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D. Ball
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ED 06 - Treatment of Elderly and High Risk Patients with Localized NSCLC (ID 6)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:A. Ardizzoni
- Coordinates: 9/08/2015, 14:15 - 15:45, 702+704+706
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ED06.02 - Radiation Therapy (ID 1795)
14:40 - 15:00 | Author(s): D. Ball
- Abstract
- Presentation
Abstract:
Non-small cell lung cancer is a disease of the elderly. In Australia in 2010, 84% of new lung cancers in men and 81% in women were diagnosed in people aged 60 years and older. The definition of “elderly” in the lung cancer radiotherapy literature varies with the lower limit ranging from 65 years (1) up to 85 (2). Older patients are not only more likely to develop toxicities of intensive treatment, but also to have less physiologic reserve to tolerate these toxicities. They include fatigue, pneumonitis, esophagitis and myelosuppression. Although older patients may have good performance status (ECOG 0-1), and be judged suitable for radical treatment, they may become deconditioned and harmed by treatment. Identification of these patients pre-treatment is challenging. An instrument to measure “frailty”, such as that devised by Fried et al (3) to predict post surgery complications would be useful in the radiotherapy setting. Frailty should be distinguished from performance status, which is only one measure of physiologic reserve; Fried’s frailty score includes measures of weight loss, grip strength and walking speed as well. Given the above, it is not surprising that older patients have worse survival than younger patients (4). Partly this may be due to a higher likelihood of suboptimal treatment (radiotherapy alone rather than concomitant chemoradiotherapy), and partly to the competing risks of non-neoplastic comorbidities. Once survival is adjusted for these effects, age is no longer associated with increased risk of death (4). It is generally agreed that functional rather than chronological age is a more important consideration in patient selection for radical treatment (2, 5). Age is certainly not a contraindication to treatment with SABR for stage I disease (6). The choice of chemotherapy to accompany radiotherapy in pateints with locally advanced disease is unclear because of a lack of trials performed specifically in a geriatric population. Carboplatin is usually preferred to cisplatin in patients over 70 because of its more favorable toxicity profile. The evidence for two drugs rather than one is limited. In a study of the Japan Clinical Oncology Group limited to patients 70 years and older, daily carboplatin added to 60 Gy of radiotherapy improved median survival from 16.9 to 22.4 months (p=0.02) compared with radiotherapy alone (7). Performance status, in the absence of a validated frailty score, remains a critical determinant of suitability for (chemo)radiotherapy. Patients with performance status ECOG 2 or worse seem not to benefit from treatment intensification, including when the intent of treatment is palliation (8). Comorbidity scores (Charlson, Colinet) appear to be closely linked to performance status, but there is insufficient evidence to support their use in clinical decision making. Diminished pulmonary function is sometimes thought to be a contraindication to radical radiotherapy - yet patients who are unfit for surgery, usually because of diminished cardiopulmonary reserve, are the very patients most likely to be referred for stereotactic ablative body radiotherapy (SABR). In fact, some studies suggest that patients developing symptomatic radiation induced lung injury were more likely to have a higher FEV1(9). However caution should be exercised in treating patients with pre-existing interstitial lung disease, including with SABR (10). Our approach is to judge a patient’s suitability for treatment based on their biological age. In older patients with locoregional disease and performance status ECOG 0-1 who are suitable for radical treatment, we would recommend full dose SABR for patients with peripheral stage I disease, and chemoradiation for locally advanced disease, 60 Gy with concomitant carboplatin and paclitaxel. Patients who are not fit for chemotherapy are treated with radiotherapy alone. If there is concern regarding the patient’s capacity to undergo a six week course, we either review the patient at 40 Gy , and if there is evidence of diminished tolerance, cease at that point. If there is concern that a patient will not tolerate a risk of grade 3 esophagitis, but the aim is improved local control rather than paliiation, we would offer a split course to allow for mucosal recovery (20 Gy in 5 fractions, followed by a 4 week break, then another 20 Gy). Although thought to be suboptimal because of the risk of repopulation, a split course schedule is less likely to produce high grade esophagitis than 36 Gy in 12 continuous fractions. For older patients with diminished performance status (ECOG 2 or greater) and for whom palliation is the objective, 20 Gy in five fractions is a reasonable option, and little more demanding on resources and patient inconvenience than a large single dose. References 1. Sigel K, Lurslurchachai L, Bonomi M, Mhango G, Bergamo C, Kale M, et al. Effectiveness of radiation therapy alone for elderly patients with unresected stage III non-small cell lung cancer. Lung Cancer. 2013;82(2):266-70. 2. Khor RC, Bressel M, Tedesco J, Tai KH, Ball DL, Duchesne GM, et al. Tolerability and outcomes of curative radiotherapy in patients aged 85 or more years. Med J Aust. 2015;202(3):153-5. 3. Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210(6):901-8. 4. Aridgides PD, Janik A, Bogart JA, Duffy S, Rosenbaum P, Gajra A. Radiotherapy for stage III non-small-cell lung carcinoma in the elderly (age >/= 70 years). Clin Lung Cancer. 2013;14(6):674-9. 5. Wanders R, Steevens J, Botterweck A, Dingemans A-MC, Reymen B, Baardwijk Av, et al. Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: A prospective population-based study. European Journal of Cancer. 2011;47(18):2691-7. 6. Palma D, Visser O, Lagerwaard FJ, Belderbos J, Slotman B, Senan S. Treatment of stage I NSCLC in elderly patients: a population-based matched-pair comparison of stereotactic radiotherapy versus surgery. Radiother Oncol. 2011;101(2):240-4. 7. Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, et al. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012;13(7):671-8. 8. Strom HH, Bremnes RM, Sundstrom SH, Helbekkmo N, Aasebo U. How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial. Clin Lung Cancer. 2015;16(3):183-92. 9. Kong FM, Wang S. Nondosimetric risk factors for radiation-induced lung toxicity. Semin Radiat Oncol. 2015;25(2):100-9. 10. Ueki N, Matsuo Y, Togashi Y, Kubo T, Shibuya K, Iizuka Y, et al. Impact of pretreatment interstitial lung disease on radiation pneumonitis and survival after stereotactic body radiation therapy for lung cancer. J Thorac Oncol. 2015;10(1):116-25.
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MINI 20 - Surgery (ID 137)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Veronesi, R. Flores
- Coordinates: 9/08/2015, 16:45 - 18:15, 201+203
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MINI20.13 - A Prospective Comparison of FDG-PET & EBUS for Determining the Extent of Mediastinal Lymph Node Involvement in NSCLC (ID 2323)
17:55 - 18:00 | Author(s): D. Ball
- Abstract
- Presentation
Background:
Non-small cell lung cancer (NSCLC) may be treated with curative intent using radiotherapy, either as single modality or in combination with systemic chemotherapy. Most commonly, radiation treatment is planned based on findings at 18-Fluorodeoxyglucose Positron Emission Tomography (PET), following pathologic confirmation of involvement at a single mediastinal site. We hypothesized that systematic mediastinal evaluation with EBUS-TBNA in NSCLC patients considered for radical radiation therapy may identify disease extent discrepant with that indicated by PET-CT.
Methods:
This prospective ethics board-approved multi-centre cohort study in three Austrailan tertiary centres consented patients prior to mediastinal evaluation with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) for NSCLC,where non-invasive imaging indicated the likely treatment modality would include radical radiotherapy. EBUS evaluation was performed systematically with sampling of any lymph node (LN) exceeding 6mm diameter.
Results:
Thirty eligible patients with NSCLC form the basis of this report. No procedural complications occurred during performance of EBUS-TBNA. LN sampling was performed from a mean 2.5 lymph node stations per patient (median 3,range 1–5). Adequate samples were obtained from all sites examined by EBUS-TBNA. Mean long-axis size of sampled LN was 16+7.8mm (median 13mm,range 5–36mm). 24% of sampled LN were 10mm or less. Discordant findings were observed in 10 of 30 patients (33%) (Figure 1) EBUS-TBNA identified a greater extent of mediastinal involvement than PET in four patients, with invasive sampling resulting in upstaging in three patients. In one further patient, extent of disease was greater than noted on PET due to more proximal involvement of LN disease not resulting in stage advancement. Median size of LN upstaged by EBUS was 7.5mm (range 7–9). In eleven mediastinal LN in six patients, EBUS identified a lesser extent of mediastinal disease than PET, including two patients down-staged from N3 à N2. Median size of LN down-staged by EBUS was 12mm (range 6–21). FIGURE 1. Flowchart of patients Figure 1
Conclusion:
Our findings demonstrate clinically significant discrepancy between two modalities frequently used to stage mediastinal disease extent in NSCLC patients being considered for radiotherapy. PET-based radiotherapy planning alone may not be appropriate given the risk of excessively large, or insufficiently large, radiation fields where planning is not based on invasive LN sampling. These results suggest minimally invasive comprehensive/systematic mediastinal staging should be considered for all patients prior to radiotherapy to accurately assess pathologic stage and extent of disease, and to ensure treatment fields most accurately encompass all sites of disease.
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ORAL 10 - SCLC (ID 98)
- Event: WCLC 2015
- Type: Oral Session
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:C. Faivre-Finn, P. Lara Jr.
- Coordinates: 9/07/2015, 10:45 - 12:15, 605+607
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ORAL10.08 - Discussant for ORAL10.06, ORAL10.07 (ID 3330)
12:21 - 12:31 | Author(s): D. Ball
- Abstract
- Presentation
Abstract not provided
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ORAL 36 - Translational Science/Radiation (ID 151)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:E. Vokes, B. Kavanagh
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL36.06 - 4D-VQ-PET/CT Imaging Allows Strong Correlation Between Radiotherapy Dose and Change in Lung Ventilation, Perfusion and Density (ID 211)
17:39 - 17:50 | Author(s): D. Ball
- Abstract
- Presentation
Background:
[68]Ga-V/Q PET/CT is a novel imaging modality for assessment of perfusion(Q), ventilation(V) and lung density changes in the context of radiotherapy (RT) for non-small cell lung cancer.
Methods:
In a prospective clinical trial, 20 patients underwent 4D-V/Q PET/CT before treatment, 4 weeks into treatment and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT and isodose volumes averaged into 10 Gy bins. Within each dose bin, relative loss in SUV was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models and goodness of fit assessed using Akaike Information Criterion (AIC).
Results:
A total of 179 imaging datasets were available for analysis (1 scan unrecoverable). An almost perfectly linear dose-response relationship was observed for perfusion and air-filled fraction (r[2] = 0.99, p < 0.01), with ventilation also strongly linear (r[2] = 0.95, p < 0.01) [Figure]. Logistic models did not provide a better fit as evaluated by AIC [Table]. Perfusion, ventilation and the air-filled fraction changed by -7.5% ± 0.3%, -7.1% ± 0.6% and 4.9% ± 0.02% per 10 Gy, respectively. Within high-dose regions, higher baseline SUV was associated with greater rate of loss. At 50Gy and 60Gy the rate of loss was 1.35% (p = 0.07) and 1.73% (p = 0.05) per SUV, respectively. Of 8/20 patients with peri-tumoral reperfusion / re-ventilation during treatment, 7/8 did not sustain this effect post-treatment. Figure 1 Figure 2
Conclusion:
RT induced regional lung functional deficits occur in a dose dependent manner and can be estimated using simple linear models with 4D-V/Q PET/CT imaging. These findings may inform functional lung sparing by planning RT using this novel imaging technology.
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