Recent advances in detection of genomic DNA from plasma samples allow us to follow the alteration of shedding tumor DNA in plasma before and after systemic treatment with multiple biopsies. Osimertinib is the standard of care for NSCLC patients with T790M mutations. We plan to use serial plasma cfDNA genomic alteration to predict osimertinib efficacy and search for possible resistance mechanisms. We prospectively collected plasma from patients of EGFR mutation-positive NSCLC who harbored acquired EGFR T790M mutation following prior EGFR-TKI therapy. Plasma samples were collected before starting osimertinib treatment, 4 weeks following osimertinib treatment and upon disease progression. ctDNA were detected by Guardant360 gene panel test. Fifteen patients (median age 62 [range 48-77], 53% men, 53% exon 19 deletion and 47% exon 21 L858R mutation) received osimertinib treatment. Acquired T790M mutation was diagnosed by using plasma sample only (Cobas® or digital PCR) (n = 11), tissue or pleural effusion only (n = 2), and both tissue and plasma samples (n = 2). Before starting osimertinib treatment, activating mutations were detected in plasma in all patients, T790M was detected in 93% (n = 14) and TP53 mutation was detected in 47% (n = 7) of the patients by using Guardant360. After osimertinib treatment, 11 out of the 14 patients had non-detectable plasma T790M at the 4th week. Follow-up CT at least 8 weeks following osimertinib treatment of the 11 patients disclosed decreased tumor size (6 confirmed PR, 1 unconfirmed PR and 5 SD by RECIST criteria). The remaining 3 patients who had detectable plasma T790M (n = 2) or increased activating mutation allele frequency (n = 1) at the 4th week had progressive disease within 16 weeks. The first patient had initial PR but later developed C797S on progression. The second patient developed new liver tumor following prior stable disease. This patient had baseline TP53 and CDKN2A mutations detected in the plasma, and allele frequencies decreased at the 4th week and increased on progression. The last patient had rapid progression on osimertinib treatment, and alterations in PTEN and TP53 were detected on baseline and increased at the 4th week and on progression. In that patient, T790M mutation was not detectable at the 4th week but activating mutation increased in allele frequency at the 4th week and on progression. Regarding patients with baseline TP53 mutation, 4 (57%) patients who had non-detectable plasma TP53 mutation at the 4th week achieved disease control, and 2 (29%) patients had detectable or increased TP53 mutation allele frequency had PD within 16 weeks. 4 week plasma ctDNA following osimertinib treatment may predict early progression within 16 weeks.

Purpose/Objective(s)The vague difference of cervical spine curvature (CSC) between simulation film and port films has put doubts on accurate target irradiation. We measured the CSC variation during treatment to identify its clinical importance.Materials/MethodsDuring 2005∼2008, thirty-three patients with nasopharyngeal cancer were treated with chemoradiation or radiation alone at our hospital. After excluded 9 patients who had re-simulation during treatment, twenty-four patients were included in our study. Port films were acquired 1∼ 2 times per week for each patient. On the orthogonal lateral view, we defined the most superior anterior point of 4th cervical vertebrae (C4) as point O, the most anterior point of anterior tubercle of atlas as A, the most inferior anterior point of C5 as B, and most superior posterior point of C4 vertebral body as Z. The ∠AOZ, ∠BOZ, and ∠AOB were measured retrospectively in 214 port films. The reason we picked the line extended from superior border of C4 to divide CSC into two parts was that C4 usually located at the highest point of the pillow. Therefore we can tell if the upper portion of neck is more stable than the lower. In order to find out if the variation of CSC increases during treatment, which indicates increasing inadequacy of immobilization, the port films of each patient were divided into films taken within first 2 weeks, mid-term, and final 2 weeks. One-way analysis of variance (ANOVA) was used to evaluate if the variation increased with time.ResultsThe average difference of ∠AOZ, ∠BOZ, and ∠AOB between each port film and Day 1 port film was 2.27 ± 1.69, 2.2 ± 1.79° and, 2.25°±1.79°, respectively. The p value of ANOVA analysis of Δ∠AOZ, Δ∠BOZ, and Δ∠AOB variation in time course was 0.14, 0.21, and 0.49, respectively.ConclusionsThere was no difference in the immobility of the upper and lower neck. CSC change didn't show any trend in time course as long as the correlation between isocenter and bony landmarks was verified on orthogonal films. However, our data indicates a random CSC variation around 2°, which may affect the accuracy of dose delivery in distant treatment region such as lower neck lymphatic drainage. Better immobilization of the flexible neck is required to increase reproducibility. Purpose/Objective(s)The vague difference of cervical spine curvature (CSC) between simulation film and port films has put doubts on accurate target irradiation. We measured the CSC variation during treatment to identify its clinical importance. The vague difference of cervical spine curvature (CSC) between simulation film and port films has put doubts on accurate target irradiation. We measured the CSC variation during treatment to identify its clinical importance. Materials/MethodsDuring 2005∼2008, thirty-three patients with nasopharyngeal cancer were treated with chemoradiation or radiation alone at our hospital. After excluded 9 patients who had re-simulation during treatment, twenty-four patients were included in our study. Port films were acquired 1∼ 2 times per week for each patient. On the orthogonal lateral view, we defined the most superior anterior point of 4th cervical vertebrae (C4) as point O, the most anterior point of anterior tubercle of atlas as A, the most inferior anterior point of C5 as B, and most superior posterior point of C4 vertebral body as Z. The ∠AOZ, ∠BOZ, and ∠AOB were measured retrospectively in 214 port films. The reason we picked the line extended from superior border of C4 to divide CSC into two parts was that C4 usually located at the highest point of the pillow. Therefore we can tell if the upper portion of neck is more stable than the lower. In order to find out if the variation of CSC increases during treatment, which indicates increasing inadequacy of immobilization, the port films of each patient were divided into films taken within first 2 weeks, mid-term, and final 2 weeks. One-way analysis of variance (ANOVA) was used to evaluate if the variation increased with time. During 2005∼2008, thirty-three patients with nasopharyngeal cancer were treated with chemoradiation or radiation alone at our hospital. After excluded 9 patients who had re-simulation during treatment, twenty-four patients were included in our study. Port films were acquired 1∼ 2 times per week for each patient. On the orthogonal lateral view, we defined the most superior anterior point of 4th cervical vertebrae (C4) as point O, the most anterior point of anterior tubercle of atlas as A, the most inferior anterior point of C5 as B, and most superior posterior point of C4 vertebral body as Z. The ∠AOZ, ∠BOZ, and ∠AOB were measured retrospectively in 214 port films. The reason we picked the line extended from superior border of C4 to divide CSC into two parts was that C4 usually located at the highest point of the pillow. Therefore we can tell if the upper portion of neck is more stable than the lower. In order to find out if the variation of CSC increases during treatment, which indicates increasing inadequacy of immobilization, the port films of each patient were divided into films taken within first 2 weeks, mid-term, and final 2 weeks. One-way analysis of variance (ANOVA) was used to evaluate if the variation increased with time. ResultsThe average difference of ∠AOZ, ∠BOZ, and ∠AOB between each port film and Day 1 port film was 2.27 ± 1.69, 2.2 ± 1.79° and, 2.25°±1.79°, respectively. The p value of ANOVA analysis of Δ∠AOZ, Δ∠BOZ, and Δ∠AOB variation in time course was 0.14, 0.21, and 0.49, respectively. The average difference of ∠AOZ, ∠BOZ, and ∠AOB between each port film and Day 1 port film was 2.27 ± 1.69, 2.2 ± 1.79° and, 2.25°±1.79°, respectively. The p value of ANOVA analysis of Δ∠AOZ, Δ∠BOZ, and Δ∠AOB variation in time course was 0.14, 0.21, and 0.49, respectively. ConclusionsThere was no difference in the immobility of the upper and lower neck. CSC change didn't show any trend in time course as long as the correlation between isocenter and bony landmarks was verified on orthogonal films. However, our data indicates a random CSC variation around 2°, which may affect the accuracy of dose delivery in distant treatment region such as lower neck lymphatic drainage. Better immobilization of the flexible neck is required to increase reproducibility. There was no difference in the immobility of the upper and lower neck. CSC change didn't show any trend in time course as long as the correlation between isocenter and bony landmarks was verified on orthogonal films. However, our data indicates a random CSC variation around 2°, which may affect the accuracy of dose delivery in distant treatment region such as lower neck lymphatic drainage. Better immobilization of the flexible neck is required to increase reproducibility.

e15659 Background: Although classified as end-stage, patients of stage IV esophageal squamous cell carcinoma (SCC) without visceral or bone metastases (nodal stage IV) often have good performance status and are medically fit for curative treatment. The objective of this study was to compare the prognosis of patients of stage III and nodal stage IV. Methods: The retrospective study included patients who were diagnosed esophageal squamous cell carcinoma at Tzu Chi General Hospital from Jan, 2005 to Aug, 2008. Eligible patients must meet the following criteria: (1) stage III or nodal stage IV; (2) underwent esophagectomy or chemoradiation with curative intent; (3) Eastern Cooperative Oncology Group performance status ≤2. The standard order-set of chemotherapy was two monthly cycles of fluorouracil (1,000 mg/m2/24 hours for 4 days) and cisplatin (75 mg/m2 bolus day 1). Radiotherapy dose was 59.4 Gy for concurrent chemoradiation (CCRT) or 54 Gy for adjuvant setting after esophagectomy. Results: Patients characteristics were listed in Table . The median follow-up was 8 months (range: 1∼42 months). In 38 patients underwent definitive CCRT, ten achieved complete response (CR) and 13 achieved partial response. Two-year disease-free survival rate in 28 patients who achieved CR or underwent esophagectomy was 29.9%. Median survival of stage III and nodal IV were 11.5 and 8 months. Two-year overall survival (OS) rate of stage III and nodal IV were 23.9% and 33% (p=0.814). The only significant poor prognostic factor in both univariate and multivariate analyses was tumor length longer than 5 cm. Conclusions: In our study, medically fit patients of nodal stage IV esophageal SCC could achieve OS similar to those of stage III after intensive treatment. The result may indicate the necessity of developing a selection criterion in deciding which nodal stage IV patient should undergo curative treatment. [Table: see text] No significant financial relationships to disclose.

This retrospective study compares the outcomes of different treatment modalities for resectable advanced hypopharyngeal cancer. (i.e., T4b, N3, T1N0, and small T2N0 were excluded.) From 2003 to 2007, a total of 46 patients with resectable advanced hypopharyngeal cancer were included in this study. According to major or minor risk factors revealed after laryngectomy and neck dissection, seventeen patients underwent adjuvant CCRT (13/17) or radiotherapy (RT) alone (4/17). Twenty-nine patients were treated with definitive CCRT, and four of them underwent unilateral radical neck dissection in advance. Thirty-two stage IVa patients were distributed in laryngectomy-CCRT arm (14/17) and CCRT arm (18/29). Intensity modulated radiation therapy (IMRT) plans treated gross tumor volume (GTV), high-risk, and low-risk areas to 70, 63, and 54 Gy, respectively, in the CCRT arm, and to high-risk and low-risk areas to 63 and 54 Gy in the laryngectomy-CCRT arm. Fractionation was 1.8 per day. Concurrent cisplatin-based chemotherapy was administered for 5 days every 3 weeks. The mean follow-up time was 15.9 months (range, 2-42 months). The mean overall survival in the laryngectomy-CCRT arm has a superior trend over CCRT arm (28.4 vs. 21.93 months, p = 0.18). In the CCRT arm, one refused to complete treatment and one died both due to severe neutropenia. The numbers of patients with complete response (CR), partial response (PR), and stable or progressive disease (SPD) in the CCRT arm were 17 (58.6%), 6 (20.7%), and 6 (20.7%), respectively. Salvage laryngectomy were performed for 2 patients who had CR and for only 2 who had PR or SPD. The CR arm had similar mean overall survival comparing to the laryngectomy-CCRT arm (32.2 vs. 28.4 months, p = 0.59) but less favorable 2-year disease-free survival (DFS) rate (66% vs. 86%, p = 0.23). Patients who required gastrostomy were correlated with poorer DFS significantly. In patients who had CR, definitive CCRT provides an overall survival equivalent to laryngectomy-CCRT, with much better functional and cosmetic results. Further investigation of a reliable molecular or clinical indicator for assessing the probability of achieving CR with CCRT will be invaluable for organ preservation purpose in patients of resectable advanced hypopharyngeal cancer.