Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment

Quality of life of adult retinoblastoma survivors in the Netherlands

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Adventively established Leptopilina japonica: a new opportunity for augmentative biocontrol of Drosophila suzukii

The invasive spotted-wing drosophila, Drosophila suzukii, has emerged as a significant global pest over the past decade, threatening fruit production worldwide. The parasitoid Leptopilina japonica, presumed native to East Asia, has established adventive populations in Europe and North America and is increasingly recognized for its ability to parasitize substantial proportions of D. suzukii larvae across diverse habitats. Here, we provide a broad review of the biology, establishment, distribution, and potential impacts of L. japonica. Using field data from international monitoring programs, we document the seasonal dynamics of plant–host–parasitoid associations and assess evidence for L. japonica’s impact on D. suzukii and non-target organisms. Findings indicate that L. japonica has successfully established in several areas where D. suzukii is present in Europe and North America, showing promise as a biological control agent to support sustainable pest management. Current data suggest it provides some suppression of D. suzukii populations with minimal non-target effects. However, long-term studies are necessary to clarify its food web interactions and efficacy as a biological control agent. In areas where L. japonica has been established, we propose its use in augmentative biological control programs to enhance its impacts in specific agricultural settings. Case-specific evaluations of its ecological effects and role in integrated pest management, supported by continued monitoring, are essential. The case of L. japonica illustrates the need for clear, research-informed policies to guide the use of adventively established non-indigenous natural enemies in pest management

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Beyond Greetings and Making Friends: Social Skills from a Broader Perspective

Many students with learning disabilities encounter social difficulties in that they are less accepted and/or more rejected than their nondisabled peers (Bryan, 1974, 1986; La Greca & Stone, 1990; Stone & La Greca, 1990; see for review Vaughn & La Greca, 1988). Concern about these youngsters’ peer relations and social skills has led to an interest in intervention strategies for remediating the social difficulties many learning-disabled (LD) students display

Subgroups of Rejected Boys: Aggressive Responses to Peer Conflict Situations

Evaluated strategies for resolving peer conflict among boys who varied with respect to peer status (rejected w nonrejected) and behavior (aggressive vs. nonaggressive). Using sociometric measures and the Revised Behavior Problem Checklist, 113 six year olds were screened to identify four subject groups: aggressive rejected, rejected nonaggressive, aggressive nonrejected, and controls who were neither rejected nor aggressive. Boys completed a task in which they reported solutions to hypothetical peer conflicts. In half of the situations intentionality was deliberate, and in half it was ambiguous. Responses were coded for physical aggression, indirect aggression, and assertiveness. Multivariate analyses indicated that aggressive-rejected boys used more indirect aggression, whereas aggressive-nonrejected boys used more assertiveness compared with other groups. Results suggest that the type of aggressive responding may be a better determinant of boys' social problems than the rate of aggression