Adult Nasopharyngeal Carcinoma Research Articles

Toripalimab (Loqtorzi) for nasopharyngeal carcinoma.

Toripalimab-tpzi (Loqtorzi – Coherus Biosciences), a programmed death receptor-1 (PD-1)-blocking antibody, has been approved by the FDA for use in combination with cisplatin and gemcitabine for first-line treatment of recurrent locally advanced or metastatic nasopharyngeal carcinoma and for use as monotherapy for treatment of recurrent unresectable or metastatic nasopharyngeal carcinoma in adults with disease progression on or after platinum-based chemotherapy. It is the first immune checkpoint inhibitor to be approved in the US for treatment of nasopharyngeal carcinoma.

Abstract PR002: Single-cell spatial analysis reveals microenvironmental features that contribute to immune discrepancies between adult and pediatric nasopharyngeal carcinomas

Abstract Background: Nasopharyngeal carcinoma (NPC) is an EBV-positive malignancy with high immune infiltrates but also high immunosuppressive activities. Pediatric NPC only constitutes 0.1-1% of the total NPC incidences and exhibits superior treatment responses and prognosis compared to adult NPC. Clinically, we consider that the differences in the tumor landscape between adult and pediatric NPC patients are the vital driver of such immune discrepancies. Therefore, we apply scRNA-seq and Visium spatial sequencing to primary pediatric NPC tissues and paired peripheral blood samples, and integrate our data with multiple independent adult NPC scRNA-seq cohorts. Furthermore, we establish a bioinformatics analysis pipeline that can calculate spatial cellular compositions and biological activities. Here, we demonstrate that low lipid metabolism, disrupted interactions between NPC cells and regulatory T cells (Tregs)/CD8+ T cells, and high infiltration of central stem memory T cells, contribute to more potent and enduring anti-tumor immunity in pediatric NPC patients, and these microenvironmental features might serve as new immunotherapeutic vulnerabilities. Method: 5' scRNA-seq coupled with TCR/BCR profiling was performed on 5 primary and treatment-naïve pediatric NPC tissues with 5 paired peripheral blood samples. Visium spatial-seq was performed on 4 paired pediatric and 7 adult NPC tissues. We incorporated our scRNA-seq cohort with three independent adult NPC cohorts. Our computational framework was integrated with existing analysis packages, including Seurat, Spacexr, and SpaCET, to analyze single-cell-referenced spatial data. The key results in our study were validated by multiplex IHC staining and flow cytometry on patient samples. Results: We established a multi-center NPC scRNA spatial cohort containing 503,021 cells from 69 samples, and 15,222 spatial spots from 11 samples. We developed a computational framework to calculate spatial co-localization and biological activities. We unveiled that lipid metabolism was elevated in the tumor-T cell core in adult NPC. Strong co-localizations between NPC cells and Tregs/CD8+ T cells were found in adult NPC, with spatially enriched CD70-CD27 and LGALS9-TIM3 interactions. This finding was corroborated by multiplex IHC staining of KRT19+ NPC cells, CD4+/FOXP3+ Tregs, and CD8+/PD-1/TIM-3+ exhausted T cells. We also identified and characterized novel IL7R+ central stem memory T cells in pediatric NPC tissues and blood, with strong resilience to immunosuppressive cues, including TGF-β, PEG2, and cyclic AMP, and could lead to enduring immunity and anti-PD-1/PD-L1 responses. Conclusion: We demonstrate that higher T-cell immunosuppression and exhaustion caused by aberrant lipid metabolism, tumor-T interactions, and a lower age-associated central stem memory T-cell pool, are vital drivers of immune discrepancies in adult and pediatric NPC patients. Thus, screening and targeting these molecular microenvironmental characteristics might help stratify immunotherapy responders and generate therapeutic benefits in NPC patients. Citation Format: Lanqi Gong, Yu Zhang, Grace Guan, Beibei Ru, Peng Jiang. Single-cell spatial analysis reveals microenvironmental features that contribute to immune discrepancies between adult and pediatric nasopharyngeal carcinomas [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR002.

357MO Comparison of long-term quality of life between survivors of adolescent and adult nasopharyngeal carcinoma

357MO Comparison of long-term quality of life between survivors of adolescent and adult nasopharyngeal carcinoma

Nasopharyngeal carcinoma in adolescent patients: A case series.

1. Majority of adolescent nasopharyngeal carcinoma (NPC) patients present with advanced locoregional disease. 2. The ethnic distribution of patients with adolescent NPC could be different from that of adult NPC suggesting a possible difference in aetiopathogenesis. 3. The late presentation of adolescent NPC underlies the importance of recognizing the clinical presentation and characteristics of this cancer.

Neuroimaging Characteristics of Nasopharyngeal Carcinoma in Children.

Pediatric nasopharyngeal carcinoma (NPC) is a rare epithelial origin tumor associated with undifferentiated histology, Epstein-Barr virus (EBV) infection, and genetic risk factors. Childhood NPC is usually clinically silent, often presenting with advanced locoregional compromise, including skull base invasion and cervical lymphadenopathy, and has a better prognosis than adult NPC. This article describes computed tomography (CT) and magnetic resonance imaging (MRI) features in a cohort of 28 pediatric NPC patients. A retrospective review was performed among children with histopathology proven NPC diagnoses between 1996 and 2019 for this study. The electronic medical records were reviewed to determine demographics, EBV serology, and World Health Organization (WHO) type. Nasopharyngeal CT and/or MRI at presentation for tumor spread as well as density and/or intensity, lymphadenopathy, postcontrast enhancement and diffusion characteristics before treatment were evaluated. Twenty-eight patients (21 males, 7 females) were included. The mean patient age at diagnosis was 13.3 (range 7 to 17) years. EBV was positive in 71.4% of patients. The majority of patients (78.6%) had a WHO type III tumor, unilateral fossa of Rosenmuller involvement (71.4%). Neuroimaging features were CT isodensity, T1-isointensity, T2-hyperintensity, and heterogeneous postcontrast enhancement for all patients (100%) and restricted diffusion (90%). Although uncommon in pediatric patients, NPC should be in the differential diagnosis of adolescents presenting with a nasopharyngeal mass. Recognizing key imaging characteristics is helpful in the diagnosis of NPC.

Clinical Implications of Plasma Epstein-Barr Virus DNA in Children and Adolescent Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy.

Background: Plasma Epstein–Barr virus (EBV) DNA has been determined as a prognostic factor in adult nasopharyngeal carcinoma (NPC) patients. This study was designed to evaluate the prognostic value of plasma pretreatment EBV DNA in children and adolescent NPC patients receiving intensity-modulated radiotherapy (IMRT).Methods: Pretreatment EBV DNA was retrospectively assessed in 147 children with newly diagnosed, non-metastatic NPC. All patients were treated using IMRT. Receiver operating characteristic (ROC) curve was used to identify the optimal EBV DNA cutoff point. Prognostic value was examined using a multivariate Cox proportional hazards model.Results: The median follow-up for the entire cohort was 58 months (range, 10–119 months), and the 5-year survival rates for all patients were as follows: overall survival (OS), 88.7%; locoregional relapse-free survival, 95.2%; distant metastasis-free survival (DMFS), 84.8%; and disease-free survival (DFS), 81.5%. For ROC curve analysis, the optimal cutoff value of pretreatment EBV DNA load for DFS was 40,000 copies/mL. High plasma EBV DNA was significantly associated with poorer 5-year DMFS (70.6 vs. 89.1%, P = 0.003) and DFS (63.9 vs. 86.9%, P < 0.001). In multivariate analysis, high plasma EBV DNA was an independent predictor for DMFS and DFS.Conclusions: Pretreatment EBV DNA level was a powerful prognostic discriminator for DMFS and DFS in children and adolescent NPC patients treated with IMRT.

A Multicentre UK Study of Outcomes of Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy ± Chemotherapy

AimsTo report the outcomes of nasopharyngeal carcinoma in adults across three large centres in a non-endemic region in the era of intensity-modulated radiotherapy (IMRT). Materials and methodsAdult patients with nasopharyngeal carcinoma treated in three large cancer centres with IMRT ± chemotherapy with curative intent between 2009 and 2016 were identified from institutional databases. Radiotherapy was delivered with 70 Gy in 33–35 daily fractions. A univariable analysis was carried out to evaluate the relationship of patient, tumour and treatment factors with progression-free survival (PFS) and overall survival. ResultsIn total, 151 patients were identified with a median follow-up of 5.2 years. The median age was 52 years (range 18–85). Seventy-five per cent were of Caucasian origin; 75% had non-keratinising tumours; Epstein Barr virus status was only available in 23% of patients; 74% of patients had stage III or IV disease; 54% of patients received induction chemotherapy; 86% of patients received concurrent chemotherapy. Five-year overall survival, PFS, local disease-free survival, regional disease-free survival and distant disease-free survival were 70%, 65%, 91%, 94% and 82%, respectively. Keratinising squamous cell carcinoma, older age, worse performance status, smoking and alcohol intake were associated with inferior overall survival and PFS. ConclusionsLocal, regional and distant disease control are relatively high following IMRT ± chemotherapy in a non-endemic population. There was considerable heterogeneity in terms of radiotherapy treatment and the use of chemotherapy, encouraging the development of treatment protocols and expert peer review in non-endemic regions.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy

Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

Update in pediatric nasopharyngeal undifferentiated carcinoma.

Many of the principles established in adults with undifferentiated nasopharyngeal carcinoma (NPC) apply to children, adolescents and young adults. However, NPC in young patients should be distinguished from the adult form by several points. This review focuses mainly on differences between adult and pediatric NPC. The role of biology and genetics in pediatric NPC is discussed. Systemic treatment modalities including type of chemotherapy induction, timing of treatment, role of immunotherapy as adjuvant treatment, or in relapsing/ metastatic diseases are reported. Radiation modalities (doses, techniques…) in children are also reviewed. Long-term effects including secondary cancers are finally be discussed in this young NPC population.

315P - Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma in adults: Results from a non-endemic cohort of South India

315P - Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma in adults: Results from a non-endemic cohort of South India

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma in adults: Results from a nonendemic region

Recently published prospective clinical trials and two meta-analyses have shown that addition of induction chemotherapy (IC) to concurrent chemoradiation (CRT) could potentially improve outcomes in comparison to CRT alone, in locoregionally advanced nasopharyngeal carcinoma (LANPC). Although it remains unclear which is the best IC regimen to be offered and for how many cycles. Unfortunately, till date, there are no published data from India regarding the outcomes of various commonly used IC regimens before CRT, in LANPC. Patients diagnosed with LANPC from January 2012 to December 2017, who received three cycles of IC before definitive CRT were reviewed retrospectively. Patients' profile, toxicity of IC, response rates, failure-free survival, and overall survival (OS) were evaluated. A total 34 patients with LANPC who received IC were reviewed. The median age at diagnosis was 36 years, and the majority were males (67.6%, n = 23). Nineteen patients received IC with paclitaxel plus cisplatin regimen (TP) and the remaining 15 patients received IC with docetaxel/paclitaxel plus cisplatin plus 5-FU regimen (TPF). The overall response rates after three cycles of TP and TPF IC were 68.4% and 80%, respectively, and the corresponding rates were 84.2%and 93.3%, respectively, 2 months after completion of CRT. At a median follow-up of 24 months, 2-year failure-free survival and OS for TP arm were 78.9% and 89.5%, and the corresponding rates for TPF arm were 86.7% and 93.3%, respectively. All Grade III-IV toxicities were numerically higher with triplet IC regimen in comparison to doublet regimen. In this retrospective analysis, there was no significant difference between taxane-based doublet and triplet IC regimens, in terms of survival outcomes, although Grade III-IV toxicities were numerically higher with triplet IC regimen. Clearly, these hypothesis-generating findings should be tested in a prospective randomized setting.

Factors associated with early diagnosis in pediatric vs adult nasopharyngeal carcinoma

Objective: To improve understanding of the initial symptom between pediatric and adult nasopharyngeal carcinoma (NPC) and to improve the early diagnosis of NPC.Methods: This retrospective cohort study included all 353 patients with a primary diagnosis of NPC in the First Affiliated Hospital of Zhengzhou University from January 2010 to December 2016. Of these, 34 patients were 21 years or younger (pediatric); 319 patients, older than 21 years (adult). Data were analyzed after data collection.Results: We found no difference between pediatric and adult patients in terms of their sex distribution (p > .05).Type III, undifferentiated carcinoma is the most common subtype in Pediatric patients, while adult patients had more squamous cell tumors (p < .01). Pediatric patients were more likely to present with stage IV disease (p < .05). Of the 353 patients, 120 (34.0%) had only one presenting symptom initially; however, most patients presented two or more episodes. Neck mass was the most common presenting symptom initially in children and adolescents, while multiple ear symptoms in adult patients (p = .003). The median time from onset of the presenting symptom to diagnosis is three months, adult patient presented longer history (64.7% vs 44.55, p < .05). Of the 319 adult patients, there were 142 which the time from onset of the presenting symptom to diagnosis is less than 3 months and there were 177 more than 3 months, the difference was significant between the two groups (p < .05). There were no differences in the misdiagnosis rate between pediatric and adult (35.1 vs 31.0, p > .05). Among pediatric patients, 31 (91.2%) had positive EBV DNA in peripheral plasma. EBV DNA was significantly associated with stage (p < .05).Conclusions: Although uncommon, pediatric NPC appears to affect a different patient demographic relative to adult NPC. NPC in children is associated with undifferentiated carcinoma and more advanced disease presentation.

1403 - Does post-induction chemotherapy PET/CT response predict outcome in young adult nasopharyngeal carcinoma? Prospective study from CCHE

1403 - Does post-induction chemotherapy PET/CT response predict outcome in young adult nasopharyngeal carcinoma? Prospective study from CCHE

Trismus as a rare presenting symptom in a pediatric nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has a diverse incidence pattern but remains a rare tumour in the pediatric age group. Childhood nasopharyngeal carcinoma usually presents in the second decade of life. Paediatric NPC cases present a diagnostic challenge due to the high prevalence of common NPC presenting symptoms of nasal obstruction, serous otitis media and hearing problems among children. Furthermore, adenoid tissue is most often present, and a biopsy in an outpatient setup would be difficult. However, trismus on initial presentation is uncommon, and even in adults is a therapy related complication. As such, surgeons should have a high index of suspicion in NPC endemic areas, and a lower threshold for imaging in these cases as overall outcome appeared to be similar between adult and childhood NPC.

979P - Does post-induction chemotherapy PET/CT response predict outcome in young adult nasopharyngeal carcinoma? Prospective study from CCHE

979P - Does post-induction chemotherapy PET/CT response predict outcome in young adult nasopharyngeal carcinoma? Prospective study from CCHE

Factors Associated With Mortality in Pediatric vs Adult Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is endemic in some Asian regions but is uncommon in the United States. Little is known about the racial, demographic, and biological characteristics of the disease in pediatric patients. To improve understanding of the differences between pediatric and adult NPC and to determine whether race conferred a survival difference among pediatric patients with NPC. This retrospective cohort study included all 17 317 patients with a primary diagnosis of NCP in the National Cancer Data Base from January 1, 1998, to December 31, 2011. Of these, 699 patients were 21 years or younger (pediatric); 16 618 patients, older than 21 years (adult). Data were analyzed after data collection. Pediatric age at diagnosis of NPC. Demographic, tumor, and treatment characteristics of pediatric patients with NPC were compared with those of adults using the χ2 test for categorical variables. An adjusted Cox proportional hazards regression model was used to examine survival differences in pediatric patients relative to adult patients. In addition, the risk for pediatric mortality by race was estimated. Of the 17 317 patients, a total of 699 pediatric and 16 618 adult patients were identified with a primary diagnosis of NPC (female, 239 pediatric patients [34.2%] and 5153 adult patients [32.4%]). Pediatric patients were most commonly black (299 of 686 [43.6%]), whereas adults were most likely to be non-Hispanic white (9839 of 16 504 [60.0%]; P < .001). Pediatric patients were less likely to be Asian (39 of 686 [5.7%]) than were adults (3226 of 16 405 [19.7%]; P < .001). Pediatric patients were more likely to have regional nodal evaluation and to present with stage IV disease (227 of 643 [35.3%] and 330 of 565 [58.4%], respectively) than were adult patients (3748 of 15 631 [24.0%] and 6553 of 13 721 [47.8%], respectively; P < .001 for both comparisons). Pediatric patients had a lower risk for mortality relative to adults (hazard ratio, 0.37; 95% CI, 0.25-0.56). No difference in mortality by racial group was found among pediatric patients (hazard ratio, 1.10; 95% CI, 0.82-1.40). Pediatric patients with NPC were more commonly black and presented more frequently with stage IV disease. Pediatric patients had a decreased mortality risk relative to adults, even after adjusting for covariables. Asian race was not associated with increased mortality in pediatric patients with NPC. Racial differences are not associated with an increased risk for mortality among pediatric patients.

Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study.

Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I—but not on the aMed—showed a significant association with a lower risk of NPC (p-trends, <0.001–0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32–0.68) (HEI-2005), 0.48 (0.33–0.70) (aHEI), and 0.43 (0.30–0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men.

Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg.

Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma incidence in North Tunisia: negative trends in adults but not adolescents, 1994-2006.

Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and neck in Tunisia. The distribution is bimodal with a first period occurrence between 15 and 20 years old and a second peak at around 50 years of age. Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant histological type (93.4%). Data of cancer registry of North Tunisia confirmed that it is an intermediate risk area for NPC with overall ASRs of 3.6 and 1.6/100,000 respectively in males and females. This study aimed to present the evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of the Tunisian population, were used to determine evolution of NPC incidence, calculated by 5 year periods. The estimated annual percentage change (EAPC) was used as an estimate of the trend. To best summarize the behavior or the data trend across years, we used a join-point regression program. Between 1994 and 2006, we observed negative annual average change of standardized incidence in men and women (-3.3% and -2.7%) also for the standardized incidences which showed a rather important decline (26.4% in males and 22.3% in females). The truncated age standardized incidence rate of NPC in adults aged of 30 years old and more (N=1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable during this period among youths aged 0-29 years (N=233) in both sexes. NPC demonstrated a favorable evolution from 1994-2006 probably due to a improvement in socioeconomic conditions.

A Retrospective Study of Clinicoepidemiological Aspects of Nasopharyngeal Cancer at NCI-Cairo (2000-2010)

Aim of Work: The aim of this work was to study the clinico-epidemiological characteristics of the patients with nasopharyngeal carcinoma (NPC), analyse the prognostic factors of the disease and to analyse the results of different treatment modalities and their effect on loco-regional, distal metastatic disease control and both overall survival (OS) and disease free survival (DFS) rates. Patients and Methods: This is a retrospective study reviewing all adult nasopharyngeal carcinoma (NPC) patients who presented to the radiotherapy department—National Cancer Institute Cairo University in the period from (2000-2010). Results: In this study, it was found that the mean age was 45 years; most of the patients were of locally advanced stages. Multivariate cox proportional hazards regression identified T-stage, radiotherapy course completion & addition of chemotherapy as independent prognostic factors for local control (LC), DFS, & OS. The 5-year LC, DFS and OS rates for all studied patients were 38.2%, 33.5% & 37.2% respectively. The median DFS was 26 months and median OS was 36.5 months. Conclusion: This study matches the published data that support that radical concurrent chemoradiation is the mainstay of treatment of locally advanced NPC, & that T-stage, M-stage, prescribed dose completion, response to initial treatment are independent prognostic factors for survival. All measures should be taken to improve the local response during primary treatment as this will improve survival rates of patients with NPC.