PURPOSE The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments for a small number of metastases, there is a high risk of developing additional brain metastases. The role of adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases is controversial, with a lack of high-level evidence specifically for melanoma. METHODS In this randomized phase III trial, patients who had local treatment of one to three melanoma brain metastases were randomly assigned to WBRT or observation. The primary end point was distant intracranial failure within 12 months, and secondary end points included time to intracranial failure, survival, and time to deterioration in performance status. RESULTS Between April 2009 and September 2017, 215 patients were randomly assigned from 24 centers. Median follow-up was 48.1 months (range, 39.6 to 68 months). Forty-two percent of patients in the WBRT group and 50.5% of those in the observation developed distant intracranial failure within 12 months (odds ratio, 0.71; 95% CI, 0.41 to 1.23; P = .22) and the rates over the entire follow-up period were 52.0% and 57.9%, respectively (odds ratio, 0.79; 95% CI, 0.45 to 1.36; P = .39). Local failure rate was lower after WBRT (20.0% v 33.6%; P = .03). At 12 months, 41.5% of patients in the WBRT group and 51.4% of patients in the observation group had died ( P = .28), with no difference in the rate of neurologic death. Median time to deterioration in performance status was 3.8 months after WBRT and 4.4 months with observation ( P = .32). WBRT was associated with more grade 1 to 2 acute toxicity. CONCLUSION After local treatment of one to three melanoma brain metastases, adjuvant WBRT does not provide clinical benefit in terms of distant intracranial control, survival, or preservation of performance status.
Earlier access to lung cancer specialist (LCS) care improves survival, highlighting the need for streamlined patient referral. International guidelines recommend 14-day maximum time intervals from general practitioner (GP) referral to first LCS appointment ("GP-LCS interval"), and diagnosis to treatment ("treatment interval"). We compared time intervals in lung cancer care against timeframe benchmarks, and explored barriers and facilitators to timely care.We conducted a scoping review of literature from MEDLINE, Embase, Scopus and hand searches. Primary end-points were GP-LCS and treatment intervals. Performance against guidelines and factors responsible for delays were explored. We used descriptive statistics and nonparametric Wilcoxon rank sum tests to compare intervals in studies reporting fast-track interventions.Of 1343 identified studies, 128 full-text articles were eligible. Only 33 (26%) studies reported GP-LCS intervals, with an overall median of 7 days and distributions largely meeting guidelines. Overall, 52 (41%) studies reported treatment intervals, with a median of 27 days, and distributions of times falling short of guidelines. There was no effect of fast-track interventions on reducing time intervals. Lack of symptoms and multiple procedures or specialist visits were suggested causes for delay.Although most patients with lung cancer see a specialist within a reasonable timeframe, treatment commencement is often delayed. There is regional variation in establishing timeliness of care.
Cancer patients with non-central nervous system tumors often suffer from cognitive impairment. While chemotherapy has long been attributed as the cause of these memory, learning and concentration difficulties, we recently observed cognitive impairment in cancer patients prior to treatment. This suggests the cancer alone may be sufficient to induce cognitive impairment, however the mechanisms are unknown. Here, we show that we can experimentally replicate the clinical phenomenon of cancer-associated cognitive impairment and we identify inflammation as a causal mechanism. We demonstrate that a peripheral tumor is sufficient to induce memory loss. Using an othotopic mouse model of breast cancer, we found that mice with 4T1.2 or EO771 mammary tumors had significantly poorer memory than mice without tumors. Memory impairment was independent of cancer-induced sickness behavior, which was only observed during the later stage of cancer progression in mice with high metastatic burden. Tumor-secreted factors were sufficient to induce memory impairment and pro-inflammatory cytokines were elevated in the plasma of tumor-bearing mice. Oral treatment with low-dose aspirin completely blocked tumor-induced memory impairment without affecting tumor-induced sickness or tumor growth, demonstrating a causal role for inflammation in cognitive impairment. These findings suggest that anti-inflammatories may be a safe and readily translatable strategy that could be used to prevent cancer-associated cognitive impairment in patients.
BackgroundThe number of people living with and beyond cancer is increasing substantially. Primary care has an important role in the ongoing management of cancer survivors.
ObjectiveThe aim of this article is to outline common concerns of cancer survivors, evidence to support the role of general practitioners (GP) in survivorship care and key aspects of primary care-led survivorship care.
DiscussionClinical trials have shown that, in particular circumstances and with well-designed models, GP-led care is as effective as oncology specialist-led care. Regardless of the model of care, general practice has key roles in care coordination, management of multimorbidity, secondary prevention and health promotion, management of psychosocial care and promotion of self-management. Communication and collaboration between GPs and specialist cancer services is critical to support patients and healthcare providers in the delivery of care.
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