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A.J. Wu
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-004 - Occult Primary Non-Small Cell Lung Cancer with Mediastinal Lymph Node Involvement (ID 1573)
09:30 - 09:30 | Author(s): A.J. Wu
- Abstract
Background:
Non-small cell lung cancer (NSCLC) involving mediastinal lymph nodes without an identifiable primary tumor is a rare presentation. While definitive surgery or radiotherapy with or without concurrent chemotherapy is typically recommended, little is known about the treatment outcomes. As such, we reviewed our institutional experience to determine if subsequent development of lung tumors is common and whether prognosis is comparable to stage III NSCLC in general.
Methods:
This study was an IRB-approved retrospective review of an institutional NSCLC database. Twenty-six patients with biopsy-proven NSCLC involving mediastinal lymph nodes with no identifiable lung primary lesion and no evidence of distant metastases treated with curative intent between 1995-2013 were identified. PET-CT staging was performed in 25 of 26 patients. All followup was calculated from date of diagnosis.
Results:
The median followup was 44 months. The median age at diagnosis was 60 years (range 51-81) among the 18 males (69%) and 8 females (31%). N2 and N3 disease were each present in 13 (50%) patients, respectively. Histologies included adenocarcinoma in 12 (46%), squamous cell carcinoma in 10 (38%), NSCLC not otherwise specified in 3 (12%), and large cell lung carcinoma in 1 (4%). Eleven patients underwent EGFR mutation analysis, with no sensitizing mutations identified. All patients had a smoking history (median 35 pack-years). Four (15%) patients underwent complete surgical resection, of whom 3 underwent induction chemotherapy and 1 was treated with surgery alone. One of the four patients underwent post-operative radiation therapy to 54 Gy. Twenty-two (85%) patients were treated with definitive radiation therapy including sequential chemotherapy and radiation in 8 (mean RT dose = 70 Gy), concurrent chemoradiation in 10 (mean RT dose = 60 Gy), neoadjuvant chemotherapy followed by concurrent chemoradiation in 3 (mean RT dose = 66 Gy), and radiation alone in 1 (treated to 60 Gy). The median overall survival was 78.1 months with actuarial 2- and 5-year survival rates of 78% and 67%, respectively. Five patients developed intrathoracic failure at a median of 19.8 months. One patient had an isolated lung failure at 13.6 years, but this likely represents a secondary primary and not tumor recurrence. Two patients had isolated mediastinal lymph node failures at 18.1 and 19.8 months and 2 patients initially had a mediastinal lymph node recurrence at 0.2 and 3.4 years, but subsequently failed in the lung at 8.5 and 3.6 years respectively. The actuarial 2- and 5-year intrathoracic control rates were 85.7% and 78.6%. Nine patients developed metastatic disease at a median of 16.5 months. The 2- and 5-year actuarial freedom from distant metastases was 70.9% and 59.1%. Among patients receiving definitive radiation, there was no difference between those receiving concurrent chemotherapy and those who did not.
Conclusion:
To our knowledge, this is the largest reported series of occult primary NSCLC involving mediastinal nodes. Definitive local therapy, including radiotherapy and surgery, was associated with very favorable locoregional control and survival, particularly compared with expected outcomes for stage III NSCLC.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-022 - Intraoperative Brachytherapy for Thoracic Malignancies Resected with Close or Positive Margins (ID 2795)
09:30 - 09:30 | Author(s): A.J. Wu
- Abstract
Background:
Local recurrence is a significant problem after surgical resection of thoracic tumors, particularly when close or positive margins are anticipated. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we used this technique in an attempt to reduce local recurrence, particularly for patients who had already received external beam radiation. We updated our experience with thoracic IORT to assess disease control and toxicity outcomes.
Methods:
We performed a retrospective review of patients undergoing permanent I-125 mesh placement or temporary Ir-192 afterloading therapy during surgical resection of primary or metastatic thoracic tumors between 2001 and 2013. In general, for I-125 brachytherapy, iodine seeds were sutured into a mesh at 1cm intervals to form a planar implant delivering 85-250Gy to the MPD, which was then sutured onto the at-risk site. For Ir-192 brachytherapy, a HAM applicator was apposed to the at-risk site, then connected to the afterloader to deliver 7.5-16Gy to a depth of 0.5cm from the applicator surface. Kaplan-Meier method was used to estimate local control and overall survival, and logrank test was used to assess the impact of various clinical or treatment factors on local control.
Results:
Fifty-nine procedures (41 permanent, 18 temporary) were performed on fifty-eight patients (median 56 years old, range 19-77). Most common tumor histologies were NSCLC (n=23), sarcoma (n=18), thymic carcinoma (n=10), and mesothelioma (n=3). Treated sites were chest wall/paraspinal (n=31), lung (n=16), and mediastinum (n=12). Thirty-four procedures were performed on patients who had previously received external beam RT (EBRT) to the area (median 53.1 Gy). Final margins were microscopically negative in 25 cases (42.4%) and positive or not assessed in the remainder. The median size of the treated area was 27cm[2] (range: 4-152cm[2]). Median followup was 28.5 months. Actuarial local control at 1 and 2 years was 68.1% and 63.4% respectively. Median survival was 46.2 months. Overall survival at 1 and 2 years was 80.2% and 70.4% respectively. No perioperative deaths occurred. There was no significant difference in local control according to margin status, brachytherapy technique, use of adjuvant EBRT, or metastatic vs. primary tumor. Two patients (3.4%) experienced grade 3+ toxicities possibly related to IORT: one patient who also received preoperative EBRT developed pneumonitis; a second patient with prior EBRT for lymphoma died from complications of SVC syndrome likely induced by radiation fibrosis. An additional 8 patients had grade 3+ postsurgical complications (such as empyema, chylothorax, and pulmonary emboli) unlikely related to IORT. Four patients had grade 2 nerve injury also unlikely related to IORT.
Conclusion:
Intraoperative brachytherapy is associated with good local control after resection of thoracic tumors felt to be at very high risk for recurrence due to close or positive margins. There is a very low incidence of severe toxicity attributable to brachytherapy. Intraoperative brachytherapy should be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-032 - Prognostic Impact of EGFR and KRAS Mutations in Patients with Lung Adenocarcinoma Treated with Definitive Radiation Therapy (ID 2422)
09:30 - 09:30 | Author(s): A.J. Wu
- Abstract
Background:
An association of EGFR and KRAS mutations with radiation sensitivity has been postulated in preclinical studies. Recent clinical studies reported longer local control and survival in patients (pts) harboring EGFR mutations treated with definitive radiotherapy (RT). Here, we sought to evaluate the prognostic impact of EGFR and KRAS mutations in 223 adenocarcinoma pts treated with definitive RT at our institution.
Methods:
Between 2004 and 2013, 466 inoperable pts with non-squamous lung cancer were treated with definitive RT ± chemotherapy. Mutational testing was performed in 223 pts. 44% were male, 56% female. 65% were former, 13% never, and 22% current smokers. Clinical stage was II in 5%, IIIA in 37% and IIIB in 58%. Median size of tumor was 3.8 cm (range 0.5-12.2 cm). 60% received concurrent, 31% sequential chemo-RT and 9% RT alone. The median RT dose was 63Gy (range 50-80Gy). OS was estimated by the Kaplan-Meier method. Cumulative incidence functions were used to estimate local failure (LF) and distal failure (DF), using death without failure as a competing risk. Association of factors with OS was analyzed by Cox regression and association with LF and DF by competing risk regression.
Results:
EGFR status was wild-type in 205 pts (92%) and mutated in 18 (8%). The most common EGFR mutations were exon 19 deletion (8 pts), followed by exon 21 L858R (7 pts), and exon 20 insertion (3 pts). KRAS status was wild- type in 142 pts (64%), mutated in 63 (28%), and not performed in 18 (8%). The most common mutations were G12C (13%), followed by G12V (5%) and G12A and G12D (3% each). With a median follow-up among survivors of 32.7 months (range 0.6-114), the median OS was 38 months for pts with EGFR mutation versus 26 months for pts without (p=0.96); 21 months for patients with KRAS mutation versus 31 months for pts without (p=0.24). 2-year LF was 37% and 46% for pts with and without EGFR mutation, and 48% and 46% for pts with and without KRAS mutation, respectively. 2-year DF was 80% and 64% for pts with and without EGFR mutation, and 62% and 64% for pts with and without KRAS mutation, respectively. On univariate analysis, factors significantly associated with improved OS included KPS ≥ 80 (p=0.01), increasing RT dose (p=0.04) and use of concurrent chemotherapy compared to RT alone (p=0.001). Factors associated with higher risk of LF included stage IIIB (p=0.04) and sequential rather than concurrent chemotherapy (p=0.05). Factors associated with a higher risk of DM included stage IIIB (p=0.03) and lower RT dose (p=0.003). Association of EGFR and KRAS mutations did not reach statistical significance on univariate analysis, thus we did not further investigate their effects by multivariable analysis.
Conclusion:
Despite analyzing the largest patient population to date, we did not identify a significant prognostic impact by EGFR or KRAS mutational status. The lack of an observed association could be related to the low rate of EGFR mutations identified. RT dose and use of concurrent chemotherapy were significantly associated with overall survival.
