Prospective Comparisons of Clinical Trial and Real-world Outcomes in Nasopharyngeal Carcinoma

Study results from randomized controlled trials (RCTs) usually have been found not adequately inform practice. A RCT is optimized to determine efficacy, while real-world study is conducted in a routine care setting aimed to determine effectiveness. Thus, it is necessary to evaluate the pragmatism of clinical trials for a better understanding of the external generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world studies still lack well elucidation. By capitalizing on a nasopharyngeal carcinoma (NPC)-specific big-data, real-world database and individual patient data extracted from three landmark RCTs, investigators conducted the direct comparison of NPC cohorts receiving same treatment strategy in clinical trial versus real-world settings, and examined the comparative pragmatic features and their influences on survival outcomes, safety profile, and the probability of returning to society.

Study results from randomized controlled trials (RCTs) usually have been found not adequately inform practice. A RCT is optimized to determine efficacy. Such trials were performed with relatively small samples at sites with experienced investigators and highly selected participants, they could be overestimating benefits and underestimating harm. Real-world study is conducted in a routine care setting aimed to determine effectiveness. Thus, it is necessary to evaluate the pragmatism of clinical trials for a better understanding of the external generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world studies still lack well elucidation. Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with the highest incidences in endemic regions such as Southern China, where over 60,600 new cases were diagnosed in 2015 representing 40% of all cases worldwide. Studies conducted in China are critical in optimizing clinical decision-making of NPC. In the past two decades, the recommendation level of induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) has been improved evidently from Category 3 to 2A, and CCRT alone has long been a stable (Category 2B) and classic treatment option of NPC and therefore becomes the most commonly used control group in comparative studies. By capitalizing on a NPC-specific big-data, real-world database via a cancer registry in Southern China and individual patient data extracted from the three landmark RCTs, investigators conducted the direct comparison on IC+CCRT cohort or CCRT cohort of clinical trial versus real-world settings, and examined the comparative pragmatic features and their influences on survival outcomes, safety profile, and the probability of returning to society, with the aim to provide new insight into the optimization of trial design and the translation of study evidences into tangible benefits.

Eligibility Criteria:
Inclusion Criteria:

1. Patients treated in our center from April 2009 to December 2016;
2. All patients were pathologically diagnosed, non-metastatic nasopharyngeal carcinoma;
3. Only included cases staged as T3-4N1 \& T1-4N2-3 according to the 6th or 7th edition American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) system;
4. For trial patients, treatment strategies only limited to concurrent chemoradiotherapy, induction chemotherapy combined with concurrent chemoradiotherapy, or concurrent chemoradiotherapy combined with adjuvant chemotherapy;
5. For patients from real-world database, patients are permitted to receive additional targeted therapy to standard chemoradiotherapy, as far as it met clinical needs and was approved by physicians.
6. The patient's basic information, prognosis related data, and follow-up data are complete.

Exclusion Criteria:

1. The clinical stage of T3-4N0 was excluded;
2. Cases from large real-world databases need to exclude patients who participate in clinical trials;