Yuk Tung

What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.

Improved local control for early T-stage nasopharyngeal carcinoma - a tale of two hospitals

PURPOSE To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS All early T-stage (T1 and T2 nasal cavity tumour) NPC treated with a curative intent up to 1996 were analyzed (n=743), 163 from the Prince of Wales Hospital (PWH) and 25 from Tuen Mun Hospital (TMH) were given ICT after radical external radiotherapy (ERT; group A). They were compared with 555 patients treated with ERT alone (group B). The radiotherapy techniques were identical between the two hospitals. The ERT delivered the tumoricidal dose (uncorrected biological equivalent dose (BED)-10, > or = 75 Gy) to the primary tumour, and this did not differ in technique or dosage between the two groups. The ICT delivered a dose of 18-24 Gy in three fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. RESULTS The local failure was significantly less (crude rates, 6.9 vs. 13.0%; 5-year actuarial rates, 5.8 vs. 11.7%) and the disease-specific mortality was significantly lower (crude rates, 13.8 vs. 18.9%; 5-year actuarial rates, 12.2 vs. 15.2%) in group A compared with group B. ICT was the only significant independent prognostic factor predictive of fewer local failures. When ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumour repopulation became significant in predicting the ultimate local failure rate. The two groups were comparable in the rate of the chronic radiation complications. A significant dose-tumour-control relationship existed, plotting the local failure as a function of the total physical dose or the total BED. CONCLUSIONS Supplementing ERT, which delivered the tumoricidal dose (uncorrected BED-10, > or = 75 Gy), with ICT significantly enhanced ultimate local control in early T-stage (T1/T2 nasal infiltration) NPC. A significant dose-tumour-control relationship exists above the conventional tumoricidal dose level.

Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis

Background: Our objective was to evaluate progression-free survival (PFS) and distant metastasis–free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Methods: Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient &rgr; and at the trial level using a correlation coefficient R2 between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. Results: PFS was strongly correlated with OS at the individual level (&rgr; = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R2 = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (&rgr; = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R2 = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (&rgr; = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R2 = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (&rgr; = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R2 = 0.78, 95% CI = 0.33 to 1.00). Conclusions: PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.

Primary yolk sac tumour of the urinary bladder: A case report and review of the literature

We present a case of rare primary yolk sac tumour of the urinary bladder in adulthood. A 31-year-old female patient presented with a history of chronic ketamine abuse, which has not previously been shown to be associated with malignancy development. The final diagnosis was established only after radical cystectomy. A computed tomography (CT) scan showed paraaortic lymph node metastasis. The patient was treated with systemic chemotherapy. A review of the literature revealed that surgical excision and cisplatin-based chemotherapy remain to be the standard of care for extragonadal yolk sac tumours.

Toxicity of docetaxel plus cyclophosphamide as adjuvant therapy for breast cancer in Chinese patients – the Hong Kong experience

Aims:  The docetaxel and cyclophosphamide (TC) regimen is increasingly popular as adjuvant chemotherapy for operable breast cancers. We conducted a retrospective study in Hong Kong to evaluate the toxicity of this regimen in Chinese patients.

Comparison of clinical efficacy and renal safety of telbivudine and entecavir in chronic hepatitis B patients receiving cytotoxic chemotherapy.

Limited data is available on the clinical outcomes of telbivudine (LdT) and entecavir (ETV) in pre‐emptive antiviral chemoprophylaxis. This study aimed to evaluate the clinical efficacy and renal safety of LdT and ETV in patients with chronic hepatitis B (CHB) who received cytotoxic chemotherapy.

PO-0698: Clinical outcomes of 4D CBCT-guided stereotactic body radiotherapy for inoperable hepatocellular carcinomas

Purpose/Objective: In this retrospective study, nextgeneration exomic sequencing (NGS) was utilized in biliary and pancreatic adenocarcinoma samples to identify potential novel therapeutic targets that are not routinely assayed in the clinical setting. Materials and Methods: Patients with confirmed pancreatic adenocarcinoma or cholangiocarcinoma were selected based on availability of tissues. A total of 236 somatic genes were surveyed in this review, including 3,230 exons and 47 introns at >900x mapping coverage. NGS reports were generated from 2011 to 2013 and reviewed restrospectively. Statistical analysis was performed using univariate analysis and KaplanMeier survival estimates. Results: Seventeen (95%) of cases harbored at least one potentially actionable mutation, including BRACA (10.5%), CDKN2 (26.3%), FGFR (15.8%), KRAS (42.1%), MLL (26.3%), NRAS (5.3%), PIK3CA (10.5%), and TP53 (42.1%). Notably, KRAS mutations were found at a higher frequency in pancreatic adenocarcinomas in comparison to cholangiocarcinomas (87.5% vs 9.1%). Overall, the most frequent genomic alterations were found within KRAS (42.1%), TP53 (42.1%), CDKN2 (26.3%), and MLL (26.3%). All patients with SMAD alterations were also found to have concurrent KRAS mutations, which is consistent with reported literature. KRAS mutations most commonly involved codon 12, while the locations of SMAD and Tp53 mutations were heterogeneous. In addition, concurrent mutations were found within genes that have been shown to potentially modulate or interact with KRAS-mediated signaling pathways, including CCND3, CDKN2A/B, and RB1. Alterations of BCOR, CCND3, CRKL, NF1, STK11, and TSC1 were rare events (<6%). Furthermore, 95% of patients had multiple, novel mutations that have not been associated with pancreatic or biliary adenocarcinoma. The majority (63.2%) of patients had greater than five mutations identified. Median survival and 5yr OS in pancreatic adenocarcinoma were 30.1 months and 41%, respectively. 5-yr OS in cholangiocarcinoma cases was substantially higher (85.7%), and 27.2% of these patients received EBRT as a component of their treatment. For either subset of patients, there was no significant correlation between number of mutations and OS. Overall, 63% of patients were found to have mutations associated with targeted therapies. One quarter of these patients possessed multiple, concurrent molecular targets for which FDAapproved chemotherapeutic agents are currently available. Conclusions: Novel mutations were identified in the majority of patients, including mutations within a number of genes which have the potential to influence KRAS-mediated signaling, as well as other prominent signaling pathways. These results could potentially serve to identify targets for novel chemotherapeutic agents and to guide personalized, combinatorial therapy in appropriately selected patients. PO-0697 Comparative study failure model esophageal carcinoma with elective nodal regional and involved field irradiation S. Zhu, W. Shen, Z. Liu, J. Li, J. Su Fourth Hospital of Hebei Medical University, Department of Radiation Oncology, Sijiazhuang Hebei, China