Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

Integrative Palliative Care Service Model Improved End-of-Life Care and Overall Survival of Advanced Cancer Patients in Hong Kong: A Review of Ten-Year Territory-Wide Cohort.

Background: Integrated palliative care in oncology service has been widely implemented in Hong Kong since 2006. Aim: The study aimed to review its impact on end-of-life outcomes and overall survival (OS) of cancer patients, as well as its utilization of health care resources in the past 10 years. Design: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Setting/Participants: Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at four time points (2006, 2009, 2012, and 2015). Individual patient records were thoroughly reviewed. Propensity score-matched (PSM) analysis was employed to compare the survival of patients. Results: Palliative care provision was associated with improved palliative care outcome, including more prescription of strong opioid, fewer cardiopulmonary resuscitations and intensive care unit admissions, and less futile chemotherapy usage in the end-of-life period (all p < 0.001). In the PSM analysis, the median OS in patients with palliative service (5.10 months, 95% confidence interval [CI] 4.52-5.68 months) was significantly better than those without palliative service (1.96 months, 95% CI 1.66-2.27 months). Patients in the palliative care group had more specialist clinic visits (p < 0.001) and longer hospital stay (p < 0.001) in the last six months of life, although the duration of last admission stay at acute general ward was shortened (p < 0.001). Conclusion: Our results suggested palliative care has played a role in the remarkable improvement in end-of-life outcomes and OS. However, current palliative care model relied heavily on hospital resources. Future work is needed to strengthen community care and to build up quality monitoring systems.

The impact of palliative care training for oncologists and integrative palliative service in a public-funded hospital cluster-a retrospective cohort study.

PURPOSE: Oncological care of advanced cancer patients was provided by multiple departments in Hong Kong. One of these departments, the clinical oncology department (COD), introduced systematic palliative care training for its oncologists since 2002. The COD was recognized as a European Society for Medical Oncology (ESMO) Designated Centre of Integrated Oncology and Palliative Care since 2009. This retrospective cohort study aims to review the impact of integrative training and service on palliative care coverage and outcome. METHODS: Clinical information, palliative service provision, and end-of-life outcomes of patients who passed away from lung, colorectal, liver, stomach, or breast cancer in the Hong Kong West public hospital network during July 2015 to December 2015 were collected. RESULTS: A total of 307 patients were analyzed. Around half (49.2%) were attended primarily by COD, and 68.9% received palliative service. There are significantly fewer patients referred to palliative care from other departments (p < 0.001), with only 19.9% of this patient group receiving palliative referral. COD patients had longer palliative coverage before death (median 65 days versus 24 days, p < 0.001), higher chance of receiving end-of-life care at hospice units (36.4 versus 21.2%, p = 0.003), lower ICU admission (0.66 versus 5.1%, p = 0.02), and higher percentage of receiving strong opioid in the last 30 days of life (51.0 versus 28.9%, p < 0.001) compared to other departments. In multivariable analysis, COD being the primary care team (odds ratio 12.2, p < 0.001) was associated with higher palliative care coverage. CONCLUSION: The study results suggested that systematic palliative care training of oncologists and integrative palliative service model was associated with higher palliative service coverage and improved palliative care outcomes.

Can the analysis of ERCC1 expression contribute to individualized therapy in nasopharyngeal carcinoma?

PURPOSE: To analyze the expression of excision repair cross-complementation group 1 (ERCC1) protein in predicting the clinical outcome of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The histologic specimens of 258 patients with Stage III to IVB nonkeratinizing NPC who were treated with radiotherapy alone (Group I) or concurrent-adjuvant chemoradiotherapy (Group II) were retrieved. Immunostaining on ERCC1 protein was performed. The relationship of ERCC1 expression and clinical outcomes was analyzed. RESULTS: The median ERCC1 score (proportion score of positively stained cells times intensity) was 200 (range, 0-300), and ERCC1 expression was defined as high if the score was above the median. In Group I high-score tumor had a statistically lower locoregional failure-free rate (LRFFR) compared with low-score tumor (p < 0.05) but not distant failure-free rate (DFFR) and overall survival (OS). In Group II no statistically differences were noted in LRFFR, DFFR and OS with regard to the ERCC1 expression. Resistance to cisplatin-containing chemotherapy in high-ERCC1 score tumor was not observed in Group II. Interestingly, low-score tumor in Group I achieved similar local and distant control compared with Group II. Multivariate analysis showed that ERCC1 score was an independent prognostic factor in LRFFR (p < 0.05) and approached statistical significance in failure-free survival (p = 0.08) and OS (p = 0.07). Tumor with high ERCC1 score had a 2-fold (95% confidence interval, 1.02-3.85) increased risk of locoregional failure. This may imply an association of ERCC1 expression with the repair of radiation damage. CONCLUSIONS: High ERCC1 expression predicts poor locoregional control in NPC. Chemotherapy response is not affected by ERCC1 expression. Further validation is required.

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. RESULTS: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. CONCLUSIONS: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.