Long-term survival in patients with brain-only metastatic non-small cell lung cancer undergoing upfront intracranial stereotactic radiosurgery and definitive treatment to the thoracic primary site.

BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared. RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death. CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.

Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp.

BACKGROUND: Dissecting cellulitis of the scalp can be an extremely painful and disfiguring dermatological condition. The associated pain can be severe enough in some cases to require opioid analgesics, and this pain in conjunction with the disfigurement can induce significant emotional distress. Conservative treatments often fail to provide relief. Radiation therapy has been successfully used in the past but with outdated equipment and techniques. OBJECTIVES: To evaluate the efficacy and toxicity of modern external beam radiation therapy techniques for the treatment of dissecting cellulitis of the scalp. METHODS: Four patients with intractable dissecting cellulitis of the scalp were treated with electrons or a combination of electrons and photons to the entire scalp. Daily fraction sizes were 2.5 or 3 Gy and initially prescribed to 15-21 Gy. Patients were re-evaluated 3-4 weeks after completion of therapy. Any residual hair growth was treated with additional radiation treatments to ensure full epilation, up to a maximum dose of 35 Gy. RESULTS: Rapid resolution of pain was seen in all patients with pain. Regression of nodules and decreased discharge was seen in all patients following treatment and cosmesis was subjectively improved. No long-term toxicity has been observed. CONCLUSIONS: Using modern techniques and equipment, radiation therapy appears to be a reasonable option for patients with severe/refractory dissecting cellulitis of the scalp. Acute effects are mild and well tolerated. Aside from alopecia, which was present to some extent in all patients before treatment, no long-term complications have been observed.

Renal cellular transport, metabolism, and cytotoxicity of S-(6-purinyl)glutathione, a prodrug of 6-mercaptopurine, and analogues.

The disposition of S-(6-purinyl)glutathione (6-PG) and its metabolites, including the antitumor agent 6-mercaptopurine (6-MP), was characterized in freshly isolated renal cortical cells from male F344 rats to assess the ability of the kidney to convert 6-PG to 6-MP. The intracellular transport and accumulation of 6-PG and 6-MP, the metabolism of 6-PG to 6-MP, and the potential cytotoxicity of 6-MP, 6-thioxanthine (6-ThXan), and 6-thioguanine (6-ThGua) were determined. 6-PG and 6-MP were accumulated by renal cortical cells by time- and concentration-dependent processes, reaching maximal levels of 14.2 and 1.52 nmol/10(6) cells, respectively, with 1 mM concentrations of each compound. Treatment with acivicin, an inhibitor of 6-PG metabolism by gamma-glutamyltransferase, increased accumulation of 6-PG, and treatment with alpha-keto-gamma-methiolbutyrate, a keto acid cosubstrate that stimulates activity of the cysteine conjugate beta-lyase (beta-lyase), which generates 6-MP, decreased accumulation of 6-PG. Incubation of renal cells with 10 mM 6-PG generated 6-MP at a rate of 2.4 nmol/min per 10(6) cells, demonstrating that the beta-lyase pathway forms the desired product from the prodrug within the intact renal cell. Preincubation of cells with acivicin or aminooxyacetic acid, an inhibitor of the beta-lyase, decreased the net formation of 6-MP, demonstrating further the function of the beta-lyase. 6-MP, 6-ThXan, and 6-ThGua exhibited approximately equivalent cytotoxicity (45-55% release of lactate dehydrogenase with 1 mM at 2 hr) in isolated renal cells. Based on the known antitumor potency of these agents, this suggests that cytotoxicity and antitumor activity occur by distinct mechanisms. The high amount of accumulation of 6-PG and its subsequent metabolism to 6-MP, as compared with the relatively low amount of accumulation of 6-MP, in renal cells suggest that 6-PG can function as a prodrug and is a more effective delivery vehicle for 6-MP to renal cells than 6-MP itself. Administration of 6-PG may be an effective means of treating renal tumors or suppressing renal transplant rejection.