Summary Background A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy ...to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. Methods We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov , and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. Findings We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2–11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio HR 0·79, 95% CI 0·73–0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5–9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56–0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70–0·93) but not adjuvant chemotherapy alone (0·87, 0·68–1·12) or induction chemotherapy alone (0·96, 0·80–1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69–0·81), locoregional control (0·73, 0·64–0·83), distant control (0·67, 0·59–0·75), and cancer mortality (0·76, 0·69–0·84). Interpretation Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. Funding French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the ...Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs 95% CIs) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.
Aim: This was a prospective investigation of longitudinal body composition changes in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy (CCRT) and a comparison of the ...Patient-Generated Subjective Global Assessment (PG-SGA) and the ESPEN (European Society for Clinical Nutrition and Metabolism) diagnostic criteria (EDC) as evaluation methods. Methods: All patients received standard CCRT according to 2 centers’ current practices. Body composition parameters were determined by bioelectrical impedance analysis and obtained weekly from baseline until the end of treatment. The nutritional status of all patients was evaluated by the PG-SGA and EDC. Results: Forty-eight patients were eligible for analysis. Most body composition parameters, including body cell mass, fat mass, fat-free mass, and skeletal mass, as well as body weight, body mass index, and PG-SGA score, significantly decreased during CCRT (P = .00). The PG-SGA was shown to have better sensitivity than the EDC; however, the 2 different evaluation methods were found to have a perfect concordance at Week 4 and Week 6 (κ = 0.91 and 0.96, P = .00 and .00, respectively). Pearson correlation analyses showed that fat-free mass index and body weight were positively correlated with global quality of life score (r = 0.81, P = .00; r = 0.78, P = .00, respectively). Conclusions: This study has shown that body composition parameters, especially fat-free mass index, are valuable for diagnosing malnutrition in patients with nasopharyngeal carcinoma receiving CCRT. We recommend that these bioelectrical impedance analysis techniques should be increasingly implemented in nutritional assessments.
Background:
Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or ...metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN.
Methods:
In this phase II single-arm, prospective study, patients aged 15–75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment.
Results:
Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% 95% confidence interval (CI): 83–97.5%, 75.2% (95% CI: 61.5–84.0%) and 44.7% (95% CI: 32.3–57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7–59.0%) and 98.5% (95% CI: 91.7–100.0%), respectively. The median duration of response was 17.7 months interquartile range (IQR) 14.0–20.9. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0–97.5%) and 82.3% (95% CI: 70–90.4%), respectively. The most common adverse events of grades 3–4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage.
Conclusion:
An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation.
This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016)
To summarize our experience and treatment results in lymph node-negative nasopharyngeal carcinoma treated in a single institution.
From January 2000 to December 2003, 410 patients with lymph ...node-negative nasopharyngeal carcinoma were retrospectively analyzed. The T-stage distribution was 18.8% in T1, 54.6% in T2 (T2a, 41 patients; T2b, 183 patients), 13.2% in T3, and 13.4% in T4. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas, including levels II, III, and VA. The dose was 64-74 Gy, 1. 8-2.0 Gy per fraction over 6.5-7.5 weeks to the primary tumor with (60)Co or 6-MV X-rays, and 50-56 Gy to levels II, III, and VA. Residual disease was boosted with either (192)Ir afterloading brachytherapy or small external beam fields.
The median follow-up time was 54 months (range, 3-90 months). Four patients developed neck recurrence, and only 1 patient (0.2%) experienced relapse outside the irradiation fields. The 5-year overall survival rate was 84.2%. The 5-year relapse-free survival rate, distant metastasis-free survival rate, and disease-free survival rate were 88.6%, 90.6% and 80.1%, respectively. Both univariate and multivariate analyses demonstrated that T classification was the only significant prognostic factor for predicting overall survival. The observed serious late toxicities were radiation-induced brain damage (7 cases), cranial nerve palsy (16 cases), and severe trismus (13 cases; the distance between the incisors was < or = 1 cm).
Elective levels II, III, and VA irradiation is suitable for nasopharyngeal carcinoma without neck lymph node metastasis.
Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to ...identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes.
Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy.
Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients.
HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.
Summary Objective To determine whether concurrent chemoradiotherapy (CCRT) can improve survival rates compared to the neoadjuvant chemotherapy (NACT) regimen in locoregionally advanced nasopharyngeal ...carcinoma (NPC) patients. Materials and methods A total of 338 patients with biopsy-proven NPC were randomly assigned to receive NACT followed by radical radiotherapy (RT) then adjuvant chemotherapy (AC) or CCRT followed by AC. Results With a median follow-up of 60 months, the 5-year overall survival (OS) rate did not differ significantly between two groups (75.5% vs 79.4% in CCRT and NACT group respectively, P = 0.47, HR = 0.84, 95%CI 0.53–1.33). Metastasis-free survival (MFS) rate was significantly improved by the CCRT (79.0% vs 86.9%, P = 0.05, HR = 0.59, 95%CI 0.35–1.00). Subgroup analysis indicated that the benefit of CCRT was derived from N0/N1 tumors (78.0% vs 93.5%, P = 0.05, HR = 0.35, 95%CI 0.12–0.99). Higher rates of mucositis (52.4% vs. 35.9% P = 0.02) and vomiting (13.7% vs. 4.7% P = 0.00) were noted in the CCRT arm. Late toxicities were similar in two groups. Conclusions The updated results demonstrated no significant survival benefit of CCRT over NACT in patients with locoregionally advanced NPC. CCRT only showed significant MFS efficacy in T3-4N0-1 populations.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. ...Research on predictive biomarkers in clinical settings is urgently needed.
Next-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher's exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05).
Chromosome 11q13 amplification (
,
,
, and
) and
mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1.
Chromosome 11q13 amplification and
mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.
The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has ...been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC.
This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7
edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment.
From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval CI: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable.
Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit.
https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.
Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations ...and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11–0.92; p = 0.035 and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12–0.94; p = 0.037. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.
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