What is the value of third-line chemotherapy in advanced gastroesophageal cancer? A 5-year retrospective analysis at a single center.

AIM: The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution. METHODS: Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed. RESULTS: Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities. CONCLUSION: The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred.

Outcomes and prognostic factors of post-irradiation and de novo sarcomas of the head and neck: a histologically matched case-control study.

BACKGROUND: This study was designed to compare post-irradiation sarcomas (PIS) and de novo sarcomas (DN) of the head and neck in terms of tumor characteristics, prognostic factors, and survival outcomes. METHODS: All (N=83) head and neck sarcoma patients treated at National Cancer Centre, Singapore (Feb 2002-May 2011) were included: DN (N=60; 72%); PIS (N=23; 28%). Clinicopathologic features and outcomes of all patients and histologically matched pairs were compared. Prognostic factors were identified using univariate and multivariate analyses. RESULTS: Median age, gender, smoking status, and tumor size were not significantly different. Significant differences were seen in histology (most prevalent: PIS-sarcoma-NOS; DN-angiosarcoma) and tumor subsite (most prevalent: PIS-nasal cavity and sinuses; DN-skin). Median latency of PIS development was 16.7 years. PIS patients had shorter overall survival (OS) and disease-specific survival (DSS) compared with DN patients, most clearly seen on histologically matched pair analysis: 2-year OS (PIS: 54%; DN: 83%; P=0.028). Multivariate analyses showed that age>50 years (hazard ratio (HR)=3.68; P=0.007), ever-smokers (HR=2.79; P=0.017), and larger tumor-size (cm) (HR=1.12; P=0.045) were associated with worse OS, and age at >50 years (HR=2.77; P=0.04) and ever-smokers (HR=2.94; P=0.021) were associated with worse DSS. When treated with curative intent, no significant survival difference was noted between DN and PIS patients. CONCLUSIONS: In our cohort, PIS constituted 28% of head and neck sarcomas. Poorer prognosis traditionally associated with PIS compared with DN was not seen amongst patients treated with curative intent.