Of the 20,928 one-year HL survivors diagnosed between 1973 and 2003, 55% were male and the mean age at diagnosis was 37 years (). Fifty three percent (n=11,047) of the patients were initially treated with RT and 37% (n=7,811) received CT only. Among patients treated with RT, 56% were diagnosed with HL before 1992 and 49% at 30 years or older. Patients diagnosed at a younger age (< 30 years) and those diagnosed before 1992 more frequently received RT for their first course of therapy than others. Overall, HL patients had more than an 11-fold risk (O/E=11.2, 95% CI 7.3 to 16.4) of developing a subsequent SGC compared with the SEER general population and the EAR was 11.8 cases per 100,000 PY.
Characteristics of 20,928 One-year Survivors of Hodgkin Lymphoma Diagnosed Between 1973 and 2003 and Followed-up Through 2004, SEER-11 Registries
Because of the established carcinogenic effect of radiation, we focused our investigation on patients who received RT as part of initial therapy for HL. Overall, 5,745, 3,764 and 2,205 patients treated with RT were followed 10+, 15+, and 20+ years after HL diagnosis, respectively. The mean age at HL diagnosis was 34 years, the mean interval between diagnosis of HL and SGC was 9.6 years, and the mean age at diagnosis of SGC was 48 years.
Patients treated with RT had a significant 17-fold risk of SGC compared to general population rates (O=21, O/E=16.9, 95% CI 10.4 to 25.8). This risk was significantly higher than patients initially treated with CT without RT (O=4, O/E=4.8, 95% CI 1.31 to 12.29, PHET=0.01). Patients treated with combined modalities (RT and CT) at first treatment (O=7, O/E=18.8, 95% CI 7.6 to 38.7) had a risk similar to that of those treated with RT alone (O=14, O/E=16.1, 95% CI 8.81 to 27.05). Markedly elevated risks of 30–40-fold were seen for mucoepidermoid carcinoma (O=14, O/E=44.2, 95% CI 24.2 to 74.2) and adenocarcinoma (O=4, O/E=30.6, 95% CI 8.3 to 78.2). The risk of SGC was substantially lower for other salivary gland histologic types combined (O=3, O/E=3.8, 95% CI 0.8 to 11.0, PHET < 0.0001).
Two-thirds of SGC (14/21) were diagnosed in females (). Risk of SGC was three times higher among women compared to males when measured in relative terms (PHET=0.02). This gender difference was also seen for mucoepidermoid SGC. When measured on an absolute scale, radiation-related risk for SGC was 2-fold higher for females compared to males (EAR=22.6 and 10.0 per 100,000 PY for females and males, respectively, PHET=0.09) and for mucoepidermoid SGC (EAR=16.5 and 6.1 per 100,000 PY for females and males, respectively, PHET=0.09) however, statistically, the differences were not significant.
Table 2 Risk of Subsequent Salivary Gland Carcinoma Overall and Mucoepidermoid Carcinoma Among 11,047 One-year Survivors of Hodgkin Lymphoma Diagnosed Between 1973–2003, Initially Treated With Radiotherapy, and Followed-up Through 2004, SEER-11 Registries. (more ...)
Risk of radiation-related SGC was higher for HL patients treated between 1973 and 1991 compared withthose treated from 1992 to 2003 (PHET=0.06) (). However, the median follow-up period for HL survivors treated during 1992–2003 was relatively short (4.80 years), and thus risk for this later time period may rise when patients are followed for 15 or more years.
A strong pattern of decreasing O/Es with increasing age at HL diagnosis was observed for SGC of all subtypes combined (PTrend<0.001) (). Based on only four cases, there was a 45-fold risk of developing a subsequent SGC among patients first irradiated before age 20 years, whereas significantly elevated, but lower O/Es were observed for patients treated at later ages. EARs were 14.6, 16.6, 17.6, and 15.3 per 100,000 PY for age categories <20, 20–29, 30–39, and 40+ years, respectively (PTrend=0.78). The age at irradiation pattern for mucoepidermoid carcinomas was attenuated somewhat (PTrend=0.15).
A less pronounced age effect was noted for age attained at follow-up. The risk of developing SGC before age 40 years was larger (O/E=28.6) than for those who developed a SGC at age 40+ years (O/E=13.5) (). However, this difference was statistically significant only for mucoepidermoid carcinoma.
A significantly increased risk for SGC was noted beginning 5 years after RT for HL. Risk continued to rise with longer follow-up time (PTrend=0.008) reaching over 30 times that expected for those followed for 15 or more years (). The EAR indicated that the risk of developing a secondary SGC continues even after 20 years of follow-up (EAR=44.0 per 100,000 PYR). For mucoepidermoid carcinomas, significant increased risk was observed within 5 years following initial RT (), however, no significant trend with increasing follow-up was noted (PTrend=0.4).
Most SGC occurred in the parotid gland (O=17) with only 3 cases observed in the submandibular gland and none in the sublingual gland (), but there was no statistical evidence that risk differed by site of SGC (PHET=0.97). Among the mucoepidermoid SGC, 12 of the 14 occurred in the parotid gland, one in the submandibular gland and one at an unspecified site. Similar to the results for all SGC, no significant difference in relative risk was noted by site of occurrence (PHET=0.7).
Among 21 survivors initially treated with RT for HL who developed subsequent SGC, 2 died from SGC, 4 died from HL, 3 died from other cancers and 12 were alive at the end of study follow-up.