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Valerie W Rusch
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ES 05 - Surgical Skills (ID 514)
- Event: WCLC 2017
- Type: Educational Session
- Track: Surgery
- Presentations: 1
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ES 05.02 - Superior Sulcus Tumor (ID 7600)
16:00 - 16:15 | Presenting Author(s): Valerie W Rusch
- Abstract
- Presentation
Abstract:
The unique location of Pancoast tumors makes complete resection challenging and usually includes the upper lobe, involved chest wall with or without the subclavian vessels, portions of the vertebral column and T1 nerve root, and dorsal sympathetic chain. Several approaches are used depending on tumor location. Posterior Approach The patient is positioned in the lateral decubitus position, rotated slightly anteriorly to expose the paravertebral region. The chest is explored via a posterolateral thoracotomy in the 5[th] intercostal space. If the tumor appears resectable, the incision is extended to the base of the neck posteriorly and around the anterior border of the scapula anteriorly. The scapula is elevated with an internal mammary retractor. The scalene muscles are detached from the first and second ribs. Involved ribs are divided anteriorly. Dissection is carried along the superior border of the first rib in the subperiosteal plane. The erector spinae muscles are retracted off the thoracic spine to expose the costovertebral gutter. The transverse processes and rib heads are resected en-bloc at the lateral border of the facet joint. The chest wall is retracted anteriorly, and the intercostal nerves ligated before division to prevent cerebrospinal fluid leak. Thoracic nerve roots below T1 are transected without neurologic sequelae. Since the T1 nerve root provides motor innervation to the hand, it is ligated only in cases of tumor invasion. Division of the C8 nerve root will result in permanent arm/hand paralysis. The detached chest wall is allowed to fall into the chest cavity and an upper lobectomy and lymph node dissection is completed. Reconstruction of the chest wall is necessary when the defect is larger than the first three ribs and can be performed with a 2 mm thick PTFE patch. Tumors Involving the Vertebral Bodies and Epidural Region Vertebral body invasion by Pancoast tumors no longer a contraindication to surgical resection because of contemporary spine instrumentation. With multimodality therapy, T4 lesions with vertebral body or epidural extension can be resected with curative intent. We use spine MRI to divide tumors into four classes, A-D, based on the degree of spinal column and neural tube involvement. Class A and B tumors are T3 lesions amenable to complete R0 resection. Class C and D tumors are T4 lesions not amenable to en-bloc resection but can still be completely resected. Class C tumors extend into the neural foramina with limited or no vertebral body involvement but have unilateral epidural compression. Class D tumors involve the vertebral column, either the vertebral body and/or lamina with or without epidural compression. Class A, B and some class C tumors are approached through a posterolateral thoracotomy. A high-speed drill is used to remove involved vertebral bodies. The posterior longitudinal ligament is removed and provides a margin on the anterior dura. The disc spaces adjacent to the tumor are exenterated in order to aid in spinal fixation. Anterior reconstruction alone is sufficient for resections of 1-2 vertebral bodies. Autologous bone from the iliac crest or non-diseased rib, allograft fibula, methymethacrylate with Steinman pins, or corpectomy cages can all be used for reconstruction. Patients requiring any degree of epidural decompression in the upper thoracic spine undergo combined posterior and anterior approach. Long segment posterolateral spinal instrumentation and fusion avoids the development of debilitating deformity. Class D tumors involving the posterior elements (spinous process, laminae, and pedicles) are also resected through a combined posterior/anterior approach. Patients are first positioned prone and a posterior midline incision made. The involved areas of the spinous process, laminae, and pedicles are resected. Epidural tumor is dissected off the dura and a multilevel resection of affected nerve roots done. Posterior fixation is accomplished in order to maintain coronal and sagittal stability. Muscle flap rotation by a plastic surgeon can be done to reduce the risk of skin breakdown and infection of the spine hardware. The incision is then closed, the patient turned to the lateral decubitus position, a posterolateral thoracotomy performed, and the lung and chest wall resection completed. Anterior Approaches Pancoast tumors involving the subclavian vessels are best approached anteriorly, using the anterior transcervical approach originally described by Dartevelle and modified by others. The patient is positioned supine with the neck hyperextended and the head turned to the opposite side of the lesion. An inverted L-shaped incision is carried down the anterior border of the sternocleidomastoid muscle and extended below the clavicle to the level of the second intercostal space, then turned horizontally following a parallel line below the clavicle to the deltopectoral groove. The sternal attachment of the sternocleidomastoid is divided along with the insertion of the pectoralis major. The scalene fat pad and lymph nodes are excised. If the tumor is resectable, the upper part of the manubrium is divided and the incision carried into the second intercostal space via an L-shaped incision. The involved section of the subclavian vein is resected but not reconstructed. The anterior scalene muscle is divided at its insertion onto the first rib. The phrenic nerve is preserved. The subclavian artery is resected and reconstructed with a 8 or 10 mm PTFE graft. The middle scalene muscle is detached from the first rib to expose the C8 and T1 nerve roots. The ipsilateral prevertebral muscles and paravertebral sympathetic chain and stellate ganglion are resected off the anterior aspect of the vertebral bodies of C7 and T1. TheT1 nerve root is commonly divided just lateral to the T1 intervertebral foramen. The anterolateral arch of the first rib is divided at the costochondral junction and the second rib is divided at its midpoint. The third rib is dissected on its superior border in a posterior direction toward the costovertebral angle and the first two through three ribs are disarticulated from the transverse processes. From this cavity, an upper lobectomy is completed. If exposure for the lobectomy and chest wall resection is inadequate, the anterior incision is closed, the patient turned into the lateral decubitus position and the rest of the resection performed via a posterolateral thoracotomy
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OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)
- Event: WCLC 2017
- Type: Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:M. Chida, Jhingook Kim
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 311 + 312
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OA 03.03 - Phase II Trial of Cetuximab and Chemotherapy Followed by Surgical Resection for Locally Advanced Thymoma (ID 10288)
11:20 - 11:30 | Author(s): Valerie W Rusch
- Abstract
- Presentation
Background:
The mainstay of treatment for thymoma is surgery with neoadjuvant chemotherapy recommended to patients with locally advanced disease. EGFR is overexpressed in thymoma. Clinical responses to single-agent cetuximab have been reported in patients with advanced cetuximab. We conducted this two-site prospective phase II trial of cetuximab combined with a standard induction chemotherapy regimen of cisplatin, doxorubicin and cyclophosphamide (PAC) in patients with locally advanced thymoma prior to surgical resection.
Method:
Patients with clinical Masaoka stage III-IVA thymoma were treated with cetuximab (250mg/m[2] weekly x 4 weeks) followed by cetuximab (250 mg/m[2] weekly) combined with cisplatin (50mg/m[2]), doxorubicin (50 mg/m[2]) and cyclophosphamide (500mg/m[2]) 3 weeks x 4 cycles). Radiographic response was assessed by CT using RECIST 1.1 and FDG-PET using PERCIST. All patients went on to surgery after completion of induction therapy. The primary endpoint was major pathologic response (MPR, >90% treatment effect). Planned enrollment was 18 patients in first stage of a two stage design. If 1 MPR was observed, then enrollment would expand to 28 patients.
Result:
Eighteen patients were enrolled: 8 women, median age 53 (range 32-73). WHO Histologic subtype A: 2, AB: 3, B1: 3, B2: 7, B3: 3. Final Masaoka stage I: 2, II: 2, III: 5, IVA: 9. There were no responses to cetuximab alone by RECIST criteria, although 1 patient had a 25% reduction in indicator lesions. Response rate (CR+PR), in evaluable patients after complete treatment course was 50% (8/16, 95% CI 28-72%). Partial responses by PERCIST criteria were seen on PET in 11/18 (61%) evaluable patients. There were no MPRs. R0 resection was obtained in 7 patients; 5 had R1 and 6 had R2 resections.
Conclusion:
The addition of cetuximab to PAC chemotherapy did not lead to pathologic complete responses in the neoadjuvant setting. Cetuximab alone appears to have little effect during 4 weeks of treatment. There was no apparent increase in radiographic response rate with the addition of cetuximab to PAC chemotherapy compared to historical series.
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.03 - Liquid Biopsy in the Lung Cancer Clinic: A Prospective Study of Plasma DNA next Generation Sequencing to Guide Matched Therapy (ID 8218)
11:20 - 11:30 | Author(s): Valerie W Rusch
- Abstract
- Presentation
Background:
Liquid biopsy for plasma circulating tumor DNA (ctDNA) next generation sequencing (NGS) is now commercially available and increasingly adopted in clinical practice with a paucity of evidence based guidance. We set out to prospectively determine the utility of plasma ctDNA NGS in the lung cancer clinic.
Method:
Patients (pts) with advanced NSCLC who were driver unknown or resistance mechanism unknown were eligible. Pts were enrolled prospectively at Memorial Sloan Kettering (NY, USA) and Northern Cancer Institute (Sydney, Australia). Peripheral blood was collected in Streck tubes (10-20mL) and sent to Resolution Bioscience (Bellevue, WA) for targeted NGS of extracted DNA using a bias corrected hybrid capture 21 gene assay in a CLIA laboratory with unique reads at 3000x and sensitive detection at variant allele frequency above 0.1%. Clinical endpoints included detection of oncogenic drivers, turnaround time, comparison to tissue NGS when available, and ability to match pts to targeted therapy along with their treatment outcomes.
Result:
Seventy-six pts were prospectively accrued. Plasma NGS detected an oncogenic driver in 36% (27/76) of pts, of whom 14% (11/76) were matched to targeted therapy; including pts matched to clinical trials for HER2 exon 20 insYVMA, BRAF L597Q and MET exon14. Of the 10 evaluable pts, 10 partial responses were observed. Mean turnaround time for plasma was 6 days (3-12) vs 21 days (16-30) for tissue (P <0.0001). Plasma ctDNA was detected in 60% (46/76) of pts; detection rate was 46% (16/35) if blood was drawn on active therapy and 73% (30/41) if drawn off therapy, either at diagnosis or progression (Odds ratio 0.31, 95% CI 0.12 – 0.81; P=0.02). Of the 25 concurrent tissue NGS performed to date, there was a 96% plasma concordance with tissue and a 60% tissue concordance with plasma for driver mutations.
Conclusion:
In pts who were driver or resistance mechanism unknown, plasma NGS identified a variety of oncogenic drivers with significantly shorter turnaround time compared to tissue NGS, and matched patients onto targeted therapy with clinical benefit. Plasma ctDNA is best detected at diagnosis of metastatic disease or at progression. A positive finding of an oncogenic driver in plasma is highly specific and can immediately guide treatment, but a negative finding may still require tissue biopsy. Our findings provide evidence to support the incorporation of plasma NGS into practice guidelines.
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