Toxicity
A summary of the most clinically significant toxicities associated with this protocol are included in the table below:
Toxicity ~ Grade 3-4 |
Study/Year |
Treatment |
Incidence (%) |
Neutropenia |
Persky et al. 2008r |
Chemotherapy and RT |
65% |
Febrile neutropenia |
Persky et al. 2008r
Miller et al. 1998r
|
Chemotherapy and RT
Chemotherapy (CHOP x 3) and RT
Chemotherapy (CHOP x 8) alone
|
15%
27%
35%
|
GI (acute) |
Persky et al. 2008r
Lowry et al 2011r
|
Chemotherapy and RT
RT alone (30 Gy)
RT alone (40 Gy)
|
15%
Grade 5: 2%
2%
1%
|
GI (late) |
Lowry et al. 2011r
|
RT alone (30 Gy)
RT alone (40 Gy)
|
1%
1%
|
Infection |
Persky et al. 2008r |
Chemotherapy and RT |
27% |
Skin (acute) |
Persky et al. 2008r
Lowry et al. 2011r
|
Chemotherapy and RT
RT alone (30 Gy)
RT alone (40 Gy)
|
2%
5%
11%
|
Skin (late) |
Lowry et al. 2011r
|
RT alone (30 Gy)
RT alone (40 Gy)
|
1%
3%
|
Decreased left ventricular ejection fraction |
Miller et al. 1998r
|
Chemotherapy (CHOP x 3) and RT
Chemotherapy (CHOP x 8) alone
|
0%
3.5%
|
Late toxicity
In the long-term follow-up study of SWOG S8736, 24 patients in the CHOPx8 alone arm developed second malignancies at median of 4.8 years (5-year and 10-year cumulative incidence of 9% and 11%), whereas 30 patients in the CHOP+RT arm developed second malignancies at median of 7.6 years (5-year and 10-year cumulative incidence of 6% and 12% respectively). There were no significant differences in cumulative differences in secondary malignancy between CHOP alone vs CHOP+RT arms (P=0.24).r SWOG 0014 study reported 7 (12%) patients developed secondary solid tumour, all of which outside the radiation fields (3 breast cancers, 1 liver, 1 rectal, 1 sarcoma, 1 gastrointestinal stromal tumors).r
The case-control study by van Nimwegen et al. 2016 demonstrated a 2.5-fold increased risk of coronary heart disease for patients receiving a median heart dose of 20 Gy from mediastinal RT compared with patients not treated with mediastinal radiation therapy.r Excess relative risk [ERR] per Gy was 7.4% (95% CI 3.3-14.8%).
In a population based study by Tward et al. 2006 of NHL patients, irradiated patients demonstrated an increased risk of sarcoma, secondary breast cancer and mesothelioma development.r The aggregate absolute excess risk for soft tissue malignancies, female breast cancer, and mesothelioma in irradiated patients was 1.57 cases per 10,000 PYs. The observed to expected ratio risk of secondary malignancy was found to be greatest for those in the younger cohort (age < 25 years). The absolute excess risk for secondary malignancy peaked for the cohort aged 25 to 49 years at the time of their initial NHL diagnosis and then declined with advancing age.