Cutaneous versus non-cutaneous angiosarcoma: clinicopathologic features and treatment outcomes in 60 patients at a single Asian cancer centre.

BACKGROUND: Angiosarcoma (AS) is an uncommon soft tissue sarcoma with dismal prognosis that presents either cutaneously (C-AS) or non-cutaneously (NC-AS). We compared the clinical features and treatment outcomes between these 2 groups. METHODS: A single-centre study evaluating 60 AS patients between 2002 and 2012 was performed. RESULTS: The median age was 70 years. C-AS of the scalp or face comprised 66% of patients. C-AS patients were older than NC-AS (median age 74 vs. 56 years; p < 0.001). Proportionately more C-AS patients presented with non-metastatic disease (86 vs. 50%; p = 0.007). Amongst resected C-AS and NC-AS patients, rates of positive surgical margins (53 vs. 50%; p = 1.00) and adjuvant therapy (25 vs. 43%; p = 0.626) were not significantly different, though proportionately fewer C-AS patients relapsed (36 vs. 78%; p = 0.038). Paclitaxel was the most common agent in first line palliative systemic therapy, achieving an objective response rate of 56%. Median overall survival was 11.2 months, with no significant difference between C-AS and NC-AS (11.3 vs. 9.8 months; p = 0.895). CONCLUSION: Distinct from AS in the West, our series demonstrates a clear preponderance of scalp AS. Disparities in clinical characteristics between C-AS and NC-AS did not translate into survival differences.

Stage 4 pancreatic adenocarcinoma harbouring an FGFR2-TACC2 fusion mutation with complete response to erdafitinib a pan-fibroblastic growth factor receptor inhibitor.

We report a case of a frail 68-year-old woman with stage 4 pancreatic carcinoma harbouring a fibroblastic growth factor receptor 2 (FGFR2) fusion who achieved a durable complete response after treatment with erdafitinib a pan-FGFR inhibitor. The FGFR2-TACC2 fusion was detected on comprehensive tumour somatic mutation profiling. There is ongoing complete response at 10 months after initiation of erdafitinib. Transient central serous retinopathy, grade 2 hyperphosphataemia and diarrhoea were the adverse events encountered.

AZD6244 enhances the anti-tumor activity of sorafenib in ectopic and orthotopic models of human hepatocellular carcinoma (HCC).

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a particularly vascularized solid tumor where the Raf/MEK/ERK pathway is activated; suggesting that inhibition of this pathway may have therapeutic potential. METHODS: We treated patient-derived HCC xenografts with (i) sorafenib, (ii) AZD6244 (ARRY-142886), and (iii) sorafenib plus AZD6244. Western blotting was employed to determine pharmacodynamic changes in biomarkers relevant to both angiogenesis and MEK signaling. Apoptosis, microvessel density, and cell proliferation were analyzed by immunohistochemistry. RESULTS: We report here that sorafenib treatment resulted in suppression of tumor growth, reduction in cell proliferation, induction of apoptosis and inhibition of mTOR targets. Sorafenib-induced elevation of the insulin-like growth factor receptor 1 (IGF-1R), phospho-c-Raf Ser338, phospho-MEK Ser217/221 and phospho-ERK Thr202/Tyr204 was attenuated by co-treating cells with anti-human IGF-1R antibody or over-expression of activated mutant p70S6K. Pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the anti-tumor effect of sorafenib in both orthotopic and ectopic models of HCC. Such inhibition led to a further increase in pro-apoptotic Bim, apoptosis and a profound inhibition of cell proliferation. CONCLUSION: Our findings underscore the potential of a combined therapeutic approach with sorafenib and MEK inhibitors in the treatment of HCC.

Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009.

Asia has a disproportionately large share of the world's hepatocellular carcinoma (HCC), mainly because of the endemic status of chronic hepatitis B and C viruses, which leads to liver cirrhosis and an increased risk of HCC. This etiological factor presents important opportunities for prevention, early detection, diagnosis, and treatment of HCC. This consensus statement reviews the available medical evidence for management of HCC in Asia, and gives treatment recommendations that are adapted to resource availability in this diverse region with disparate health-care delivery systems.

RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient-derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration of RAD001 to mice bearing patient-derived HCC xenografts resulted in a dose-dependent inhibition of tumour growth. RAD001-induced growth suppression was associated with inactivation of downstream targets of mTOR, reduction in VEGF expression and microvessel density, inhibition of cell proliferation, up-regulation of p27(Kip1) and down-regulation of p21(Cip1/Waf1), Cdk-6, Cdk-2, Cdk-4, cdc-25C, cyclin B1 and c-Myc. Our data indicate that the mTOR pathway plays an important role in angiogenesis, cell cycle progression and proliferation of liver cancer cells. Our study provides a strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients with HCC.

Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Vascular endothelial growth factor, platelet derived growth factor and the Raf/mitogen-activated protein kinase/extracellular signal regulated kinase (Raf/MEK/ERK) signalling pathway regulates the growth, neovascularization, invasiveness and metastatic potential of HCC. In this study, we investigated the in vivo antitumour activity and mechanisms of action of sorafenib tosylate on four patient-derived HCC xenografts. Sorafenib dosed at 50 mg/kg and 100 mg/kg inhibited tumour growth by 85% and 96%, respectively. Sorafenib-induced growth suppression and apoptosis were associated with inhibition of angiogenesis, down-regulation of phospho-platelet-derived growth factor receptor beta Tyr1021, phospho-eIF4E Ser209, phospho-c-Raf Ser259, c-Raf, Mcl-1, Bcl-2, Bcl-x and positive cell cycle regulators, up-regulation of apoptosis signalling kinase-1, p27 and p21. Expression of IGF-1Rbeta and phosphorylation of c-Raf Ser338, MEK1/2 Ser217/221 and ERK1/2 Thr202/Tyr204 were increased by sorafenib treatment. Phosphorylation of mammalian target-of-rapamycin (mTOR) targets (p70S6K, S6R and 4EBP1) was reduced by sorafenib in sorafenib-sensitive lines but activated in sorafenib-less-sensitive 10-0505 xenograft. Sorafenib-induced phosphorylation of c-met, p70S6K and 4EBP1 was significantly reduced when 10-0505 cells were co-treated with anti-human anti-HGF antibody, suggesting that treatment with sorafenib leads to increased HGF secretion and activation of c-met and mTOR targets. Treatment of 10-0505 tumours with sorafenib plus rapamycin resulted in growth inhibition, inhibition of vascular endothelial growth factor receptor-2 phosphorylation, increased apoptosis and completely blocked sorafenib-induced phosphorylation of mTOR targets and cyclin B1 expression. These data also provide a strong rationale for clinical investigation of sorafenib in combination with mTOR inhibitors in patients with HCC.

Dynamic contrast-enhanced CT imaging of hepatocellular carcinoma in cirrhosis: feasibility of a prolonged dual-phase imaging protocol with tracer kinetics modeling.

Dynamic contrast-enhanced (DCE) CT imaging of four patients with hepatocellular carcinoma (HCC) was performed using a dual-phase imaging protocol designed with initial rapid dynamic imaging to capture the initial increase in contrast medium enhancement in order to assess perfusion, followed by a delayed imaging phase with progressively longer intervals to monitor subsequent tissue enhancement behaviour in order to assess tissue permeability. The DCE CT images were analysed using a dual-input two-compartment distributed parameter model to yield separate estimates for blood flow and permeability, as well as fractional intravascular and extravascular volumes. The HCCs and surrounding cirrhotic liver tissues were found to exhibit enhancement curves that can be appropriately described by two distinct compartments separated by a semipermeable barrier. Early contrast arrival was also found for HCC as compared with background liver. These findings are consistent with the current understanding of sinusoidal capillarization and hepatocarcinogenesis.

Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma.

INTRODUCTION: Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant. We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma. The trial considered a "no further interest" response rate of 10% and a target response rate of 30%. Utilising a Simon's minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required. Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed. MATERIALS AND METHODS: Patients with advanced HCC, diagnosed based on histology or by World Health Organization (WHO) criteria, were administered gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on day 1 and day 8 of a 21-day schedule. Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy. RESULTS: The trial was stopped early due to a lack of efficacy. A total of 15 patients were accrued. Twelve patients were hepatitis B positive and the other 3 patients were negative for both hepatitis B and C. Only 1 patient had a history of prior heavy alcohol use. Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis. This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities. Only 5 of 15 patients experienced grade III toxicities (nausea and emesis, 1 patient; anemia, 1 patient; thrombocytopenia, 1 patient; and neutropaenia, 2 patients). Only 1 patient experienced a partial response to the combination of gemcitabine and cisplatin. A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy. The median time to progression was 6 weeks. The progression-free curve showed a sharp descent in the initial part of the study, suggesting that many patients had disease progression after enrollment. The median overall survival was 18 weeks. CONCLUSION: The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HCC.

Comprehensive Geriatric Assessment (CGA) based risk factors for increased caregiver burden among elderly Asian patients with cancer.

OBJECTIVE: This study aims to identify Comprehensive Geriatric Assessment (CGA) based risk factors to help predict caregiver burden among elderly patients with cancer. MATERIALS AND METHOD: The study evaluated 249 patients newly diagnosed with cancer, aged 70years and above, who attended the geriatric oncology clinic at the National Cancer Centre Singapore between 2007 and 2010. RESULTS: Out of 249 patients, 244 patients had information available on family caregiver burden and were analysed. On univariate analysis, ADL dependence, lower IADL scores, ECOG performance status of 3-4, higher fall risk, lower scores in dominant hand grip strength test and mini mental state examination, polypharmacy, higher nutritional risk, haemoglobin <12g/dL and presence of geriatric syndromes were significantly associated with mild to severe caregiver burden. On multivariate analysis, only ECOG performance status of 3-4 (odds ratio [OR], 4.47; 95% confidence interval [CI], 2.27-8.80) and haemoglobin <12g/dL (OR, 2.38; 95% CI, 1.14-4.99) were associated with an increased probability of mild to severe caregiver burden. The model achieved a good fit (Hosmer-Lemeshow's p=0.196) and discrimination (area under the curve [AUC]=0.742; bias-corrected AUC=0.737). Based on this, patients were stratified into 3 risk groups with different proportion of patients with increased caregiver burden (low risk: 3.9% vs intermediate risk: 18.8% vs high risk: 39.6%; p<0.001). CONCLUSION: ECOG performance status and haemoglobin were associated with increased caregiver burden among elderly patients with cancer. Using these two factors in the clinic may help clinicians identify caregivers at risk and take preventive action to mitigate that.

Identification of Comprehensive Geriatric Assessment Based Risk Factors for Malnutrition in Elderly Asian Cancer Patients.

PURPOSE: Elderly cancer patients are at increased risk for malnutrition. We aim to identify comprehensive geriatric assessment (CGA) based clinical factors associated with increased nutritional risk and develop a clinical scoring system to identify nutritional risk in elderly cancer patients. PATIENTS AND METHODS: CGA data was collected from 249 Asian patients aged 70 years or older. Nutritional risk was assessed based on the Nutrition Screening Initiative (NSI) checklist. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test. Discrimination ability was assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping. RESULTS: Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3-4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14-5.69), ECOG performance status of 2-4 (OR 3.04; 95% CI, 1.57-5.88), presence of depression (OR 5.99; 95% CI, 1.99-18.02) and haemoglobin levels <12 g/dL (OR 3.00; 95% CI 1.54-5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test's p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation. CONCLUSION: Having advanced stage of cancer, poor performance status, depression and anaemia were found to be predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions that may improve treatment tolerance, quality of life and survival outcomes.

Adrenal insufficiency in intestinal obstruction from carcinomatosis peritonei--a factor of potential importance in symptom palliation.

Corticosteroids are used in the management of intestinal obstruction (IO) in carcinomatosis peritonei. There is considerable overlap in the symptoms experienced in IO and functional adrenal insufficiency (AI). The success of symptom palliation in IO may be related to the presence of AI. The aim of this preliminary study was to evaluate the incidence of functional adrenal insufficiency in patients with IO and its relation to clinical outcome and symptom control. Twenty-nine consecutive patients with IO and carcinomatosis peritonei from gastrointestinal cancers admitted to our inpatient service between January and October 2002 were analyzed. They were screened for AI using the short corticotropin stimulation test. Thirteen patients (45%) had functional AI. Differences in characteristics of patients with normal adrenal function (Group 1) and adrenal insufficiency (Group 2) were not statistically significant. Time taken to control symptoms in Group 2 was longer. Mean duration of hospitalization per month of survival was two times longer in Group 2 relative to Group 1 (7.9 versus 4.0 days, P=0.011). Functional AI may be caused by cytokines produced in advanced cancer mediating direct adrenal suppression. Prompt corticosteroid therapy in the presence of AI may facilitate IO symptom palliation.

Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues.

In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27-1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89-4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 - not reached) with pasireotide versus 6.8 months (5.6 - not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20-0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR.

Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma.

PURPOSE: To analyze the results of concurrent chemoradiotherapy in patients with locoregional recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective analysis of 35 patients with locoregional recurrent nasopharyngeal carcinoma referred to our department between March 1994 and November 2002. Most patients were male (77%), Chinese (97%), and had undifferentiated carcinoma (89%). Most had extensive locally recurrent Stage rT3-T4 disease (66%) with a median age at recurrence of 49 years (range, 35-69 years). A repeat course of radiotherapy was given concurrently with cisplatin, with cisplatin/5-fluorouracil as consolidation treatment. Significant morbidities were present, including cranial nerve palsies due to extensive recurrent local disease before treatment of the recurrence. RESULTS: The response rate to concurrent chemoradiotherapy was 58% (29% complete response and 29% partial response). The 5-year progression-free and overall survival rate, calculated using the Kaplan-Meier method, was 15% and 26%, respectively. Only 3 patients developed systemic metastases. Grade 3-4 acute toxicities included emesis (9%) and neutropenia (14%), and Grade 3-4 late toxicities consisted of temporal lobe necrosis (3%), cranial neuropathy (6%), and endocrine abnormalities (14%). CONCLUSION: Concurrent chemoradiotherapy is feasible in a selected group of patients with locoregional recurrent NPC, but the risk of major late toxicities is significant.

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

BACKGROUND: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. METHODS: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). RESULTS: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. CONCLUSIONS: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712790.

The influence of primary site on outcomes in leiomyosarcoma: a review of clinicopathologic differences between uterine and extrauterine disease.

BACKGROUND: Leiomyosarcomas (LMS) comprise 25% of soft tissue sarcomas. Recent reports suggest differences in treatment outcomes between uterine (uLMS) and extrauterine (eLMS) disease that may reflect distinct disease biologies. We sought to identify prognostic factors in LMS and clinicopathologic differences between uLMS and eLMS. METHODS: This is a single-center retrospective study evaluating 97 eligible patients treated for LMS between 2002 and 2010. RESULTS: Median follow-up was 21.2 months. uLMS affected 53% of patients, and was less common beyond age 60 years compared with eLMS (10% vs. 37%, P = 0.002). Seventy-two percent of patients presented with nonmetastatic disease. Of these, 94% underwent curative surgery, among whom more uLMS patients achieved negative surgical margins (90% vs. 45%, P = 0.003). There were no significant differences in adjuvant therapy use and relapse patterns between uLMS and eLMS. Half of metastatic patients received palliative chemotherapy, among whom 76% received anthracycline-based chemotherapy in first line to which response rate was 31%. Median overall survival was 45.2 months, 49.8 months in uLMS, and 40.5 months in eLMS (P = 0.294). Among patients without metastases, median survival was 60.8 months (77.3 vs. 48.1 mo in uLMS and eLMS, respectively, P = 0.194). In metastatic disease, median survival was 20.7 months (22.0 vs. 17.5 mo in uLMS and eLMS, respectively, P = 0.936). Advanced disease stage, bone metastases and lack of metastasectomy prognosticated for inferior survival. CONCLUSIONS: While demonstrating interesting clinicopathologic differences, the evidence for uLMS and eLMS being biologically distinct remains inconclusive. Disease stage is prognostically most important in LMS.

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.

Analysis of prognostic factors of comprehensive geriatric assessment and development of a clinical scoring system in elderly Asian patients with cancer.

PURPOSE: To determine the impact of each comprehensive geriatric assessment (CGA) domain on overall survival (OS) and develop a prognostic scoring system for elderly patients with cancer. PATIENTS AND METHODS: A retrospective analysis of CGA data collected from 249 consecutive patients with cancer who attended the outpatient geriatric oncology clinic at the National Cancer Center Singapore age 70 years or older was performed. Univariate and multivariate analyses were performed using Cox proportional hazards method to identify significant prognostic factors within the CGA. A simple nomogram to predict OS was developed using regression coefficients from the multivariate model. Concordance between predicted and observed response of the individual patient score was evaluated by means of Harrell's c-index. Calibration was performed using simulated data via bootstrap. RESULTS: Median age of the patients was 77 years (range, 70 to 94 years). In our model, age (hazard ratio [HR], 1.04; 95% CI, 1.01 to 1.07), abnormal albumin level (HR, 1.97; 95% CI, 1.23 to 3.15), poor Eastern Cooperative Oncology Group performance status (≥ 2 v < 2: HR, 1.77; 95% CI, 1.15 to 2.72), abnormal geriatric depression scale status (HR, 1.81; 95% CI, 1.29 to 2.56), high malnutrition risk (high v low risk: HR, 1.84; 95% CI, 1.17 to 2.87), and advanced disease stage (late v early: HR, 1.71; 95% CI, 0.98 to 2.95) were independent predictors of survival. CONCLUSION: Results confirm the importance of the CGA in assessment of elderly patients with cancer. The development of this nomogram incorporating these prognostic factors helps predict OS of patients, for further intervention.

Molecular and other novel advances in treatment of metastatic epithelial and medullary thyroid cancers.

An understanding of the mutations of the proto-oncogenes and tumor suppressor genes that occur in thyroid cancers should eventually explain the diverse clinical characteristics of these tumors and also direct therapy. Some insights have already emerged in the last decade; some abnormalities in tumor genes are consistently associated with specific clinical and pathologic findings. These genetic abnormalities usually represent somatic mutations in tumors of follicular epithelial origin, as opposed to inherited mutations in medullary thyroid cancers of parafollicular C cells origin because most thyroid tumors are sporadic and not familial. This is different from the multiple endocrine neoplasia syndromes in which the primary tumorigenic gene mutations are inherited. This improved understanding of the molecular basis of these diseases has led to the development of novel targeted therapeutic approaches which will be discussed in this paper.

Impact of comorbidities on clinical outcomes in non-small cell lung cancer patients who are elderly and/or have poor performance status.

AIM: We evaluated the effect of comorbidities on clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who have poor performance status (PS 2/3) and/or are elderly (≥70 years old). SUMMARIZED DESCRIPTION: The impact of age (<70 versus >70), PS, and comorbidity score - Cumulative Illness Rating Scale for Geriatrics (CIRS-G) on treatment response, toxicities, QOL and overall survival (OS) was analyzed using data from a completed phase II trial that randomly assigned patients with advanced NSCLC who had PS 2/3 and/or were aged ≥70 to receive gemcitabine (GEM), vinorelbine (VIN) or docetaxel (DOC). RESULTS: Data from records of 134 patients accrued during the trial were available for analysis. Eighty-eight patients (66%) were aged ≥70 years. 59 patients (67%) had PS of ECOG 0-2 and 29 patients (33%) had ECOG 3. In those aged ≥70, 53 (60%) had at least one comorbidity rated CIRS-G category 3/4 while those aged <70, 12 (26%) had at least one CIRS-G 3/4 comorbidity. Age, PS, and comorbidity scores had no significant association with PFS and QOL scores changes, although PS had marginal influence on OS (0.05

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers.

AIM: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers. METHODS: All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers. RESULTS: A total of 108 patients were reviewed. Median age at diagnosis was 60. The majority of the patients (64.8%) had advanced stage III and IV disease (with no distant metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients (19.4%) had positive surgical resection margins. Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For the patients in the chemotherapy-only group, all had fluoropyrimidine-based therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU-RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo) and the chemotherapy-only groups (44 mo) (P = 0.5). CONCLUSION: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.