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K.N. Franks
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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): K.N. Franks
- 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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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-011 - Clinical Outcomes Correlated with Percentage of Positive Anaplastic-Lymphoma Kinase Cells Tested by FISH Analysis in NSCLC. (ID 9291)
09:30 - 09:30 | Author(s): K.N. Franks
- Abstract
Background:
Testing for Anaplastic Lymphoma Kinase (ALK) rearrangement in patients diagnosed with Non-Small Cell lung Cancer (NSCLC) is the standard of care in the UK. 2-7% of tumours are positive and subsequently patients may be eligible for treatment with Tyrosine Kinase Inhibitors (TKIs). Response rates to TKIs range from 65-75% with a median PFS of 7.7-10.7 Months. We investigated the relationship between the percentage of ALK positive cells and clinical outcomes in a local patient cohort.
Method:
All patients found to have an ALK rearrangement between 1/1/13 - 1/4/17 in the Leeds Cancer Centre, UK were included. ALK analysis was performed using Fluorescent in situ Hybridisation (FISH) and the percentage of positive abnormal cells was recorded. Retrospective review of the medical notes was performed and outcomes documented including, whether the patient received a TKI, response to TKI, duration of response and overall survival. Chi-squared, Kaplan-Meier survival curves and log-rank test were used to assess survival outcomes.
Result:
75 patients were found to have an ALK rearrangement in total. Median age was 66 (range 51-92). Only 23 patients received a TKI. Until 2016 TKIs were not available in the first line setting in the UK and many patients were unable to receive a TKI either because first line chemotherapy was contra-indicated or because their performance status had deteriorated during first line chemotherapy making them unsuitable for a TKI. Some patients had early stage disease and therefore a TKI was not indicated (n=7). Median percentage of ALK positive cells was 27% and this was used as a cut off for further statistical analysis. Patients with > 26% of cells positive for ALK had a significantly higher chance of response (91.67% Vs. 42.86% p= 0.025). There was a trend towards improved PFS (107 vs 70 days) for those patients with >26% positivity. This was not statistically significant (PFS p=0.102) and no difference in overall survival was observed (OS p=0.421).
Conclusion:
In this small cohort, patients whose tumours had a higher proportion of tumour cells with an ALK rearrangement, were more likely to respond to TKI. They also had better PFS, though this was not significant. This study was limited by small numbers. TKIs are now available in the first-line setting, allowing more patients to access them. Future investigations will benefit from these increased numbers and if confirmed prospective studies, assessing more targeted use of TKIs on the basis of cellular positivity, could be considered.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-060 - Outcomes Following Gamma Knife Radiosurgery in Patients with Non-Small Cell Lung Cancer with Brain Metastases (ID 8056)
09:00 - 09:00 | Author(s): K.N. Franks
- Abstract
Background:
Gamma knife (GK) radiosurgery is a common treatment for brain metastases from non-small cell lung cancer (NSCLC). This study reports outcome results for patients with synchronous brain metastases and delayed brain metastases from NSCLC at Leeds Cancer Centre (LCC).
Method:
Data was obtained by retrospective case note review for 72 patients, who were all treated with GK from 2009 until 2014. Radical thoracic therapy (surgery, chemoradiotherapy or stereotactic ablative radiotherapy) was also undertaken for 58 patients. Statistical analysis using Kaplan-Meier curves was performed to estimate time to intracranial progression, survival from diagnosis of brain metastases, and overall survival.
Result:
Demographic data identified a median age of 65 years (range 43 – 83 years). For patients with delayed brain metastases (47 patients), TNM stage at diagnosis was stage I (7 patients), stage II (11 patients), stage IIIA (12 patients) or stage IIIB/IV (17 patients). Histology was majority adenocarcinoma (50%) or squamous cell carcinoma (22%). The median time to intracranial progression for all patients treated with GK was 9 months. In patients treated with radical thoracic therapy, of which 88% completed treatment, the median survival from diagnosis of brain metastases was 15 months for those with synchronous brain metastases (18 patients), and 14 months for those with delayed brain metastases (40 patients). In those with synchronous brain metastases, 83% received GK prior to radical thoracic therapy (median survival 18 months vs. 14 months for delayed GK). In those with intracranial progression following GK prior to death, 25% were treated with salvage GK with a median survival of 23 months. This compares to 18 months for those treated with salvage whole brain radiotherapy and 8 months for those not suitable for salvage treatment. The overall median survival for patients treated with combination radical thoracic therapy and GK at LCC was 21 months (median survival in synchronous brain metastases at diagnosis = 16 months vs. median survival in delayed brain metastases = 27 months).
Conclusion:
In conclusion, GK radiosurgery is an effective treatment for brain metastases in NSCLC. Beneficial effects are seen in patients with synchronous and delayed brain metastases, demonstrating its role in a wide subset of patients with advanced NSCLC. Use of GK, in combination with radical thoracic therapy, therefore has the potential to dramatically improve survival in patients who may not have previously been suitable for radical treatment.
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P2.08 - Locally Advanced Nsclc (ID 709)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.08-003 - An Audit of Concurrent Chemoradiotherapy for Non-Small Cell Lung Cancer at the Leeds Cancer Centre (LCC) (ID 9547)
09:30 - 09:30 | Author(s): K.N. Franks
- Abstract
Background:
Concurrent chemoradiotherapy is the standard non surgical management of locally advanced NSCLC. Radiation pneumonitis is a well recognized complication of lung radiotherapy. This retrospective study examines the clinical outcomes and treatment toxicities of patients treated with chemoradiotherapy(CRT) for NSCLC in 2014 at the LCC in UK.
Method:
Data was retrospectively collected from patients with locally advanced NSCLC treated with concurrent CRT from 1/1/14-31/12/14 at LCC. Patients received 3-D conformal radiotherapy to a dose of 60-66Gy/30-33# over 6-6.5 weeks. Individual patient’s clinical data was reviewed on Patient Pathway Manager for tumour and patient demographics. Radiotherapy dosimetric data were studied with V20, mean lung dose(MLD) and PTV volume. Treatment associated haematological toxicities and radiation pneumonitis were analysed. Overall and progression free survival were calculated. In addition, correlations between clinical/dosimetry parameter and clinical diagnosis of radiation pneumonitis were analysed.
Result:
58 patients were included in the study. Median follow up was 18.6 months. 66% of patients received weekly carboplatin/paclitaxel and the rest received 3 weekly cisplatin or carboplatin with etoposide. 78% of patients completed both chemotherapy and radiotherapy. For all radiotherapy plans, median V20 was 20.9Gy (range 3.4-29.8Gy), median MLD was 12.8Gy (range 2.3-16.5Gy) and median PTV was 395cc (range 73-819cc). 34% of patients developed grade 3-4 neutropenia, 64% grade 3-4 lymphopenia and 5% grade 3-4 thrombocytopenia. Neutropenic sepsis occurred in 10% of patients with one grade 5 toxicity. Radiation pneumonitis was diagnosed in 17% of patients, all below grade 3. Median time to pneumonitis was 133 days post radiotherapy. Radiation pneumonitis correlated strongly with V20(r = 0.93). Correlations with MLD and PTV were less. There were no correlations with neutropenia, lymphopenia or thrombocytopenia during treatment. 2/3 of the recurrences were distant metastases. 90 day mortality was 5%(three patients died from oesophageal perforation, colitis and pneumonia). The median progression free survival was 20.1 months. The median overall survival was not reached.
Conclusion:
At the LCC, chemoradiotherapy has been a safe and effective treatment for locally advanced lung cancer. Consistent with existing evidence, V20 remains the most powerful predictor of radiation pneumonitis following lung radiotherapy.
