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Fatal exacerbation of stable interstitial pulmonary fibrosis following CHART
S28 Conclusion: Immediate ILT did not lead to improved palliation. However it was associated with little toxicity. 87 Determining internal target volume (ITV) for mobile lung tumours: 2-D kilovoltage (kV) fluoroscopy, 3D or 4D cone-beam CT (CBCT)? P. Jain1,4 , T. Marchant2 , J. Davies3 , M. Duffy3 , G.R. Watkins4 , P.A. Burt1 , C. Faivre-Finn1 , M. Harris1 , R. Stout1 , C. Moore2 , P. Price4 . 1 Clinical Oncology; 2 North Western Medical Physics; 3 Wade Centre for Radiotherapy Research, Christie Hospital; 4 Academic Radiation Oncology, University of Manchester, UK Introduction: ICRU 62 recommends the generation of an ITV for mobile tumours. Several modalities can identify tumour motion. The study aims were (i) to assess how best to measure tumour motion & how representative the tumour motion seen at simulation is to that during treatment and (ii) compare slow 3D CBCT with 4D CBCT with respect to ITV generation. Methods: 8 patients undergoing radical radiotherapy with mobile lung tumours were studied. 2-D kV-fluoroscopy was carried out at simulation, and kV-fluoroscopy and 3D CBCT were obtained during treatment. Dynamic, 4-D CBCT images were subsequently reconstructed by sorting the images from the CBCT into 6 respiratory phases. Longitudinal tumor motion was measured during treatment using 2-D KV-fluoroscopy and 4-D CBCT images and compared to that documented at simulation. Gross tumour volume (GTV), using similar window settings, were contoured and compared on the 3D CBCT & 4-D CBCT acquired during treatment. Results: There was a weak correlation between tumour motion measured at d0 and the mean tumour motion measured during treatment using 4-D CBCT. There was good correlation between tumour motion measured during treatment with 4-D CBCT and 2-D kV-fluoroscopy (Spearman’s correlation, ø = 0.833, p = 0.01). GTVs contoured on images acquired during treatment were consistently smaller in all patients on 3D CBCT compared with 4D CBCT by a factor of 1.4 1.9. Conclusion: The underestimation of tumour volume by 3D CBCT reflects the extremes of breathing motion not represented by a slow scan. An ITV generated using a 3D CBCT is likely to be inferior to a 4-D scan as it lacks accuracy and clarity in delineation of GTV. All mobile tumours should ideally be planned using a 4-D CT scan to account for the correct magnitude of tumour motion, and allow individualisation of planning margins. Tumour motion at simulator may not always be representative of that seen during treatment. Attempts should be made to verify tumour motion during treatment to validate the ITV obtained at planning either using 2-D fluoroscopy or 4-D CBCT. 88 Can hyperpolarized 3 He MRI detect radiation induced lung damage? R.H. Ireland1,2 , J.M. Wild1 , N. Woodhouse1 , N. Hoggard1 , G. Brown2 , J.A. Swinscoe2 , O. Din2 , M.Q. Hatton2 . Academic Units of 1 Radiology and 2 Clinical Oncology, University of Sheffield, Sheffield, UK Introduction: Initial studies indicate that hyperpolarized helium-3 (3 He) MRI may be a useful adjuvant for the evaluation of radiotherapy treatment and its side effects [1,2]. The aim of this study was to develop techniques for the comparison of 3 He MR images acquired from lung cancer patients before and after radiotherapy treatment. Methods: Five NSCLC radiotherapy patients gave informed consent to undergo 3 He MRI for an ethics approved study. 3 He gas was polarized on site and ventilation images were acquired during a single breath-hold. With patients in the treatment position, 3 He MRI was acquired using an elliptical birdcage coil with a 3D acquisition sequence [3]. Images were acquired prior to radiotherapy and 3 months post-treatment. Radiotherapy planning CT was also obtained. The 3 He MR images
Posters, 6th Annual BTOG Meeting, 2008 were transferred to a radiotherapy planning system. Pre and post treatment MRI were registered to each other and to the treatment planning CT using anatomical landmark based rigid registration. 3 He MRI were then fused with the dose distribution calculated from the radiotherapy plan. Results: Registration of pre and post treatment images was possible for all five patients and enabled comparison with the planning CT and dose distribution.
Left) Pre-treatment 3He MRI. Middle) Post-treatment 3He MRI. Right) Planning CT and radiotherapy dose distribution.
Conclusions: This study demonstrates the feasibility of assessing pre and post therapy regional ventilation changes in lung cancer patients. Fusion of the 3 He MRI and radiation dose may enable effects on lung ventilation to be investigated. Acknowledgments: Supported by a Postdoctoral Award from the UK National Institute of Health Research, EPSRC, Sheffield Teaching Hospitals Research Trust and Yorkshire Cancer Research. We are also grateful for the loan of the 3 He gas polarizer from GE Healthcare and support from Spectra Gases and Philips Medical Systems. References: Reference(s) [1] Ireland RH et al. Int J Radiat Oncol Biol Phys 68(1):273 281, 2007. [2] Ward ER et al. Int J Radiat Oncol Biol Phys 58(5):1562 1569, 2004. [3] Wild JM et al. Magn Reson Med 52(3):673 678, 2004.
89 Fatal exacerbation of stable interstitial pulmonary fibrosis following CHART J. Duckers1 , D. Vardill1 , R. Mehta1 , D. Parry1 , S. Williams2 , J.F. Lester2 . 1 Princess of Wales Hospital, Bridgend; 2 Velindre Hospital, Cardiff, UK Introduction: Acute radiation pneumonitis within a treatment field is well described in thoracic radiotherapy (RT). We present a case of fatal bilateral acute pneumonitis in a patient with stable Interstitial Pulmonary Fibrosis (IPF) treated with CHART. Case History: A 67 year old man with stable IPF (azathioprine 150 mg, prednisolone 5 mg daily maintenance) received CHART in April 2007 for a 2 cm peripheral stage IIB non small cell lung carcinoma. Two months later he developed progressive dyspnoea and a dry cough. CXR showed new bilateral interstitial pulmonary infiltrates. His blood gas showed an oxygen of 8.0 kPa (FiO2 0.98). His CRP was 66 mg/L and his white blood cell count was 9.5×109 /L. Blood and sputum cultures were negative. Bronchoscopy was not attempted because of the severe hypoxaemia. He was treated with broad spectrum intravenous antibiotics including co-trimoxazole, pulsed intravenous methylprednisolone and diuretics. Despite intensive management, he died of respiratory failure 18 days after admission and six weeks after completing CHART. Discussion: Unilateral chest wall RT is known to cause bilateral lymphocytic alveolitis in patients with breast cancer. This phenomenon is thought to be responsible for the occurrence of cryptogenic organising pneumonia (COP) seen after thoracic RT, irrespective of tumour type. Our patient had steroid unresponsive disease which makes COP less likely. IPF is a significant comorbidity which may restrict patients’ access to surgery or radical RT. Patients with IPF may be more vulnerable to the pneumonitic effects of some chemotherapy agents such as gefitinib. In addition anticancer therapy for lung cancer (chemotherapy, RT and surgery) has been associated
Posters, 6th Annual BTOG Meeting, 2008 with an exacerbation of pre-existing pulmonary fibrosis. These observations have led some authors to suggest that lung cancer patients with pre-existing IPF should not receive any anticancer therapy. Conclusion: Patients with pre-existing IPF form a unique and vulnerable subset of patients with lung cancer. We report a case of acute fatal exacerbation of pulmonary fibrosis associated with CHART. The additional risks facing patients with IPF should be considered when making lung cancer management decisions. 90 The effect of hypofractionated accelerated radiotherapy on pulmonary function in non small cell lung cancer S. Brennan1 , D. Fitzpatrick2 , J. Armstrong1 , C. O’Shea2 , C. Flemming2 , P. Thirion1 . 1 Radiotherapy Department, St Lukes Hospital, Rathgar, Dublin 6, Ireland, 2 Clinical trials unit, St Lukes Hospital, Rathgar, Dublin 6, Ireland Purpose: Radiotherapy for non small cell lung cancer (nsclca) is known to affect pulmonary function. The aim was to prospectively determine the effect of high dose hypofractionated accelerated radiotherapy on pulmonary function tests, as a sensitive indicator of radiation induced pulmonary toxicity. Methods and Materials: 51 patients (pts) with inoperable NSCLCA were treated with 72 Gy in 24 fractions at 3 Gy per fraction over 5 weeks. Mean age was 66 years with range of 46 to 82 years. Patients underwent pulmonary function testing (PFTs) pre and post irradiation. FEV1 (forced expiratory lung volume in 1 second), FVC (forced vital capacity) and DLCO (carbon monoxide diffusing capacity) were measured pre RT (within 3 months) and post RT (first measurement at 3 months) and then at 6 monthly intervals, using single breath technique. The median follow up was 5 months with a maximum of 61 months. Data for PFTs for 27 pts with adequate follow up were available for analysis. Results: There was only a modest reduction in PFTs and this was statistically significant only for FEV1 (p = 0.011). 21 of 27 pts (77%) had a reduction in FEV1 but 6 pts (23%) had an increase in FEV1. The mean reduction in FEV1 was 13.4% (range 0.4 26.7%), which is comparable to conventionally fractionated RT. The reduction in FEV1 was not predictable on basis of baseline characteristics, such as age, sex, smoking history, use of prior chemotherapy or baseline pre RT FEV1. Pearsons correlation was performed to assess the effect of V5, V10, V15, V20, V25, V30, and MLD on FEV1. (V5 = volume of lung receiving 5 y). Those variables found to be statistically significantly associated with FEV1 were V5 (p = 0.014), V15 (p = 0.033), V20 (p = 0.027), V25 (p = 0.017), V30 (p = 0.011). On multivariate regression analysis V30 was most significantly associated with a greater reduction in FEV1, (adjusted r sq = 0.256, ANOVA = 0.011). Conclusions: The effect of hypofractionated lung RT on pulmonary function is comparable to conventional fractionation. The reduction in FEV1 may be predicted by V30. The effect may be seen as early as 3 months post radiotherapy. 91 What is the role of palliative chemotherapy in metastatic non small cell lung cancer with brain metastases? Q. Ghafoor1 , D.W.Y. Wong1 , L. Capaldi1 , S. Collins2 , A. El-Modir1 , A.D. Chetiyawardana1 . 1 Queen Elizabeth Hospital, Birmingham; 2 Cancer Research UK Clinical Trials Unit, University of Birmingham, UK Background: The overall risk of developing brain metastases in non-small cell lung cancer (NSCLC) is 20 to 40%. Palliative chemotherapy improves the outcome of metastatic NSCLC but there is no randomised controlled evidence to support its use in the presence of brain metastases. A retrospective analysis of NSCLC patients with brain metastases was performed to determine the value of chemotherapy within this group of patients.
S29 Methods: Patients with NSCLC who received palliative whole brain radiotherapy (WBRT) for brain metastasis between January 2002 and April 2005 were identified from the radiotherapy database. Case notes and electronic records were analysed retrospectively. The primary endpoint was overall survival (OS) calculated from the date of confirmation of brain metastases and estimated using the Kaplan-Meier method. A multivariate analysis was performed using Cox regression to examine the effect of prognostic variables. Results: A total of 159 patients were identified. 87 patients (53.7%) had brain metastases at presentation. In addition to WBRT, 4 patients (2.5%) underwent surgical resection of brain metastases. 1 patient had stereotactic radiosurgery. 60 patients (37.7%) received chemotherapy following WBRT. The median number of cycles of chemotherapy administered following WBRT was 3 (range 1 6). Median OS was 3.91 months (95% CI 3.22 to 4.83 months) and 1 year survival 8.8%. Patients who were performance status (PS) 0 1 had a median OS of 6.31 months versus 2.92 months for those who were PS 2 3 (HR=0.52; 95% CI 0.38 to 0.72; p < 0.0001). Patients receiving chemotherapy following WBRT had a median OS of 6.55 months versus 2.92 months for those who did not receive chemotherapy (HR=0.48; 95% CI 0.35 to 0.67; p < 0.0001). In multivariate analysis, chemotherapy following WBRT remained a significant favourable prognostic factor after controlling for performance status, age, histological subtype, number and sites of brain metastases, synchronicity of brain metastases, dose of radiotherapy and presence of other distant metastases. Conclusion: Palliative chemotherapy following WBRT in patients with metastatic NSCLC with brain metastases improves survival and should be considered in good performance status patients. 92 Quality of life after radiotherapy and steroids in patients with inoperable brain metastases from non-small cell lung cancer: the QUARTZ trial C. Pugh, P. Mulvenna, R. Barton, R.J. Stephens. MRC Clinical Trials Unit, 222 Euston Road, London, UK For patients with multiple inoperable brain metastases the standard therapy is a combination of steroids and whole brain radiotherapy (WBRT). However, WBRT causes side effects and has never been shown to correlate with an improved quality or length of survival. Therefore, it is uncertain whether those clinicians who treat this group of patients should continue to include WBRT within the package of optimal supportive care (OSC) offered via the multidisciplinary team. The QUARTZ trial compares OSC with OSC plus WBRT in the treatment of patients with inoperable brain metastases from NSCLC (where OSC includes dexamethasone titrated to clinical effect to the lowest dose possible). The two arms will be compared in terms of quality of life (using QUALYs as the primary outcome measure), overall survival, and side-effects. Hence QUARTZ is addressing a clinical area where significant uncertainty continues to exist. QUARTZ is now open to recruitment with 44 recruiting centres, including 3 centres from TROG (Trans Tasman Radiation Oncology Group in Australia), with a further 25 centres organising ethics and R&D submissions. Data for the QUARTZ trial are collected via weekly telephone assessments between the patient (and carer if consented for participation) and their nurse using a questionnaire including the EQ-5D, EQ-VAS and a list of symptoms. Updated recruitment and compliance with the weekly collection of data will be presented, which to date has proved very successful. For more details or to register your centre’s interest please contact [email protected].
Posters, 6th Annual BTOG Meeting, 2008 were transferred to a radiotherapy planning system. Pre and post treatment MRI were registered to each other and to the treatment planning CT using anatomical landmark based rigid registration. 3 He MRI were then fused with the dose distribution calculated from the radiotherapy plan. Results: Registration of pre and post treatment images was possible for all five patients and enabled comparison with the planning CT and dose distribution.
Left) Pre-treatment 3He MRI. Middle) Post-treatment 3He MRI. Right) Planning CT and radiotherapy dose distribution.
Conclusions: This study demonstrates the feasibility of assessing pre and post therapy regional ventilation changes in lung cancer patients. Fusion of the 3 He MRI and radiation dose may enable effects on lung ventilation to be investigated. Acknowledgments: Supported by a Postdoctoral Award from the UK National Institute of Health Research, EPSRC, Sheffield Teaching Hospitals Research Trust and Yorkshire Cancer Research. We are also grateful for the loan of the 3 He gas polarizer from GE Healthcare and support from Spectra Gases and Philips Medical Systems. References: Reference(s) [1] Ireland RH et al. Int J Radiat Oncol Biol Phys 68(1):273 281, 2007. [2] Ward ER et al. Int J Radiat Oncol Biol Phys 58(5):1562 1569, 2004. [3] Wild JM et al. Magn Reson Med 52(3):673 678, 2004.
89 Fatal exacerbation of stable interstitial pulmonary fibrosis following CHART J. Duckers1 , D. Vardill1 , R. Mehta1 , D. Parry1 , S. Williams2 , J.F. Lester2 . 1 Princess of Wales Hospital, Bridgend; 2 Velindre Hospital, Cardiff, UK Introduction: Acute radiation pneumonitis within a treatment field is well described in thoracic radiotherapy (RT). We present a case of fatal bilateral acute pneumonitis in a patient with stable Interstitial Pulmonary Fibrosis (IPF) treated with CHART. Case History: A 67 year old man with stable IPF (azathioprine 150 mg, prednisolone 5 mg daily maintenance) received CHART in April 2007 for a 2 cm peripheral stage IIB non small cell lung carcinoma. Two months later he developed progressive dyspnoea and a dry cough. CXR showed new bilateral interstitial pulmonary infiltrates. His blood gas showed an oxygen of 8.0 kPa (FiO2 0.98). His CRP was 66 mg/L and his white blood cell count was 9.5×109 /L. Blood and sputum cultures were negative. Bronchoscopy was not attempted because of the severe hypoxaemia. He was treated with broad spectrum intravenous antibiotics including co-trimoxazole, pulsed intravenous methylprednisolone and diuretics. Despite intensive management, he died of respiratory failure 18 days after admission and six weeks after completing CHART. Discussion: Unilateral chest wall RT is known to cause bilateral lymphocytic alveolitis in patients with breast cancer. This phenomenon is thought to be responsible for the occurrence of cryptogenic organising pneumonia (COP) seen after thoracic RT, irrespective of tumour type. Our patient had steroid unresponsive disease which makes COP less likely. IPF is a significant comorbidity which may restrict patients’ access to surgery or radical RT. Patients with IPF may be more vulnerable to the pneumonitic effects of some chemotherapy agents such as gefitinib. In addition anticancer therapy for lung cancer (chemotherapy, RT and surgery) has been associated
Posters, 6th Annual BTOG Meeting, 2008 with an exacerbation of pre-existing pulmonary fibrosis. These observations have led some authors to suggest that lung cancer patients with pre-existing IPF should not receive any anticancer therapy. Conclusion: Patients with pre-existing IPF form a unique and vulnerable subset of patients with lung cancer. We report a case of acute fatal exacerbation of pulmonary fibrosis associated with CHART. The additional risks facing patients with IPF should be considered when making lung cancer management decisions. 90 The effect of hypofractionated accelerated radiotherapy on pulmonary function in non small cell lung cancer S. Brennan1 , D. Fitzpatrick2 , J. Armstrong1 , C. O’Shea2 , C. Flemming2 , P. Thirion1 . 1 Radiotherapy Department, St Lukes Hospital, Rathgar, Dublin 6, Ireland, 2 Clinical trials unit, St Lukes Hospital, Rathgar, Dublin 6, Ireland Purpose: Radiotherapy for non small cell lung cancer (nsclca) is known to affect pulmonary function. The aim was to prospectively determine the effect of high dose hypofractionated accelerated radiotherapy on pulmonary function tests, as a sensitive indicator of radiation induced pulmonary toxicity. Methods and Materials: 51 patients (pts) with inoperable NSCLCA were treated with 72 Gy in 24 fractions at 3 Gy per fraction over 5 weeks. Mean age was 66 years with range of 46 to 82 years. Patients underwent pulmonary function testing (PFTs) pre and post irradiation. FEV1 (forced expiratory lung volume in 1 second), FVC (forced vital capacity) and DLCO (carbon monoxide diffusing capacity) were measured pre RT (within 3 months) and post RT (first measurement at 3 months) and then at 6 monthly intervals, using single breath technique. The median follow up was 5 months with a maximum of 61 months. Data for PFTs for 27 pts with adequate follow up were available for analysis. Results: There was only a modest reduction in PFTs and this was statistically significant only for FEV1 (p = 0.011). 21 of 27 pts (77%) had a reduction in FEV1 but 6 pts (23%) had an increase in FEV1. The mean reduction in FEV1 was 13.4% (range 0.4 26.7%), which is comparable to conventionally fractionated RT. The reduction in FEV1 was not predictable on basis of baseline characteristics, such as age, sex, smoking history, use of prior chemotherapy or baseline pre RT FEV1. Pearsons correlation was performed to assess the effect of V5, V10, V15, V20, V25, V30, and MLD on FEV1. (V5 = volume of lung receiving 5 y). Those variables found to be statistically significantly associated with FEV1 were V5 (p = 0.014), V15 (p = 0.033), V20 (p = 0.027), V25 (p = 0.017), V30 (p = 0.011). On multivariate regression analysis V30 was most significantly associated with a greater reduction in FEV1, (adjusted r sq = 0.256, ANOVA = 0.011). Conclusions: The effect of hypofractionated lung RT on pulmonary function is comparable to conventional fractionation. The reduction in FEV1 may be predicted by V30. The effect may be seen as early as 3 months post radiotherapy. 91 What is the role of palliative chemotherapy in metastatic non small cell lung cancer with brain metastases? Q. Ghafoor1 , D.W.Y. Wong1 , L. Capaldi1 , S. Collins2 , A. El-Modir1 , A.D. Chetiyawardana1 . 1 Queen Elizabeth Hospital, Birmingham; 2 Cancer Research UK Clinical Trials Unit, University of Birmingham, UK Background: The overall risk of developing brain metastases in non-small cell lung cancer (NSCLC) is 20 to 40%. Palliative chemotherapy improves the outcome of metastatic NSCLC but there is no randomised controlled evidence to support its use in the presence of brain metastases. A retrospective analysis of NSCLC patients with brain metastases was performed to determine the value of chemotherapy within this group of patients.
S29 Methods: Patients with NSCLC who received palliative whole brain radiotherapy (WBRT) for brain metastasis between January 2002 and April 2005 were identified from the radiotherapy database. Case notes and electronic records were analysed retrospectively. The primary endpoint was overall survival (OS) calculated from the date of confirmation of brain metastases and estimated using the Kaplan-Meier method. A multivariate analysis was performed using Cox regression to examine the effect of prognostic variables. Results: A total of 159 patients were identified. 87 patients (53.7%) had brain metastases at presentation. In addition to WBRT, 4 patients (2.5%) underwent surgical resection of brain metastases. 1 patient had stereotactic radiosurgery. 60 patients (37.7%) received chemotherapy following WBRT. The median number of cycles of chemotherapy administered following WBRT was 3 (range 1 6). Median OS was 3.91 months (95% CI 3.22 to 4.83 months) and 1 year survival 8.8%. Patients who were performance status (PS) 0 1 had a median OS of 6.31 months versus 2.92 months for those who were PS 2 3 (HR=0.52; 95% CI 0.38 to 0.72; p < 0.0001). Patients receiving chemotherapy following WBRT had a median OS of 6.55 months versus 2.92 months for those who did not receive chemotherapy (HR=0.48; 95% CI 0.35 to 0.67; p < 0.0001). In multivariate analysis, chemotherapy following WBRT remained a significant favourable prognostic factor after controlling for performance status, age, histological subtype, number and sites of brain metastases, synchronicity of brain metastases, dose of radiotherapy and presence of other distant metastases. Conclusion: Palliative chemotherapy following WBRT in patients with metastatic NSCLC with brain metastases improves survival and should be considered in good performance status patients. 92 Quality of life after radiotherapy and steroids in patients with inoperable brain metastases from non-small cell lung cancer: the QUARTZ trial C. Pugh, P. Mulvenna, R. Barton, R.J. Stephens. MRC Clinical Trials Unit, 222 Euston Road, London, UK For patients with multiple inoperable brain metastases the standard therapy is a combination of steroids and whole brain radiotherapy (WBRT). However, WBRT causes side effects and has never been shown to correlate with an improved quality or length of survival. Therefore, it is uncertain whether those clinicians who treat this group of patients should continue to include WBRT within the package of optimal supportive care (OSC) offered via the multidisciplinary team. The QUARTZ trial compares OSC with OSC plus WBRT in the treatment of patients with inoperable brain metastases from NSCLC (where OSC includes dexamethasone titrated to clinical effect to the lowest dose possible). The two arms will be compared in terms of quality of life (using QUALYs as the primary outcome measure), overall survival, and side-effects. Hence QUARTZ is addressing a clinical area where significant uncertainty continues to exist. QUARTZ is now open to recruitment with 44 recruiting centres, including 3 centres from TROG (Trans Tasman Radiation Oncology Group in Australia), with a further 25 centres organising ethics and R&D submissions. Data for the QUARTZ trial are collected via weekly telephone assessments between the patient (and carer if consented for participation) and their nurse using a questionnaire including the EQ-5D, EQ-VAS and a list of symptoms. Updated recruitment and compliance with the weekly collection of data will be presented, which to date has proved very successful. For more details or to register your centre’s interest please contact [email protected].