Survival Outcome Superiority of Total Pharyngolaryngectomy Compared with Chemoradiotherapy for T4aM0 Hypopharyngeal Squamous Cell Carcinoma: A Nationwide Database Study of Japan.

BACKGROUND: The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database. METHODS: All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses. RESULTS: Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively). CONCLUSIONS: Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT.

Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.

OBJECTIVE: This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data. METHODS: A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage. RESULTS: A total of 457 patients met the inclusion criteria. The median age was 60 years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively. CONCLUSIONS: This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence.

Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.

BACKGROUND: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan. METHODS: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included. RESULTS: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05). CONCLUSION: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients.

Elective neck dissection for T3-T4N0 laryngeal carcinoma: evidence from Japan's National Head and Neck Cancer Registry.

BACKGROUND: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. METHODS: We conducted a retrospective nationwide observational study on patients with T3-T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. RESULTS: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%-19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. CONCLUSION: Omission of END during laryngectomy for T3-T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Clinical benefits of combining oral cytotoxic chemotherapeutic agents with radiotherapy in patients with T2N0 glottic squamous cell carcinoma based on the reports of the Head and Neck Cancer Registry of Japan.

BACKGROUND: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC. METHODS: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics. RESULTS: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026). CONCLUSIONS: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation.

A Pragmatic Method to Integrate Data from Pre-existing Cohort Studies using the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model: Practical use of REDCap2SDTM.

BACKGROUND: In recent years, many researchers have focused on legacy data utilization, such as pooled analyses that collect and re-analyze data from multiple studies. However, the methodology for the integration of pre-existing databases whose data were collected for different purposes has not been established. Previously, we developed a tool to efficiently generate Study Data Tabulation Model (SDTM) data from hypothetical clinical trial data using the Clinical Data Interchange Standards Consortium (CDISC) SDTM. OBJECTIVE: To design a practical model for integrating pre-existing databases using the CDISC SDTM. METHODS: Data integration was performed in three phases: i) confirmation of the variables, ii) SDTM mapping, and iii) generation of the SDTM data. In phase 1, the definitions of the variables in detail were confirmed, and the datasets were converted to vertical datasets. In phase 2, the items derived from the SDTM format were set as mapping items. Three types of metadata (domain name, variable name, and test code), based on the CDISC SDTM, were embedded in the REDCap field annotation. In phase 3, the data dictionary, including the SDTM metadata, were output in the Operational Data Model (ODM) format. Finally, the mapped SDTM were generated using REDCap2SDTM v2. RESULTS: SDTM data were generated as a comma-separated values file for each of the seven domains defined in the metadata. Twenty-two items were commonly mapped to three databases. Because the SDTM data were set in each database correctly, we were able to integrate three independently pre-existing databases into one database in the CDISC SDTM format. CONCLUSIONS: Our project suggests that the CDISC SDTM is useful for integrating multiple pre-existing databases.

A Pragmatic Method to Integrate Data From Preexisting Cohort Studies Using the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model: Case Study.

Background: In recent years, many researchers have focused on the use of legacy data, such as pooled analyses that collect and reanalyze data from multiple studies. However, the methodology for the integration of preexisting databases whose data were collected for different purposes has not been established. Previously, we developed a tool to efficiently generate Study Data Tabulation Model (SDTM) data from hypothetical clinical trial data using the Clinical Data Interchange Standards Consortium (CDISC) SDTM. Objective: This study aimed to design a practical model for integrating preexisting databases using the CDISC SDTM. Methods: Data integration was performed in three phases: (1) the confirmation of the variables, (2) SDTM mapping, and (3) the generation of the SDTM data. In phase 1, the definitions of the variables in detail were confirmed, and the data sets were converted to a vertical structure. In phase 2, the items derived from the SDTM format were set as mapping items. Three types of metadata (domain name, variable name, and test code), based on the CDISC SDTM, were embedded in the Research Electronic Data Capture (REDCap) field annotation. In phase 3, the data dictionary, including the SDTM metadata, was outputted in the Operational Data Model (ODM) format. Finally, the mapped SDTM data were generated using REDCap2SDTM version 2. Results: SDTM data were generated as a comma-separated values file for each of the 7 domains defined in the metadata. A total of 17 items were commonly mapped to 3 databases. Because the SDTM data were set in each database correctly, we were able to integrate 3 independently preexisting databases into 1 database in the CDISC SDTM format. Conclusions: Our project suggests that the CDISC SDTM is useful for integrating multiple preexisting databases.