World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://www.wjon.org

Original Article

Volume 000, Number 000, June 2024, pages 000-000


Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study

Figures

Figure 1.
Figure 1. Flow diagram depicting the study population obtained from SEER database. PSM: propensity score matching; RT: radiotherapy; NRT: no radiation therapy.
Figure 2.
Figure 2. Comparisons of cumulative incidence related to SHNC between the patients who received RT and patients who did not receive RT. EC: esophageal cancer; SHNC: secondary head and neck cancer; RT: radiotherapy; NRT: no radiation therapy.
Figure 3.
Figure 3. Comparisons of cumulative incidence rates of SHNCs of different pathological origins between patients who received RT and those who did not. (a) Cumulative incidences of SHNC originated from ESCC. (b) Cumulative incidences of SHNC originated from EAC. (c) Cumulative incidences of secondary HNSCC originated from ESCC. EAC: esophageal adenocarcinoma; EC: esophageal cancer; ESCC: esophageal squamous cell cancer; HNSCC: head and neck squamous cell cancer; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
Figure 4.
Figure 4. Subgroup analyses of competing risk regression for the risk of developing SHNC. CI: confidence interval; EC: esophageal cancer; HR: hazard ratio; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
Figure 5.
Figure 5. Dynamic standardized incidence ratio of SHNC. (a) Year of EC diagnosis. (b) Age at EC diagnosis (years). (c) Latency after EC diagnosis (months). EC: esophageal cancer; NRT: no radiation therapy; RT: radiotherapy.
Figure 6.
Figure 6. Comparison of overall survival between EC patients who developed SHNC after RT and NRT. EC: esophageal cancer; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
Figure 7.
Figure 7. Comparison of overall survival between EC patients who developed SHNC and matched only primary HNC. (a) SHNC after RT and matched only primary HNC. (b) SHNC after NRT and matched only primary HNC. EC: esophageal cancer; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.

Tables

Table 1. Baseline Characteristics of Patients With EC Depending on RT or NRT and Their Comparison
 
CharacteristicsNRT (N = 4,919)RT (N = 9,239)P-value
EC: esophageal cancer; IQR: interquartile range; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
Race< 0.001
  Black432 (8.8%)1,184 (12.8%)
  White4,239 (86.2%)7,513 (81.3%)
  Other248 (5.0%)542 (5.9%)
Sex< 0.001
  Female1,040 (21.1%)2,231 (24.1%)
  Male3,879 (78.9%)7,008 (75.9%)
Age of EC diagnosis0.002
  20 - 49462 (9.4%)756 (8.2%)
  50 - 743,454 (70.2%)6,741 (73.0%)
  ≥ 751,003 (20.4%)1,742 (18.9%)
Year of EC diagnosis0.004
  1975 - 1984551 (11.2%)1,037 (11.2%)
  1985 - 1994960 (19.5%)1,580 (17.1%)
  1995 - 20041,271 (25.8%)2,433 (26.3%)
  ≥ 20052,137 (43.4%)4,189 (45.3%)
Tumor stage of EC< 0.001
  Distant722 (14.7%)1,513 (16.4%)
  Localized2,150 (43.7%)2,416 (26.2%)
  Regional1,053 (21.4%)3,603 (39.0%)
  Unknown994 (20.2%)1,707 (18.5%)
Tumor histology of EC< 0.001
  Adenocarcinoma2,963 (60.2%)4,227 (45.8%)
  Squamous carcinoma1,347 (27.4%)4,263 (46.1%)
  Others609 (12.4%)749 (8.1%)
Tumor grade of EC< 0.001
  Grade I/II1,956 (39.8%)3,631 (39.3%)
  Grade III/IV1,545 (31.4%)3,702 (40.1%)
  Unknown1,418 (28.8%)1,906 (20.6%)
Tumor primary site of EC< 0.001
  Upper esophagus188 (3.8%)981 (10.6%)
  Middle esophagus700 (14.2%)1,911 (20.7%)
  Lower esophagus3,187 (64.8%)5,119 (55.4%)
  NOS723 (14.7%)827 (9.0%)
  Overlapping121 (2.5%)401 (4.3%)
Tumor size of EC< 0.001
  < 2 cm360 (7.3%)214 (2.3%)
  ≥ 2 cm771 (15.7%)2,430 (26.3%)
  Unknown3,788 (77.0%)6,595 (71.4%)
Chemotherapy of EC< 0.001
  No/unknown3,763 (76.5%)1,666 (18.0%)
  Yes1,156 (23.5%)7,573 (82.0%)
Surgery of EC< 0.001
  No surgery1,824 (37.1%)5,542 (60.0%)
  Surgery performed3,095 (62.9%)3,697 (40.0%)
Patients who developed SHNC36 (0.7%)110 (1.2%)0.011
Median age of EC diagnosis (IQR), years65 (57.0 - 73.0)65 (57.0 - 72.0)0.397
Median year of EC diagnosis (IQR)2,002 (1,992.0 - 2,010.0)2,003 (1,993.0 - 2,011.0)0.006
Median latency between esophagus cancer and SHNC (IQR), months93.5 (41.5 - 156.0)45.5 (25.3 - 84.3)< 0.001
Median follow-up time of patients with EC (IQR), months36 (19.0 - 91.5)27 (17.0 - 56.0)< 0.001

 

Table 2. Baseline Characteristics of EC Patients Who Experienced SHNC Categorized by Therapeutic Modalities Including RT and NRT
 
CharacteristicsNRT (N = 36)RT (N = 110)P-value
EC: esophageal cancer; IQR: interquartile range; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
Race0.576
  Black8 (22.2%)34 (30.9%)
  White26 (72.2%)68 (61.8%)
  Other2 (5.6%)8 (7.3%)
Year of EC diagnosis0.052
  1975 - 198412 (33.3%)16 (14.5%)
  1985 - 19948 (22.2%)32 (29.1%)
  1995 - 200412 (33.3%)34 (30.9%)
  ≥ 20054 (11.1%)28 (25.5%)
Age of EC diagnosis0.929
  20 - 495 (13.9%)13 (11.8%)
  50 - 7429 (80.6%)90 (81.8%)
  ≥ 752 (5.6%)7 (6.4%)
Sex0.226
  Female9 (25.0%)41 (37.3%)
  Male27 (75.0%)69 (62.7%)
Tumor stage of EC0.148
  Distant2 (5.6%)8 (7.3%)
  Localized21 (58.3%)42 (38.2%)
  Regional7 (19.4%)41 (37.3%)
  Unknown6 (16.7%)19 (17.3%)
Tumor histology of EC0.094
  Adenocarcinoma6 (16.7%)7 (6.4%)
  Squamous carcinoma27 (75.0%)98 (89.1%)
  Others3 (8.3%)5 (4.5%)
Tumor grade of EC0.630
  Grade I/II21 (58.3%)53 (48.2%)
  Grade III/IV7 (19.4%)27 (24.5%)
  Unknown8 (22.2%)30 (27.3%)
Tumor primary site of EC0.002
  Upper esophagus1 (2.8%)34 (30.9%)
  Middle esophagus9 (25.0%)25 (22.7%)
  Lower esophagus19 (52.8%)31 (28.2%)
  NOS6 (16.7%)15 (13.6%)
  Overlapping1 (2.8%)5 (4.5%)
Tumor size of EC0.461
  < 2 cm0 (0%)1 (0.9%)
  ≥ 2 cm3 (8.3%)18 (16.4%)
  Unknown33 (91.7%)91 (82.7%)
Chemotherapy of EC< 0.001
  No/unknown31 (86.1%)18 (16.4%)
  Yes5 (13.9%)92 (83.6%)
Surgery of EC< 0.001
  No surgery9 (25.0%)75 (68.2%)
  Surgery performed27 (75.0%)35 (31.8%)
Median age of EC diagnosis (IQR), years59 (56.0 - 65.3)59 (54.0 - 66.0)0.969
Median year of EC diagnosis (IQR)1,991 (1,983.8 - 2,000.5)1,996 (1,989.0 - 2,004.8)0.063
Median follow-up time of patients with EC (IQR), months151 (73.5 - 203.0)82 (42.5 - 117.8)< 0.001

 

Table 3. Pathological Origins of Primary Tumors in Patients With SHNC
 
ESCCEACOther histological types of ECTotal
EAC: esophageal adenocarcinoma; EC: esophageal cancer; ESCC: esophageal squamous cell cancer; HNAC: head and neck adenocarcinoma; HNSCC: head and neck squamous cell cancer; SHNC: secondary head and neck cancer.
Secondary HNSCC117138138
Secondary HNAC1001
Other histological types of SHNC7007
Total125138146

 

Table 4. Standardized Incidence Ratio Related to the SHNC
 
Total (n = 14,158)NRT (n = 4,919)RT
*P < 0.05. EC: esophageal cancer; NRT: no radiation therapy; RT: radiotherapy; SHNC: secondary head and neck cancer.
All5.95 (5.15 - 6.84)*3.51 (2.64 - 4.58)*8.04 (6.78 - 9.47)*
Race
  White4.33 (3.60 - 5.16)*2.56 (1.78 - 3.56)*5.95 (4.77 - 7.32)*
  Black16.74 (12.77 - 21.55)*13.96 (8.13 - 22.36)*18.17 (13.15 - 24.47)*
  Other13.43 (7.34 - 22.53)*4.17 (0.51 - 15.07)21.31 (11.01 - 37.22)*
Sex
  Female18.18 (13.87 - 23.40)*8.71 (4.50 - 15.22)*24.95 (18.40 - 33.08)*
  Male4.60 (3.87 - 5.44)*3.00 (2.16 - 4.06)*6.01 (4.87 - 7.34)*
Age
  20 - 599.13 (7.45 - 11.09)*5.69 (3.84 - 8.13)*12.20 (9.55 - 15.37)*
  60 - 744.82 (3.85 - 5.95)*2.62 (1.62 - 4.01)*6.64 (5.11 - 8.47)*
  ≥ 752.47 (1.23 - 4.42)*1.43 (0.30 - 4.19)3.40 (1.47 - 6.70)*
Year of EC diagnosis
  1975 - 19849.41 (6.59 - 13.02)*7.86 (4.58 - 12.58)*11.42 (6.88 - 17.84)*
  1985 - 19947.66 (5.78 - 9.94)*2.81 (1.35 - 5.16)*12.26 (8.97 - 16.35)*
  1995 - 20046.11 (4.73 - 7.78)*4.07 (2.48 - 6.28)*7.83 (5.73 - 10.44)*
  ≥ 20053.53 (2.52 - 4.81)*1.48 (0.60 - 3.05)4.99 (3.44 - 7.01)*
Tumor grade
  Grade I/II7.92 (6.50 - 9.57)*5.01 (3.42 - 7.07)*10.50 (8.27 - 13.14)*
  Grade III/IV4.00 (2.89 - 5.38)*2.55 (1.22 - 4.69)*4.82 (3.32 - 6.77)*
  Unknown5.23 (3.83 - 6.97)*2.40 (1.24 - 4.19)*8.95 (6.20 - 12.51)*
Tumor stage
  Distant3.74 (1.79 - 6.87)*3.00 (0.36 - 10.83)3.98 (1.72 - 7.84)*
  Localized5.32 (4.26 - 6.57)*3.01 (2.03 - 4.30)*9.03 (6.82 - 11.72)*
  Regional6.09 (4.66 - 7.83)*4.70 (2.43 - 8.21)*6.57 (4.86 - 8.68)*
  Unknown9.27 (6.65 - 12.58)*4.56 (2.18 - 8.38)*13.91 (9.45 - 19.75)*
Surgery
  Yes3.94 (3.14 - 4.88)*3.18 (2.25 - 4.36)*4.92 (3.60 - 6.56)*
  No9.53 (7.86 - 11.45)*4.69 (2.68 - 7.62)*11.46 (9.30 - 13.97)*
Chemotherapy
  Yes7.59 (6.33 - 9.02)*3.84 (1.41 - 8.36)*7.97 (6.62 - 9.52)*
  No4.27 (3.33 - 5.39)*3.48 (2.56 - 4.61)*8.48 (5.31 - 12.84)*
Latency
  12 - 595.26 (4.25 - 6.44)*2.23 (1.27 - 3.62)*7.31 (5.77 - 9.12)*
  60 - 1197.20 (5.53 - 9.21)*3.47 (1.94 - 5.72)*10.83 (7.99 - 14.36)*
  120 - 2397.13 (5.12 - 9.67)*7.22 (4.58 - 10.84)*7.01 (4.16 - 11.08)*
  ≥ 2400.00 (0.00 - 4.10)0.00 (0.00 - 5.45)0.00 (0.00 - 16.45)