Accelerated Fractionation Radiotherapy Research Articles

A comparative study of the treatment outcome of moderately accelerated radiation fractionation (with concurrent chemotherapy in daily dosing) to conventional chemo-radiotherapy in locally advanced head and neck cancers: Supportive in a resource constrained environment

Background: In our country, head and neck cancers account for about a third of all cancers. Moreover, the patients typically present in advanced stages, which entails intensive multimodality therapy; but there is not much scope for improved survival outcomes. In view of this, a study was conducted to know the effects of treatment intensification, wherein moderately accelerated fractionation radiotherapy was given to patients presenting with advanced cancer of head and neck. This treatment was further intensified by accompanying radiation with concurrent cisplatin chemotherapy in daily doses. The control arm received the current standard therapy of conventional fractionation radiotherapy with weekly cisplatin chemotherapy. Methods: The primary objective of the study was to determine the prospect of tumor control (TC), disease-free survival (DFS), and overall survival (OS). The secondary objective was to study acute toxicity and late toxicity of the highest grade in both treatment groups. The study was conducted on a total of 60 patients who presented with locally advanced squamous cell carcinoma of the head and neck. The 30 patients in the control group received conventional fractionated radiotherapy (five fractions per week) with weekly cisplatin chemotherapy (40 mg/m2), whereas the remaining 30 in the study group received moderately accelerated radiotherapy (six fractions per week with same treatment field) along with daily cisplatin chemotherapy (6 mg/m2) with a reduction in treatment time by 1 week. Results: The overall response to therapy assessed as TC, DFS, and OS was compared, and no statistically significant difference between the two treatment arms was observed. However, the mean overall treatment time was reduced in the study group to 45 days as compared with 49 days in the control group (P = 0.001). The acute toxicities of xerostomia (P = 0.057) and skin (P = 0.052) and late toxicity of aspiration/laryngeal toxicity (P = 0.002) were higher in grade and number in the study group with accelerated fractionation. Conclusions: Hence, the study results suggest that it is a feasible option to combine the therapeutic benefits of accelerated fractionation radiotherapy with concurrent chemotherapy in patients with locally advanced head and neck carcinomas. There is a significant decrease in the overall treatment time and a considerable reduction in the load on the resource-constrained healthcare system. It would be equitable to point out that higher grade of few toxicities in the acceleration arm are likely due to doses to organs at risk being intensified with accelerated fractionation, which can now be delivered in a controlled manner with the latest high precision techniques, resulting in improved toxicity profile and quality of life which is the way forward for future studies.

A comparative and prospective study of two different radiation fractionation schedules with concurrent chemotherapy in locally advanced head-and-neck squamous cell carcinoma

Background: Accelerated fractionation radiotherapy has radiobiological advantage of preventing accelerated tumor repopulation and logistic advantage of treating more patients than conventionally fractionated radiotherapy because of its relatively shorter treatment duration. Aims and Objectives: In this study, we compared accelerated fractionation with conventionally fractionated radiotherapy in terms of tumor response and acute toxicities for the treatment of locally advanced head-and-neck carcinomas. Materials and Methods: Patients with Stage III and IVA carcinoma of head-and-neck region were randomized into two groups. The study group patients received accelerated radiotherapy to a total dose of 66Gy in 33 fractions, 2Gy/fraction, 6 fractions/week over a time period of 5.5 weeks. Control group received conventionally fractionated radiotherapy to same total dose and fraction size but 5 fractions/week, over a time period of 6.5 weeks. Both groups received concurrent weekly Cisplatin. All patients were followed up weekly for treatment related acute toxicity during the treatment and then at every month for 6 months after completion of treatment. Results: About 26.6% patients of study arm achieved complete response in comparison to 25.6% of control arm, but the difference was not statistically significant (P=0.957). Although statistically not significant, higher grade of skin toxicity (60%vs.35%, P=0.179) and xerostomia (46% vs. 29%, P=0.155) was also numerically higher in accelerated fractionation. Conclusion: For locally advanced head-and-neck carcinoma, accelerated fractionation radiotherapy with concurrent chemotherapy can be considered as an acceptable and effective alternative of conventionally fractionated concurrent chemoradiotherapy in terms of treatment response and acute toxicity profile.

Accelerated Fractionation Radiotherapy and Chemotherapy Might Improve Loco-Regional Control of Head and Neck Squamous Cell Carcinoma

Accelerated Fractionation Radiotherapy and Chemotherapy Might Improve Loco-Regional Control of Head and Neck Squamous Cell Carcinoma

Применение лучевой терапии в комбинированном лечении сарком мягких тканей конечностей с поражением длинных трубчатых костей

Soft tissue sarcomas (STS) are rare malignant tumors of mesenchymal origin. They account for about 1% of all malignant neoplasms. Haematogenous spread is the most common route of me-tastasis for STS and bone metastases occur in 9.4% of cases. When creating treatment plan for STS, it is necessary to consider a multimodal approach. Combination treatment can include pre-operative or postoperative radiation therapy (RT), chemotherapy (CT), and local hyperthermia (LHT). Surgery for STS should be radical. This paper presents 9 STS clinical cases and treatment outcomes in patients with secondary bone disease. Four patients underwent chemotherapy and surgery. Two patients received chemoradiotherapy (CRT) and surgery. Three patients received thermo-chemo-radiotherapy (TCHRT) followed by surgery. Accelerated fractionation radiotherapy was given using a single tumor dose of 3 Gy, twice a day with interval of 4 hours between ses-sions, 3 times a week to a total tumor dose (TTD) of 30 Gy (isoeffective TTD – 42 Gy, TDF – 69 Gy). Local hyperthermia for soft tissue tumor treatment was performed over 6 sessions: 2 ses-sions were combined with CHT courses before and after RT, and 4 sessions were combined with RT. The follow up period for 6 patients varied from 12 to 1.5 months, for 3 patients it varied from 6 to 8 months, for 1 patient it lasted 3 months and for 1 patient – 2 years. According to the RECIST criteria, more than half of the patients had tumor stabilization and 22% of patients had a partial response. Grade III-IV the rapeutic pathomorphosis was observed in 70% of patients after pre-operative combination treatment. The use of CT, CRT or TCHRT in combination treatment of STS with secondary bone disease enabled us to achieve a pronounced therapeutic pathomorphosis of tumors and to perform organ preservation surgery with endoprosthetic replacement.

Comparison of Conventional Radiotherapy with Accelerated Fractionation Radiotherapy in Squamous Cell Head and Neck Cancers – A Prospective Study

Comparison of Conventional Radiotherapy with Accelerated Fractionation Radiotherapy in Squamous Cell Head and Neck Cancers – A Prospective Study

A Prospective Randomised Study of Comparison between Conventional and Accelerated Fractionation Radiotherapy in Treatment of Head and Neck Cancers

A Prospective Randomised Study of Comparison between Conventional and Accelerated Fractionation Radiotherapy in Treatment of Head and Neck Cancers

Altered fractionation radiotherapy with or without chemotherapy in the treatment of head and neck cancer: a network meta-analysis.

ObjectivesA Bayesian network meta-analysis (NMA) was conducted in patients with head and neck cancers (HNCs) to estimate the efficacy and safety of treatment with conventional fractionation radiotherapy (CF), conventional fractionation chemoradiotherapy (CF_CRT), hyperfractionated radiotherapy (HF), hyperfractionated chemoradiotherapy (HF_CRT), accelerated fractionation radiotherapy, accelerated fractionation chemoradiotherapy, accelerated hyperfractionated radiotherapy (HART) or accelerated hyperfractionated chemoradiotherapy (HACRT) to identify superior treatments to aid in clinical decisions.MethodsPubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for potentially eligible randomized controlled trials up to December 2016. Overall survival (OS), disease-free survival (DFS) and locoregional control (LRC) were considered efficacy outcomes, whereas acute toxicity and late toxicity on skin and mucosa were considered safety outcomes. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment in each index.ResultsData from 72 trials with 21,868 participants were included in the analysis. Concerning OS, all treatments were associated with a significant advantage compared to CF alone, with HR effect sizes ranging from 0.64 to 0.83, and HACRT was significantly more effective than all the other treatments. The network comparisons of both HACRT vs HART and HF_CRT vs HF demonstrated a higher OS benefit, with an HR of 0.78 (95% credible interval [CrI]: 0.64–0.95) and 0.78 (95% CrI: 0.61–0.99), respectively. The results of SUCRA indicated that HACRT had the best ranking for OS and LRC, HF_CRT for DFS, HART for acute and late skin toxicity, CF_CRT for acute mucosal toxicity and HF_CRT for late mucosal toxicity.ConclusionThe NMA results support the notion that HACRT is the preferable treatment modality for HNCs because it has better rankings in all three efficacy indexes, although it does present a high risk of acute mucosal toxicity.

Accelerated Fractionation Radiotherapy in Treating Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

Accelerated Fractionation Radiotherapy in Treating Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma

The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab. A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011. Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B). Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety. Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25). With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies. clinicaltrials.gov Identifier: NCT00820248.

Accelerated Fractionation Radiotherapy in Head and Neck Cancer: A Boon to Centers with High Patient-Resource Ratio

Accelerated Fractionation Radiotherapy in Head and Neck Cancer: A Boon to Centers with High Patient-Resource Ratio

Cervical osteoradionecrosis following accelerated fractionation radiation therapy for laryngeal cancer

Osteoradionecrosis is a serious complication that may occur following radiation therapy, particularly head and neck–directed radiation therapy. A very limited number of cases of cervical-spine osteoradionecrosis have been reported1-6 and only 2 involve altered fractionation radiation therapy.6 We present a patient with extensive osteoradionecrosis 9 years after receiving accelerated fractionation radiation therapy with concurrent chemotherapy.

Phase III randomized trial of standard fractionation radiotherapy (SFX) with concurrent cisplatin (CIS) versus accelerated fractionation radiotherapy (AFX) with panitumumab (PMab) in patients (pts) with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): NCIC Clinical Trials Group HN.6 trial.

6000 Background: Concurrent administration of anti-EGFR monoclonal antibody with radiotherapy (RT) increases survival compared to RT alone in pts with LA-SCCHN. No prospective data are available co...

Quality of life (QOL) in a phase III randomized trial of standard fractionation radiotherapy (SFX) with concurrent cisplatin (CIS) versus accelerated fractionation radiotherapy (AFX) with panitumumab (PMab) in patients (pts) with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): NCIC Clinical Trials Group HN.6 (NCT00820248).

6053 Background: Addition of concurrent anti-EGFR monoclonal antibody to radiotherapy alone did not worsen QOL (Curran 2007). We compared standard chemoradiotherapy (cRT) to bioradiotherapy (bRT). ...

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

We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. Amgen.

Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.

Accelerated radiotherapy for T1 to T2 glottic cancer

Accelerated fractionation radiotherapy (RT) was administered in an attempt to improve the local control rates in patients with T1/T2 N0 glottic cancer. Medical charts of 148 consecutive patients who had undergone RT using 2.4 Gray (Gy) once-daily fractionation between July 1999 and April 2007 were reviewed. Of 104 patients with T1 disease treated by RT, 82 received 60 Gy/25 fractions, and the remaining 22 with large tumor volumes and/or slow response to RT received 64.8 Gy/27 fractions. All 44 patients with T2 disease received 64.8 Gy/27 fractions. The 5-year local control and overall survival (OS) rates were 93% and 96%, respectively, in patients with T1 disease, and 77% and 91%, respectively, in patients with T2 disease. No severe acute toxicities were observed, although 2 patients (1%) developed severe late toxicity. Accelerated RT for early glottic cancer is feasible, with encouraging local control rates.

Risk factors for clinician‐reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129

Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters. Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters. Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy. Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies.

1016O - Phase 2, Randomized Trial (CONCERT-2) of Panitumumab (PMAB) Plus Radiotherapy (PRT) Compared with Chemoradiotherapy (CRT) in Patients (PTS) with Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LASCCHN)

ABSTRACT Background We evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, by comparing PRT with CRT in pts with LASCCHN. Methods Pts with stage III, IVA, or IVB previously untreated LASCCHN of all sites excluding the nasopharynx were randomized 2:3 to open-label CRT or PRT. CRT included 2 cycles of cisplatin 100 mg/m2 during accelerated fractionation radiotherapy (XRT; 70-72 Gy over 6-6.5 weeks). Pmab included 3 cycles at a dose of 9.0 mg/kg with each cycle administered with XRT. This was an estimation study with no formal hypothesis testing. The primary endpoint was locoregional control (LRC) rate at 2 years; key secondary endpoints were progression free survival (PFS), overall survival (OS), and safety. Preplanned HPV subset analysis (determined by p16 immunohistochemistry) was performed on available samples. Results Of 151 treated pts (90 PRT, 61 CRT), 84% were men; median age was 58 years; ECOG PS 0: 64%. Overall, the 2-year LRC rate (95% CI) was 51% (40%-62%) for PRT and 61% (47%-72%) for CRT. For both PFS (hazard ratio [HR] = 1.73 [95% CI: 1.07-2.81]; p = 0.03) and OS (HR = 1.59 [95% Cl: 0.91-2.79]; p = 0.10), outcomes favored the CRT arm. Of 99 pts with tumors evaluable for HPV, 24% were HPV+. In 75 HPV- tumors, a difference was observed in PFS (HR = 2.04 [95% Cl: 1.05-3.96]; p = 0.04), with trends also favoring CRT in LRC and OS. Overall, dose intensity was high for all components of therapy in both arms (median relative dose intensity: 100% for pmab and 99% for cisplatin, median XRT dose: 100% in both arms). Grade 3+ adverse events (AEs) occurred in 85% PRT vs 81% CRT pts. Key differences in grade 3+ toxicity between arms (PRT, CRT) included skin disorders (which is a composite of skin-related AEs) (35%, 3%), neutropenia (0%, 13%), and febrile neutropenia (0%, 8%). Conclusions Trends favored the CRT arm for the primary endpoint (LRC at 2 years), as well as other measures of efficacy, in this predominantly HPV- LASCCHN population. Small numbers limit conclusions in the HPV+ group. Both PRT and CRT appeared well tolerated. Disclosure G. Hatoum: Advisory Board Member for Amgen K. Oliner: Amgen stock A. Vanderwalde: Corporate-sponsored research (Amgen), full-time employee of Amgen All other authors have declared no conflicts of interest.

The influence of institutional head and neck cancer (HNC) clinical trial accrual on overall survival (OS): An analysis of RTOG 0129.

5530 Background: NCCN recommends HNC patients (pts) be treated by providers with experience in HNC management. Whether treatment by experienced providers (measured by no. of pts treated) is associated with HNC survival outcome is unknown. Methods: Analysis included 471 pts in RTOG 0129 with stage III-IVa HNC with known tumor HPV and smoking status randomized to cisplatin concurrent with standard or accelerated fractionation radiotherapy (RT). Participating centers were stratified into pt accrual tertiles (ATs) to 21 RTOG HNC trials from 1997-2002. As a surrogate for experience, we investigated the independent effect of AT on OS and progression-free survival (PFS) in multivariable cox proportional hazards models. Results: Median follow up was 4.8 yrs (range 1.1 - 6.5). In Kaplan-Meier analysis, OS and PFS for pts at centers in the two lower AT (low accruing centers [LAC]) were similar and compared to the upper AT (high accruing centers [HAC]). Median accrual in LAC vs HAC was 11 vs 82 pts. Pts treated at LAC and HAC had similar age, HPV status, pack-years, N stage, comorbidities and study arm assignment (SAA), but pts at LAC had better performance status (PS)(Zubrod 0; 62% vs 52%; p=0.04), fewer T4 tumors (27% vs. 35%; p=0.05) and were more likely uninsured (12% vs 4%; p=0.009). Compared to HAC, LAC pts had significantly worse OS, (5 yr 51.0% vs 69.1%; p = 0.002), and PFS (5 yr 42.7% vs 61.8%; p = 0.001) and more locoregional failure (5 yr 36.4% vs 20.8%; p <0.001). Treatment at LAC was associated with ~90% increase in risk of death (OS HR 1.91, 95%CI 1.37-2.65) and progression (PFS HR 1.89, 95%CI 1.39-2.56) when compared to pts treated at HAC, after adjustment for age, PS, pack-years, T and N stage, SAA and HPV status. Acute and chronic toxicities, RT dose, fractions, and treatment duration did not differ for pts at LAC vs HAC. RT at LAC was more likely than HAC to differ from protocol (18% [16.8% acceptable variation {AV}, 1.2% unacceptable deviation {UD}] vs 6% [4.7% AV, 1.3% UD]; p<0.001). Conclusions: Pts with HNC treated at LAC in RTOG trials were associated with significantly worse survival outcomes compared to pts treated at HAC.

A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6).

TPS5600 Background: Standard treatment for locally advanced SCCHN, chemoradiotherapy (CRT), leads to significant acute and long-term morbidity. The demonstration that EGFR antibody (Ab) therapy improves outcome when added to standard RT (Bonner NEJM 2006) and that altered fractionation RT improves outcome compared to standard RT that is of similar magnitude as CRT (Bourhis Lancet 2006), led to the hypothesis that the combination of the two treatment strategies will improve efficacy compared to standard CRT with good tolerability. Methods: HN.6 is a Canadian phase III randomized study comparing standard RT 70Gy/35 over 7 weeks + cisplatin 100mg/m2 d 1, 22, 43 to accelerated RT 70Gy/35 over 6 weeks + panitumumab (anti EGFR Ab)) 9mg/kg 1 week prior to RT, d15, 36. Key eligibility criteria are: SCC of oral cavity, oropharynx, larynx or hypopharynx; TanyN+M0 or T3-4N0M0; adequate organ function and PS. Primary endpoint is progression free survival (PFS). Secondary endpoints include OS, local PFS, regional PFS, distant metastases, swallowing related QOL, functional swallowing outcomes, and economic evaluation (healthcare utilization, health utilities, indirect costs). Tissue and blood collection will allow biomarker evaluation including HPV status. Real time quality review of RT plans with plan data and radiology archiving will allow future analysis of RT parameters relative to toxicity and patterns of failure. Clinical epidemiological data will be prospectively collected and correlated with biomarkers and outcome. Planned sample size is 320 patients over 3.2 years with 3 more years of follow-up and target hazard ratio = 0.7 (absolute difference in control arm 2 year PFS of 12%, power 80%, 2-tail type 1 error 0.05). If superiority is not demonstrated, noninferiority will be tested. One interim analysis is planned. Conduct to Date: Study activation: Dec 2008 and completed accrual in Nov 2011. In Oct 2011, the DSMC recommended trial continuation. Supported by CCSRI grant 021039 and Amgen Inc. ClinicalTrials.gov: NCT00820248.