Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). ...This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database.
We used the keyword "nasopharyngeal carcinoma" to search the ClinicalTrials.gov database and assessed the characteristics of these trials.
Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001).
The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.
Background
The purpose of this study was to verify 10‐year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity‐modulated radiotherapy (IMRT) versus ...two‐dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006.
Results
Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow‐up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure‐free survival (L‐FFS; 90% vs. 84%; hazard ratio HR, 0.57, 95% confidence interval CI, 0.40–0.81; p = .001), failure‐free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57–0.83; p < .001), and overall survival (OS; 75% vs. 63%; HR, 0.62, 95% CI, 0.51–0.77; p < .001). Subgroup multivariate analyses showed that radiotherapeutic technique (IMRT vs. 2DRT) remained an independent prognostic factor for L‐FFS in the T1 subgroup (HR, 0.30; 95% CI, 0.11–0.80; p = .02); for FFS in the stage II subgroup (HR, 0.42; 95% CI, 0.24–0.73; p = .002); and for OS in the stage I (HR, 0.20; 95% CI, 0.04–0.96; p = .04), stage II (HR, 0.39; 95% CI, 0.21–0.75; p = .004), and stage IVA–B (HR, 0.74, 95% CI, 0.56–0.98; p = .04) subgroups. The incidence of grade 3–4 temporal lobe necrosis, cranial neuropathy, eye damage, ear damage, neck soft tissue damage, trismus, and dry mouth was significantly lower in the IMRT group than in the 2DRT group.
Conclusion
IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10‐year follow‐up, with significant improvement of L‐FFS, FFS, and OS and decrease in most late toxicities.
Implications for Practice
The ultimate therapeutic ratio of intensity‐modulated radiotherapy versus two‐dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow‐up of 115 months, intensity‐modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two‐dimensional radiotherapy, with significant improvement of local failure‐free survival, failure‐free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.
摘要
背景。本研究旨在验证鼻咽癌 (NPC) 患者调强放疗 (IMRT) 对比二维放疗 (2DRT) 的生存率和晚期毒性的 10 年结果并评估最终治疗比。
材料和方法。我们对 1 276 名在 2003 年 1 月至 2006 年 12 月期间接受 IMRT 或 2DRT 的非转移性 NPC 患者的数据进行回顾性分析。
结果。在这 1 276 名患者中,512 名患者接受 IMRT 治疗,764 名患者接受 2DRT 治疗。中位随访时间为 115 个月。到第 10 年的时候,IMRT 组比 2DRT 组在局部无失败生存率L‐FFS;90% vs. 84%;风险比(HR),0.57,95% 置信区间(CI),0.40–0.81;p = 0.001、无失败生存率(FFS;69% vs. 58%;HR,0.69,95% CI,0.57–0.83;p < 0.001)以及总生存率(OS;75% vs. 63%;HR,0.62,95% CI,0.51–0.77;p <0.001)等方面显示出明显更好的结果。亚组多变量分析表明, 就 T1 亚组中的 L‐FFS(HR,0.30;95% CI,0.11–0.80;p = 0.02) ;II 期亚组中的 FFS(HR,0.42;95% CI,0.24–0.73;p = 0.002);以及 I 期亚组中的 OS(HR,0.20;95% CI,0.04–0.96;p = 0.04)、II 期亚组中的 OS(HR,0.39;95% CI,0.21–0.75;p = 0.004)与 IVA–B 期亚组中的 OS(HR,0.74;95% CI,0.56–0.98;p = 0.04)而言,放疗技术(IMRT 与 2DRT)仍然是独立的预后因素。与 2DRT 组相比,IMRT 组的 3–4 级颞叶坏死、颅神经病变、眼部损伤、耳部损伤、颈部软组织损伤、牙关紧闭以及口腔干燥的发病率明显更低。
结论。在 10 年随访之后,与 2DRT 相比,IMRT 在 NPC 患者中显示出更好的最终治疗比,在 L‐FFS、FFS 和 OS 方面均有显著改进,大多数晚期毒性有所减少。
对临床实践的提示
鼻咽癌患者调强放疗对比二维放疗的最终治疗比尚不明确。在本次针对 1 276 名随访期历时 115 个月的非转移性鼻咽癌患者的回顾性研究中,与二维放疗相比,调强放疗显示出更好的最终治疗比,在局部无失败生存率、无失败生存率和总生存率方面均有显著改进,大多数晚期毒性和非肿瘤死亡均有减少。但是,远程控制对于这种治疗方式而言仍然不足。
Radiotherapy is the primary treatment modality for nondisseminated nasopharyngeal carcinoma. Treatment with two‐dimensional radiotherapy transitioned to three‐dimensional conformal radiotherapy, and in particular to intensity‐modulated radiotherapy, is a step forward in the treatment of nasopharyngeal carcinoma. This article describes a long‐term follow‐up to verify ten‐year results of survival and late toxicities and to assess ultimate therapeutic ratio by intensity‐modulated radiotherapy versus two‐dimensional radiotherapy in patients with nasopharyngeal carcinoma.
To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional ...radiotherapy (2D-CRT).
1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).
The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).
IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.
To better understand the relationship between dietary factors and thyroid cancer risk, we summarized the published evidence on relationship between dietary factors and thyroid cancer incidence. ...Searching several databases for relevant studies published by March 2014 included a total of 19 studies. We calculated summary odds ratios (ORs) for each risk factor. Based on the highest level of total consumption vs. the lowest level, the summary OR 95% (confidence interval) CI of thyroid cancer was 0.79 (0.66, 0.94) for fish; 0.95 (0.74, 1.23) for salt water fish; 0.86 (0.63, 1.16) for fresh water fish; 0.76 (0.58, 1.00) for vegetables; 0.88 (0.72, 1.08) for shellfish; 0.93 (0.66, 1.29) for cruciferous vegetables; 0.97 (0.78, 1.21) for fruits; 0.96 (0.70, 1.34) for meat; and 1.11 (0.86, 1.42) for grains. Subgroup analysis showed that fish (OR 0.74, 95%CI: 0.59, 0.92) and shellfish (OR 0.46, 95%CI: 0.27, 0.75) consumption have a protective effect in iodine deficiency areas, whereas the ORs were not statistically significant in iodine-rich areas. Our findings indicated that fish and shellfish consumption may decrease the risk of thyroid cancer in iodine deficiency areas, although no such effect was observed in iodine-rich areas.
Objectives
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC) merged T4N0–2 and T1–4N3 to create stage IVa. In the present study, we ...aimed to assess the difference in clinical outcomes and patterns of failure between 8th AJCC T4N0–2 and T1–4N3 NPC patients treated with intensity-modulated radiotherapy (IMRT).
Methods
We included 3107 patients with stage IVa NPC disease (1871 with T4N0–2 and 1236 with T1–4N3) according to the 8th AJCC staging system. Overall survival (OS) was the primary endpoint. The clinical outcomes between T4N0–2 and T1–4N3 patients were compared.
Results
T1–4N3 patients had significantly worse 3-year OS (84.1% vs. 89.2%;
p
< 0.001) and distant metastasis–free survival (DMFS; 78.3% vs. 85.9%;
p
< 0.001), but better local relapse–free survival (LRFS; 94.9% vs. 92.2%;
p
= 0.003), as compared with T4N0–2 patients. Multivariate analysis showed that T1–4N3 was still an independent adverse prognostic factor for both DMFS (hazard ratio HR = 1.517, 95% confidence interval CI = 1.274–1.806,
p
< 0.001) and OS (HR = 1.315, 95% CI = 1.100–1.572,
p
= 0.003), whereas T4N0–2 was an independent adverse prognostic factor for LRFS (HR = 1.581, 95% CI = 1.158–2.158,
p
= 0.004).
Conclusions
In terms of the OS, T4N0–2 patients had better prognosis compared with T1–4N3 patients, and the patterns of failure differed between T4N0–2 and T1–4N3 patients. We believe that future modifications of the AJCC/UICC staging system should separate T4N0–2 from T1–4N3.
Key Points
• In nasopharyngeal carcinoma, T4N0–2 patients tended to develop local relapse, whereas T1–4N3 patients were more likely to develop distant metastasis.
• In terms of overall survival, T4N0–2 patients had better prognosis than T1–4N3 patients.
• T4N0–2 should be separated from T1–4N3 in the UICC/AJCC staging system.
This cross‐sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno‐oncology (IO) trials and provide insight into the resolution of IO‐related ...controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple‐arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid‐/infection‐related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3‐4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1‐2 trials. The “partial‐use‐of‐corticosteroids” strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P < .001) but is associated with the poor dissemination of results (P ≤ .020), while the complete disclosure and standardization of dose/timing limits are still lacking. Disparities in design features and dissemination of results are widespread in IO trials and are modulated by IO category, cancer type and sponsor. We propose policy reforms to redefine the timely publication of IO trials and standardize the resolution of corticosteroid‐/infection‐related issues.
What's new?
In recent decades, immunotherapy has emerged and advanced to become a key part of cancer‐fighting strategies. The rapid growth of immuno‐oncology, however, has been accompanied by controversy in suitable interventions and trial design. In this cross‐sectional and longitudinal analysis, disparities in design were found to be common in immuno‐oncology trials, with differences influenced by factors such as cancer type and trial sponsor. Trials with strict limitations on corticosteroid use had significantly higher publications rates than trials permitting partial corticosteroid administration. The data further suggest that timely publication of immuno‐oncology trials is the third year after trial completion.
To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma.
...We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment.
The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages.
Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.
The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and ...classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era.
We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease.
The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994).
In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.
To compare intensity‐modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II‐IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with ...stage II–IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well‐balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well‐balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3‐year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco‐regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4–4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related‐skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP‐IMRT combination for maximizing survival for patients with stage II‐IVb NPC.
What's new?
Standard treatment for nasopharyngeal carcinoma (NPC) that has spread to lymph nodes in the head and neck entails concurrent cisplatin (CDDP) and intensity‐modulated radiotherapy (IMRT). High toxicity rates, however, limit the utility of this approach. The present study examines an alternative strategy: cetuximab (CTX) and nimotuzumab (NTZ) plus IMRT. No differences in risk of disease progression, relapse, metastasis or death were observed in a direct comparison between CDDP plus IMRT and CTX/NTZ plus IMRT in NPC patients. Both regimens were associated with hematologic toxicities and with toxicities targeting different tissues, warranting further investigation of side effects specific to CTX/NTZ.
PDF
