Nasopharyngeal carcinoma Chua, Melvin L K, Dr; Wee, Joseph T S, FRCR; Hui, Edwin P, FRCP ...
The Lancet (British edition),
03/2016, Letnik:
387, Številka:
10022
Journal Article
Recenzirano
Summary Epidemiological trends during the past decade suggest that although incidence of nasopharyngeal carcinoma is gradually declining, even in endemic regions, mortality from the disease has ...fallen substantially. This finding is probably a result of a combination of lifestyle modification, population screening coupled with better imaging, advances in radiotherapy, and effective systemic agents. In particular, intensity-modulated radiotherapy has driven the improvement in tumour control and reduction in toxic effects in survivors. Clinical use of Epstein-Barr virus (EBV) as a surrogate biomarker in nasopharyngeal carcinoma continues to increase, with quantitative assessment of circulating EBV DNA used for population screening, prognostication, and disease surveillance. Randomised trials are investigating the role of EBV DNA in stratification of patients for treatment intensification and deintensification. Among the exciting developments in nasopharyngeal carcinoma, vascular endothelial growth factor inhibition and novel immunotherapies targeted at immune checkpoint and EBV-specific tumour antigens offer promising alternatives to patients with metastatic disease.
The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic ...by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches.
Implications for Practice
The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology.
Cancer patients have an increased risk of contracting COVID‐19. This article addresses the challenges associated with managing cancer patients during the COVID‐19 infection pandemic and suggests some practical approaches.
Upconversion nanoparticles (UCNPs) are the preferred choice for deep-tissue photoactivation, owing to their unique capability of converting deep tissue-penetrating near-infrared light to UV/visible ...light for photoactivation. Programmed photoactivation of multiple molecules is critical for controlling many biological processes. However, syntheses of such UCNPs require epitaxial growth of multiple shells on the core nanocrystals and are highly complex/time-consuming. To overcome this bottleneck, we have modularly assembled two distinct UCNPs which can individually be excited by 980/808 nm light, but not both. These orthogonal photoactivable UCNPs superballs are used for programmed photoactivation of multiple therapeutic processes for enhanced efficacy. These include sequential activation of endosomal escape through photochemical-internalization for enhanced cellular uptake, followed by photocontrolled gene knockdown of superoxide dismutase-1 to increase sensitivity to reactive oxygen species and finally, photodynamic therapy under these favorable conditions. Such programmed activation translated to significantly higher therapeutic efficacy in vitro and in vivo in comparison to conventional, non-programmed activation.
The coronavirus disease 2019 (COVID-19) pandemic has burdened health care resources and disrupted care of patients with cancer. Virtual care (VC) represents a potential solution. However, few ...quantitative data support its rapid implementation and positive associations with service capacity and quality.
To examine the outcomes of a cancer center-wide virtual care program in response to the COVID-19 pandemic.
This cohort study applied a hospitalwide agile service design to map gaps and develop a customized digital solution to enable at-scale VC across a publicly funded comprehensive cancer center. Data were collected from a high-volume cancer center in Ontario, Canada, from March 23 to May 22, 2020.
Outcome measures were care delivery volumes, quality of care, patient and practitioner experiences, and cost savings to patients.
The VC solution was developed and launched 12 days after the declaration of the COVID-19 pandemic. A total of 22 085 VC visits (mean, 514 visits per day) were conducted, comprising 68.4% (range, 18.8%-100%) of daily visits compared with 0.8% before launch (P < .001). Ambulatory clinic volumes recovered a month after deployment (3714-4091 patients per week), whereas chemotherapy and radiotherapy caseloads (1943-2461 patients per week) remained stable throughout. No changes in institutional or provincial quality-of-care indexes were observed. A total of 3791 surveys (3507 patients and 284 practitioners) were completed; 2207 patients (82%) and 92 practitioners (72%) indicated overall satisfaction with VC. The direct cost of this initiative was CAD$ 202 537, and displacement-related cost savings to patients totaled CAD$ 3 155 946.
These findings suggest that implementation of VC at scale at a high-volume cancer center may be feasible. An agile service design approach was able to preserve outpatient caseloads and maintain care quality, while rendering high patient and practitioner satisfaction. These findings may help guide the transformation of telemedicine in the post COVID-19 era.
Liquid biopsies have the utility for detecting minimal residual disease in several cancer types. Here, we investigate if liquid biopsy tracking on-treatment informs on tumour phenotypes by ...longitudinally quantifying circulating Epstein-barr virus (EBV) DNA copy number in 673 nasopharyngeal carcinoma patients undergoing radical induction chemotherapy (IC) and chemo-radiotherapy (CRT). We observe significant inter-patient heterogeneity in viral copy number clearance that is classifiable into eight distinct patterns based on clearance kinetics and bounce occurrence, including a substantial proportion of complete responders (≈30%) to only one IC cycle. Using a supervised statistical clustering of disease relapse risks, we further bin these eight subgroups into four prognostic phenotypes (early responders, intermediate responders, late responders, and treatment resistant) that are correlated with efficacy of chemotherapy intensity. Taken together, we show that real-time monitoring of liquid biopsy response adds prognostic information, and has the potential utility for risk-adapted treatment de-intensification/intensification in nasopharyngeal carcinoma.
Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some ...promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.
What's new?
Given limited recent advances in chemotherapeutic regimens, there is an urgent need to develop targeted therapies for metastatic nasopharyngeal carcinoma (NPC) that reduce toxicity and improve survival benefit. This review of clinical trials with monoclonal antibodies against checkpoint inhibitors shows that anti‐PD1 is a potential treatment option for patients with recurrent/metastatic NPC. Camrelizumab combination therapy achieved the best clinical outcome, but was associated with a high rate of serious adverse events. As immunotherapy gets incorporated into standard treatments, issues of optimal combinations with targeting agents and immune adjuvants and sequence with chemotherapy and radiation therapy will need to be addressed.
Background
Patients with cancer have a higher risk of coronavirus disease 2019 (COVID‐19) than noncancer patients. The authors conducted a multicenter retrospective study to investigate the clinical ...manifestations and outcomes of patients with cancer who are diagnosed with COVID‐19.
Methods
The authors reviewed the medical records of hospitalized patients who were treated at 5 hospitals in Wuhan City, China, between January 5 and March 18, 2020. Clinical parameters relating to cancer history (type and treatment) and COVID‐19 were collected. The primary outcome was overall survival (OS). Secondary analyses were the association between clinical factors and severe COVID‐19 and OS.
Results
A total of 107 patients with cancer were diagnosed with COVID‐19, with a median age of 66 years (range, 37‐98 years). Lung (21 patients; 19.6%), gastrointestinal (20 patients; 18.7%), and genitourinary (20 patients; 18.7%) cancers were the most common cancer diagnoses. A total of 37 patients (34.6%) were receiving active anticancer treatment when diagnosed with COVID‐19, whereas 70 patients (65.4%) were on follow‐up. Overall, 52.3% of patients (56 patients) developed severe COVID‐19; this rate was found to be higher among patients receiving anticancer treatment than those on follow‐up (64.9% vs 45.7%), which corresponded to an inferior OS in the former subgroup of patients (hazard ratio, 3.365; 95% CI, 1.455‐7.782 P = .005). The detrimental effect of anticancer treatment on OS was found to be independent of exposure to systemic therapy (case fatality rate of 33.3% systemic therapy vs 43.8% nonsystemic therapy).
Conclusions
The results of the current study demonstrated that >50.0% of infected patients with cancer are susceptible to severe COVID‐19. This risk is aggravated by simultaneous anticancer treatment and portends for a worse survival, despite treatment for COVID‐19.
Patients with cancer who are receiving anticancer treatment have a 3‐fold higher risk of death from coronavirus disease 2019 (COVID‐19) than those on follow‐up. The authors report that this detrimental effect on survival appears to be independent of anticancer treatment modalities.
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