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Kevin Franks
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-43 - PD-RAD: A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-Small Cell Lung Cancer - Trial in Progress (ID 1811)
09:45 - 18:00 | Author(s): Kevin Franks
- Abstract
Background
Radiotherapy (RT) is delivered to 30-50% of NSCLC patients. However, over half of patients progress following RT and mechanisms of resistance are poorly understood. RT has immune-modulatory properties such as the ability to upregulate tumour PD-L1 expression and can recalibrate the immune contexture. Blockade of the PD-1/PD-L1 axis has been shown to enhance the efficacy of RT in several pre-clinical models and the recent PACIFIC trial. Exploiting immuno-regulatory effects of RT therefore has the ability to enhance local and distant anti-cancer effects of RT, especially when combining RT with immunotherapies such as anti-PD-1 or costimulatory agonists.
Method
PDRAD is a prospective UK multi-centre feasibility study of paired pre- and post-treatment biopsies in NSCLC patients receiving palliative or radical RT. The study will recruit up to 30 patients with inoperable disease that is accessible to core biopsy by CT or bronchoscopy within the proposed RT field. Patients with archival baseline histology containing sufficient tumour material are eligible. Consented patients undergo a repeat biopsy in the second week of RT (fig.1). Blood samples will be collected at baseline, repeat biopsy, and following RT to assess immune changes that may correlate with the tumour microenvironment (TME). PDRAD opened to recruitment in November 2018 and will continue recruitment over 16 months.
Research aims include investigating:
Feasibility and acceptability of obtaining paired biopsies
Changes in the immune contexture in irradiated tumour and ‘out of field’ sites
Immune changes in the TME and peripheral blood
Interim feasibility results after recruitment of 15 patients will be presented at World Lung.
Result
Section not applicable
Conclusion
We are at a pivotal point in evolving our knowledge of how the TME may influence responses to RT. The PDRAD study will help to influence further clinical trials, including combination studies with immunotherapies and predictive and prognostic biomarker development within the field.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-20 - Trial in Progress: Cardiac Toxicity in Patients Undergoing Curative Intent Radiotherapy for Lung Cancer (Now Available) (ID 787)
09:45 - 18:00 | Author(s): Kevin Franks
- Abstract
Background
The cardiotoxic effects of radiotherapy (RT) in long term survivors of breast cancer or lymphoma are well documented. Post-mortem studies and animal models have shown that RT causes fibrosis of cardiac structures leading to a wide variety of cardiac pathology. RTOG 0617 has highlighted a link between survival and cardiac dose and has led to a number of studies of cardiac toxicity in lung cancer patients. It is difficult to draw conclusions on cardiac dose constraints from available studies due to their retrospective nature and heterogeneity. We present an ongoing multicentre retrospective data mining study and prospective trial of cardiac biomarkers and imaging in patients undergoing radical lung RT, the aim of which is to define cardiac dose contraints leading to cardiac sparing treatment strategies.
Method
Retrospective Validation
Image based data mining results for heart substructures will be validated using a larger cohort. We will obtain data from Public Health England on cardiac risk factors, hospital admissions and cause of death for these patients to conduct a multivariate survival analysis.
Clinical Trial (NCT03645317)
A prospective study will collect cardiac risk factors (Qrisk 3), detailed cardiac imaging (CT and echocardiogram), ECG and cardiac blood biomarkers to evaluate effect of the radiotherapy on the heart. Figure 1 shows an overview of the clinical trial.
Result
Over 4000 patients treated with curative intent RT from 1/1/2010 to 30/12/206 have been identified. Details on 600 patients have been obtained and will be presented at WCLC 2019. Fifty-two patients (9%) had cardiac events following RT.
The prospective trial is due to open in May 2019
Conclusion
Studies of cardiac toxicity in lung RT have so far mainly been heterogeneous and retrospective. We describe a package of work incorporating large retrospective datasets with prospective imaging and blood biomarker collection to define cardiac dose parameters. This will improve the outcomes of lung cancer patients treated with radical radiotherapy by limiting heart dose and reducing cardiac events.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-22 - Do Statins Improve Outcomes After Radical Radiotherapy for Lung Cancer? An In-Depth Analysis of Over 1100 Patients (Now Available) (ID 1138)
09:45 - 18:00 | Author(s): Kevin Franks
- Abstract
Background
Statins exhibit anti-cancer activity in vitro in addition to cardiovascular protection effects. Trials using statins in lung cancer have shown mixed results. This study investigates statins’ impact on patients treated with curative radiotherapy for lung cancer.
Method
All patients who received radical radiotherapy for lung cancer from 01/01/2010-31/12/2016 at a large cancer centre were included. Individual patient information, including drug history at diagnosis, has been retrieved from hospital electronic database. Pre-existing cardiac conditions, Charlson Co-mobidity index and Qrisk3 scores were calculated.
Result
1181 patients were identified. Patient and treatment demographics are summarised in table 1. Patients in the statin group were older, had more co-morbidities and higher Qrisk3 scores. For the whole patient population, being on stains at the time of diagnosis was not significantly associated with better Overall Survival (OS) or Progression Free Survival (PFS). A ‘High Risk Cohort’(HRC) was identified, which consists of patients with a history of cardiac disease or Qrisk3 score >40. In HRC, statins significantly improved OS and PFS (p=0.016 and p=0.031 respectively), Graph 1.
Table 1
Total
N = 1181
Patients NOT on Statins N = 652
Patients ON statins N = 529
Sex
Male
603
298
305
Female
578
354
224
Age at RT treatment
Median = 73
Range 24 - 97
Median = 71
Range 24 - 92
Median = 74
Range 48 - 97
PS
0
94
67
27
1
578
347
231
2
438
212
226
3
71
26
45
Smoking Status
Unknown
16
7
9
Never smoked
43
28
15
Ex-Smoker <10 PY
14
9
5
Ex-smoker <20 PY
158
76
82
Ex-Smoker 20-40PY
276
132
144
Ex-Smoker >40 PY
259
140
119
Current Smoker(at time of seeing oncologist)
415
260
155
Charlson Score
(2 points for having lung cancer)
Median = 6
(2% estimated 10 year survival)
Median = 5
Median = 6
Qrisk3 Score
(For those without history of MI/IHD/CVA and < 84)
Median = 21% (%risk of stroke/MI in next 10 years)
Median = 18.7
Median = 25.7
Known pre-existing cardiac condition
= 349
101 had previous MI
113 had no MI but IHD/Angina
105
-15 previous MI
-33 IHD/Angina
244
-86 previous MI
-78 IHD/Angina
RT indication
Adjuvant RT
70
46
24
SBRT
478
240
238
Concurrent ChemoRT
202
135
67
Sequential ChemoRT
122
84
38
Radical RT
278
112
166
Consolidation RT after chemo for stage 4
31
10
21
Graph 1
Conclusion
In this retrospective analysis, patients who were on statins in the HRC had better survival outcomes, despite being older and have more comobidities. Mechanism of action of statins in lung cancer remains unclear and may be different in the post radiotherapy setting. Prospective studies would be useful to evaluate statins in this setting.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-08 - Clinical Trial in Progress: CONCORDE - A Phase 1B Study of Novel Agents in Combination with Conventional Radiotherapy in NSCLC (ID 600)
10:15 - 18:15 | Author(s): Kevin Franks
- Abstract
Background
The majority of patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative intent receive radiotherapy (RT) as part of their treatment. Despite considerable technological advances in RT delivery, the survival of these patients has barely changed over the last 60 years. A major factor in this failure to improve outcomes is the relative radioresistance of NSCLC. Attempts to overcome radioresistance by escalating RT doses have demonstrated inferior outcome likely secondary to normal tissue toxicity. Therefore an alternate approach is to exploit genetic dependencies in the DNA damage response of NSCLC, using biological inhibitors to selectively radiosensitise tumours whilst sparing normal tissues. The CONCORDE study is a multi-arm phase 1B platform study to investigate the combination of radical RT with DNA damage response inhibitors (DDR-i) targeting five different proteins: PARP, ATR, WEE1, ATM, DNA-PK.
Method
CONCORDE is a hypothesis-driven combination study of novel therapeutics and RT using an innovative adaptive early-phase trial design. The study will address two main research questions:
- What are the recommended phase 2 doses (RP2D) of individual DDR-i in combination with curative RT in patients with stage IIB/III NSCLC?
- What are the safety profiles of individual DDR-i combined with curative RT in this population?
Key inclusion criteria are stage IIB and III NSCLC planned to receive curative intent RT doses (+/- neoadjuvant chemotherapy) and PS 0-1. Participants will be randomised on a 3:1 basis between DDR-i with RT or RT alone. Patients receiving RT alone will be pooled across the arms to provide contemporary data on toxicity. All patients will receive external beam RT with a planned dose of 60 Gy in 30 fractions.
The study will use a Bayesian adaptive model-based approach to dose-escalation, with separate Time-To-Event Continual Reassessment Method (TiTE-CRM) models in each experimental arm. The primary endpoints are dose-limiting toxicities occurring within 12 months of the start of radiotherapy. Secondary endpoints include safety and toxicity (acute and late toxicity up to 2 years including using patient reported outcome (PRO) measures), treatment compliance, and best overall response (using RECIST 1.1, progression-free, and overall survival).
Correlative studies will be carried out to identify biomarkers of toxicity and response. We have secured high-level agreement from leading pharmaceutical partners to invest in 5 treatment arms and funding approval from Cancer Research UK is pending. The first participant is estimated to commence treatment in late 2019
Result
Section not applicable
Conclusion
Section not applicable
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P2.08 - Oligometastatic NSCLC (ID 172)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.08-01 - Outcomes Following Gamma Knife Radiosurgery for Oligometastatic Brain Metastases in Patients with NSCLC at Leeds Cancer Centre (ID 1856)
10:15 - 18:15 | Author(s): Kevin Franks
- Abstract
Background
Gamma knife (GK) radiosurgery has increasingly been used for brain metastases from NSCLC in the oligometastatic setting. This study reports outcome results for patients with synchronous brain and new brain metastases from NSCLC at Leeds Cancer Centre (LCC).
Method
251 patients, who were treated with GK at LCC from 2009 until 2018 were analysed. Retrospective analysis of notes was performed using electronic patient records.
Statistical analysis was performed using SPSS. Kaplan-Meier curves were performed to estimate time to intracranial progression, survival from diagnosis of brain metastases, and overall survival.
Result
Median age was 65 years (range 33 – 90 years). For patients with new brain metastasis (147 patients), TNM stage at diagnosis was stage I (14 patients), stage II (42 patients), stage IIIA (26 patients) or stage IIIB/IV (65 patients).
Histology was majority adenocarcinoma (59%), squamous cell carcinoma (16%) or NSCLC NOS (13%).
Radical thoracic treatment (surgery, chemoradiotherapy or stereotactic ablative radiotherapy) was undertaken for 158 patients. 92% completed radical thoracic treatment. Median survival from diagnosis of brain metastases was 382 days (446 days for those with synchronous brain metastases (48 patients), and 325 days for those with new brain metastases (110 patients)).
For all patients, median time to intracranial progression after GK was 242 days and overall survival after GK was 293 days.
For patients with synchronous brain metastases at presentation (104 patients), median time for overall survival from date of diagnosis was 435 days. For all patients without brain metastases at presentation, median time to intracranial progression from date of diagnosis was 305 days and overall survival was 693 days.
Conclusion
In conclusion, GK radiosurgery is an effective treatment for brain metastases in NSCLC, providing high rates of local control and improved survival. Beneficial effects are seen in patients with synchronous and new 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.
