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Low-dose CT screening for lung cancer is a complex and controversial topic. This article reviews the history of lung cancer screening trials and addresses the principles and confounding biases associated with screening. Chest radiography was initially used for lung cancer screening in the 1970s. In the mid-1990s helical single-detector CT came into use, followed by helical multidetector CT, the current method of screening. Results from prevalence studies and a few single-arm incidence studies have raised concerns about overdiagnosis and the high rate of nodule detection. Follow-up studies and further investigation are needed. To this end, a randomized, controlled trial sponsored by the National Cancer Institute is underway to evaluate disease-specific mortality.

Primary sarcomas of the thorax are rare. The diagnosis is established only after sarcomalike primary lung malignancies and metastatic disease have been excluded. Primary sarcomas of the thorax are classified according to their histologic features and constitute a large group of tumors that occur in the lung, mediastinum, pleura, and chest wall. Angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, and mesothelioma (sarcomatoid variant) are the most common primary intrathoracic sarcomas. Ewing sarcoma, primitive neuroectodermal tumor, chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, synovial sarcoma, and fibrosarcoma usually arise in the chest wall. Although primary thoracic sarcomas commonly manifest as large, heterogeneous masses, they have a wide spectrum of radiologic manifestations, including solitary pulmonary nodules, central endobronchial tumors, and intraluminal masses within the pulmonary arteries. The different histologic types of sarcomas are frequently indistinguishable at radiologic analysis. However, differences in clinical presentation and the location of the tumor, as well as morphologic features such as calcification within the mass and rib involvement, can be useful in suggesting the appropriate diagnosis. For example, a large rib mass in a child with fever and malaise indicates a Ewing sarcoma, a mass with a calcified matrix is likely a chondrosarcoma or osteosarcoma, and a pulmonary artery mass is likely a leiomyosarcoma.

We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat.Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities.Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHF. Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%).Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process.

7098 Background: Patients with CLL that develop Richter’s syndrome (RS) have a very poor prognosis. Similarly, pts with CLL that have clinical and histological features (increased large cells/prolymphocytes in CLL tissue biopsy) of increased aggressiveness (defined as accelerated phase CLL, AP) have a poor prognosis. In order to identify prognostic factors in pts with AP and RS, collectively referred to as TC, we reviewed our center experience. Methods: Pts with TC and complete evaluation including biopsy and concomitant FDG/PET were included. Pts with de novo TC were excluded as their prognosis is substantially superior versus previously treated pts. Pts with N+ or M+ concurrent solid tumors were also excluded. Since FDG/PET-derived SUV reflects tumor proliferative rate, we used SUVmax≥10 to indicate high-risk disease (Falchi, Blood. 2012;120: abstr # 927). We identified factors associated with outcome and performed a multivariable model for OS. Results: One hundred eighty-three consecutive pts with TC (99 with AP and 84 with RS) were evaluated at MDACC between 2002 and 2012. Demographic and clinical characteristics were similar between pts with AP and pts with RS. 30% and 77% of pts with AP and RS, respectively had an SUVmax≥10. Approximately half of the pts were treated with intensive chemoimmunotherapy after the TC diagnosis. CR rates were 21% and 16% and overall response rates were 37% and 26% for pts with AP and RS, respectively. At the time of this analysis 144/183 pts have died, for a median OS of 9.6 months (7.9-14.7). Age ≥65, B symptoms, LDH, β2-microglobulin, del17p, SUVmax≥10, extensive disease by FDG/PET (SUVmax≥5 on both sides of the diaphragm), PS≥2 bulky disease and high Ki67 correlated with shorter OS. In multivariable analysis SUV uptake (max≥10), PS higher than 1 and bulky nodal disease (>5 cm) retained independent significance. Conclusions: Based on our experience, an SUVmax of 10 or higher, PS higher than 1 and bulky nodal disease (>5 cm) are the most important factors predicting outcome in pts with TC. A prognostic model for survival is being developed for pts with TC.

Malignant pleural mesothelioma (MPM) is an uncommon neoplasm arising from mesothelial cells of the pleura and less commonly of the pericardium or peritoneum. The annual incidence of 3000 cases is expected to increase by more than 50% in the coming decade due to the patterns of occupational exposure to asbestos and latency period of 30–40 years [1, 2]. Treatment options depend on stage at presentation with an increasing tendency to perform surgical resection in limited disease. Primarily in an attempt to distinguish those patients who are potentially resectable and stratify patients into categories with similar prognosis, the new international staging system for MPM describes the anatomic extent of disease in a traditional TNM (tumor, node, metastasis) system. Because accurate anatomic staging is becoming important in determining the selection of patients for potentially curative resection, imaging evaluation is an essential component in the appropriate management of these patients.

Abstract 927 Introduction. Richter's transformation (RT) occurs in 2–8% of pts with chronic lymphocytic leukemia (CLL) and is associated with poor prognosis. Moreover, pts with CLL often show clinical and/or histologic features of aggressive disease, but do not fulfill the histological criteria for RT. FDG/PET is a diagnostic tool in hematologic malignancies. Standardized uptake values (SUV) measured by FDG/PET correlates with tumor cell proliferation and aggressiveness. FDG/PET is increasingly used to evaluate pts suspicious for RT. We therefore reviewed the experience with FDG/PET in the diagnosis and management of pts with aggressive CLL and RT seen at our Institution and correlated FDG/PET data, histology, and clinical outcomes in these pts. Methods. We studied pts assessed with FDG/PET and concurrent lymph node biopsy (or marrow diagnosis of transformation). According to the histological characteristics pts were grouped in 3 categories: chronic phase (CP), increased aggressiveness (IA) or overt RT. IA was defined for this report by the presence of either increased number of large cells or ≥10% prolymphocytes in the tissue specimen. The extent of disease was assessed by FDG/PET and defined: limited = hypermetabolic sites with SUVbwmax≥5 on one side of the diaphragm; extensive = hypermetabolic sites with SUVbwmax≥5 on both sides of the diaphragm. After therapy, restaging FDG/PET was analyzed, when available, for response assessment. Results. 750 pts with CLL had at least 1 complete FDG/PET report, 422 were excluded from this analysis because of: no biopsy in 341 pts, no FDG/PET at time of biopsy in 34, concurrent cancer in 25, benign histology in 18, CP histology in pt with past RT/IA in 4. 328 pts had both FDG/PET and histological characterization and are the focus of this report. 93 pts had RT, 116 had IA and 119 had CP. Patient characteristics are summarized in table 1. We analyzed FDG/PET results in these 328 pts. Median highest SUV (SUVbwmax) was 17.9 (0-56.3) for pts with RT, 6.7 (0-37.8) for pts with IA and 3.6 (0-14.3) for pts with CP. Using an SUVbwmax cutoff of 5 sensitivity, specificity, positive and negative predictive value for the detection of RT were 88%, 48%, 40% and 91%, respectively. We next correlated FDG/PET result, histology and survival. Median overall survival (OS) was 7.9, 19.7, and 77.3 months in pts with RT, IA and CP, respectively. SUVbwmax correlated with OS. An SUVbwmax cutoff of 10 showed the highest discriminatory power: median OS was 56.4 months (95% CI: 36.4 – 71.3) in pts with SUVbwmax Conclusion. In our experience, FDG/PET accurately suggested the presence of RT in pts with CLL. SUVbwmax correlates with OS in pts with transformed CLL, independently of disease histology and extension. Restaging FDG/PET also predicted OS in pts with RT or IA. Prospective studies to validate the role of FDG/PET in the evaluation and management of pts with CLL are ongoing Disclosures: No relevant conflicts of interest to declare.

e19645 Background: The natural history of isolated gonadal vein thrombosis (GVT) occurring in cancer patients (pts) is not well described in the medical literature. GVT in cancer pts it is of uncertain clinical significance. Methods: Utilizing a software program allowing a searchable database of radiology reports, the computerized tomographic scan (CT) reports of pts at a single cancer center from January 1, 2004 to June 30, 2011, were searched for the term “gonadal vein thrombus”. Pts included in this analysis had a diagnosis of cancer, isolated GVT (i.e. no evidence of thrombosis at another site), and at least six months of follow-up information. Results: 162 cancer pts with GVT were identified for analysis [median age 57.8 ± 12 years, right GVT 89 pts (54.9%), left GVT 59 pts (36.4%), bilateral 14 pts (8.6%)]; the majority of the pts (96, 59.3%) had a non-gynecologic malignancy. At the time of diagnosis of GVT the majority of pts were receiving chemotherapy (84, 51.9%); 70 pts (43.2%) had surgery within the prior six months (the most common being hysterectomy, 127 pts, 78.6%). The majority of pts in this study had metastatic disease (93, 57.4%) as well as active cancer (138, 85.1%, defined as GVT occurring at the time of cancer diagnosis, disease recurrence, metastatic disease, or treatment for cancer within the prior six months); median follow-up time was 22 months. A minority of pts received anticoagulation (28pts, 17.2%). Twenty-two pts (13.6%) developed a recurrent venous thromboembolic event (VTE); these events were pulmonary embolism (12 pts, 7.4%), deep venous thrombosis (5 pts, 3.1%), inferior vena cava thrombosis (4 pts, 2.5%). Median time to development of re-thrombosis was 7 months (range 2-13.5 months). Active cancer was the only risk factor significantly associated with recurrent VTE (p = 0.047); pts with prior hysterectomy had a significantly reduced risk of recurrent VTE (p = 0.036). Conclusions: Incidental isolated GVT identified in cancer pts has a high risk of recurrent VTE (13.6%). Based upon specific pts risk factors for VTE, treatment of an incidentally detected GVT in cancer pts with anticoagulation, as per guidelines for other VTE sites, may be indicated.

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

7527 Background: Æ-941 is a shark cartilage extract with antiangiogenic properties. We conducted a placebo-controlled trial testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria included performance status (PS) < 2, weight loss < 10%. Subjects received one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) × 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) × 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) × 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) × 2 cycles. Subjects were randomized to receive Æ-941 (Arm A) or placebo (Arm B), 120 mL orally twice daily, at the start of IC and continuing after CRT as maintenance therapy. Randomization was stratified for stage, gender, and type of chemotherapy. The primary endpoint was overall survival (OS), with a planned sample size of 756 subjects providing 80% power to detect a 25% difference in OS, assuming a control arm median survival time (MST) of 13 months, type I error 0.05. Results: Between 6/00 and 2/06, 384 subjects were enrolled onto the trial and randomized. In 2/06 the trial was closed to new patient entry due to insufficient accrual. This final analysis is based on 379 randomized and eligible subjects (188 arm A, 191 arm B). Subject characteristics: 60% male, median age 63 years (range 37–84), 56% stage IIIB, 58% C-based chemotherapy, median follow-up 3.7 years. There was no significant difference in OS between arms A and B, with MSTs of 14.4 (95% CI 12.6–17.9) and 15.6 (95% CI 13.8–18.1) months, respectively (log-rank p=0.73). OS by pre-specified stratification factors: stage IIIB vs IIIA (MST 13.9 vs. 17.4 months, p=0.25), C vs. CDDP chemotherapy (MST 14.4 vs. 16.7 months, p=0.13), and male vs. female (MST 15.7 vs. 15.1 months, p=0.74). The study drug was well tolerated. Fewer subjects in arm A experienced grade 3 or higher adverse events (66% vs. 77%, p=0.018). Conclusions: The addition of Æ−941 to IC and CRT does not improve OS in patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

5521 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for advanced or recurrent HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received one regimen of induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75mg/m2 and cisplatin 75mg/m2, intravenously every 3 weeks and erlotinib 150 mg by mouth daily. Patients were treated with growth factor support. Results: 37 pts have been enrolled thus far. Median age is 56 years (range 39–72). Median ECOG PS is 1 (range 0–2). 32 pts are evaluable for confirmed response using RECIST criteria. Complete responses have been in observed in 3 pts, partial responses in 18 pts and 8 pts have stable disease for an overall response rate of 66% and disease control rate of 91%. Only 2 pts progressed after 2 cycles of treatment. 5 pts had grade 3/4 neutropenia (2 febrile),1 pt had grade 4 diarrhea, and 2 pts had grade 3 rash. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusion: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in advanced HNSCC. Data collection for response rate, duration of response and survival is ongoing. Trial accrual continues up to 50 patients and biopsies are being collected for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). The full data set will be presented at the annual meeting. [Table: see text]

7144 Background: AE-941(Neovastat, Aeterna Laboratories) is a standardized shark cartilage extract with antiangiogenic properties (inhibition of VEGF signaling and MMP activity, induction of endothelial cell apoptosis). An ongoing placebo-controlled trial is testing AE-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria include performance status (PS) < 2, weight loss < 10%. Subjects receive one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) x 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) x 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) x 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) x 2 cycles. AE-941 or placebo (120 ml orally twice daily) is started with IC and continued after CRT as maintenance therapy. Planned sample size: 756. Results: A data safety board review of the first 4...

5565 Background: Treatment options for advanced disease are limited and for those patients failing chemotherapy, there are few viable options. Lonafarnib is a novel tricyclic peptidomimetic compound that is a potent and specific inhibitor of farnesyl protein transferase. We have previously reported clinical activity of lonafarnib in untreated HNSCC (4 of 22 patients showed response despite drug exposure for only 7–14 days). We proposed to assess the activity of lonafarnib in advanced HNSCC patients. Methods: An open-label phase II single-center study was conducted to determine the objective response rate of lonafarnib administered at 200 mg bid, enrolling patients who were incurable and who failed at least one platinum-containing regimen, but received no more than three prior regimens. Results: Fifteen patients, aged 32 to 66 (median age 57) were enrolled. All patients had baseline ECOG PS 0 or 1. Median treatment duration was 61 days (range 0–224 days). Median time to progression was 62 days. No objectiv...

7140 Background: TLK286 (Telcyta) is a novel glutathione analog prodrug activated by GST P1–1, which is overexpressed in NSCLC, releasing two electrophilic fragments that induce apoptosis. TLK286 has demonstrated significant single agent activity by RECIST in two Phase 2 NSCLC trials. In preclinical models, TLK286 is not cross resistant to docetaxel and shows synergistic inhibition in MCF-7 cells. Methods: The objectives were to determine the MTD of the TLK286/docetaxel combination and the objective response rate (ORR) by RECIST. NSCLC patients (pts) who had failed prior platinum-based therapy were treated with TLK286 at 500, 750 or 960 mg/m2 and docetaxel at 75 mg/m2 every 3 weeks until tumor progression or unacceptable toxicity. Results: At interim analysis, 30 pts (16 M, 14 F), median age 65 (range 46–80), median ECOG performance status 1, median prior regimens 1.5 (range 1–3) have received 103+ cycles (mean 3.4 cycles/pt, range 1–11). Pts failed prior therapies with: platinum (100%), paclitaxel (70%),...

Hypothesis Positron emission tomography can be useful in predicting response of esophageal cancer after preoperative chemo-radiation therapy (CRT). We evaluated the use of integrated computed tomography (CT)-PET among patients with esophageal cancer being considered for resection after CRT. Methods Three reviewers blinded to clinical and pathologic staging retrospectively reviewed the CT-PET scans of patients with esophageal cancer after preoperative CRT who underwent esophagectomy. [ 18 F]-fluoro-2-deoxy-D-glucose uptake for residual malignancy was determined by visual analysis and semi-quantitatively when standardized uptake value (SUV) was ≥4. Results Forty-two patients underwent esophageal resection. Using visual analysis, CT-PET had a sensitivity of 47% and specificity of 58% in detecting residual malignancy. Using semi-quantitative analysis, 19 patients had a SUV ≥4 in the region of the primary esophageal tumor and were interpreted as having residual malignancy (sensitivity 43%, specificity 50%). Of these 19, six had complete pathologic response to CRT. These false-positive results, due to therapy-induced ulceration detected at endoscopy, limit the use of CT-PET alone in detecting residual malignancy. Similarly, sensitivity (25%) and specificity (73%) of endoscopy/biopsy in detecting residual malignancy were poor. However, the accuracy of CT-PET in detecting residual malignancy was improved when combined with endoscopic findings. In the absence of ulceration at endoscopy, 8 of 8 patients with SUV ≥4 after chemo-radiation had residual malignancy at surgery. Conclusions CRT-induced ulceration results in false-positive results on CT-PET and precludes accurate detection of residual esophageal tumor. However, CT-PET in combination with endoscopy is useful in identifying patients with a high risk of residual tumor post-CRT.