The influence of field size and other radiotherapy parameters on acute toxicity in pharyngolaryngeal cancers.

BACKGROUND: Accelerated radiotherapy and/or chemo-radiotherapy of the head and neck region decrease the tolerance of acute responding tissues. Tissue tolerance is also field size dependent. PATIENTS AND METHOD: An attempt to retrospectively quantify the risk of acute toxicity (peak scores) with field size was undertaken in 286 patients irradiated for unresected head and neck tumors with or without chemotherapy, and with or without accelerated radiotherapy between 1979 and 1990. A Grade-3 to -4 acute toxicity score (RTOG) and > 5% weight loss were chosen as endpoints. RESULTS: For Grade-3 to -4 toxicity, the risk increased from 0.06 for 5 x 5 cm2 to 0.68 for 17 x 17 cm2 fields and conventional radiotherapy, and from 0.33 for 5 x 5 cm2 to 0.94 for 17 x 17 cm2 and multiple daily fractionation. For > 5% weight loss, the risk ranged from 0.07 for 5 x 5 cm2 to 0.94 for 17 x 17 cm2 fields. CONCLUSIONS: The size of the cervical fields receiving the first 50 Gy was an indicator for severe acute toxicity and weight loss. Taking these data into account may help to improve preventive and treatment measures.

Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.

PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed. RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.