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S. Menon
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-036 - The Safety and Efficacy of Thoracic Reirradiation (ID 3070)
09:30 - 09:30 | Author(s): S. Menon
- Abstract
Background:
Intrathoracic malignancies including lung, esophageal, and pulmonary metastases frequently recur locally or regionally after initial therapy. The existing literature on the safety and efficacy of multiple courses of thoracic irradiation is limited. The purpose of this study was to evaluate local regional control and toxicity in patients who received up to three courses of thoracic radiation.
Methods:
We conducted a retrospective review of 51 patients who had undergone at least two courses of thoracic radiation. Two patients were found to have only a previous course of whole breast irradiation and were thus excluded for a total of 49 patients. Patient age, diagnosis, courses and doses of radiation therapy, chemotherapy and surgery were extracted from the record. Time to recurrence was determined by time from last radiation treatment to pathological confirmation or radiographic progression. Six potential treatment related grade 4 or 5 toxicities were identified (5 deaths).
Results:
The median age at diagnosis was 64. Median follow up was 3 years (range 0.76-12). 43 of the patients were with primary lung malignancy, 2 with esophageal, 3 with metastases and 1 unknown. 49 patients received at least two courses of intrathoracic radiation, 5 received 3 courses. 38 patients had died at time of last follow up, 10 were alive and one lost to follow up. 46% had local-regional recurrence at time of last follow up while 24% were disease free. The median cumulative dose was 111Gy for all patients, 113 Gy in those with Grade 4 or higher toxicity (NS). Median survival after completion of the first radiation treatment was 3.2 years. Median survival after completion of the last course of radiation was 1.25 years versus 0.58 years for those without and with Grade 4-5 toxicity respectively. The median time between the first and last course of radiation was 1.7 years. Five of the six patients with severe toxicity were disease free at time of death or last follow up. Grade 5 toxicities included massive hemoptysis, tracheal erosion, cardiac arrest, and respiratory failure. Dosimetric evaluation of these patients is underway. 50% of patients with severe toxicity had previous or subsequent thoracic surgery versus 23% in those without. Median time from end of first treatment to end of last treatment was 634 days (range: 0.39 -7.5 years) versus 465 days (range: 0.6-2.3 years) for patients without and with Grade 4-5 toxicity, respectively. None of the 5 patients who received 3 courses of radiation exhibited severe toxicity.
Conclusion:
Repeat courses of thoracic irradiation appear to be generally safe and effective with a median survival of 1.26 years following the last radiation treatment with 10% Gr4-5 toxicity in this population with cancer specific mortality of 78%. Future studies will identify clinical and dosimetric parameters that predict for severe toxicity.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-003 - Novel Fusion Protein ALK-MPRIP Exhibits ALK Activation and Sensitivity to Crizotinib (ID 1294)
09:30 - 09:30 | Author(s): S. Menon
- Abstract
Background:
Rearrangement of the ALK gene is an important therapeutic pathway in NSCLC. EML4 is the partner gene in the vast majority of ALK driven cancers, with other variants rarely reported. The clinical characteristics and sensitivity to ALK targeted agents in patients with non-EML4 variants are unknown.
Methods:
We report a patient case with a novel fusion of ALK-MPRIP (myosin phosphatase-Rho-interacting protein gene). A 49-year-old Caucasian female with less than 10 pack-year smoking history presented with chest pain and dyspnea on exertion. Chest x-ray showed mild CHF. An echocardiogram demonstrated a large pericardial effusion with tamponade physiology. She underwent a pericardial window with cytology of the pericardial fluid demonstrating adenocarcinoma, positive for TTF1 and napsin, consistent with lung primary. CT imaging revealed cervical and mediastinal adenopathy, bilateral pleural effusions, small lung nodules. She was staged as TxN3M1a. She was negative for EGFR and ALK by FISH. Tissue was sent for next generation sequencing due to her light smoking history, which revealed a never before characterized ALK-MPRIP fusion. As the functional significance of this alteration was unknown, she continued Carboplatin/Pemetrexed/Bevacizumab therapy for 4 cycles followed by 6 cycles of maintenance Pemetrexed/Bevacizumab before documented progression. She was subsequently started on Crizotinib.
Results:
Two months after starting Crizotinib, CT scans demonstrated decreased lung nodules, lymphadenopathy and improved interstitial thickening. After 5 months of treatment CT scans demonstrated new ground glass opacities with increasing bilateral interlobular septal thickening concerning for either Crizotinib-induced lung toxicity or lymphangitic carcinomatosis. Bronchoscopy with transbronchial biopsy demonstrated lymphangitic spread suggestive of progression on Crizotinib within 6 months of therapy. The average PFS of Crizotinib treated EML4-ALK translocated patients is 7.7 months.Figure 1Figure 2
Conclusion:
ALK-MPRIP is a novel fusion gene causing ALK activation. Our patient responded to Crizotinib but had a shorter than average PFS compared to EML4-ALK mutated patients.
