Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

The microbial flora of clinically infected cutaneous metastases: a retrospective study.

Symptomatic cutaneous metastases are associated with discharge, malodour, pruritus and pain, all of which may negatively impact quality of life and cutaneous health. We conducted a retrospective chart review of patients referred to the Dermatology Service at Memorial Sloan Kettering Cancer Center between August 2006 and June 2015, and characterized the microbial flora and antimicrobial management of cutaneous metastases in 64 patients. We detected pathogenic and/or opportunistic bacteria in 50% of skin lesions. The most commonly isolated organisms were Staphylococcus aureus and Pseudomonas aeruginosa. Patients treated with oral antibiotics, alone or in combination with topical agents, had a statistically significant better improvement in infectious symptoms than those treated without oral antibiotics. Our findings suggest that the normal skin microbial flora is disrupted in patients with symptomatic skin metastases. Oral antibiotics may provide benefit when used as first-line therapy for infected skin lesions in patients with symptomatic cutaneous metastases.

Cortical correlates of neuromotor development in healthy children.

OBJECTIVE: To examine the relationship between acquisition of fine motor skills in childhood and development of the motor cortex. METHODS: We measured finger tapping speed and mirror movements in 43 healthy right-handed subjects (6-26 years of age). While recording surface electromyographic activity from right and left first dorsal interosseus, we delivered focal transcranial magnetic stimulation (TMS) over the hand areas of each motor cortex. We measured motor evoked potential (MEP) threshold, and ipsilateral (iSP) and contralateral (CSP) silent periods. RESULTS: As children got older, finger speeds got faster, MEP threshold decreased, iSP duration increased and latency decreased. Finger tapping speed got faster as motor thresholds and iSP latency decreased, but was unrelated to CSP duration. In all subjects right hemisphere MEP thresholds were higher than those on the left and duration of right hemisphere CSP was longer than that on the left. Children under 10 years of age had higher left hand mirror movement scores, and fewer left hemisphere iSPs which were of longer duration. CONCLUSIONS: Maturation of finger tapping skills is closely related to developmental changes in the motor threshold and iSP latency. Studies are warranted to explore the relationship between these measures and other neuromotor skills in children with motor disorders. SIGNIFICANCE: TMS can provide important insights into certain functional aspects of neurodevelopment in children.

New graphical method to measure silent periods evoked by transcranial magnetic stimulation.

OBJECTIVES: Manual methods of measuring duration of cortical silent periods (CSP) evoked by transcranial magnetic stimulation (TMS) depend upon subjective visual estimation of onset and offset. Because of this, the measurements are susceptible to poor rater reliability. We describe a graphical method to measure silent periods with greater precision. The statistical process underlying this new method is simple and particularly suited to signal detection in serially dependent data. METHODS: TMS-evoked silent periods were recorded in 13 healthy subjects. Two investigators subjectively measured silent period duration on each subject to estimate rater reliability. Using the graphical method, the mean and 99.76% variation limits of pre-stimulus electromyogram (EMG) activity were computed. Each averaged trial was displayed and CSP onset and offset detected when post-stimulus EMG activity moved outside the 99.76% limits. RESULTS: Maximum variation in silent period duration was 21.8 ms between the two investigators' subjective measurements. Silent period duration measured with the graphical method closely approximated measurements obtained using the manual method. It was possible to automate the procedure. CONCLUSIONS: This graphical method allowed precise measurement of CSP duration, independent of subjective estimations of onset or offset points. Further studies are necessary to determine if this method can provide a framework for other physiologic measures.

Serum progesterone concentrations associated with superovulation and premature corpus luteum failure in dairy goats.

The incidence and cause of premature corpora lutea failure and the response to luteinizing hormone treatment was investigated in superovulated dairy goats. Does were treated with 1000 IU pregnant mare serum gonadotropin intramuscularly, followed by either luteinizing hormone (treated group) or saline (control group). Serum progesterone concentrations were used to monitor corpus luteum function. The dose of pregnant mare serum gonadotropin used induced superovulation in a majority of the does, but the responses varied depending on the time of year. Premature regression of the corpora lutea occurred in 4 of 18 does after pregnant mare serum gonadotropin treatment, but there was no difference in the incidence of corpora lutea failure between treated and control groups. Decreases in serum progesterone concentrations were evident by day 3 after ovulation in does that experienced corpora lutea failure indicating this to be the critical time for premature regression of the corpora lutea in superovulated does.

Steroid levels after intramuscular injection of testosterone propionate in the caprine.

Nine sexually mature intact grade does were injected intramuscularly with testosterone propionate and subsequent plasma steroid concentrations determined and male-like behavior recorded. The does received either 100 mg testosterone propionate every three days for six treatments, total dose 600 mg (N = 5); 50 mg testosterone propionate daily for eighteen days, total dose 900 mg (N = 2) or 10 mg testosterone propionate daily for eighteen days, total dose 180 mg (N = 2). The treatments induced male-like sex behavior, the intensity of which was related to the dose of exogenous testosterone used, the regimen of administration, and the plasma levels of testosterone. Exogenous testosterone treatment had minimal effect on the subsequent reproductive activity of the does.