T.K. Yau

Preliminary Results of a Randomized Study on Therapeutic Gain by Concurrent Chemotherapy for Regionally-Advanced Nasopharyngeal Carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group

PURPOSE This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.

Randomized Trial of Radiotherapy Plus Concurrent–Adjuvant Chemotherapy vs Radiotherapy Alone for Regionally Advanced Nasopharyngeal Carcinoma

BACKGROUND Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. METHODS Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. RESULTS The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). CONCLUSIONS Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.

Survival outcome of patients with nasopharyngeal carcinoma with first local failure: A study by the Hong Kong nasopharyngeal carcinoma study group

The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS.

Sensorineural Hearing Loss After Treatment of Nasopharyngeal Carcinoma: A Longitudinal Analysis

PURPOSE To analyze the effects of radiotherapy (RT) and chemotherapy in relation to sensorineural hearing loss (SNHL) after contemporary treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS A total of 87 nasopharyngeal carcinoma patients were treated with RT or chemoradiotherapy using either three-dimensional conformal RT or intensity-modulated RT between 2004 and 2005. Tympanometry and pure-tone audiogram assessments were performed before treatment and then serially at 6-month intervals. The dose-volume data of the cochlea were analyzed. The effects of cisplatin administered in concurrent and nonconcurrent phases was explored. RESULTS Of the 170 eligible ears, RT (n = 30) and chemoradiotherapy (n = 140) resulted in 40% (n = 12) and 56.4% (n = 79) persistent SNHL (> or = 15 dB loss), respectively, after a median follow-up of 2 years. SNHL at a high frequency was more frequent statistically in the chemoradiotherapy group than in the RT-alone group (55% vs. 33.3%, p < 0.01), but not at a low frequency (7.9% vs. 16.7%, p = 0.14). Within the chemoradiotherapy group, the mean cochlea dose and concurrent cisplatin dose were important determinants of high-frequency SNHL, with an odds ratio of 1.07/Gy increase (p = 0.01) and an odds ratio of 1.008/mg/m(2) increase (p < 0.01), respectively. Age, gender, and nonconcurrent cisplatin dose were not statistically significant factors. A mean radiation dose to the cochlea of <47 Gy would result in <15% of patients developing severe (> or = 30 dB) high-frequency SNHL. CONCLUSION The results of our study have shown that high-frequency SNHL is significantly related to the mean cochlea dose and the concurrent cisplatin dose. A mean dose constraint of 47 Gy to the cochlea is recommended to minimize SNHL after chemoradiotherapy.

The strength/weakness of the AJCC/UICC staging system (7th edition) for nasopharyngeal cancer and suggestions for future improvement

BACKGROUND AND PURPOSE To evaluate the current AJCC/UICC staging system (7th edition) for nasopharyngeal carcinoma and to explore for future improvement. MATERIALS AND METHODS A total of 985 patients, initially staged with preceding 5-6th edition, were retrospectively re-staged with the 7th edition. All were assessed by magnetic resonance imaging, and all 945 non-disseminated patients were irradiated with conformal/intensity-modulated technique. RESULTS Staging factors by both the 5-6th edition and the 7th edition were strongly significance for important endpoints (p<0.001). Down-staging of the previous T2a to T1 and, stages IIA to I in the 7th edition was appropriate. However, the impacts on overall stage distribution and prognostication were minimal. Further down-staging of the current T2 to T1, N2 to N1, stages II to I, and merging of N3a and N3b, stages IVA and IVB were suggested. With the 7th edition, the 5-year disease-specific survival (DSS) was 100% for stage I, 95% for II, 90% for III, 67% for IVA, 68% for IVB and 18% for IVC. The corresponding DSS for the proposed stages I, II, III and IV were 95%, 86%, 67% and 18%, respectively. CONCLUSIONS The changes introduced in the 7th edition were appropriate, but the magnitude of improvement was minimal. With improving results by modern management, further simplification of the staging system is suggested. The proposed system could lead to more accurate prognostication, further validation is warranted.

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study

Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non‐Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC.

A phase II study of pemetrexed combined with cisplatin in patients with recurrent or metastatic nanopharyngeal carcinoma

Pemetrexed is a novel chemotherapy agent with good efficacy and toxicity profiles. This phase II study aimed at evaluating its use in combination with cisplatin for recurrent or metastatic nasopharyngeal carcinoma (NPC). All participating patients had metastatic or recurrent NPC with prior treatment by platinum-based chemotherapy. The study regimen comprised of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2), repeated 3-weekly for 4 cycles. Efficacy evaluation was based on both radiological and biochemical responses. Patients with no progressive disease and good tolerance were given another 2-4 cycles. Fifteen patients were treated for a total of 4-8 cycles (median, 6 cycles); 9 had distant metastases and 6 had loco-regional recurrences only. Reduction of DNA copies of EB virus by ≥50% was observed in 93% accessible patients, with 21% of them being biochemical complete response (CR). Radiologically, 1 (7%) patient achieved CR, 2 (13%) achieved partial response and 8 (53%) had stable diseases. The median time to progression was 30 weeks. Treatment was well tolerated with only 1 (7%) patient developing grade 4 toxicity (of anemia). The most common grade 3 toxicities were neutropenia (27%) and anemia (20%). The baseline mean total QOL scores (as measured with FACT-H&N version 4) was 100.4 and showed no significant change after the fourth cycle (95.6, p=0.20) and sixth cycle (91.9, p=0.15). Pemetrexed in combination with cisplatin is a well tolerated regimen with encouraging efficacy for metastatic and recurrent NPC. Further evaluation of its role in the management of NPC is warranted.

Goal adjustment influence on psychological well-being following advanced breast cancer diagnosis

A diagnosis of advanced breast cancer (ABC) challenges a womans ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment.

Trajectory patterns of supportive care needs among Chinese women with advanced breast cancer

Nadine Köhle 1, Constance Drossaert2, Cornelia van Uden-Kraan3, Irma Verdonck -de Leeuw4, Ernst Bohlmeijer5 1University of Twente, Enschede, Overijssel, The Netherlands, 2University of Twente, Enschede, Overijssel, The Netherlands, 3VU University, Amsterdam, Noord-Holland, The Netherlands, 4VU University, Amsterdam, Noord-Holland, The Netherlands, 5University of Twente, Enschede, Overijssel, The NetherlandsFrom Vision to Action - Innovation and Implementation of an Integrated Cancer Rehabilitation Within Clinical Practice

A phase II study of pemetrexed combined with cisplatin in patients (pts) with recurrent or metastatic nasopharyngeal carcinoma.

5538 Background: Nasopharyngeal carcinoma (NPC) is a chemo-sensitive disease but there is yet no consensus on the best regimen for recurrent or metastatic diseases. Pemetrexed is a new agent with good efficacy and toxicity profiles in other cancers. This phase II study aims to evaluate its use in combination with cisplatin for NPC. METHODS Patients (pts) with metastatic or extensive recurrence (unsuitable for radical surgery or re-irradiation) were included. All had prior treatment with platinum-based chemotherapy. The regimen consisted of pemetrexed 500mg/m2 (with vitamin B12 and folic acid support) and cisplatin 75mg/m2 every 3 weeks. Assessments of efficacy were based on both radiological and biochemical (DNA copies of Epstein-Barr virus) response. Toxicity profile was assessed by both acute toxicity rates and quality of life (QOL) scores (measured with FACT-H&N version 4). Patients with response/stable disease and good tolerance were given another 2-4 cycles. RESULTS Fourteen pts (5 with loco-regional recurrences and 9 with metastases) were treated with this regimen; their median age was 51 (range, 39-68) years. All except one pts had elevated EBV-DNA (median, 34,750 copies/ml; range, 42-17,500,000). A total of 4-8 (median, 6) cycles had been given. Reduction of EBV-DNA copies by >=50% was observed in 12/13 (92%) pts, 2/13 (15%) pts even achieved biochemical complete remission (CR). Radiological assessment showed that one (7%) pt achieved CR, 2 (14%) had partial remission and 7 (50%) had stable diseases. The median time to progression was 30 weeks (range, 11-119 weeks). Only one pt (7%) developed grade 4 toxicity (anemia). The most common grade 3 toxicities were neutropenia (29%) and anemia (21%). All 14 pts had QOL assessment at baseline and after the fourth cycle; 12 (86%) pts had further assessment after the sixth cycle. No significant deterioration in QOL was observed: the total QOL scores (mean) changed from 99 at baseline to 95 after the fourth cycle (p=0.35) and 90 after the sixth cycle (p=0.16). CONCLUSIONS Cisplatin-pemetrexed was a well tolerated regimen and the efficacy for metastatic/recurrent NPC was encouraging. Further evaluation of its role in treatment of NPC is warranted.