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E.P. Saibishkumar
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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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MO14.12 - Neoadjuvant Hemithoracic Intensity Modulated Radiotherapy: The "SMART" Approach for Managing Malignant Pleural Mesothelioma (ID 2328)
10:30 - 12:00 | Author(s): E.P. Saibishkumar
- Abstract
- Presentation
Background
Management of malignant pleural mesothelioma (MPM) remains controversial. After extra-pleural pneumonectomy (EPP) and adjuvant radiotherapy, many fail distantly (peritoneal cavity, contralateral lung), possibly due to inadvertent tumour spillage at time of EPP. We hypothesize that neoadjuvant radiation followed by planned imminent EPP can limit the proliferation of clonogens spilt intraoperatively. The radiotherapy technique developed for the Surgery for Mesothelioma After Radiation Therapy (SMART) study is described.Methods
We conducted a phase II prospective REB approved single cohort clinical feasibility study on surgically resectable stage T1-3N0M0 MPM. The pre-operative clinical target volume (CTV) was defined as the ipsilateral hemithorax, , including biopsy and drainage tract sites. The gross tumour volume (GTV) was defined as any tumour seen on imaging. The dose prescription to the CTV was 25 Gy in 5 daily fractions over approximately 1 week with a concomitant boost of 5 Gy to the GTV and tract sites. All patients underwent EPP within 1 week of completing the neoadjuvant RT. If ypN2 found, patients were offered adjuvant chemotherapy. Treatment related toxicity was defined by the CTCAE v3.Results
The accrual goal of 25 patients was completed between Nov 2008 and Oct 2012. All completed their intended RT and EPP. IMRT was well tolerated with only grade 1-2 toxicities noted (fatigue, nausea, and esophagitis). EPP was performed 6±2 days after completion of IMRT. Dosimetric values are shown in the table below.Dosimetric Parameter dose max (cGy) 3290.5 CTV>2750 cGy (%) 95.5 CTV>2300 cGy (%) 97.8 PTV>2750 cGy (%) 93.3 PTV>2300 cGy (%) 91.7 LUNG>700 cGy 4.9 LUNG mean (cGy) 315.0 LIVER>1400 cGy (%) 45.3 LIVER mean (cGy) 1371.8 HEART>1400 cGy (%) 50.3 HEART mean (cGy) 1473.7 contra KIDNEY>750 cGy (%) 19.6 contra KIDNEY mean (cGy) 318.1 ipsi KIDNEY>750 cGy (%) 49.5 ipsi KIDNEY mean (cGy) 561.6 ESOPHAGUS 2880.1 CANAL max (cGy) 2026.1 prv3mmCANAL max (cGy) 2125.4 Conclusion
Short neoadjuvant hemithoracic radiotherapy (30 Gy in 5 daily fractions over 1 week) using the SMART protocol constraints are well tolerated. The SMART protocol is technically demanding, requiring very close and careful coordination and planning between the multiple disciplines.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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MO17.03 - Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated with SBRT: A Case-Matched Analysis (ID 2024)
16:15 - 17:45 | Author(s): E.P. Saibishkumar
- Abstract
- Presentation
Background
Reported non-small cell lung cancer (NSCLC) nodal failure rates following stereotactic body radiotherapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesize that this effect is due to incidental prophylactic nodal irradiation.Methods
A prospectively collected group of medically inoperable early stage NSCLC patients (n=179) from 2004 to 2010 was used to identify a patient cohort with nodal relapses (n=19). These cases were matched, 1:2, to controls, controlling for tumour volume (i.e. same or greater) and tumour location (i.e. same lobe). Reference (normalized total) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical record. Multivariate logistical regression analyses determined variables of interest.Results
The case and control cohorts were well matched with respect to age, sex, method of nodal staging, SUVmax, histology subtype, dose and length of follow up.. The controls, as expected, had larger gross tumour volumes (p=0.02). The mean hilar doses were 9.6 and 22.4 Gy for cases and controls, respectively (p=0.014). Similarly, the mean carinal doses were 7.0 and 9.2 Gy, respectively (p=0.13). The mean ipsilateral hilar doses were 19.8 and 3.6 Gy for ipsilateral non-hilar and hilar nodal relapses, respectively (p=0.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse (Figure 1).Figure 1Conclusion
Incidental hilar dose greater than 20 Gy (normalized to 2Gy/fraction) appears to be correlated with lack of hilar relapses in inoperable early stage NSCLC patients treated with 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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O01 - Prognostic and Predictive Biomarkers I (ID 94)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:T. Mitsudomi, V. Gregorc
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Auditorium, Level 1
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O01.01 - Genetic polymorphisms of inflammatory and DNA repair pathways, radiation-related esophagitis and pneumonitis in definitive chemoradiation treated non-small cell lung cancer patients. (ID 2997)
10:30 - 12:00 | Author(s): E.P. Saibishkumar
- Abstract
- Presentation
Background
The benefits of concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC) are tempered by treatment toxicity. Germline genetic variants have been associated with intrinsic radiosensitivity and radiotoxicity in various cancer settings. We investigated whether variants in genes involved in inflammation response and DNA repair pathways independently influence radiation-induced phenotypes of esophagitis and pneumonitis. From 19 candidate genes, 52 polymorphisms, directed by literature and by tagging procedures, were systematically selected for assessment. The candidate genes were involved in DNA repair (double-strand breaks, homology directed, nucleotide excision) and pro/anti-inflammatory signaling. The this investigation sought to evaluate the association of genetic sequence markers for two clinically significant radiation-induced toxicities - esophagitis and pneumonitis – seen in NSCLC patients treated with a curative intent.Methods
From 312 patients treated at PMCC between 2005-12, a training cohort was defined consisting of 92 definitive concurrent chemoradiation/radiation-treated NSCLC patients with genotype information on the 52 polymorphisms. A second, validation cohort consisted of 209 patients. Multivariate logistic regression was performed for each polymorphism of interest, adjusting for known clinical and dosimetric prognostic factors on the dichotomized outcomes of radiation esophagitis (Grades 0-2 vs 3-5) and pneumonitis (Grades 0-1 vs 2-5). The CTCAEv4.03 grading criteria were used. Additive genetic models were used for genetic association analysis. In the training set, genetic variants, genotyped by IlluminaGoldenGate, with p<=0.05 were identified for validation; HWE was set at p>0.01, a criteria met by all polymorphisms with statistical significance.Results
In the combined training and validation datasets, 63% were males, with median age of 65 years. Specifically in the training dataset, 65% were male, with median age of 62, median mean lung doses of 15.9, median max esophageal dose of 67.1 and median V20 of 27.6. For esophagitis, the final models were adjusted for concurrent chemotherapy, V20 and max esophageal dose. Five genetic variants linked to TNF and IL6 were significantly associated with outcome (each using wild-type genotype as reference) (Table 1). For pneumonitis, the final models adjusted for V20 and smoking status. Eight genetic variants found within four genes (ATM, BRCA2, IL1alpha, IL1RN) were associated with significant pneumonitis (Table 1).ESOPHAGITIS Function / Pathway Gene refSNP OR 95% CI P value pro-inflammatory cytokine TNF rs3093662 3.54 1.9-10.6 0.02 pro-inflammatory cytokine TNF rs3093664 3.42 1.2-10.2 0.03 pro-inflammatory cytokine TNF rs3093665 4.95 1.2-21.1 0.03 anti-inflammatory cytokine IL6 rs1800797 2.53 1.0-6.2 0.04 anti-inflammatory cytokine IL6 rs1800795 2.45 1.0-5.9 0.046 PNEUMONITIS Function / Pathway Gene refSNP OR 95% CI P value double-strand break repair ATM rs664143 2.67 1.3-5.6 0.01 double-strand break repair ATM rs664677 2.37 1.2-4.7 0.01 homology-directed repair BRCA2 rs1799955 2.59 1.3-5.3 0.01 homology-directed repair BRCA2 rs1801406 2.42 1.2-4.8 0.01 homology-directed repair BRCA2 rs1799943 2.09 1.0-4.2 0.04 anti-inflammatory cytokine IL1alpha rs17561 2.63 1.2-5.7 0.01 anti-inflammatory cytokine IL1alpha rs2856863 2.60 1.1-5.9 0.02 anti-inflammatory cytokine IL1RN rs3087263 0.17 0.04-0.8 0.04 Conclusion
In our 92 patient training set, genetic variations in TNF and IL6 are associated with radiation esophagitis, while genetic variations in ATM, BRCA2, IL1alpha and IL1RN are associated with pneumonitis. Results from the 209 patients in the validation dataset will be presented at the meeting (A.H. and G. L are co-senior authors).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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P2.08 - Poster Session 2 - Radiotherapy (ID 198)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.08-004 - Impact of medical co-morbidities on survival in patients treated with stereotactic body radiotherapy for early stage non-small cell lung cancer (ID 827)
09:30 - 16:30 | Author(s): E.P. Saibishkumar
- Abstract
Background
Stereotactic body radiotherapy (SBRT) is an effective treatment for early stage inoperable non-small cell lung cancer (NSCLC), with loco-regional control of 80-90%. However, the median overall survival of these patients is limited. We evaluate the impact of co-morbidities on patient survival and whether a subset of patients who may not benefit from SBRT can be identified.Methods
Patients treated on a prospective protocol at a single cancer center with SBRT for T1-T2N0 NSCLC from Oct 2004-May 2012 were evaluated. The most common doses delivered were 48Gy/4fr and 54Gy/3fr. The presence of significant medical co-morbidities including cardiac disease, COPD, cerebro-vascular disease, diabetes, previous pneumonectomy and oxygen dependence were recorded at baseline. Patient, tumor, and treatment data as well as outcomes were prospectively collected. Log rank tests were performed for survival analysis and chi squared tests used to analyze deaths within 1 year from radiotherapy treatment (D<1y). Cancer specific deaths (CSD) were defined as any death following a recurrence of the previously treated NSCLC.Results
There were 279 patients identified, 134 female (48%) and 145 male (52%). The median age was 76 years (range 48-93). The performance status was ECOG 0 in 87 patients (31%), ECOG 1 in 127 patients (46%), ECOG 2 in 53 patients (19%) and ECOG 3 in 9 patients (3%). There were 212 (76%) with T1 tumors, the remainder (24%) T2 tumors. The median follow up was 1.3 years. At last follow up, 111 patients (40%) had died, including 42 (15%) patients with D<1y. Of all deaths, 25 (22.5%) were CSD, the remainder from other causes. There were 222 patients (80%) identified as having a significant co-morbidity, collectively these conditions did not influence deaths from any cause (DAC) or CSD. The presence of cardiac disease (N=67) led to an increased risk of DAC (HR 4.1, p = 0.04) but not CSD (HR 1.2, p=0.28). These results were more pronounced for D<1y, patients with cardiac disease having increased D<1y, (HR 7.34, p=0.007), but not CSD<1y, (HR 2.9, p=0.09). Other co-morbidities were not correlated of survival. ECOG status was correlated with both DAC (HR 15.1, p=0.005) and CSD (HR 9.3, p=0.05).Conclusion
The presence of respiratory and vascular co-morbidities should not necessarily preclude a patient from receiving SBRT. ECOG status and prognosis from a cardiac point of view may be associated with poorer overall survival at 1 year and should be considered when assessing a patient’s suitability for SBRT.
