Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma.

The outcomes for patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical efficacy, but it has never been evaluated in the first-line treatment setting in combination with chemotherapy. To evaluate the safety and efficacy of a chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase 2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC) followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and 35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4% with 3 complete responses and 22 partial responses. With a median follow up of 29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%, respectively. Five patients did not require further chemotherapy for more than 34 months since initiation of CTL. Infusion of CTL products containing T cells specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95% confidence interval: 0.14-0.84; P = 0.014). Our study achieved one of the best survival outcomes in patients with advanced NPC, setting the stage for a future randomized study of chemotherapy with and without EBV-CTL.

Effects of chemotherapy and psychosocial distress on perceived cognitive disturbances in Asian breast cancer patients.

BACKGROUND: There is conflicting evidence on the effect of chemotherapy and psychosocial distress on perceived cognitive changes in cancer patients. OBJECTIVE: To compare the severity of perceived cognitive disturbance in Asian breast cancer patients receiving chemotherapy and those not receiving chemotherapy, and identify clinical characteristics associated with perceived cognitive disturbances. METHODS: A cross-sectional, observational study was conducted at the largest cancer center in Singapore. Breast cancer patients receiving chemotherapy and not receiving chemotherapy completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30), and Beck Anxiety Inventory to assess their perceived cognitive functioning, health-related quality of life, and anxiety, respectively. Multiple regression was conducted to delineate the factors associated with perceived cognitive disturbances. RESULTS: A total of 85 breast cancer patients receiving chemotherapy and 81 not receiving chemotherapy were recruited. Chemotherapy patients experienced more fatigue (QLQ-C30 fatigue scores: 33.3 vs 22.2 points; p = 0.005) and moderate-to-severe anxiety (21.9% vs 8.6%; p = 0.002) compared to non-chemotherapy patients. Non-chemotherapy patients reported better perceived cognitive functioning than those who received chemotherapy (FACT-Cog scores: 124 vs 110 points, respectively; p < 0.001). Chemotherapy and endocrine therapy were strongly associated with perceived cognitive disturbances (p < 0.001 and 0.021, respectively). The interacting effect between anxiety and fatigue was moderately associated with perceived cognitive disturbances (ß = -0.29; p = 0.037). CONCLUSIONS: Chemotherapy and endocrine treatment were associated with significant cognitive disturbances among Asian breast cancer patients. Psychosocial factors could be used to identify cancer patients who are more susceptible to cognitive disturbances in the clinical setting.

Metastatic Thymic Carcinoma on Restaging 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Thymic carcinoma is a rare thymic epithelial cancer which is not only locally invasive but also highly aggressive disease. The prognosis for this cancer is poor and the surgery remains the mainstay of treatment. Thymic carcinomas have been shown to metastasize to the lymph nodes, lung, and liver. A 63-year old male who was successfully treated for thymic cancer in 2015, presented with metastatic disease recurrence to the spinal cord. We share interesting images of the spinal cord lesions as well as pituitary metastases that were incidentally detected on restaging 18F-fluorodeoxyglucose positron emission tomography-computed tomography.

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.

The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.

BACKGROUND AND AIMS: Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection. METHODS: Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis. RESULTS: A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities. CONCLUSION: The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

Minimal clinically important difference (MCID) for the functional assessment of cancer therapy: cognitive function (FACT-Cog) in breast cancer patients.

OBJECTIVES: This is the first reported study to determine the minimal clinically important difference (MCID) of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), a validated subjective neuropsychological instrument designed to evaluate cancer patients' perceived cognitive deterioration. STUDY DESIGN AND SETTING: Breast cancer patients (n = 220) completed FACT-Cog and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at baseline and at least 3 months later. Anchor-based approach used the validated EORTC-QLQ-C30-Cognitive Functioning scale (EORTC-CF) as the anchor for patients who showed minimal deterioration and a receiver operating characteristic (ROC) curve to identify the optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement (SEM) of the total FACT-Cog score (148 points). RESULTS: There was a moderate correlation between changes in FACT-Cog and EORTC-CF scores (r = 0.43; P < 0.001). The EORTC-CF-anchored MCID was 9.6 points (95% confidence interval: 4.4, 14.8). The MCID from the ROC method was 7.5 points (area under the curve: 0.75; sensitivity: 75.6%; specificity: 68.8%). For the distribution-based approach, the MCIDs corresponding to one-third SD, half SD, and one SEM were 6.9, 10.3, and 10.6 points, respectively. Combining the approaches, the MCID identified for FACT-Cog ranged from 6.9 to 10.6 points (4.7-7.2% of the total score). CONCLUSION: The estimates of 6.9-10.6 points as MCID can facilitate the interpretation of patient-reported cognitive deterioration and sample size estimates in future studies.

Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC.

Activity of thalidomide and capecitabine in patients with advanced hepatocellular carcinoma.

BACKGROUND: Thalidomide has shown modest activity in advanced hepatocellular carcinomas (HCCs). Single-agent capecitabine has also been used in patients with HCC, with objective responses being reported. In our study, we review the use of thalidomide and capecitabine combination in advanced HCC. METHODS: From November 2003 and September 2008, 42 patients with advanced HCC who were not eligible for clinical trial or conventional chemotherapy were treated with oral capecitabine (2000 mg/m/d) for 14 days every 3 weeks and oral thalidomide at the doses of 50 to 200 mg/d. RESULTS: Almost 50% of patients had Child-Pugh B or C liver cirrhosis and a history of regional or systemic therapy. Three patients achieved complete responses lasting more than 52 weeks, including 1 patient who achieved pathological complete response and underwent curative resection. There were 3 patients with partial responses and 13 with stable disease. Median overall survival of all 42 patients was 9.9 months. The median progression-free survival was 5.1 months. The presence of ascites, portal vein thrombosis, and poorer Child-Pugh liver cirrhosis status also resulted in significantly poorer survival outcome. Treatment was well tolerated. Fatigue was the most common side effect occurring in 16 (38%) patients, but only 1 patient had grade 3 toxicity and had to stop treatment. Two other patients developed grade 3 palmar-plantar erythrodysesthesia from capecitabine. CONCLUSIONS: The combination of thalidomide and capecitabine has activity in advanced HCC and can result in complete pathological response. Treatment is well tolerated even in less-fit patients who have been pretreated and deserve further study.