences of head- and -neck cancer result ed in 80 % overall response with acceptable toxicity . A significant minority of patients had durable tumor control with a chance of long-term survival PURPOSE Salvage options for unresectable locally recurrent , previously irradiated squamous cell carcinoma of the head and neck ( rSCCHN ) are limited . Although the addition of reirradiation may improve outcomes compared to chemotherapy alone , significant toxicities limit salvage reirradiation strategies , leading to suboptimal outcomes . We therefore design ed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy ( SBRT ) plus cetuximab for rSCCHN . METHODS AND MATERIAL S From July 2007 to March 2013 , 50 patients > 18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy , with a Zubrod performance status of 0 to 2 , and normal hepatic and renal function were enrolled . Patients received concurrent cetuximab ( 400 mg/m(2 ) on day -7 and then 250 mg/m(2 ) on days 0 and + 8) plus SBRT ( 40 - 44 Gy in 5 fractions on alternating days over 1 - 2 weeks ) . Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 grade d toxicity . RESULTS Median follow-up for surviving patients was 18 months ( range : 10 - 70 ) . The 1-year local PFS rate was 60 % ( 95 % confidence interval [ CI ] : 44%-75 % ) , locoregional PFS was 37 % ( 95 % CI : 23%-53 % ) , distant PFS was 71 % ( 95 % CI : 54%-85 % ) , and PFS was 33 % ( 95 % CI : 20%-49 % ) . The median overall survival was 10 months ( 95 % CI : 7 - 16 ) , with a 1-year overall survival of 40 % ( 95 % CI : 26%-54 % ) . At last follow-up , 69 % died of disease , 4 % died with disease , 15 % died without progression , 10 % were alive without progression , and 2 % were alive with progression . Acute and late grade 3 toxicity was observed in 6 % of patients respectively . CONCLUSIONS SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time BACKGROUND AND PURPOSE In this prospect i ve study , the effect of a second course of primary radiotherapy on locoregional control , survival and toxicity was investigated , in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma ( HNSCC ) in a previously irradiated area . PATIENTS AND METHODS A total of 34 patients with second primary ( n=26 ) or locoregional recurrent ( n=8 ) tumours were treated with a second course of high dose radiotherapy . Patients were selected for re-irradiation in case of inoperable and /or unresectable tumours . In most cases , the target volume for re-irradiation was confined to the gross tumour volume ( GTV ) . No elective radiotherapy was applied in the former high-dose area . A total dose of 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation . The median follow-up period was 32 months . RESULTS The locoregional control rate after 2 years was 27 % . The 3-year overall survival was 22 % . The most frequently reported acute side-effect was acute mucositis result ing in swallowing complaints . Pharyngeal and oesophageal late morbidity was also the most important late side-effect . In general , acute and late radiation-induced morbidity remained within acceptable limits . CONCLUSIONS In conclusion , primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity . To improve outcome in terms locoregional control and survival , future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy PURPOSE The purpose of this study was to review the outcome following concomitant chemoradiation therapy in previously irradiated patients with locally or regionally recurrent or persistent head and neck cancer considered unresectable for cure . METHODS AND MATERIAL S We identified 45 patients treated between 1986 and 1993 with unresectable locally or regionally recurrent disease who were treated on one of four concomitant chemoradiotherapy phase I/II studies at the University of Chicago . All patients received hydroxyurea ( HU ) , 5-fluorouracil ( 5-FU ) and concomitant radiation therapy on an alternate week schedule ( FHX ) . Cisplatin was added to FHX in three of the studies . RESULTS The overall survival , progression-free survival , and local/regional control at 5 years was 14.6 % , 13.5 % and 20 % , respectively , in a cohort of patients whose disease is almost universally fatal . Fatal treatment related complications were observed in 5 ( 11 % ) of patients . Two of these complications were related to radiation therapy . Stepwise Cox regression analysis revealed that dose and protocol were significantly correlated with survival , progression-free survival and local/regional control . A direct correlation was observed with radiation dose and an inverse correlation was observed with the initial FHX dose escalation study . The 2-year survival was 35 % in patients receiving over 58 Gy compared to 8 % for those receiving less than 58 Gy . CONCLUSIONS Our results show that aggressive re-irradiation with concomitant chemotherapy of recurrent head and neck cancer results in the cure of some patients with acceptable toxicity if tumoricidal doses are applied . These results are in contrast to historical series of chemotherapy alone which results in limited palliation of brief duration and almost no chance of cure . Thus , re-irradiation with concomitant chemotherapy should be further investigated as an alternative to chemotherapy alone in multi-center or cooperative group r and omized trials In this prospect i ve study , the effects of a second course of postoperative radiation therapy on locoregional control , survival , toxicity , and quality of life were investigated in patients who underwent resection of a second primary or locoregional recurrent head and neck tumor in a previously irradiated area PURPOSE To evaluate the safety and efficacy of stereotactic body radiotherapy ( SBRT ) in previously irradiated patients with squamous cell carcinoma of the head and neck ( SCCHN ) . PATIENTS AND METHODS In this Phase I dose-escalation clinical trial , 25 patients were treated in five dose tiers up to 44 Gy , administered in 5 fractions over a 2-week course . Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [(18)F]-fluorodeoxyglucose st  and ardized uptake value change on  positron emission tomography-computed tomography ( PET-CT ) . RESULTS No Grade 3/4 or dose-limiting toxicities occurred . Four patients had Grade 1/2 acute toxicities . Four objective responses were observed , for a response rate of 17 % ( 95 % confidence interval 2%-33 % ) . The maximum duration of response was 4 months . Twelve patients had stable disease . Median time to disease progression was 4 months , and median overall survival was 6 months . Self-reported quality of life was not significantly affected by treatment . Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes . CONCLUSION Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies PURPOSE The Southwest Oncology Group ( SWOG ) conducted a r and omized comparison of cisplatin plus fluorouracil ( 5-FU ) and carboplatin plus 5-FU versus single-agent methotrexate ( MTX ) in patients with recurrent and metastatic squamous-cell carcinoma ( SCC ) of the head and neck . The primary objective was to compare separately the response rates of each combination regimen to st and ard weekly MTX . PATIENTS AND METHODS Two hundred seventy-seven patients diagnosed with SCC of the head and neck were r and omized to one of three treatments : ( 1 ) cisplatin 100 mg/m2 intravenously ( IV ) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days ; ( 2 ) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days ; and ( 3 ) MTX 40 mg/m2 IV given weekly . RESULTS All three treatment regimens were well tolerated . However , both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX ( P = .001 ) . Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens . The complete and partial response rates were 32 % for cisplatin plus 5-FU , 21 % for carboplatin plus 5-FU , and 10 % for MTX . The comparison of cisplatin plus 5-FU to MTX was statistically significant ( P less than .001 ) , and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance ( P = .05 ) . Median response duration s and median survival times were similar for all three treatment groups . Logistic regression models showed that only treatment assigned was associated significantly with response ( P = .001 ) . Cox proportional hazards models indicated that only performance status was associated significantly with survival ( P less than .01 ) . CONCLUSIONS We conclude that combination chemotherapy result ed in improved response rates but was associated with an increased toxicity and no improvement in overall survival . Therefore , new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified BACKGROUND The management of recurrent unresectable head and neck cancer remains a challenging problem . Based on the circadian rhythm concept , we sought to determine the maximum tolerated dose ( MTD ) of infusional 5-flourouracil ( 5-FU ) , hydroxyurea ( HU ) , and reirradiation ( RT ) . METHOD Bolus 5-FU was escalated from 300 mg/m(2)/d to a 10-hour infusion beginning at midnight , increased at 150 mg/m(2)/d increments . HU , 1.5 g , remained constant . Chemotherapy was given on weeks 1 and 4 . RT was given daily , 2.0 Gy per fraction on weeks 1 and 2 followed by a 1-week break , then hyperfractionated weeks 4 and 5 , total dose 50 Gy . The goal was to deliver a continuous course of RT to 60 Gy after the MTD was determined with an additional week of chemotherapy . RESULTS Six cohorts were treated to establish the 5-FU MTD of 900 mg/m(2)/d . The seventh cohort received continuous RT and 5-FU , 750 mg/m(2)/d , one dose level below the MTD . Two hematologic , three skin , and six mucosal > or= grade 3 toxicities were noted in 7 of 16 patients . The median survival was 10.2 months and the 1-year survival was 41 % . The median survival for the entire group was 9.4 months , with a 1- and 2-year survival of 39 % and 15 % , respectively . CONCLUSION RT can be given in a continuous fashion with concurrent 5-FU and HU . Because radiation sensitization should be achievable at nontoxic doses of 5-FU , we recommend 600 mg/m(2)/d in phase a II setting PURPOSE Salvage surgery alone after radiotherapy ( RT ) failure for locally advanced head- and -neck cancer is frequently unsuccessful because of subsequent recurrence . We design ed a prospect i ve protocol to determine the feasibility , toxicity , and preliminary efficacy of a regimen of postoperative reirradiation , chemotherapy and the radioprotector amifostine after salvage head- and -neck surgery . METHODS AND MATERIAL S Eligible patients had biopsy-proven locally advanced , but resectable , recurrence without distant metastases > 6 months after previous RT . After adequate healing from surgery , patients underwent RT to 54 - 66 Gy within 5 - 5.5 weeks to the resection bed ( lifetime RT dose , 100 - 130 Gy ) . The fractionation was 1.5 Gy b.i.d . within 2 weeks , followed by a 1-week break , followed by 1.5 Gy b.i.d . to a total of 54 - 66 Gy . Chemotherapy consisted of cisplatin 25 mg/m(2)/d three times and 5-fluorouracil 500 mg/m(2)/d continuous infusion for 4 days , for two cycles ( Weeks 1 and 5 ) . Amifostine ( 500 mg i.v . ) was administered daily , 30 min before either the morning or the afternoon RT . RESULTS Between 1998 and 2001 , 16 patients were enrolled and studied . Two patients had gross residual disease after surgery ; all other patients underwent complete surgical resection but had high-risk features ( rT3-T4 and /or N+ disease ) . Three patients ( 19 % ) had serious acute toxicity events ( nonneutropenic infections ) that were reversible . The median follow-up was 35 months . The actuarial locoregional control rate was 81 % at 3 years . Three patients developed isolated distant metastases and one developed a fatal second primary cancer ( hepatoma ) . The 2- and 3-year actuarial event-free survival rate was 81 % and 50 % , respectively . The 2- and 3-year actuarial overall survival rate was 81 % and 63 % , respectively . Both patients who had gross residual disease after surgery had early recurrence ; if these patients were excluded from analysis , the 3-year actuarial survival and event-free survival rate was 67 % and 59 % , respectively . Of the 16 patients , 6 ( 38 % ) developed Grade 3 + late toxicity , including one fatal stroke and two life-threatening major vessel necrosis and /or bleeding events . CONCLUSION This regimen of postoperative reirradiation/chemotherapy plus amifostine is feasible and was well tolerated acutely , with encouraging oncologic efficacy . However , the incidence and severity of late effects was significant and suggests that modifications are necessary for future studies in this patient population PURPOSE To determine the response rate , survival and toxicity of infusional cisplatin plus fluorouracil ( CF ) versus cisplatin plus paclitaxel ( CP ) in patients with incurable squamous cell cancer of the head and neck , with the hypothesis that CP is superior . PATIENTS AND METHODS Two hundred eighteen patients with locally advanced , recurrent , or metastatic disease were r and omly assigned to CF ( cisplatin 100 mg/m2 day 1 and fluorouracil 1,000 mg/m2/24 hours by continuous intravenous infusion day 1 through 4 ) or CP ( cisplatin 75 mg/m2 day 1 and paclitaxel 175 mg/m2 over 3 hours on day 1 ) . Cycles were repeated every 3 weeks until progression or a minimum of 6 cycles with complete response or stable disease . The primary outcome was overall survival . Secondary outcomes included response rate and toxicity . RESULTS No significant difference in overall survival or response rate was seen . Estimated median survival was 8.7 months in the CF group and 8.1 month in the CP group . Objective response rate ( complete response plus partial response ) was 27 % in the CF group and 26 % in the CP group . Toxicity was similar between groups , with the most frequent including myelosuppression , thrombocytopenia , anemia , nausea , vomiting , and stomatitis . A total of 12 deaths occurred ( CF , seven ; CP , five ) during treatment ; eight from infection , two from hemorrhage , one from cardiac causes and one from unknown causes . Gastrointestinal and hematologic toxicities were more common in the CF group , whereas neurotoxicity was equivalent between groups . CONCLUSION This phase III , r and omized , multicenter trial showed no difference in survival between patients treated with CF or CP BACKGROUND Despite the use of resection and postoperative radiotherapy , high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed . We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control . METHODS Between September 9 , 1995 , and April 28 , 2000 , 459 patients were enrolled . After undergoing total resection of all visible and palpable disease , 231 patients were r and omly assigned to receive radiotherapy alone  ( 60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks ) and 228 patients to receive the identical treatment plus concurrent cisplatin ( 100 mg per square meter of body-surface area intravenously on days 1 , 22 , and 43 ) . RESULTS After a median follow-up of 45.9 months , the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone ( hazard ratio for local or regional recurrence , 0.61 ; 95 percent confidence interval , 0.41 to 0.91 ; P=0.01 ) . The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group , as compared with 72 percent in the radiotherapy group . Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group ( hazard ratio for disease or death , 0.78 ; 95 percent confidence interval , 0.61 to 0.99 ; P=0.04 ) , but overall survival was not ( hazard ratio for death , 0.84 ; 95 percent confidence interval , 0.65 to 1.09 ; P=0.19 ) . The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group ( P<0.001 ) . Four patients who received combined therapy died as a direct result of the treatment . CONCLUSIONS Among high-risk patients with resected head and neck cancer , concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival . However , the combined treatment is associated with a substantial increase in adverse effects BACKGROUND Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck . We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . METHODS We r and omly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin ( at a dose of 100 mg per square meter of body-surface area on day 1 ) or carboplatin ( at an area under the curve of 5 mg per milliliter per minute , as a 1-hour intravenous infusion on day 1 ) plus fluorouracil ( at a dose of 1000 mg per square meter per day for 4 days ) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab ( at a dose of 400 mg per square meter initially , as a 2-hour intravenous infusion , then 250 mg per square meter , as a 1-hour intravenous infusion per week ) for a maximum of 6 cycles . Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects , whichever occurred first . RESULTS Adding cetuximab to platinum-based chemotherapy with fluorouracil ( platinum-fluorouracil ) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab ( hazard ratio for death , 0.80 ; 95 % confidence interval , 0.64 to 0.99 ; P=0.04 ) . The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months ( hazard ratio for progression , 0.54 ; P<0.001 ) and increased the response rate from 20 % to 36 % ( P<0.001 ) . The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia ( 19 % and 13 % , respectively ) , neutropenia ( 23 % and 22 % ) , and thrombocytopenia ( 11 % in both groups ) . Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group ( P=0.02 ) . Of 219 patients receiving cetuximab , 9 % had grade 3 skin reactions and 3 % had grade 3 or 4 infusion-related reactions . There were no cetuximab-related deaths . CONCLUSIONS As compared with platinum-based chemotherapy plus fluorouracil alone , cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00122460 . PURPOSE This r and omized phase III trial investigated the potential benefit of concurrent re-irradiation , fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma ( HNSCC ) in previously irradiated area . PATIENTS AND METHODS Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were r and omized to the R-RT arm ( concurrent re-irradiation , fluorouracil and hydroxyurea ) or to the Ch-T arm ( methotrexate ) . The primary endpoint was overall survival ( OS ) . Due to a very slow accrual , the trial was closed after inclusion of 57 patients . RESULTS Fifty-seven patients were included . All patients died in the two arms with a maximal follow-up of 5years . Although four complete responses were achieved in R-RT arm , ( none in Ch-T arm ) re-irradiation did not improve OS  compared with methotrexate ( 23 % versus 22 % at 1year , NS ) . Sixteen patients experienced clinical grade ⩾3 late toxicities ( > 6months ) , 11 in R-RT arm and five in Ch-T arm . CONCLUSIONS Premature discontinuation of the trial did not allow us to draw firm conclusions . However , there was no suggestion that concurrent re-irradiation , fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC PURPOSE To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma ( HNC ) . PATIENTS AND METHODS Between January 1980 and December 1996 , 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series . The median time between the first and the second irradiation was 33 months . Reirradiation protocol s were as follows : radiotherapy alone ( 65 Gy over 6.5 weeks at 2 Gy/d ) , 27 patients ; Vokes protocol , ie , five to six cycles of radiotherapy ( median total dose , 60 Gy ; 2 Gy/d ) with simultaneous fluorouracil ( 5-FU ) and hydroxyurea , 106 patients ; and bifractionated radiotherapy ( median total dose , 60 Gy ; 2 x 1.5 Gy/d ) with concomitant mitomycin , 5-FU , and cisplatin , 36 patients . The median cumulative dose of the two irradiations was 120 Gy . Eighty-five percent of the tumors were squamous cell carcinoma , 14 % undifferentiated carcinoma of nasopharyngeal type , and 1 % adenocarcinoma . Forty-four percent were local recurrences , 23 % nodal recurrences , 14 % both local and nodal , and 19 % second primary tumors . RESULTS Mucositis grade 3 ( World Health Organization [ WHO ] ) was found in 32 % and grade 4 in 14 % of cases . Four patients presented with neutropenia or thrombocytopenia ( grade 3 or 4 WHO ) . Late toxicities ( > 6 months ) were as follows : cervical fibrosis ( grade 2 to 3 Radiation Therapy Oncology Group [ RTOG ] ) , 41 % ; mucosal necrosis , 21 % ; osteoradionecrosis , 8 % ; and trismus , 30 % . Five patients died of carotid hemorrhage , apparently in complete remission . Six months after the onset of reirradiation , 37 % of patients were in complete response . Patterns of failure were local only ( 53 % ) , nodal only ( 20 % ) , metastatic only ( 7 % ) , and multiple ( 20 % ) . Median follow-up time was 70 months . Overall survival rate ( Kaplan-Meier ) was 21 % ( 95 % confidence interval [ CI ] , 15 % to 29 % ) at 2 years and 9 % ( 95 % CI , 5 % to 16 % ) at 5 years . Median survival time was 10 months for the entire population . Thirteen patients , of whom 12 were treated with the Vokes protocol , were long-term disease-free survivors . In a multivariate analysis , the volume of the second irradiation was the only factor significantly associated with the risk of death : relative risk=1.8 ( 95 % CI , 1.13 to 5.7 ) ( P=.01 ) . CONCLUSION Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC . The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation . Median survival was better than that generally obtained using palliative chemotherapy alone . A small proportion of patients were long-term disease-free survivors PURPOSE To present a retrospective review of treatment outcomes for recurrent head and neck ( HN ) cancer patients treated with re-irradiation ( re-RT ) at a single medical center . METHODS AND MATERIAL S From July 1996-September 2005 , 105 patients with recurrent HN cancer underwent re-RT at our institution . Sites included were : the neck ( n = 21 ) , nasopharynx ( n = 21 ) , paranasal sinus ( n = 18 ) , oropharynx ( n = 16 ) , oral cavity ( n = 9 ) , larynx ( n = 10 ) , parotid ( n = 6 ) , and hypopharynx ( n = 4 ) . The median prior RT dose was 62 Gy . Seventy-five patients received chemotherapy with their re-RT ( platinum-based in the majority of cases ) . The median re-RT dose was 59.4 Gy . In 74 ( 70 % ) , re-RT utilized intensity-modulated radiation therapy ( IMRT ) . RESULTS With a median follow-up of 35 months , 18 patients were alive with no evidence of disease . The 2-year loco-regional progression-free survival ( LRPFS ) and overall survival rates were 42 % and 37 % , respectively . Patients who underwent IMRT , compared to those who did not , had a better 2-year LRPF ( 52 % vs. 20 % , p < 0.001 ) . On multivariate analysis , non-nasopharynx and non-IMRT were associated with an increased risk of loco-regional ( LR ) failure . Patients with LR progression-free disease had better 2-year overall survival vs. those with LR failure ( 56 % vs. 21 % , p < 0.001 ) . Acute and late Grade 3 - 4 toxicities were reported in 23 % and 15 % of patients . Severe Grade 3 - 4 late complications were observed in 12 patients , with a median time to development of 6 months after re-RT . CONCLUSIONS Based on our data , achieving LR control is crucial for improved overall survival in this patient population . The use of IMRT predicted better LR tumor control . Future aggressive efforts in maximizing tumor control in the recurrent setting , including dose escalation with IMRT and improved chemotherapy , are warranted OBJECTIVE To evaluate the incidence of morbidity , mortality , and disease control for patients requiring salvage total laryngectomy ( TL ) following organ preservation therapy .  DESIGN Patients entered into a 3-arm r and omized prospect i ve multi-institutional trial for laryngeal preservation who required TL following initial treatment . SETTING The Radiation Therapy Oncology Group 91 - 11 trial for laryngeal preservation . PATIENTS From 1992 to 2000 , 517 evaluable patients were r and omized to receive chemotherapy followed by radiation therapy ( arm 1 ) , concomitant chemotherapy and radiation therapy ( arm 2 ) , or radiation therapy alone ( arm 3 ) . RESULTS Overall , TL was required in 129 patients . The incidence was 28 % , 16 % , and 31 % in arms 1 , 2 , and 3 , respectively ( P = .002 ) . Of these , 7 patients ( 5 % ) required TL for aspiration or necrosis . Following TL , the incidence of major and minor complications ranged from 52 % to 59 % and did not differ significantly among the 3 arms . Pharyngocutaneous fistula was lowest in arm 3 ( 15 % ) and highest in arm 2 ( 30 % ) ( P>.05 ) . There was 1 perioperative death . Local-regional control following salvage TL was 74 % for arms 1 and 2 and 90 % for arm 3 . At 24 months , the overall survival was 69 % ( arm 1 ) , 71 % ( arm 2 ) , and 76 % ( arm 3 ) ( P>.73 ) . CONCLUSIONS Laryngectomy following organ preservation treatment is associated with acceptable morbidity . Perioperative mortality is low but up to one third of patients will develop a pharyngocutaneous fistula . Local-regional control is excellent for this group of patients . Survival following salvage TL was not influenced by the initial organ preservation treatment PURPOSE To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck . METHODS AND MATERIAL S Twenty-one consecutive patients were prospect ively treated with intensity-modulated radiotherapy  from February 2006 to March 2009 to a median dose of 66 Gy ( range , 60 - 70 Gy ) . None of these patients received concurrent chemotherapy . Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment . RESULTS The 1- and 2-year estimates of in-field control were 72 % and 65 % , respectively . A total of 651 daily megavoltage CT scans were obtained . The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm , 1.79 ± 1.45 mm , and 1.98 ± 1.75 mm for the medial-lateral , superior-inferior , and anterior-posterior directions , respectively . Pretreatment shifts of > 3 mm occurred in 19 % of setups in the medial-lateral , 27 % in the superior-inferior , and 33 % in the anterior-posterior directions , respectively . There were no treatment-related fatalities or hospitalizations . Complications included skin desquamation , odynophagia , otitis externa , keratitis , naso-lacrimal duct stenosis , and brachial plexopathy .  CONCLUSIONS Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck PURPOSE Full-dose reirradiation combined with chemotherapy has been shown to be feasible after salvage surgery with acceptable toxicity . The Groupe d'Etude des Tumeurs de la Tête et du Cou and Groupe d'Oncologie Radiothérapie Tête Et Cou groups performed a r and omized study to assess its efficacy . PATIENTS AND METHODS Between 1999 and 2005 , 130 patients with head and neck cancer were treated with salvage surgery and r and omly assigned to full-dose reirradiation combined with chemotherapy ( RT arm ) or to observation ( a " wait and see " approach ; WS arm ) . Eligibility criteria were recurrence or a second primary tumor in a previously irradiated area , no major sequelae result ing from the first radiotherapy , good general condition , no distant metastasis , and salvage surgery with macroscopic complete resection . Patients in the RT arm received 60 Gy over 11 weeks combined with concomitant fluorouracil and hydroxyurea . RESULTS Sixty-five patients were r and omly assigned to each arm . There was no imbalance in the distribution of the main tumor and patients characteristics . The most serious acute toxicity in the RT arm was mucositis , attaining grade 3 or 4 in 28 % of patients . At 2 years , 39 % of patients in the RT arm and 10 % in the WS arm experienced grade 3 or 4 late toxicity according to Radiation Therapy Oncology Group criteria ( P = .06 ) . Disease-free survival ( DFS ) was significantly improved in the RT arm , with a hazard ratio of 1.68 ( 95 % CI , 1.13 to 2.50 ; P = .01 ) , but overall survival ( OS ) was not statistically different . CONCLUSION Full-dose reirradiation combined with chemotherapy after salvage surgery significantly improved DFS , but had no significant impact on OS . An increase in both acute and late toxicity was observed PURPOSE Recurrent head and neck cancer is associated to a poor survival prognosis . A high toxicity rate is demonstrated when surgery and /or radiotherapy and /or chemotherapy are combined . Furthermore , the duration of treatment is often not ethically compatible with the expected survival ( median survival<1year ) . Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy ( SBRT ) could offer precise irradiation while sparing healthy tissues . After completion of a feasibility study , results of a multicentric study ( Lille , Nancy & Nice ) using SBRT with cetuximab are reported . The aim of the study was to deliver non toxic short course SBRT ( 2weeks ) in order to get the same local control as the one demonstrated with longer protocol s. METHODS AND MATERIAL S Patients with inoperable recurrent , or new primary tumor in a previously irradiated area , were included ( WHO<3 ) .  Reirradiation ( RT ) dose was 36Gy in six fractions of 6Gy to the 85 % isodose line covering 95 % of the PTV with 5 injections of concomitant cetuximab ( CT ) .  All patients had previous radiotherapy , 85 % had previous surgery and 48 % previous chemotherapy .  RESULTS Between 11/2007 and 08/2010 , 60 were included ( 46 men and 14 women ) , 56 received CT+RT , 3 were not treated and 1 received only CT . Median age was 60 ( 42 - 87 ) ) and all 56 patients had squamous carcinoma and received concomitant cetuximab .  Mean time between previous radiotherapy and the start of SBRT was 38months . Cutaneous toxicity was observed for 41 patients . There was one toxic death from hemorrhage and denutrition . Median follow-up was 11.4months . At 3months , response rate was 58.4 % ( 95 % CI : 43.2 - 72.4 % ) and disease control rate was 91.7 % ( 95 % CI : 80.0 - 97.7 % ) . The one-year OS rate was 47.5 % ( 95 % CI : 30.8 - 62.4 ) . CONCLUSION These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC . Treatment is feasible and , with appropriate care to limiting critical structure , acute toxicities are acceptable . This combination may be the reference treatment is this population PURPOSE We previously demonstrated the efficacy of concurrent gemcitabine , paclitaxel , and 5-fluorouracil in conjunction with twice-daily ( 1.5-Gy ) radiotherapy delivered on alternating weeks ( TFGX(2 ) ) in locally advanced head- and -neck cancer . Here , we report the clinical outcome and late toxicity of TFGX(2 ) in a subset of patients previously irradiated to the head and neck . METHODS AND MATERIAL S Twenty-nine previously irradiated patients , presenting with recurrent or second primary head- and -neck cancer , underwent TFGX(2 ) . Twelve patients underwent attempted surgical resection before chemoradiotherapy , 10 of whom were left with no measurable disease . Patients with measurable disease received a median radiation dose of 72 Gy ; those with no measurable disease received a median dose of 61 Gy . The cumulative dose ranged from 74.4 to 156.4 Gy ( mean , 125.7 Gy ; median , 131.0 Gy ) . RESULTS The median follow-up was 19.1 months ( 50.9 months for living patients ) . The 5-year overall survival rate was 34.5 % , and the locoregional control rate was 54.5 % . In patients with measurable disease at treatment , the 5-year overall survival and locoregional control rate was 26.3 % and 45.1 % , respectively , compared with 50.0 % ( p = 0.14 ) and 70 % ( p = 0.31 ) , respectively , for those with no measurable disease . Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis . Of 14 patients assessable for late toxicity , 3 developed Grade 4 - 5 , 8 Grade 2 - 3 , and 3 Grade 0 - 1 toxicity . CONCLUSION Aggressive reirradiation with chemotherapy in locally advanced head- and -neck cancer provides a chance for long-term cure at the expense of toxicity . Attempted surgical resection before chemoradiotherapy improved disease control and survival
PURPOSE To specify the effectiveness of head and neck cancer reirradiation  and make a synthesis of prognostic factors established by published series of patients .