The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study.

PURPOSE: In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored. METHODS: In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS). RESULTS: The median WT was 117 days (range 12-581) and OTT was 58 days (43-142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log-WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09-2.61), LRC (HR 1.66; 95% ci: 1.15-2.39), and DFS (HR 1.4; 95% ci: 1.09-1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn't received concurrent chemotherapy. CONCLUSION: Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient's physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.

Photodynamic therapy as salvage therapy for patients with nasopharyngeal carcinoma experiencing local failures following definitive radiotherapy.

BACKGROUND: Treating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC. METHOD: In this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10mm. Foscan® 0.15mg/kg was administered intravenously. After 96h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis. RESULTS: Twenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed. CONCLUSION: This study showed that PDT is effective in treating local failures of NPC with a depth of less than 10mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.

Current treatment options for local residual nasopharyngeal carcinoma.

OPINION STATEMENT: Local residual disease occurs in 7-13 % after primary treatment for nasopharyngeal carcinoma (NPC). To prevent tumor progression and/or distant metastasis, treatment is indicated. Biopsy is the "gold standard" for diagnosing residual disease. Because late histological regression frequently is seen after primary treatment for NPC, biopsy should be performed when imaging or endoscopy is suspicious at 10 weeks. Different modalities can be used in the treatment of local residual disease. Interestingly, the treatment of residual disease has better outcomes than treatment of recurrent disease. For early-stage disease (rT1-2), treatment results and survival rates are very good and comparable to patients who had a complete response after the first treatment. Surgery (endoscopic or open), brachytherapy (interstitial or intracavitary), external or stereotactic beam radiotherapy, or photodynamic therapy all have very good and comparable response rates. Choice should depend on the extension of disease, feasibility of the treatment, and doctor's and patient's preferences and experience, as well as the risks of the adverse events. For the more extended tumors, choice of treatment is more difficult, because complete response rates are poorer and severe side effects are not uncommon. The results of external beam reirradiation and stereotactic radiotherapy are better than brachytherapy for T3-4 tumors. Photodynamic therapy resulted in good palliative responses in a few patients with extensive disease. Also, chemotherapeutics or the Epstein-Barr virus targeted therapies can be used when curative intent treatment is not feasible anymore. However, their advantage in isolated local failure has not been well described yet. Because residual disease often is a problem in countries with a high incidence of NPC and limited radiotherapeutic and surgical facilities, it should be understood that most of the above mentioned therapeutic modalities (radiotherapy and surgery) will not be readily available. More research with controlled, randomized trials are needed to find realistic treatment options for residual disease.