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104PD CHARLSON CO-MORBIDITY INDEX PREDICTS FOR MORTALITY AFTER STEREOTACTIC BODY RADIOTHERAPY FOR MEDICALLY INOPERABLE EARLY STAGE NON-SMALL CELL LUNG CANCER
Early and locally advanced NSCLC 102PD MAGE-A3 ANTIGEN-SPECIFIC CANCER IMMUNOTHERAPEUTIC (ASCI) AS ADJUVANT THERAPY IN RESECTED STAGE IB/II NON-SMALL CELL LUNG CANCER (NSCLC): FROM PROOF-OF-CONCEPT TO PHASE III TRIAL (MAGRIT) B. Passlick1 , J. Vansteenkiste2 , M. Zielinski3 , A. Linder4 , J. Dahabreh5 , E. Esteban6 , W. Malinowski7 , J. Jassem8 , M. Lopez-Brea9 , C. Debruyne10 1 Department of Thoracic Surgery, University Medical Center Freiburg, Freiburg, Germany, 2 Respiratory Oncology Unit (pulmonology), University Hospital Gasthuisberg, Leuven, Belgium, 3 Department of Thoracic Surgery, Szpital Chorob Pluc, ur Thoraxchirurgie, Klinikum Bremen Zakopane, Poland, 4 Klinik f¨ Ost, Bremen, Germany, 5 Thoracic Surgery Department, Athens Medical Center, Athens, Greece, 6 Medical Oncology, Hospital ob Płuc I Rehabilitacji, Central de Asturias, Oviedo, Spain, 7 Chor´ Szpital Kopernika, Tuszyn, Poland, 8 Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, 9 Oncology Department, Hospital Marqu´ es de Valdecilla, Santander, Spain, 10 Clinical Oncology, GlaxoSmithKline Biologicals, Rixensart, Belgium Background: MAGE-A3 recombinant protein combined with GSK proprietary immunological Adjuvant System AS02B as adjuvant treatment for completely resected stage IB or II MAGE-A3 (+) NSCLC has been evaluated in a Phase II study (249553/004/NCT00290355). In addition, analysis of gene expression profiling of primary tumors was performed to identify a prognostic/predictive gene signature that possibly correlates with clinical activity of MAGE-A3 ASCI treatment. Methods: Patients were randomly assigned to postoperative MAGE-A3 or placebo (2:1) with immunizations q3w×5, followed by q3m×8. Primary endpoint was disease-free interval (DFI); other endpoints were safety, disease-free survival (DFS), overall survival (OS). Results: 182 patients (122 MAGE-A3, 60 placebo) were randomized: Median age 63 (45 81); 87% male; 67% stage IB; 65% squamous cell carcinoma. After a median follow-up of 44 months, 69 recurrences and 57 deaths were recorded. Group comparisons of DFI, DFS and OS gave a hazard ratio (HR) of 0.75 (95% CI: 0.46 1.23; p = 0.127), 0.76 (95% CI: 0.48 1.21) and 0.81 (95% CI: 0.47 1.40) in favor of the MAGE-A3 group, respectively. Treatment was well tolerated. Prognostic markers associated with high risk of relapse were identified. Stage IB patients with tumors not presenting this signature have a very low risk of relapse after surgery (<3%). In addition, a gene expression signature that may predict clinical response the MAGE-A3 ASCI treatment was identified. Selection of patients with the predictive signature results in a 2-fold increase in clinical efficiency. Conclusions: The 44 month follow-up analysis confirms the positive signal for activity of the MAGE-A3 treatment in adjuvant NSCLC with good tolerability. An efficacy Phase III study (MAGRIT) is ongoing. The primary endpoint of this trial is DFS. Other endpoints are clinical and biological indicators for safety and efficacy. The identified gene signatures will also be prospectively validate in this Phase III study.
S45 103PD MULTIDISCIPLINARY REHABILITATION AFTER LUNG CANCER OPERATION B.C. Brocki1 , L. Rodkjær2 , V. Nekrasas2 , M.L. Jakobsen3 , C. Dethlefsen3 , J. Andreasen1 1 Department of Occupational Therapy and Physiotherapy, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 2 Dep. of Cardiothoracic Surgery, Centre for Cardiovascular Research, Aarhus University Hospital, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 3 Centre for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark Background: Patients radically operated for lung cancer report functional deficits as well as poor quality of life. This study investigates short term effects of a rehabilitation programme on quality of life, physical performance and lung function in patients, who are radically operated for lung cancer. Methods: The study is a randomised, stratified and single blinded controlled trial. Inclusion expected completed in June 2009, enrolling a total of 70 patients. The intervention group participates in a 3 months out-patient rehabilitation programme based on aerobic exercises, resistance training and dyspnoea management in groups. Target intensity is 60 80% of work capacity (BORG SCALE 13 15). Participants are urged to exercise at home at least twice a week. Control group receives one instruction in exercise training and dyspnoea management. All participants are offered 3 times of counselling with a nurse. Measurements in the study are: health related quality of life by the SF-36 questionnaire; physical performance by the 6 minutes walking test; spirometric measurements are FEV1 , FVC and FEV1 /FVC. Measurements are taken at baseline (3 weeks after operation) and 4 months after inclusion. Results: Preliminary results comprise 41 patients (intervention group N = 21, control group N = 20) who were radically operated for primary or secondary lung cancer. Both groups show slight improvements in all measurements. Differences between intervention and control group are as follows: FVC 4% (12% vs. 8%), SF-36 PCS Physical Score 8% (16% vs. 8%), SF-36 MCS Mental Score 11% (5% vs 16%). There are no differences in physical performance and FEV1 between groups. Women tend to report poorer MCS than men. Women represent all cases of secondary cancer, and are more likely to report poorer MCS, when compared to women with primary lung cancer, or compared to men ( 4% vs. 10%, men 13%). Conclusions: Preliminary results show no statistical differences between intervention and control groups in health related quality of life, physical performance and lung function. Women with secondary lung cancer tend to have a poorer score on mental health than other participants of both genders. 104PD CHARLSON CO-MORBIDITY INDEX PREDICTS FOR MORTALITY AFTER STEREOTACTIC BODY RADIOTHERAPY FOR MEDICALLY INOPERABLE EARLY STAGE NON-SMALL CELL LUNG CANCER N. Kopek, C. Grau, M. Hoyer Oncology, Aarhus University Hospital, Aarhus, Denmark Background: Despite improved local control rates, overall survival for early stage medically inoperable NSCLC patients treated with SBRT remains low. While it is logical that advanced age and co-morbidity could compromise the survival outcomes of SBRT, there has been little effort to quantify these competing causes of death and to analyse outcomes as a function thereof. As we look towards the application of SBRT to operable early stage lung cancer patients, such an analysis becomes of particular interest in order to substantiate the competing-causes-of-death premise and reassure that potential treatment related mortality is not being hidden under the umbrella of “co-morbidities”. The present report of long term clinical outcomes of SBRT in the treatment of early
S46 stage NSCLC investigates the age-adjusted impact of number and kinds of baseline co-morbidities upon overall survival. Methods: Between 2000 and 2007, 88 consecutive stage I primary NSCLC patients, 81 peripheral and 7 central lesions, were treated by linac-based SBRT. Forty-five gray in three fractions prescribed to the isocenter was given until 2005 when 67.5 Gy in 3 fractions was introduced for peripherally located tumors. Baseline co-morbidities were retrieved by consultation of a formal electronic registry of diagnoses as well as patients’ charts. The age-adjusted Charlson Co-morbidity index (CCI) was scored for each patient and subjected to univariate and multivariate survival analysis. Results: With a median follow-up of 44 months, 5 patients developed local failure. The local control rate at 4 years was 89% while the median overall survival was 22 months. The most frequent adverse event was asymptomatic pulmonary fibrosis. The median CCI score was 5. The CCI was a significant predictor of overall survival on both univariate (p = 0.002) and multivariate (p = 0.006) analysis. Patients with a CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more. Conclusions: Longer follow-up confirms the excellent local control of SBRT for inoperable early stage NSCLC and appears well tolerated. Much higher survival rates were observed in patients with a low CCI. The persistently low survival outcome observed with SBRT does appear to be largely attributable to the advanced age and array of competing co-morbidities characterising this patient population. 105PD SEQUENTIAL CHEMORADIATION AND RADIATION ALONE IN THE TREATMENT OF INOPERABLE, LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) AND CORRELATION OF TUMOUR ERCC1 WITH SURVIVAL R. Davda1 , J.S.G. Griffith1 , D. Smith1 , H. Makker1 , G.A. Read1 , D. Ward1 , V. Sundaresan2 , M. Falzon3 , J.M. Singer4 1 Oncology, North Middlesex Hospital, London, United Kingdom, 2 Pathology, Princess Alexandra Hospital, Harlow, United Kingdom, 3 Pathology, University College Hospital London, London, United Kingdom, 4 Oncology, Princess Alexandra Hospital, Harlow, United Kingdom Background: There is evidence supporting induction chemotherapy prior to radical radiotherapy in the treatment of locally advanced, inoperable NSCLC. However, such patients often have significant co-morbidities and/or are of an age or performance status which make them unable to tolerate the toxicities associated with chemoradiation. DNA damage induced by cisplatin used in chemoradiation may undergo nucleotide excision repair. The excision repair crosscomplementation group 1 (ERCC1) enzyme is involved in this process and therefore tumour expression of ERCC1 may be associated with resistance to cisplatin and poorer survival following treatment. Methods: Patients treated with chemoradiation received 2 cycles carboplatin (AUC5) day 1, vinorelbine 25 mg/m2 days 1, 8 followed by CT planned conformal radiotherapy 55 Gy in 20 fractions and depending on tolerance, 2 further chemotherapy cycles. Patients who were considered unable to tolerate chemoradiation but still PS < 2 received radiotherapy 55 Gy in 20 fractions. We are currently performing ERCC1 immunohistochemical analysis in tumour biopsies taken at diagnosis and we will correlate these results with survival. Results: 127 patients were treated; 82 received chemoradiation, 45 radiotherapy alone. In the chemoradiation group the age range was 40 85 yrs with a median age of 67 yrs. In the radiotherapy group the age range was 42 89 yrs with a median age of 74 yrs. Median survival in the chemoradiation group was 554 days (18.2 months). Median survival in the radiotherapy group was 533 days (17.5 months). Using a chi squared test there was found to be no statistically significant difference in survival between the two groups (p = 0.35).
Early and locally advanced NSCLC Conclusions: Patients with inoperable stages II/III NSCLC who are judged unable to tolerate chemoradiation can be treated with radiation alone, giving comparable overall survival. We await ERCC1 analysis to compare expression with survival. 106PD DOES ELASTIC REGISTRATION ALTER FDG-PET BASED GTVS FOR RADIOTHERAPY PLANNING OF LUNG CANCER? U. Nestle1 , A. Grgic2 , N. Moca2 , S. Kremp3 , A. Schaefer2 , J. Fleckenstein3 , C. Kirsch4 1 Klinik f¨ ur Strahlenheilkunde, Universit¨ atsklinikum ur Nuklearmedizin, Freiburg, Freiburg, Germany, 2 Klinik f¨ Universit¨ atsklinikum des Saarlandes, Homburg/Saar, Germany, 3 Klinik f¨ ur Radioonkologie, Universit¨ atsklinikum des Saarlandes, ur Strahlenheilkunde, Homburg/Saar, Germany, 4 Klinik f¨ Universit¨ atsklinikum Freiburg, Homburg/Saar, Germany Background: FDG-PET and PET/CT is increasingly used for radiotherapy (RT) planning in non-small-cell lung carcinoma (NSCLC). For registration of PET and CT data, non rigid (“elastic”) methods have been proposed. As by elastic fusion errors concerning lesion size or depiction of tracer uptake might occur and lead to false delineation of the radiotherapy target volume (GTV), we compared FDG-based GTVs (P-GTV) in rigidly (LR) and elastically (ER) fused PET-CT-datasets. Methods: 16 patients with histologically proven NSCLC underwent FDG-PET acquisition and 3 CT acquisitions in different breathing positions (expiration, inspiration, mid-breathhold) all in the same RT position on the same day. The PET-scans were registered to all CT-scans using a linear and a elastic method. In all resulting fused datasets, P-GTVs of the primary tumors were delineated using the same contrast oriented contouring algorithm. Results: The mean P-GTV determined after LR was 86.1±106.2 ml, whereas after ER it was 93.2±110.1 ml (r = 0.98). The mean maximum standardized uptake values (SUVmax) were 10.1 (±4.1) after LR and 10.1 (±3.9) after ER (r = 0.98). In intra- and interindividual comparison, there were no significant differences in size and SUVs of the tumors depending on the registration method. Conclusions: Our results indicate no clinically significant error concerning size and/or uptake depiction of lung tumors after elastic registration of FDG-PET-data to CT data acquired in different breathing positions. The question of tumor localisation is subject to further studies. 107PD DOSE-PER-FRACTION ESCALATION OF ACCELERATED HYPOFRACTIONATED THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER L. Kepka, D. Tyc-Szczepaniak, M. Kolodziejczyk, K. Bujko Radiation Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Background: To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with doseper-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Methods: Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the limited elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 Gy through 2.8 Gy to 2.9 Gy. The total dose increased from 56.7 Gy through 58.8 Gy (level 1 escalation) to 60.9 Gy (level 2 escalation). The dose to the elective area and the overall treatment time
S45 103PD MULTIDISCIPLINARY REHABILITATION AFTER LUNG CANCER OPERATION B.C. Brocki1 , L. Rodkjær2 , V. Nekrasas2 , M.L. Jakobsen3 , C. Dethlefsen3 , J. Andreasen1 1 Department of Occupational Therapy and Physiotherapy, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 2 Dep. of Cardiothoracic Surgery, Centre for Cardiovascular Research, Aarhus University Hospital, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 3 Centre for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark Background: Patients radically operated for lung cancer report functional deficits as well as poor quality of life. This study investigates short term effects of a rehabilitation programme on quality of life, physical performance and lung function in patients, who are radically operated for lung cancer. Methods: The study is a randomised, stratified and single blinded controlled trial. Inclusion expected completed in June 2009, enrolling a total of 70 patients. The intervention group participates in a 3 months out-patient rehabilitation programme based on aerobic exercises, resistance training and dyspnoea management in groups. Target intensity is 60 80% of work capacity (BORG SCALE 13 15). Participants are urged to exercise at home at least twice a week. Control group receives one instruction in exercise training and dyspnoea management. All participants are offered 3 times of counselling with a nurse. Measurements in the study are: health related quality of life by the SF-36 questionnaire; physical performance by the 6 minutes walking test; spirometric measurements are FEV1 , FVC and FEV1 /FVC. Measurements are taken at baseline (3 weeks after operation) and 4 months after inclusion. Results: Preliminary results comprise 41 patients (intervention group N = 21, control group N = 20) who were radically operated for primary or secondary lung cancer. Both groups show slight improvements in all measurements. Differences between intervention and control group are as follows: FVC 4% (12% vs. 8%), SF-36 PCS Physical Score 8% (16% vs. 8%), SF-36 MCS Mental Score 11% (5% vs 16%). There are no differences in physical performance and FEV1 between groups. Women tend to report poorer MCS than men. Women represent all cases of secondary cancer, and are more likely to report poorer MCS, when compared to women with primary lung cancer, or compared to men ( 4% vs. 10%, men 13%). Conclusions: Preliminary results show no statistical differences between intervention and control groups in health related quality of life, physical performance and lung function. Women with secondary lung cancer tend to have a poorer score on mental health than other participants of both genders. 104PD CHARLSON CO-MORBIDITY INDEX PREDICTS FOR MORTALITY AFTER STEREOTACTIC BODY RADIOTHERAPY FOR MEDICALLY INOPERABLE EARLY STAGE NON-SMALL CELL LUNG CANCER N. Kopek, C. Grau, M. Hoyer Oncology, Aarhus University Hospital, Aarhus, Denmark Background: Despite improved local control rates, overall survival for early stage medically inoperable NSCLC patients treated with SBRT remains low. While it is logical that advanced age and co-morbidity could compromise the survival outcomes of SBRT, there has been little effort to quantify these competing causes of death and to analyse outcomes as a function thereof. As we look towards the application of SBRT to operable early stage lung cancer patients, such an analysis becomes of particular interest in order to substantiate the competing-causes-of-death premise and reassure that potential treatment related mortality is not being hidden under the umbrella of “co-morbidities”. The present report of long term clinical outcomes of SBRT in the treatment of early
S46 stage NSCLC investigates the age-adjusted impact of number and kinds of baseline co-morbidities upon overall survival. Methods: Between 2000 and 2007, 88 consecutive stage I primary NSCLC patients, 81 peripheral and 7 central lesions, were treated by linac-based SBRT. Forty-five gray in three fractions prescribed to the isocenter was given until 2005 when 67.5 Gy in 3 fractions was introduced for peripherally located tumors. Baseline co-morbidities were retrieved by consultation of a formal electronic registry of diagnoses as well as patients’ charts. The age-adjusted Charlson Co-morbidity index (CCI) was scored for each patient and subjected to univariate and multivariate survival analysis. Results: With a median follow-up of 44 months, 5 patients developed local failure. The local control rate at 4 years was 89% while the median overall survival was 22 months. The most frequent adverse event was asymptomatic pulmonary fibrosis. The median CCI score was 5. The CCI was a significant predictor of overall survival on both univariate (p = 0.002) and multivariate (p = 0.006) analysis. Patients with a CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more. Conclusions: Longer follow-up confirms the excellent local control of SBRT for inoperable early stage NSCLC and appears well tolerated. Much higher survival rates were observed in patients with a low CCI. The persistently low survival outcome observed with SBRT does appear to be largely attributable to the advanced age and array of competing co-morbidities characterising this patient population. 105PD SEQUENTIAL CHEMORADIATION AND RADIATION ALONE IN THE TREATMENT OF INOPERABLE, LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) AND CORRELATION OF TUMOUR ERCC1 WITH SURVIVAL R. Davda1 , J.S.G. Griffith1 , D. Smith1 , H. Makker1 , G.A. Read1 , D. Ward1 , V. Sundaresan2 , M. Falzon3 , J.M. Singer4 1 Oncology, North Middlesex Hospital, London, United Kingdom, 2 Pathology, Princess Alexandra Hospital, Harlow, United Kingdom, 3 Pathology, University College Hospital London, London, United Kingdom, 4 Oncology, Princess Alexandra Hospital, Harlow, United Kingdom Background: There is evidence supporting induction chemotherapy prior to radical radiotherapy in the treatment of locally advanced, inoperable NSCLC. However, such patients often have significant co-morbidities and/or are of an age or performance status which make them unable to tolerate the toxicities associated with chemoradiation. DNA damage induced by cisplatin used in chemoradiation may undergo nucleotide excision repair. The excision repair crosscomplementation group 1 (ERCC1) enzyme is involved in this process and therefore tumour expression of ERCC1 may be associated with resistance to cisplatin and poorer survival following treatment. Methods: Patients treated with chemoradiation received 2 cycles carboplatin (AUC5) day 1, vinorelbine 25 mg/m2 days 1, 8 followed by CT planned conformal radiotherapy 55 Gy in 20 fractions and depending on tolerance, 2 further chemotherapy cycles. Patients who were considered unable to tolerate chemoradiation but still PS < 2 received radiotherapy 55 Gy in 20 fractions. We are currently performing ERCC1 immunohistochemical analysis in tumour biopsies taken at diagnosis and we will correlate these results with survival. Results: 127 patients were treated; 82 received chemoradiation, 45 radiotherapy alone. In the chemoradiation group the age range was 40 85 yrs with a median age of 67 yrs. In the radiotherapy group the age range was 42 89 yrs with a median age of 74 yrs. Median survival in the chemoradiation group was 554 days (18.2 months). Median survival in the radiotherapy group was 533 days (17.5 months). Using a chi squared test there was found to be no statistically significant difference in survival between the two groups (p = 0.35).
Early and locally advanced NSCLC Conclusions: Patients with inoperable stages II/III NSCLC who are judged unable to tolerate chemoradiation can be treated with radiation alone, giving comparable overall survival. We await ERCC1 analysis to compare expression with survival. 106PD DOES ELASTIC REGISTRATION ALTER FDG-PET BASED GTVS FOR RADIOTHERAPY PLANNING OF LUNG CANCER? U. Nestle1 , A. Grgic2 , N. Moca2 , S. Kremp3 , A. Schaefer2 , J. Fleckenstein3 , C. Kirsch4 1 Klinik f¨ ur Strahlenheilkunde, Universit¨ atsklinikum ur Nuklearmedizin, Freiburg, Freiburg, Germany, 2 Klinik f¨ Universit¨ atsklinikum des Saarlandes, Homburg/Saar, Germany, 3 Klinik f¨ ur Radioonkologie, Universit¨ atsklinikum des Saarlandes, ur Strahlenheilkunde, Homburg/Saar, Germany, 4 Klinik f¨ Universit¨ atsklinikum Freiburg, Homburg/Saar, Germany Background: FDG-PET and PET/CT is increasingly used for radiotherapy (RT) planning in non-small-cell lung carcinoma (NSCLC). For registration of PET and CT data, non rigid (“elastic”) methods have been proposed. As by elastic fusion errors concerning lesion size or depiction of tracer uptake might occur and lead to false delineation of the radiotherapy target volume (GTV), we compared FDG-based GTVs (P-GTV) in rigidly (LR) and elastically (ER) fused PET-CT-datasets. Methods: 16 patients with histologically proven NSCLC underwent FDG-PET acquisition and 3 CT acquisitions in different breathing positions (expiration, inspiration, mid-breathhold) all in the same RT position on the same day. The PET-scans were registered to all CT-scans using a linear and a elastic method. In all resulting fused datasets, P-GTVs of the primary tumors were delineated using the same contrast oriented contouring algorithm. Results: The mean P-GTV determined after LR was 86.1±106.2 ml, whereas after ER it was 93.2±110.1 ml (r = 0.98). The mean maximum standardized uptake values (SUVmax) were 10.1 (±4.1) after LR and 10.1 (±3.9) after ER (r = 0.98). In intra- and interindividual comparison, there were no significant differences in size and SUVs of the tumors depending on the registration method. Conclusions: Our results indicate no clinically significant error concerning size and/or uptake depiction of lung tumors after elastic registration of FDG-PET-data to CT data acquired in different breathing positions. The question of tumor localisation is subject to further studies. 107PD DOSE-PER-FRACTION ESCALATION OF ACCELERATED HYPOFRACTIONATED THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER L. Kepka, D. Tyc-Szczepaniak, M. Kolodziejczyk, K. Bujko Radiation Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Background: To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with doseper-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Methods: Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the limited elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 Gy through 2.8 Gy to 2.9 Gy. The total dose increased from 56.7 Gy through 58.8 Gy (level 1 escalation) to 60.9 Gy (level 2 escalation). The dose to the elective area and the overall treatment time