Prognostic Value and Staging Classification of Retropharyngeal Lymph Node Metastasis in Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiotherapy

<p>The development of intensity-modulated radiotherapy ( IMRT)  has revolutionized the management of nasopharyngeal carcinoma . The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node  metastasis in nasopharyngeal carcinoma in the IMRT era</p

Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study

Background: The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality. Methods: In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a "watch-and-wait" policy). Findings: Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41). Interpretation: Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic. Funding: National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05)

Five-year survival rates for 481 nasopharyngeal carcinoma patients with retropharyngeal lymph nodes metastasis according to the characteristics of retropharyngeal lymph node metastasis.

<p>Abbreviations: DFS  =  disease-free survival; DMFS  =  Distant metastasis-free survival; LRRFS  =  Locoregional relapse-free survival.</p><p>*<i>P</i> values were calculated by the unadjusted log-rank test.</p><p>Five-year survival rates for 481 nasopharyngeal carcinoma patients with retropharyngeal lymph nodes metastasis according to the characteristics of retropharyngeal lymph node metastasis.</p

Survival curves for nasopharyngeal carcinoma (NPC) patients with and without retropharyngeal lymph node (RLN) metastasis.

<p>RLN (-): NPC patients without RLN metastasis; RLN (+): NPC patients with RLN metastasis.</p

The clinicpathological characters of 749 patients in this study.

<p>The clinicpathological characters of 749 patients in this study.</p

Survival curves for patients with nasopharyngeal carcinoma (NPC) stratified by the N classification of the 7^th edition of the UICC/AJCC staging system for NPC.

<p>N1 + RLN only: N1 disease with retropharyngeal lymph node metastasis and without cervical lymph node metastasis; N1 + CLN: N1 disease with cervical lymph node metastasis.</p

Summary of multivariate analysis of prognostic factors in 749 patients with nasopharyngeal carcinoma.

<p>Abbreviations: CI  =  confidence interval; HR =  hazard ratio; CLN  =  cervical lymph nodes; NS  =  not significant; SCLN = Supraclavicular lymph node.</p><p>*<i>P</i> values were calculated using an adjusted Cox proportional-hazards model. The following known important prognostic variables were included in the Cox proportional hazards model: age (≤50 vs. >50 years), gender, T-classification, chemotherapy (yes vs. no), bilateral CLN metastasis (yes vs. no), dimension of CLN metastases (≤6 vs. >6 cm), CLN location (with SCLN vs. without SCLN) and RLN metastasis (yes vs. no).</p><p>Summary of multivariate analysis of prognostic factors in 749 patients with nasopharyngeal carcinoma.</p

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study

Abstract Background Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA‐NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). Methods Patients with biopsy‐proven NPC and planned for IC + CCRT were recruited. IC entailed two cycles of 3‐weekly docetaxel 75 mg/m2 and cisplatin 75 mg/m2; CCRT entailed two to three cycles of 3‐weekly cisplatin 100 mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre‐IC, post‐cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0) by the end of treatment (W7‐CCRT). Secondary endpoints included body mass index, NRS2002 and PG‐SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicities and survivals. The associations between primary and secondary endpoints were also evaluated. Results One hundred and seventy‐one patients were enrolled. Median follow‐up was 67.4 (IQR: 64.1–71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4‐CCRT (median of 4.0% [IQR: 0.0–7.0%]) and peaked at W7‐CCRT (median of 8.5% [IQR: 4.1–11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7‐CCRT, which was associated with a higher malnutrition risk (NRS2002 ≥ 3 points: 87.7% [WL ≥ 5.0%] vs 58.7% [WL < 5.0%], P < 0.001) and requirement of nutritional intervention (PG‐SGA ≥ 9 points: 82.0% [WL ≥ 5.0%] vs 66.7% [WL < 5.0%], P = 0.038). The median %WL at W7‐CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P = 0.025) and xerostomia (9.1% vs 6.3%, P = 0.003). Besides, patients with cumulative WL5.0 also reported a higher detriment on QoL at W7‐CCRT compared with patients without, with a difference of −8.3 points (95% CI [−15.1, −1.4], P = 0.019). Conclusions We observed a high prevalence of WL among LA‐NPC patients who were treated with IC + CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC + CCRT and inform on nutritional intervention strategies

Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study

Abstract Background Famitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet-derived growth factor receptor, and stem cell factor receptor (c-kit). Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast-enhanced ultrasound (D-CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy. Methods The trial was conducted in subjects with stage III or IVa-b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D-CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti-tumour activity. Results Twenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose-limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D-CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow-up of 44 months, the 3-year progression-free survival (PFS) and distant metastasis-free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3-year PFS (90.9% vs. 44.4%, 95% CI 73.7%–100% vs. 11.9%–76.9%, P < 0.001) than those with an increase or a reduction of less than 30%. Conclusions The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. D-CEUS is a reliable and early measure of efficacy for famitinib therapies. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy