Outcome Of First-line Chemotherapy Research Articles

MO61-3 Effect of cancer cachexia on the outcomes of first-line chemotherapy in pancreatic cancer: A claims database study

MO61-3 Effect of cancer cachexia on the outcomes of first-line chemotherapy in pancreatic cancer: A claims database study

First-line chemotherapy versus chemoradiation for resectable distal esophageal adenocarcinoma.

331 Background: Multiple randomized controlled trials have shown that both neoadjuvant chemotherapy (CT) and chemoradiation (CRT) convey survival benefit as compared to upfront surgery in patients with esophageal adenocarcinoma. However, international practice remains variable. Therefore, the present study compares the outcomes of first-line CT to CRT for patients with adenocarcinoma arising from the distal esophagus. Methods: Patients with clinical stage T2-T3, N0-N+ esophageal adenocarcinoma originating from the distal esophagus who received first-line CT or CRT were identified from the National Cancer Data Base (2006-2014). Propensity-score were created for the odds of receiving CRT. Patients were matched 1:1 based on propensity score. Subset analysis was performed in patients who underwent esophagectomy. Pathological complete response was defined as ypT0N0M0. Results: In total, 709 and 8,877 patients who received first-line CT and CRT were identified, respectively. CT was associated with stage cT2 (27.2% vs. 23.3%; p = 0.017), and treatment at a high-volume center (27.2% vs. 20.2%; p < 0.001). After matching, resection rates were comparable for patients who received first-line CT and CRT (62.2% vs. 63.7%; p = 0.545). However, median overall survival was slightly lower for patients who receive CT compared to CRT (23.7 vs. 28.4 months; p = 0.044). Among patients who underwent esophagectomy, time to surgery (135 vs. 134 days; p = 0.689) and median overall survival (37.0 vs. 40.5 months; p = 0.630) was similar between matched cohorts. However, complete response (15.8% vs. 25.8%; p < 0.001) and negative margin (94.3% vs. 88.9%; p = 0.004) rates were significantly lower after CT compared to CRT. Conclusions: In patients with esophageal adenocarcinoma, first-line CRT results in significantly higher pathological complete response rates, negative resection margins rates, and improved survival. These findings suggest that first-line CRT is preferable over CT when tolerated in patients with esophageal adenocarcinoma.

EP1.12-07 High Discrepancy of Chemotherapy Outcomes Between Patients with Peripheral and Central Small Cell Lung Cancer

Previously we found that imaging central and peripheral LCNEC has distinct clinicopathologic features and survival. As LCNEC and SCLC are all neuroendocrine tumor, this study further investigated whether imaging tumor location impact the outcome of first line chemotherapy in patients with small cell lung cancer extensive disease. Patients with ES-SCLC diagnosis between May 2014 and September 2015 in Shanghai Pulmonary Hospital, Tongji University were included. Contrast enhanced CT scans were reviewed retrospectively for tumor location (central or peripheral) and imaging features. The clinical characteristics and outcomes of chemotherapy were collected and compared. 140 patients were identified with a median age of 64, 89.3%, 76.4% and 98.6% were male, smokers and ECOG PS 1 respectively. Among them, 135 received etopside based chemotherapy and 5 received irinotecan based chemotherapy.111 (79.3%) had central-type and 29 (20.7%) had peripheral-type SCLC. The patients characteristics were similar between the central and peripheral subgroups. Peripheral subgroup showed less marginal GGO (65.5% vs 84.7%, p=0.02), obstructive pneumonia (48.3% vs 80.2%, p=0.001), obstructive atelectasis (3.4% vs 40.5%, p<0.001) and effusion (37.9% vs 61.3%, p=0.011) than central tumors. Peripheral subgroup had lower ORR (44.8% vs 73%, p=0.004) and DCR (79.3% vs 92.8%, p=0.042). The median PFS was 4.6 months in the entire cohort and peripheral subgroup had significantly short PFS than central one (median PFS: 3.4 vs 5.1 months, p=0.001, figure A). The median OS was 12.9 months and peripheral subgroup had numerally short OS (median 11.6 vs 13.3 months, p=0.266, figure B). Central type tumors account for most of SCLC, while patients with peripheral tumors had a significantly lower ORR, shorter PFS and OS after the first line chemotherapy than central type.

P3.03-016 Association between the Stainability of the Neurofibromatosis Type 2 Gene-Related Protein Merlin and the Tumor Properties of Mesotheliomas: Topic: Mesothelioma Transitional

Mutations in the genes cyclin-dependent kinase inhibitor 2A (CDKN2A), BRCA-1 associated protein 1 (BAP1), and neurofibromatosis type 2 (NF2) are observed in malignant pleural mesothelioma (MPM). We observed biallelic BAP1 alterations in 61% of MPMs and found that mutations are particularly frequent in epithelioid-type malignant mesotheliomas (Cancer Sci, 103:868-74, 2012). In addition, Loss-of-function mutations in NF2 are relatively frequent (40%) in MPMs have indicated. Merlin is a tumor suppressor protein coded by NF2; both merlin and the ezrin/radixin/moesin proteins are associated with suppression of invasion and metastasis of tumor cells. In this study, we examined the association between stainability of merlin and the tumor properties of MPM. Following definitive histological diagnoses of 35 cases of MPM (epithelial: n=31, biphasic: n=2, desmoplastic: n=2), we conducted immunohistochemical staining for merlin in thin sections of paraffin-embedded tumor tissue. Stainability was assessed with H-scores. The clinical stage of MPM was defined at the time near the tumor tissue harvesting time; the association between the clinical stage and therapeutic outcomes was assessed based on the outcomes of first-line chemotherapy with cisplatin (CDDP) or carboplatin(CBDCA) plus pemetrexed (PEM). The anti-merlin antibody used was LS-B394 (LSBio, Seattle, Washington, USA). 1) Seven MPMs (20%) were negative or weakly positive for merlin (H-score 0-30); of these seven MPMs, one was desmoplastic, while six were epithelial. Six MPMs were strongly positive for merlin (H-score ≥250); all six of these MPMs were epithelial. 2) No difference in merlin stainability was observed between epithelial (n=31) and non-epithelial (n=4) MPMs. Similarly, on examination of the association between stainability and IMIG staging, no differences in stainability were observed between stages 1 to 4. 3) No differences in stainability were observed between the first-line chemotherapy partial response group and progressive disease group. Loss-of-function mutations in the tumor suppressor gene NF2 lead to enhanced expression of focal adhesion kinase; although these mutations are demonstrated in decreased normal expression of the tumor suppressor protein merlin, no trend was observed in the morphological differentiation patterns of MPM. In addition, although the ratio of cells with high aldehyde dehydrogenase enzymatic activity is increased by CDDP/PEM treatment, we observed no association between CDDP/PEM sensitivity and merlin stainability. The association between NF2/merlin and tumor properties must be studied in more cases.

Outcomes of first line chemotherapy in patients with chronic lymphocytic leukemia.

Objective:Chronic lymphocytic leukemia (CLL) is a heterogeneous disease in terms of survival with and without treatment. Many chemo and immunotherapeutic agents are available to treat this indolent disease. Aim of this study was to determine the outcomes of patients with chronic lymphocytic leukemia treated with different available chemotherapeutic regimens.Methods:All patients with diagnosis of CLL from 2008 to 2013 were included. Data were collected from hospital information system. Objective response rate (ORR) in terms of complete or partial response (CR, PR), stable or progressive disease (SD, PD), overall survival (OS), and progression free survival (PFS) were calculated.Results:Fifty seven patients were included; 42 (74%) male and 15 (26%) were female. Patients with Binet stage A 10 (18%); B 20 (35%) and C were 27(47%). Median age was 50.9 years. Forty six (80%) were treated and 11(20%) remained on watch and wait. Treatment indications were B symptoms 14 (30%), symptomatic nodal disease 18(39%), thrombocytopenia 4(9%), anemia 7(15%) and doubling of lymphocyte count 3 (7%). Chemotherapy regimens used were FC in 38 (83%), FCR 5(11%), chlorambucil 2(4%) and CVP in 1(2%) patient. Twenty two (56%) patients had CR, 13(33%) PR, 3(7.6 %) SD, and 1(2.5%) had PD. ORR was 89%. Median PFS was 23.1 months and median 3 years OS was 55%.Conclusion:Majority of patients was in a relatively younger age group and presented with advanced stage disease requiring treatment. Small number of patients received rituximab due to cost. PFS and OS are comparable with published literature.

Associations between biomarkers and outcomes of first-line chemotherapy in advanced non-small cell lung cancer (NSCLC).

7535 Background: Pemetrexed has demonstrated efficacy in the treatment of NSCLC, primarily in non-squamous cell carcinomas. One explanation may be that squamous cell carcinomas have a higher level ...

Abstract 3208: Impact of targeted therapy on circulating tumor cells in metastatic breast cancer treated by first-line chemotherapy: IC 2006-04 study

Abstract Circulating tumor cells (CTC) have been reported to be a prognostic marker in metastatic breast cancer. This study was designed to test whether changes in CTC counts during treatment are associated with outcome of first-line chemotherapy with/without targeted therapy. Methods: CTC were counted (CellSearch®) at baseline, before cycle 2 (C2) and C3/4 in 267 metastatic breast cancer patients. Usual prognostic variables, serum tumor markers, tumor response according to RECIST criteria and events were prospectively registered and compared with CTC status and outcome over time. Results: Median follow-up was 16 months, 45 patients (17%) had HER2 positive tumor and received trastuzumab, 55 (21%) had triple negative tumor, 125 received bevacizumab associated with CT. Baseline CTC positivity (65%; ≥1CTC/7.5ml threshold, 45% ≥5CTC/7.5ml threshold) was correlated with tumour markers, bone/liver involvement and number of metastatic sites, as well as performance status but was not statistically different according to breast cancer subtypes (hormone-positive, HER2-positive or triple-negative). At multivariate analysis, CTC ≥5CTC/7.5ml was an independent prognostic factor for progression-free survival (PFS), RR=1.9 (CI95% 1.26-2.88), p=0.002, with triple negative status, poor performance status and elevated CEA. For overall survival, CTC ≥5CTC/7.5ml was an independent prognostic factor with triple negative status and poor performance status (RR=2.41, p=0.02). Changes with a threshold ≥5CTC/7.5ml, between baseline and Cycle 2 were highly correlated with both PFS (p=5e-07) and OS (p=3e-07). Persistent CTC positivity at C2 was associated with lower tumor response (p=4e-03). Among CTC-positive patients at baseline treated by chemotherapy only, chemotherapy/bevacizumab and chemotherapy/anti-HER2, CTC counts decreased respectively below the ≥5CTC/7.5ml positivity threshold before cycle 2 in 53%, 64% and 83% of patients, and before cycle 3 or 4, in 62%, 77% and 100% of patients (p=0.04). Prognostic value of CTC count at baseline and C2 remained in all subgroups. Conclusions: CTC count appeared to decrease more markedly in the patients who received also bevacizumab or trastuzumab. However, CTC remain a reliable independent prognostic marker in metastatic breast cancer treated by first-line chemotherapy with/without targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3208. doi:10.1158/1538-7445.AM2011-3208

Prognostic Factors for Treatment Outcomes of First Line Chemotherapy in Metastatic Breast Cancer

Prognostic Factors for Treatment Outcomes of First Line Chemotherapy in Metastatic Breast Cancer

Outcomes of first-line chemotherapy for advanced breast cancer in women with good versus poor quality of life at baseline

1036 Background: Health-related quality of life (QL) is an established predictor of outcome in advanced breast cancer. The benefits and harms of chemotherapy in women with poor QL are unclear. Methods: We used data from 378 women receiving classical CMF in the control arms of 3 randomized trials. QL was rated at baseline by patients with linear analogue self-assessment scales (LASA) for physical well-being (PWB), mood, appetite, pain, nausea/vomiting, and overall QL; and by physicians with Spitzer's Quality-Of-Life Index (QL-I). Patients were divided into 3 groups according to their baseline QL scores: good (LASA 0–25, QL-I 5–7), intermediate (LASA 26–65, QL-I 8–10) or poor (LASA 66–100, QL-I 11–15). The main outcomes were overall survival (OS), progression-free survival (PFS), objective tumor response (OTR = CR or PR), weight loss, and grade 3 or 4 adverse events (AE). Results: All aspects of QL, except nausea/vomiting, were significant univariable predictors of OS and PFS. PWB, mood, appetite and QL-I were independently significant predictors of OS in a multivariable model with biomedical factors. Only patient's self-rated poor QL had lower rates of OTR, and higher rates of nonhematological AE than those with good QL (see Table), but rates of hematological AE were similar. Weight loss occurred more frequently in those with poor appetite (OR 5.8, p=0.05) or poor PWB (OR 4.9, p=0.05). Conclusions: Less than 25% of women with poor baseline QL responded to first line CMF but over 25% had severe non-hematological toxicity. Baseline QL predicts these outcomes beyond biomedical factors. [Table: see text] No significant financial relationships to disclose.

Outcomes of First-Line Chemotherapy in Patients with Advanced or Metastatic Leiomyosarcoma of Uterine and Non-Uterine Origin

Although leiomyosarcomas (LMSs) form the largest subgroup of soft tissue sarcomas (STSs), the efficacy of chemotherapy in this group is largely unclear, partly because older studies are contaminated with gastrointestinal stromal tumors (GISTs). In this retrospective study we investigated the outcome of first line chemotherapy in 65 patients with unresectable or metastatic LMS. The overall response rate (ORR) was 18%; and the median progression-free (PFS) and overall survival (OS) were 3.8 and 9.7 months respectively. No statistically significant differences in outcomes for uterine and non-uterine LMS were found. In non-uterine LMS, however, the PFS and OS seemed to be longer for females than for males, potentially negatively affecting outcomes in this group. If our observations are confirmed in other series, they would suggest that studies performed in STS patients should not only stratify for histological subtype but also for uterine versus non-uterine LMS and for gender.