Growth hormone treatment and pseudotumor cerebri: coincidence or close relationship?

Pseudotumor cerebri (PTC) is an uncommon disorder in the pediatric population. It is not a benign condition. It can cause permanent vision loss. The most recently recognized risk factor for this disorder is recombinant human growth hormone (GH) therapy. Data from Genentech's National Cooperative Growth Study (NCGS), a postmarketing surveillance program, are analyzed to examine the relationship between GH therapy and PTC. Several areas are addressed, including plausibility, probability, clinical and laboratory presentations, management, clinical outcome, present state of knowledge, and future recommendations.

Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: a prospective study of treatment practice at the Royal Marsden Hospital.

The results are presented of a prospective study of acute skin toxicity in 197 patients with early stage breast cancer, who were treated by conservative surgery and postoperative radiotherapy. We have examined the factors determining the severity of the acute skin reaction with particular reference to the degree of dry or moist desquamation at the completion of treatment. One hundred and ten patients had treatment with radiotherapy alone. The remaining 87 received synchronous chemotherapy with breast irradiation, using either the 3M or the 2M regimen, consisting of mitoxantrone and methotrexate, with (3M) or without Mitomycin-C (2M). Patients were analysed according to both the severity and the site of the skin reaction, age, dose, dose variation across the central outline, treatment technique, beam energy, field separation and breast size. A univariate analysis of these results, which has been presented as an odds ratio of the likelihood of developing a moderate or severe reaction in comparison with those scored as mild, has shown that several factors are associated with an increase in the acute skin reaction. These include the use of the semi-supine technique (odds ratio (OR) = 7.3 (95% CI 3.7-14.6)), beam energy (60Co: 6-10 MV photons OR = 5.9 (95% CI 2.6-13.4)), field separation (> or = 20 cm: < 20 cm OR = 4.1 (95% CI 2.2-7.8)), dose variation across the central outline (> or = 10%: < 10% OR = 9.7 (95% CI 2.6-36.4)), inclusion of the axilla (OR = 4.6 (95% CI 2.4-8.9)), and bust size (bra cup size C and D: A and B OR = 4.6 (95% CI 2.7-11.9)). Using multivariate logistic regression, the technique of radiation delivery and bust size were shown to be independently significant variables affecting acute skin reaction. In view of the high correlation between variables (e.g. radiotherapy technique and beam energy) it is still not possible to specify with definite certainty which is the primary variable causing the skin reaction. However 20/57 (35%) of patients treated by the semisupine technique sustained a severe skin reaction, with > 10% dry or moist desquamation in the treatment field. This compares with only 6/140 (4%) patients treated by the supine method. A possible mechanism by which treatment using the semisupine technique may enhance acute toxicity is discussed. We conclude that there are both treatment and patient related factors that will increase the acute skin reaction after breast irradiation.

An acute toxicity study on the effects of synchronous chemotherapy and radiotherapy in early stage breast cancer after conservative surgery.

One hundred and ninety-seven patients with early stage breast cancer, who were treated initially with conservative surgery, were evaluated prospectively for acute toxicity after completing post-operative irradiation. Eighty-seven of these patients had synchronous chemotherapy with the 3M regimen (mitoxantrone, methotrexate and Mitomycin-C) during radiotherapy. The results indicate that patients receiving chemotherapy and radiotherapy (CRT) showed no significant difference in acute skin toxicity (AST) when compared with those treated with radiotherapy alone (RTO), with an odds ratio (OR = 0.6) and 95% confidence intervals (0.3-1.1) of developing either a moderate or severe, compared with a mild, skin reaction. Even after controlling for other confounding factors, such as treatment technique and beam energy, patients treated with the supine technique using 6-10 MV photons still displayed no significant difference in AST, with 12/74 (16%) patients in the CRT group and 14/66 (21%) in the RTO group developing a moderate or severe skin reaction (OR = 0.7 (95% CI 0.3-1.7)). Four of the 87 patients treated with CRT developed symptomatic acute radiation pneumonitis, three of whom were found to have > 3 cm of lung length on their simulator or check films. The volume of lung included within the treatment field was found to be statistically significant (P = 0.005) in predicting the onset of radiation pneumonitis in the CRT group. None of these patients has suffered any symptomatic late lung toxicity. We conclude that synchronous chemotherapy and radiotherapy, when using the 3M regimen, is feasible for patients having adjuvant treatment for early stage breast carcinoma and there is no significant increase in AST. However, it is associated with an increase in acute radiation pneumonitis when a significant volume of lung is included within the radiation treatment field.