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Miranda Jane Ashton
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-006 - SYSTEMS-2: Randomised Phase II Trial of Standard Versus Dose Escalated Radiotherapy for Pain in Malignant Pleural Mesothelioma (ID 9890)
09:30 - 09:30 | Presenting Author(s): Miranda Jane Ashton
- Abstract
Background:
Pain is common in malignant pleural mesothelioma (MPM) and tends to be poorly responsive to analgesia. Radiotherapy has traditionally been used for pain control, without robust supportive evidence. ‘SYSTEMS’ was the first prospective study to use validated endpoints to assess pain response to a standard dose of palliative radiotherapy (20Gy/5#). This multicentre, phase II trial demonstrated clinically meaningful improvements in pain in one third of patients at week 5, with minimal toxicity. The SYSTEMS-2 study is comparing pain control at week 5 in the standard arm (20Gy/5#) with that in the dose escalated arm (36Gy/6#).
Method:
Recruitment target is 112 patients across 15-20 UK hospitals. Eligible patients have: • MPM diagnosis • ECOG PS 0-2 • Pain score ≥ 4/10 after analgesia optimisation • CT scan with contrast within 8 weeks of starting radiotherapy • Radiotherapy plan compatible with dose escalated arm prior to randomisation. Wire markers are used to indicate sites of pain at radiotherapy planning and doses to organs at risk (OAR) are minimised through advanced planning techniques (e.g. intensity modulated radiotherapy- IMRT). (Figure 1) The primary outcome is pain control at the radiotherapy site at week 5. A clinically significant response is defined as a drop of ≥ 2 points in a validated numerical rating scale. Radiological response will be assessed at week 9. Figure 1
Result:
SYSTEMS-2 opened to recruitment in August 2016. More than 30 patients have been screened across a total of 5 UK sites and 15 patients have been randomised. A further 19 sites are currently in set-up. PTV coverage and OAR doses have been consistently achieved, despite large treatment volumes and nearby radiosensitive structures. Radiological responses have been seen across both cohorts.
Conclusion:
This study will provide robust and accurate symptom response data for palliative radiotherapy in MPM and help to establish the optimal dose and fractionation.
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.09-002 - Can We Do Better? Feasibility Dosimetric Study for Upfront Radical Radiotherapy in Mesothelioma (ID 10141)
09:30 - 09:30 | Author(s): Miranda Jane Ashton
- Abstract
Background:
Standard treatment for mesothelioma (surgery+/-chemotherapy+/-radiotherapy) does not provide satisfactory oncologic results in view of the lack of evidence for a preferred treatment option in such a rare disease with little published evidence. We aim to assess the feasibility of delivering radical doses of radiotherapy in mesothelioma patients. We would also like to evaluate the dosimetric parameters to establish organs at risk and optimal dose potentially delivered if radiotherapy is a sole agent.
Method:
Patients with Mesothelioma were chosen from the SYSTEMS-1 and SYSTEMS-2 trial cohort. Treatment volumes and organs at risk were performed on the Eclipse planning system. The treatment volumes outlined were CTV Pleural cavity and GTV bulky disease. Doses were prescribed as follows: PTV pleural cavity (CTV + 0.8 cm) 45Gy/ 25# and PTV Bulky disease (GTV+5mm) 55Gy/25#. Physics planning was carried on the Eclipse 13.6.23 treatment planning system, by using VMAT technique with either 2 or 3 arcs, 6MV beams at a dose rate of 600MU/min. We calculated overlap volumes between PTV and Organs at Risk (OAR’s) in view of their proximity, prioritizing heart and liver dose constraints over PTV coverage.
Result:
5 patients with confirmed epitheliod mesothelioma. Ages ranged from 55 - 72 years, 4/5 patients were male. A Cisplatin or Carboplatin-Pemetrexed doublet was given to all the patients prior to the CT Scan. The table below shows the dosimetry data gathered from the plans done.Objectives Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 TNM stage T4N2M0 T3N2M0 T4N3M0 T4N2M0 T4N2M0 PTV Pleural cavity Volume (cc) D~99%~ (% of the prescribed dose) D~95%~ (% of the prescribed dose) V~105%~ (%) V~95%~ (%) Median Dose (Gy) Dose prescribed 45Gy/25# - - >95% - >95% 1615 78.6 94.3 80.7 94.6 51 2276 77 108 96 97.6 53 1465 82.8 96 58.5 96.1 47.9 3701 58 91 87.1 93.2 53.4 1840 72 89 79.7 89 48.9 PTV Bulky disease Volume (cc) D~99%~ (% of the prescribed dose) D~95%~ (% of the prescribed dose) V~105%~ (%) V~95%~ (%) Median Dose (Gy) Dose prescribed 55Gy/25# - - >95% - >95% 2905 72 89.3 15.7 90 55 3104 79 89.6 15.2 81.2 54.6 4924 56 87.7 10.7 75.9 53.6 764 83 89 4.5 74 54.3 3104 79 89.6 15 81 54.6 Contralateral lung Volume(cc) Overlap with PTV (cc) Mean lung dose (Gy) V~20Gy~ (%) V~5Gy~ (%) - - ≤8-10 to 20 ≤4-10 to 35 ≤75 1637 0.1 12.2 11.3 98.6 1636 0 18.4 35.6 100 1247 0 13 18.3 92.6 2391 10.4 16.4 25.4 100 2082 0 17.5 31.3 100 Heart Volume(cc) Overlap with PTV (cc) Mean Heart Dose (Gy) V~35Gy~ (%) - - <22-26 <35 776 44.4 33.5 33.6 619 94.9 25.5 30 790 150 27.8 28.8 681 111.7 31.1 34.7 822 65.8 32.9 34.7 Liver Volume(cc) Overlap with PTV (cc) Mean liver dose (Gy) V~30Gy~ (%) - - 28-30 ≤40 1657 232 32.3 55.1 1544 0 17.3 4.0 1534 0 89.9 0.1 1931 485 32 57.2 1333 230 31.9 54.4 Oesophagus Volume (cc) Overlap with PTV (cc) Max dose (Gy) V~50Gy~ (%) - - ≤50-55 <40 28 5.3 55.6 8.3 33.5 0 53.4 5.9 30.5 1 55.6 13.4 193 48.7 60.9 26.6 43 7.7 56.3 13 Spinal cord Volume(cc) Overlap with PTV (cc) Max dose (Gy) - - <50 70.3 0 45.7 80.4 0 52.7 55.5 0 50.7 87.6 1.9 54.5 75 0 49.6 Contralateral Kidney Volume(cc) Overlap with PTV (cc) Max dose (Gy) - - <5 279 0 17.4 115 0 20 116 0 4.4 177 0 30.1 163 0 21.9 Ipsilateral Kidney Volume(cc) Overlap with PTV (cc) V~30Gy~ (%) Mean Dose (Gy) - - <50 ≤30 N/A N/A N/A N/A 118 0 29.6 17.4 89.8 0 0 2.1 134 2.8 23.3 18.9 239 20.5 44.6 29 Small Bowel Volume(cc) Overlap with PTV (cc) Max dose (Gy) - - ≤45 183 0 18.3 348 0 27.9 307 0 10.7 672.5 0 33.2 309 0 23.4 Stomach Volume(cc) Overlap with PTV (cc) Max Dose (Gy) - - ≤45 168 0.8 33.3 352 6.4 56.7 235 5.9 45.7 182.1 0 52.4 631 0 40.4
Conclusion:
Radical radiotherapy doses are achievable in mesothelioma by respecting organs at risk adequately, despite the challenging large volumes and complex disease anatomical pattern. VMAT is a promising technique allowing to potentially treat mesothelioma with radical doses of radiotherapy. Further trials are needed to assess the feasibility of radiotherapy as an upfront treatment for these patients.
