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E. Yorke
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MO14 - Mesothelioma II - Surgery and Multimodality (ID 121)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:E. Lim, B. McCaughan
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside Gallery B, Level 1
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MO14.11 - Safety of hemithoracic pleural intensity-modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM) in the multimodality setting: interim analysis of a phase II study. (ID 2802)
11:25 - 11:30 | Author(s): E. Yorke
- Abstract
- Presentation
Background
Pleurectomy/decortication (P/D) is increasingly used for the surgical management of MPM. The presence of the remaining ipsilateral lung poses a challenge when delivering adjuvant radiation therapy, as the risk for radiation pneumonitis (RP) is high. We developed an IMRT technique targeting the entire pleura of the involved hemithorax, with promising early results. Here, we present the interim results of a prospective phase II study to determine the safety and toxicity profile of pleural IMRT following induction chemotherapy and P/D.Methods
Twenty-nine patients with locally advanced MPM have been enrolled to date. All patients received up to four cycles of pemetrexed/platinum chemotherapy. P/D was performed for all resectable patients. Sequential hemithoracic pleural IMRT was then administered with the intent of achieving a total planned dose of 50.4Gy in 28 fractions, as previously described (Rosenzweig et al., IJROBP 2012). All patients were simulated with a 4D-CT scan. A PET scan for image fusion and radiation planning was available for all patients. A Simon two-stage design was applied. A safety analysis after the first 9 patients led to the identification of only one case with ≥grade 3 RP in the first 3 months. The cohort was therefore expanded to 28 evaluable patients, defined as having initiated RT. The primary endpoint is the incidence of ≥grade 3 RP defined per Common Terminology Criteria for Adverse Events, v4.0. Steroids are typically initiated for ≥grade 2 RP.Results
To date, 21 out of 29 patients total are evaluable. The median follow-up is 10 months. The median age at diagnosis is 66 years (range 38-79). Median KPS was 90% (range 70-90%). Three patients had sarcomatoid, 3 had biphasic and 23 had epithelioid MPM. All patients received chemotherapy. Eight patients (28%) had a partial response, nine patients (38%) progressed, and all others had stable disease. Twenty-four patients (83%) underwent surgical exploration. Five patients underwent an extended P/D or P/D, 11 had a partial P/D, and 8 were found to be unresectable. Eight patients were removed from the study prior to receiving IMRT (7 due to disease progression and 1 due to grade 4 pulmonary embolism after one cycle of chemotherapy). To date, nineteen patients have completed IMRT [median dose 4680cGy (range 4500 to 5040cGy)]; one patient had distant disease progression after 16 fractions; one patient is currently on treatment. Five patients experienced grade 2 RP that was successfully controlled with steroids. One patient experienced grade 3 RP requiring supplemental oxygen, but quickly improved after steroid initiation. Other commonly observed ≥grade 2 radiation-related toxicities included fatigue (37%), dyspnea (47%), nausea (42%), esophagitis (26%), and cough (11%). No grade 4 or 5 radiation-related toxicities were observed.Conclusion
Hemithoracic pleural IMRT appears to have an acceptable toxicity profile in this ongoing phase II study. Early intervention with steroids is effective in controlling RP. This novel radiation technique has great promise as a component of lung-sparing multi-modality therapy in locally advanced MPM.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:M. Zwitter, S.K. Vinod
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside 204 A+B, Level 2
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MO17.09 - Dosimetric Predictors of Esophageal Toxicity after Stereotactic Body Radiotherapy for Central Lung Tumors (ID 1674)
17:05 - 17:10 | Author(s): E. Yorke
- Abstract
- Presentation
Background
Stereotactic body radiotherapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) and lung metastases. However, increased toxicity has been observed for SBRT to lesions near the proximal airways or mediastinal structures. Reported toxicities have primarily pertained to pulmonary complications, but little is known about the risk for esophageal toxicity. Therefore, we sought to evaluate dosimetric predictors of esophageal toxicity in this patient cohort at our institution.Methods
We identified 125 patients who received SBRT for single lung tumors within 2 cm of the proximal bronchial tree (n=81) or whose planning target volume (PTV) intersected mediastinal structures (n=44). Ninety-one patients had primary NSCLC, 12 had recurrent NSCLC, and 22 had metastatic tumors involving the lung. Patients with prior thoracic radiotherapy were excluded. Toxicity was scored using the Common Terminology Criteria for Adverse Events v.4.0. Biological equivalent doses (BED) were calculated using the linear quadratic formula with either α/β=3 or 10 Gy. Dose-volume histogram variables for the esophagus (D~v~, minimum dose to the hottest volume v and V~d~, volume receiving doses greater than d) were then examined for all patients and correlation with toxicity was assessed using logistic regression. Log rank tests were performed using median splits for variables that were significant in logistic regression.Results
With a median follow-up of 14.3 months, the overall rate of grade ≥2 esophageal toxicity was 12.8% (n=16), including two grade 3 events. The median prescription dose was 45Gy. The most common fractionation schemes were 45Gy in 5 fractions (n=56), 48Gy in 4 fractions (n=21), or 50Gy in 5 fractions (n=14). Highly significant logistic models were generated on the basis of D~3.5cc~, D~5cc~, and D~max ~(p<0.001). For a complication rate < 20%, D~3.5cc~ ≤ 29.4 Gy~10~, D~5cc~ ≤ 25.4 Gy~10~, and D~max~ ≤ 50.1 Gy~10~ was observed based on these models (BED~10~). Log rank tests showed that at 2 years, the probability of complication of those with a BED~10~ D~3.5cc~ > 16.6 Gy was 25% (p<0.001), D~5cc~ > 15.1 Gy was 26% (p<0.001), and a D~max~ > 29.6 Gy was 21% (p=0.032). The probability of complication for those with a D~3.5cc~, D~5cc~, and D~max~ (BED~10~) less than or equal to the above limits were 2%, 2% and 7%, respectively. The analysis was insensitive to α/β, and the same D~v~ variables were found to be significant using α/β =3.Conclusion
This is a novel quantitative analysis providing dose guidelines for significant esophagitis in the setting of SBRT. Dose to the hottest 3.5cc, 5cc and D~max~ were the best parameters for prediction of esophageal toxicity. Converting the BED~10~ limits to physical doses, D~3.5cc ~to the esophagus should be kept less than 18.3, 19.7 and 20.8 Gy for 3, 4, and 5 fractions, respectively, to keep the esophagitis rate < 20%. However, these guidelines must be weighed against clinical considerations and potential compromise of target coverage. This information will be valuable for treatment planning and identifying patients at risk for esophageal complications from SBRT.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O14 - Radiotherapy - Toxicity and Clinical Trials (ID 105)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:G. Pratt, S.K. Vinod
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom A, Level 1
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O14.03 - Using generalized equivalent uniform dose (gEUD) to model volume effects for brachial plexopathy after high-dose stereotactic body radiation therapy (SBRT) (ID 2835)
10:50 - 11:00 | Author(s): E. Yorke
- Abstract
- Presentation
Background
Brachial plexopathy is a rare but important toxicity of radiation therapy because of its significant impact on quality of life. For standard fractionated raiation therapy, good models of brachial plexus (BP) tolerance exist. However, the tolerance of the BP to SBRT is not well understood. We combined data from SBRT for apical lung and metastatic lesions near the BP spanning a wide range of doses and hypofractionation schemes. We determined the clinical incidence of brachial plexopathy and modeled the correlation with generalized equivalent uniform dose (gEUD) for both physical and biologically effective doses (BED) using a range of fractionation-sensitivity parameters (α/β) and volume effect parameters (a).Methods
Between 2004 and 2012, 180 lesions (76 lung lesions and 104 metastatic lesions) located above the aortic arch and below the level of C3 were treated with SBRT. Patients with prior radiation therapy to this region were excluded. Metastases were treated to 14-30 Gy in 1-5 fractions and lung tumors to 22-60 Gy in 1-5 fractions. The BP was contoured per RTOG atlas definitions. For 54 centrally located spine metastases, both left and right BP were contoured and analyzed separately for a total of 234 BPs in 180 patients. Brachial plexopathy of ≥grade 1 (CTCAE v4.0) was the primary endpoint. Maximum dose to the BP (Dmax), minimum dose to the hottest 5% of the BP (D05), and their respective BEDs were calculated using α/β= 3 Gy. The gEUD was also calculated with the volume effect parameter (a) ranging from log~10~a= -1.0 to +1.0 in log~10~a steps of 0.1. A logistic regression model (LR) was fit to the data as a function of a. Clinical dose recommendations were derived with logrank tests using median splits.Results
With median follow-up of 15.1 months, brachial plexopathy due to SBRT occurred in 9/234 BPs. Severity of brachial plexopathy was grade 1 in two, grade 2 in five and grade 3 in two patients. Median time to onset of brachial plexopathy was 6.2 months and the 1-/2-year actuarial rates were 3.3%/5.6%. For all patients the median BED for BP Dmax was 117.5 Gy and for D05 was 89.3 Gy. Median BED Dmax for patients with and without brachial plexopathy was 234 Gy and 115.2 Gy respectively (p=0.002). Brachial plexopathy was significantly associated with BP BED Dmax (p=0.002), and D05 (p=0.015), but not with physical dose. Using LR, the strongest correlation of gEUD with brachial plexopathy occurred for log~10~a= 1.0 using BED (p=0.002), which is representative of the BED Dmax. LR models of BED Dmax versus brachial plexopathy for various α/β values showed that any α/β<25 was a significantly better predictor than physical dose.Conclusion
Brachial plexopathy is significantly associated with BED Dmax ≥117.5 Gy (equivalent to a physical dose of 17 Gy x1, 9.3 Gy x3 or 7 Gy x5 fractions) and D05 ≥89.3 Gy. BED Dmax was the most important predictor of this rare but serious toxicity.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
