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L. Ashcroft
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.11 - Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) – a Feasibility Study (ID 7978)
12:10 - 12:15 | Author(s): L. Ashcroft
- Abstract
- Presentation
Background:
The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy. Alternative treatment options include sequential chemoradiotherapy and radiotherapy (RT) alone. As the rate of local failure is high there is a rationale for treatment intensification.
Method:
Isotoxic Intensity Modulated Radiotherapy (IMRT) is a multicentre feasibility study combining a number of intensification strategies; dose escalation, acceleration and hyperfractionation. Patients with inoperable stage III NSCLC, ECOG performance status (PS) 0-2, unsuitable for concurrent chemoradiotherapy were recruited. A minimum of 2 cycles of induction chemotherapy was mandated before RT. The dose of radiation was increased until one or more of the organs at risk (OAR) met predefined constraints or the maximum dose of 79.2Gy was reached. RT was delivered twice-daily in 1.8 Gy fractions. A RT quality assurance programme was in place. The primary end point was feasibility (>80% of patients achieving >60Gy EQD2 i.e. total biologically equivalent in 2 Gy fraction), with acute/late toxicity (CTCAE version 4.0), local control and overall survival as secondary end points.
Result:
Between June 2014 and March 2016, 37 patients were enrolled from 7 UK centres. Median age = 67 years (range 46-86). Male:female ratio = 18:19. ECOG PS=0, 5 (13.51%), PS=1, 29 (78.38%), PS=2, 3 (8.11%). Stage IIIa:IIIb ratio 23 (62.2%):14 (37.8%). Out of 37 patients, 2(5.4%) failed to achieve EQD2 >60Gy due to large tumour size and inability to meet OAR constraints, they received standard RT. This was due to large tumour size and inability to meet OAR constraints. Median prescribed tumour dose was 77.4Gy (61.2 – 79.2Gy) with the maximum dose of 79.2Gy delivered to 14 (37.8%) patients. All patients completed RT as scheduled except one due to disease progression. Grade (G)3 acute toxicities included: dysphagia 1 (2.9%), dypsnoea 2 (5.7%), lung infection 3 (5.7%) and radiation oesophagitis 2 (5.7%). There were three G5 events: radiation pneumonitis, trachea-oesophageal fistula and bronchopulmonary haemorrhage, which were probably treatment related. G3 late toxicities included: fatigue 1 (2.9%), dyspnoea 3 (8.6%) and 1 (2.9%) case of late G4 lung infection. At time of analysis median follow-up was 12.8 months for 20 survivors. Overall survival and progression-free survival at 1 year was 75% and 59% respectively.
Conclusion:
In the majority, treatment intensification using isotoxic IMRT is feasible. This regime will be tested alongside other intensified treatments against standard sequential chemoradiotherapy in the ADSCAN study (ISRCTN47674500).
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.14 - Phase I Trial Evaluating MEK Inhibitor Selumetinib with Concomitant Thoracic Radiotherapy in Non-Small-Cell Lung Cancer (ID 8982)
17:10 - 17:15 | Author(s): L. Ashcroft
- Abstract
- Presentation
Background:
The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating response to treatment. Selumetinib, an inhibitor of MEK, has been shown to enhance the effect of radiotherapy (RT) in preclinical studies.
Method:
Single-arm, single-centre, open-label phase I trial. Patients with stage III non-small cell lung cancer (NSCLC) not suitable for concurrent chemo-radiotherapy or stage IV with dominant thoracic symptoms. Patients were recruited to a dose-finding stage (based on the Fibonacci 3+3 design; maximum number =18) followed by the recruitment of an expanded cohort (n=15). Oral Selumetinib (AZD6244, ARRY-142886) was administered at a starting dose of 50mg twice daily commencing 7 days prior to RT, then in combination with thoracic RT for 6-6.5 weeks (60-66Gy in 30-33 fractions). The primary objective was to determine the recommended Phase II dose.
Result:
From 06/10-02/15, 21patients enrolled. Median age 63 years (range 50-73). M:F ratio 12(57%):9(43%). ECOG PS 0:1, 7(33%):14(67%). Stage III 16(76%):IV 5(24%). Mean GTV 64cm[3] (range 0.8–223.7). In the dose-finding stage, 2 out of 6 patients experienced dose-limiting toxicities (DLT) but only one DLT (G3 diarrhoea) was attributable to treatment. Despite meeting criteria for escalation, trial management group elected to treat patients on the expanded cohort (n=15) at the starting dose. All 21 patients completed RT as planned and received induction chemotherapy. Compliance rate of Selumetinib was >80%. Common adverse events are listed-see table. There were 2 survivors (24 & 26months) at analysis. The median survival was 9.7 months and 2-year survival was 24%. The main cause of disease progression was distant metastases in 16/21 (76%).
Conclusion:
The combination of thoracic RT and Selumetinib is feasible and associated with an acceptable toxicity profile. However our efficacy results, based on 21 patients, suggest that this combination should not be pursued in a subsequent phase II trial.Acute Toxicity (CTCAE v4.0) (during treatment and including up to 3 months post treatment) Toxicity Grade N = 21 (%) Acneiform rash 0 1 2 3 4 (19.04%) 7 (33.33%) 9 (42.86%) 1 (4.76%) AST[1] increased 0 1 3 17 (80.95%) 3 (14.29%) 1 (4.76%)** Diarrhoea 0 1 2 3 5 (23.81%) 13 (61.90%) 2 (9.52%) 1 (4.76%)* GGT[2] increased 0 1 2 3 16 (76.19%) 2 (9.52%) 2 (9.52%) 1 (4.76%) Haemoptysis 0 1 19 (90.48%) 2 (9.52%) Maculo-papular rash 0 1 3 16 (76.19%) 4 (19.05%) 1 (4.76%) Mucositis 0 1 2 18 (85.71%) 2 (9.52%) 1 (4.76%) Nausea 0 1 2 11 (52.38%) 9 (42.86%) 1 (4.76%) Radiation dermatitis 0 1 2 3 8 (38.10%) 7 (33.33%) 5 (23.81%) 1 (4.76%) Radiation oesophagitis 0 1 2 3 3 (14.29%) 2 (9.52%) 15 (71.43%) 1 (4.76%) Radiation pneumonitis 0 1 2 15 (71.43%) 0 6 (28.57%) Late Toxicity (follow up from 3+ months onwards) Toxicity Grade N = 21 (%) Pneumonitis 0 1 2 16 2 (9.52%) 3 (14.29%) Pulmonary fibrosis 0 1 19 2 (9.52%) Radiation oesophagitis 0 2 19 (90.48%) 2 (9.52%) * patient stopped drug on day 49 **patient stopped drug on day 29 abbreviations: 1) AST, Aspartate aminotransferase 2) GGT; Gamma-glutamyltransferase
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OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)
- Event: WCLC 2017
- Type: Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:S. Hasegawa, Anna Nowak
- Coordinates: 10/16/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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OA 02.03 - Prophylactic Irradiation of Tracts (PIT) in Patients with Pleural Mesothelioma: Results of a Multicentre Phase III Trial (ID 7980)
11:20 - 11:30 | Author(s): L. Ashcroft
- Abstract
- Presentation
Background:
It has been widespread practice across Europe to irradiate diagnostic or therapeutic chest wall (CW) intervention sites in patients with malignant pleural mesothelioma (MPM) post-procedure - a practice known as prophylactic irradiation of tracts (PIT). This study aims to determine the efficacy of PIT in reducing the incidence of CW metastases following a chest wall procedure in MPM.
Method:
In this multicentre phase III randomised controlled trial, MPM patients following a chest wall procedure were randomised 1: 1 to receive PIT (within 42-days of procedure) or no PIT. Large thoracotomies, needle biopsy sites and indwelling pleural catheters were excluded. PIT was delivered at a dose of 21Gy in 3 fractions over 3 consecutive weekdays using a single electron field adapted to maximise coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CW metastases within 6 months from randomisation, assessed in the intention-to-treat population. Stratification factors included epitheloid histology and intention to give chemotherapy. Trial registration number NCT01604005.
Result:
375 patients (186 PIT and 189 no PIT) were randomised between 06/2012-12/2015 from 54 UK centres. Comparing PIT vs no PIT, %male patients was 89.8/88.4%, median age 72.8/74.6 years, %ECOG PS (0,1,2) 32.2,56.5,11.3/23.8,56.1,20.1%, %confirmed epithelioid histology 79.6/74.1%, and %with intention to give chemotherapy 71.5/71.4%. The chest wall procedures were VATS (58.1/51.3%), open surgical biopsy (2.7/5.3%), local-anaesthetic-thoracoscopy (26.9/27.0%), chest drain (5.9/8.5%) and others (6.5/7.9%) for the PIT vs no PIT arm respectively. Radiotherapy was received as intended by 181/186 patients in the PIT arm. The proportion of CW metastases by 6 months was 6/186 (3.2%) vs 10/189 (5.3%) for the PIT vs no PIT arm respectively (odds ratio 0.60 [95% CI 0.17-1.86]; p=0.44) and by 12 months 15/186 (8.1%) versus 19/189 (10.1%) respectively (OR=0.79 [95% CI 0.36-1.69];p=0.59). Cumulative incidence of CW metastases at 6months/12 months/24 months was 3.3/8.5/10.0% in the PIT arm vs 5.6/10.9/18.7% in the no PIT arm. Evaluable patients who developed CW metastases reported a mean increase in visual analogue scale pain score of 13.3 (p<0.01) compared to baseline. Skin toxicity was the most common radiotherapy-related adverse event in the PIT arm with 96(51.6%) grade 1, 19(10.2%) grade 2, and 1(0.5%) grade 3 radiation dermatitis (CTCAE V4.0). There were no other grade 3 or higher radiotherapy-related adverse events.
Conclusion:
There is no role for the routine use of PIT following diagnostic or therapeutic CW procedures in patients with MPM.
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