4021 Background: JCOG9912, a randomized phase III trial of advanced gastric cancer (AGC), revealed significant non-inferiority of S-1 to 5-FU (P<0.001); however, neither S-1 nor irinotecan plus cisplatin (IP) was superior to 5-FU (P=0.034 and 0.055, respectively) for overall survival (Lancet Oncol 2009). We correlated expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and 5 other genes related to anticancer drug metabolism or targets with disease stage and outcome in patients treated with first-line IP, S-1, or 5-FU monotherapy under controlled conditions. Methods: Blocks from endoscopic biopsy specimens of primary lesions before chemotherapy were available from 445 of 704 pts in JCOG9912. Using laser-capture microdissection and real-time RT-PCR, we categorized mRNA expression of 8 genes into low and high values relative to the median. Covariates in multivariate Cox analysis were 9 baseline characteristics and the genes with P<0.05 in univariate analysis. Results: Baseline factors of the subjects were similar over the entire JCOG9912 trial; 322 samples were assessable for ERCC1, 317 for TS, and 304 for DPD. The median values of DPD were 0.50 in diffuse type and 0.29 in intestinal type (P<0.0001) whereas for ERCC1 the median values were 1.49 and 1.18, respectively (P=0.003). Multivariate analyses showed that high ERCC1 expression correlated with poor prognosis (HR, 1.37; 95% CI, 1.08 to 1.75; P=0.010), unresectable status (HR, 1.66; 95% CI, 1.28 to 2.16, P=0.049), ≥2 metastatic sites (HR, 1.66; 95% CI, 1.28 to 2.16, P<.0001), and PS 2 (HR, 1.45; 95% CI, 1.13-1.86, P=0.003) associated with poor prognosis. High TS was not significantly associated with worse survival (HR, 1.21; 95% CI, 0.95 to 1.54; P=0.117). While OS of IP tended to be worse than S-1 in high TS (HR, 1.31), it was similar in low TS (HR, 0.97) (P for interaction=0.24). Conclusions: These correlative analyses suggest ERCC1 as an independent prognostic factor for OS after first-line treatment of AGC. Prospective studies to validate prognostic or predictive molecular markers are warranted in future personalized phase III studies.
A 53-year-old woman was admitted for recurrent hemoptysis and cough. The chest radiograph showed an infiltrative shadow in the left upper region. Chest tomogram and CT scan showed a small calcification and consolidation in the left upper lobe. Fiberoptic bronchoscopy revealed fresh hemorrhage from the left upper bronchus but no broncholith or bleeding point were detected. Since the symptoms had disappeared by 10 days after admission, the patient was discharged and followed up as an outpatient. Three weeks later, she spontaneously expectorated a stone 3 mm in maximum diameter, with an irregular surface. Analysis revealed that the stone's composition was 56% of calcium phosphate and 44% of calcium carbonate. Hemoptysis seemed to have been caused by the broncholith, which had originated as a calcification of a peribronchial lymph node that subsequently eroded its way into the airway. After lithoptysis, no recurrence has been observed.
A 58-year-old man presented with an 8-year history of intermittent dysphagia. There was no other relevant medical history. A barium esophagogram revealed a stenotic lesion in the middle and lower thoracic esophagus with multiple intramural tracks [1]. Endoscopic examination revealed an annular stricture of the esophagus extending from 27 cm to 40 cm from the incisors, as well as multiple small orifices ([Fig. 1]).
4119 Background: Chemotherapy with gemcitabine(GEM) has been shown to be an effective agent in metastatic pancreatic cancer(MPC) with improvement of both quality of life and survival. While median survival time of MPC patients treated with GEM is reported to be about 5 months, some of them live longer than median time and others do much shorter. Methods: To determine the outcome of patients with MPC treated with GEM and to identify factors that predict treatment outcome, retrospective study was preformed on patients with MPC who received GEM in a dose of 1000mg/m2 weekly×3 followed by 1week rest at our hospital between April 2001 and October 2004. Data regarding patient factors, tumor factors obtained by computed tomography and survival data were collected. Sixty-six consecutive patients were identified and they were pathologically diagnosed as adenocarcinoma without prior chemotherapy or surgery. Results: The median age was 60 years (range 36–78 years), 60.6% were male and 39.4% were female. Multivariate analysis showed that ECOG (Eastern Cooperative Oncology Group) performance status (p=0.046), primary tumor location (head, body and tail) (p=0.017) and C-reactive protein (p=0.002) were important independent predictive factors. A prognostic index was derived from these factors. The prognostic score was calculated using the formula of prognostic score=(1 if PS=0 or 1, and 2 if PS=2 and 5 if PS=3)+(3 if primary site at head, 1 if body or tail)+(1 if CRP<1, 6 if CRP>3, 3 if others). According to the calculated score, we divided them into three groups (class1; score=3 or 4, class3; score>8, class2: all others) and median survivals were 265, 155, 65 days for class 1–3, respectively (265 vs 155 vs 65; p<0.0001). The internal validated c-index (ROC area under the curve) of this model was 0.711. Conclusions: These classifications are valid when applied to patients with MPC. Patients in class 1 have good prognosis, class 2 are likely to benefit for GEM and should be considered for trials that aim to improve their survival. Class 3 patients are unlikely to benefit from GEM. No significant financial relationships to disclose.
Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes.
