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.

Remarkable response to photodynamic therapy in residual T4N0M0 nasopharyngeal carcinoma: a case report.

Local treatment of residual or recurrent nasopharyngeal carcinoma (NPC) is a challenge. Photodynamic therapy (PDT) is an established treatment modality for incurable head and neck carcinoma. Several studies reported induction of an immune response after PDT. We present a patient with residual T4N0M0 NPC who was treated with PDT for residual disease after initial treatment with neo-adjuvant chemotherapy and radiotherapy. Five years after PDT, the tumor did not progress and the patient is still in good condition. We discuss this remarkable long-term response to PDT and speculate on possible mechanisms.

Temoporfin mediated photodynamic therapy in patients with local persistent and recurrent nasopharyngeal carcinoma after curative radiotherapy: a feasibility study.

BACKGROUND: The treatment of persistent and recurrent nasopharyngeal carcinoma (NPC) remains a challenge, especially in Indonesia. We investigated the safety and efficacy of temoporfin mediated photodynamic therapy (PDT) for patients with local persistent and recurrent NPC. MATERIAL AND METHODS: Twenty-two patients with persistent and recurrent NPC (maximum tumor depth < 10mm) underwent PDT under local anesthesia with use of a nasopharyngeal light applicator. Three different drug doses and light intervals have been administered: treatment arm A: 0.15 mg/kg Foscan; 96 h drug-light interval; B: drug dose of 0.10 mg/, 48 h drug-light interval; C: drug dose of 0.075 mg/kg, 24 h drug-light interval. Toxicity was measured by using the CTCAE 3.1 scale. RESULTS: Arm A consisted of eight patients, arms B and C consisted of seven patients. The treatment procedure was well tolerable under local anesthesia. The most common grade III toxicities for all groups is headache (n = 7; 33%). No grade IV toxicity was seen. One patient died 2 days after treatment due to a misdiagnosed pneumonia. In 17 of the 22 patients a biopsy was performed after 40 weeks and showed no tumor in all biopsies. Arm A seems, in addition to comparable toxicity, clinically more effective than arms B and C. CONCLUSION: The present study demonstrated that temoporfin mediated photodynamic therapy is a relatively simple technique that can be utilized to treat residual or recurrent nasopharyngeal cancer, restricted locally to the nasopharynx.

Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening.

Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr virus (EBV) antigen complexes, usually involving multiple serological assays, is important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through combination of two synthetic peptides representing immunodominant epitopes of EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from healthy donors (n = 367), non-NPC head and neck cancer patients (n = 43), and biopsy-proven NPC patients (n = 296) of Indonesian and Chinese origin. Higher values of optical density at 450 nm for EBV IgG were observed in NPC patients compared to the healthy EBV carriers, but the large overlap limits its use for NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of 80.1% and 70.9%, whereas combined single-well coating with both peptides yielded sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive and negative predictive values (PPV and NPV, respectively) for the combined EBNA1 plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia panel, the level of EBV IgA reactivity was not associated with NPC tumor size, lymph node involvement, and metastasis stage, sex, and age group. In the China panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and 84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC samples. The use of these combined methods for seroepidemiological screening studies is proposed.