Background
A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin ...followed by adjuvant cisplatin and 5‐fluorouracil (PF). This randomized NPC‐0501 trial evaluated the therapeutic effect of changing to an induction‐concurrent sequence or accelerated‐fractionation sequence, and/or replacing 5‐fluorouracil with capecitabine (X).
Methods
Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6‐arm full‐randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3‐arm chemotherapy cohort).
Results
A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the induction‐concurrent sequence, especially the induction‐PX regimen, achieved significant improvements in progression‐free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated‐fractionation group and the 3‐arm chemotherapy cohort, a comparison of the induction‐concurrent versus concurrent‐adjuvant sequence in the conventional‐fractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction‐PX versus the adjuvant‐PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity.
Conclusions
For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent‐adjuvant to an induction‐concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.
The 5‐year results from the NPC‐0501 trial demonstrate that conventional fractionation remains the standard recommendation for patients with locoregionally advanced nasopharyngeal carcinoma who are treated with chemoradiotherapy because acceleration does not appear to achieve any therapeutic benefit, and could affect the potential benefit of changing from concurrent‐adjuvant to induction‐concurrent chemotherapy. For patients who undergo irradiation with conventional fractionation, changing the chemotherapy sequence from concurrent‐adjuvant to induction‐concurrent, particularly using induction cisplatin and capecitabine, could improve efficacy without resulting in the development of late toxicities. However, further validation is needed for confirmation.
Intensity modulated radiation therapy (IMRT) is widely used to achieve a highly conformal dose and improve treatment outcome. However, plan quality and planning time are institute and planner ...dependent, and no standardized tool exists to recognize an optimal plan. RapidPlan, a knowledge-based algorithm, can generate constraints to assist optimization and produce high-quality IMRT plans. This report evaluated the quality and efficiency of using RapidPlan in nasopharyngeal carcinoma (NPC) IMRT planning.
RapidPlan was configured using 79 radical IMRT plans for NPC; 20 consecutive NPC patients indicated for radical radiation therapy between October 2014 and May 2015 were then recruited to assess its performance. The ability of RapidPlan to produce acceptable plans was evaluated. For plans that could not achieve clinical acceptance, manual touch-up was performed. The IMRT plans produced without RapidPlan (manual plans) and with RapidPlan (RP-2 plans, including those with manual touch-up) were compared in terms of dosimetric quality and planning efficiency.
RapidPlan by itself could produce clinically acceptable plans for 9 of the 20 patients; manual touch-up increased the number of acceptable plans (RP-2 plans) to 19. The target dose coverage and conformity were very similar. No difference was found in the maximum dose to the brainstem and optic chiasm. RP-2 plans delivered a higher maximum dose to the spinal cord (46.4 Gy vs 43.9 Gy, P=.002) but a lower dose to the parotid (mean dose to right parotid, 37.3 Gy vs 45.4 Gy; left, 34.4 Gy vs 43.1 Gy; P<.001) and the right cochlea (mean dose, 48.6 Gy vs 52.6 Gy; P=.02). The total planning time for RP-2 plans was significantly less than that for manual plans (64 minutes vs 295 minutes, P<.001).
This study shows that RapidPlan can significantly improve planning efficiency and produce quality IMRT plans for NPC patients.
Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease ...management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research.
To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).
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.
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.
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.
The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, ...a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.
•Regular surveillance monitoring is needed for early detection of local recurrence.•Surgery should be considered whenever feasible due to its lower complication risk.•The therapeutic margin in ...re-irradiation is narrow.•Most common fatal radiotherapy toxicities include mucosal necrosis and haemorrhage.•Role of systemic treatment is unclear, may only be chosen in conservative settings.
As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10–20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.
The 2019 novel coronavirus disease (COVID‐19) is a highly contagious zoonosis produced by SARS‐CoV‐2 that is spread human‐to‐human by respiratory secretions. It was declared by the WHO as a public ...health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case‐by‐case basis for patients with cancer. For those who are working with COVID‐19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID‐19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID‐19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID‐19 positive subjects, and their protection should be considered a priority in the present circumstances.
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