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N. Yousaf
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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 09.09 - Isotoxic Dose-Escalated Radiotherapy (RT) in Non-Small Cell Lung Cancer (NSCLC) with Deep Inspiration Breath Hold (DIBH) (ID 10052)
11:00 - 12:30 | Author(s): N. Yousaf
- Abstract
- Presentation
Background:
With interest in the use of isotoxic dose-escalated RT in treatment of inoperable NSCLC, this study investigated the impact of DIBH using the Active Breathing Coordinator™ (ABC- Elekta, Stockholm, Sweden) device on isotoxic dose escalation potential.
Method:
Following informed consent, a four-dimensional (4D) planning CT scan and a DIBH scan using the ABC device were acquired in patients sequentially in the same session. A motion-encompassing target volume on the 4D scan and a motion-managed target volume on the DIBH scan were created. The RayStation radiotherapy treatment planning system (research version 5.99.0.16) was used to generate two corresponding volumetric modulated arc therapy (VMAT) plans for each patient, following the guidelines of the isotoxic IMRT trial (NCT01836692). The target dose was escalated up to a maximum of 79.2 Gy in 44 twice daily fractions and plans optimised to minimise dose to normal tissues. Potential to escalate target dose and differences in dose-volume metrics between the plans were compared using the Wilcoxon signed-rank test.
Result:
21 patients were included. The mean total lung volume was significantly higher with DIBH compared to 4D scans with an increase of 44.7 % ± 17.4 % (mean ± standard deviation), p < 0.001). In 20/21 patients, the maximum target dose of 79.2 Gy was achievable in both plans, however in one patient 61.2 Gy was achieved with 4D compared to 75.6 Gy with DIBH planning. In the 20 patients achieving equivalent target dose-escalation, the mean lung dose was 17.0 Gy (± 0.3Gy ) with 4D versus 14.6 Gy (± 0.3 Gy) with DIBH (p < 0.001). There was a significant mean reduction in heart dose between the DIBH compared to 4D plans of 0.3 Gy (± 0.2 Gy, p< 0.001) and significant reductions in heart D100 %, D66 % and D33 %(p < 0.01). Mediastinal envelope and oesophageal doses were similar using both techniques.
Conclusion:
The use of DIBH compared to 4D planning aids lung and cardiac sparing in isotoxic dose escalated RT and for a small number of patients may allow an increase in target dose. Particularly given the interaction between lung and cardiac toxicity in locally advanced NSCLC treated with radical RT, use of DIBH for treatment may lead to a reduction in toxicity compared to a 4D approach. In acknowledgement of the use of a mid-ventilation technique in some institutions, comparison with this method is planned.
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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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P1.03-029 - Study of Plasma Homocysteine as a Marker of Toxicity and Depression in Patients Treated with Pemetrexed-Based Chemotherapy (ID 8643)
09:30 - 16:00 | Author(s): N. Yousaf
- Abstract
Background:
Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine levels reflect folate deficiency and are suppressed by supplementation. Depression is common in lung cancer patients. Elevated homocysteine levels are linked to neurotoxicity; its association with depression is less clear.
Method:
This prospective observational study of 112 lung cancer patients receiving pemetexed-based chemotherapy assessed homocysteine level after 3 weeks of vitamin B12 and folate supplementation, hypothesizing that high levels reflect an ongoing deficiency and would correlate with increased chemotherapy toxicity and depression. All patients received B12 and folate supplementation and had a homocysteine level checked 3 weeks later. The primary objective was proportion of patients with a treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, between patients showing normal plasma homocysteine (i.e. successfully supplemented, SS group) and patients showing high levels (i.e. unsuccessfully supplemented, US group). Secondary objectives included grade 3-4 toxicity, overall survival and exploratory analyses for depression.
Result:
100 patients were included in the primary end-point analysis. 84% of patients demonstrated appropriate supplementation (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in the SS group was 44.0% (37/84) (95% confidence interval [CI] 33.2% to 55.3%) and in the US group was 18.8% (3/16) (95% CI 4.0% to 45.6%) (p=0.093). Proportion of patients experiencing grade 3-4 toxicity in SS group was 14.5% (95% CI 7.7% to 23.9%) and in US group was 18.8% (95% CI 4.0% to 45.6%) (p=0.705). The proportion of patients with a Hospital Anxiety and Depression (HAD) score >7 (indicative of depression) in the SS group was 63.9% (95% CI 46.2% to 79.2%) and in the US group was 75% (95% CI 34.9% to 96.8%) (p=0.695). Median overall survival was 11.8 months (95% CI 8.6 – 16.5 months) in the SS group and 8.8 months (95% CI 6.6 – 16.2 months) US group (Log Rank test; p-value = 0.484).
Conclusion:
Standard vitamin supplementation was adequate in the majority of patients and thus our US population was small. Homocysteine levels at 3 weeks did not correlate with increased toxicity or overall survival and is unlikely to be useful to identify patients at an increased risk of toxicity, though analysis was limited by the smaller than expected number of patients in the US group. Depression is very common in this population, and HAD score is a feasible assessment tool in this patient group.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-049 - Early Clinical Predictors of Progressive Disease or Non-Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer (ID 10256)
09:30 - 16:00 | Author(s): N. Yousaf
- Abstract
Background:
Treatment with PD-1/PD-L1 inhibitors are now the standard of care for patients with advanced non-small cell lung cancer. PD-L1 expression, in addition to interferon score and tumour mutational burden, are predictive biomarkers, however early clinical predictive biomarkers are lacking.
Method:
Patients with NSCLC who received treatment with PD-1/PD-L1 inhibitors between 1 Jan 2014 – 31 Dec 2016 were retrospectively identified from electronic health records. Data was collected on patient, treatment and tumour characteristics. Discrete variables were compared using Fisher’s exact test. Odds ratios (OR) were calculated with 95% confidence intervals (CI) for significant associations, using contingency tables.
Result:
We identified 91 patients, with a mean age of 65 years, of whom 52% were male. The majority were ex-smokers (69.2%), followed by never smokers (23.1%). Non-squamous histology was seen in 59.3% of patients and 86.8% of the patients had ECOG performance status 0-1. The lactate dehydrogenase (LDH) at baseline, cycle 2, and the change-in LDH≥10% at cycle 2 and 6 weeks, did NOT predict for disease control rate (DCR) at the first tumour response evaluation (TRE). A LDH ≥ upper limit of normal at 6 weeks DID predict disease progression at the first TRE (P-value=0.04), with an OR of 3.58 (95% CI 1.11 – 11.52). The neutrophil-lymphocyte ratio (NLR) at baseline and 6 weeks, and the change-in NLR>10% at cycle 2 and 6 weeks did NOT predict for DCR at the first TRE. A NLR ≥5 at cycle 2 DID predict for disease progression at the first TRE (P-value=0.008), with an OR of 3.92 (95% CI 1.48 – 10.39). Receiver operator curve analysis of the early LDH/NLR score (1 point each for 6 week LDH ≥ upper limit of normal and cycle 2 NLR ≥5) predicted for disease progression at the first TRE (C-index 0.77, P-value <0.0001).
Conclusion:
The LDH greater than upper limit of normal at cycle 2 and NLR ≥5 at 6 weeks predicts for disease progression at the first TRE. These routine early predictive biomarkers could be used to identify non-responders when treating with PD-1/PD-L1 inhibitors prior to a CT scan. This data needs validation in a larger cohort.
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P3.12 - Pulmonology/Endoscopy (ID 728)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.12-003 - Optimised Inhaler Therapy Is Superior to Supportive Care Alone for Dyspnoea in Patients with Coexisting COPD and Lung Cancer (ID 9368)
09:30 - 16:00 | Author(s): N. Yousaf
- Abstract
Background:
Breathlessness is a common, debilitating symptom associated with both COPD and lung cancer. Opiates remain the mainstay of treatment for breathlessness in oncology.
Method:
Lung cancer patients were prospectively enrolled in this single-centre, open-label, randomised controlled trial. Eligible patients met British Thoracic Society diagnostic criteria for COPD, had a visual analogue score (VAS) dyspnoea ≥ 4 and had other reversible causes for breathlessness excluded. Patients were randomly assigned (1:1) between the intervention arm of salbutamol 100 mcg, 2 puffs QDS and tiotropium 18 mcg OD +/- salmeterol 50 mcg/fluticasone 500 mcg 1 puff BD (if FEV~1~ <50% predicted) in combination with best supportive care (BSC) or to BSC alone (control). Control arm patients could continue on any short-acting bronchodilators and BSC included oral morphine and/or benzodiazepines. Patients underwent spirometry, 6 minute walk test (6MWT), VAS dyspnoea and quality of life questionnaires (QOLQ) at baseline and after 2 and 4 weeks. The primary endpoint was the proportion of patients with ≥ 2 point improvement in VAS dyspnoea at 4 weeks.
Result:
Among the intention to treat population (n=63), 53 patients (84%) had NSCLC and 10 (16%) had SCLC. The median baseline VAS was 7.1 and the median baseline FEV~1~ was 1.5L (63% predicted). The primary endpoint response rate (RR) was higher in the intervention group n= 32 [RR: 53% (95%CI 35% to 71%)] than in the control group n= 31 [RR: 26% (95% CI 12% to 45%) p = 0.02]. Figure 1 There were no statistically significant differences between the groups for change in 6MWT or QOLQ between baseline and the 4 week assessments.
Conclusion:
For patients with co-existing COPD and lung cancers, VAS dyspnoea is significantly improved by the addition of inhaled therapies to best supportive care. This study highlights the importance of diagnosing and treating COPD in all lung cancer patients.
