Background Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). We sought to determine the effect of breast cancer and age at diagnosis on Quality of Life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 or before, 2) OS diagnosed between 55 and 70, and, 3) for the YS, age-matched controls (AC) of women not diagnosed with breast cancer. Methods Using a large Eastern Cooperative Oncology Group (ECOG) data base, we recruited 505 YS who were ages 45 or younger when diagnosed and 622 OS diagnosed at 55 to 70. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables. Results Compared to both AC and to OS, YS reported more depressive symptoms (p=.005) and fatigue (p<.001), poorer self-reported attention function (p<.001), and poorer sexual function (p<.001) than either comparison group. However, YS also reported a greater sense of personal growth (p<.001) and perceived less social constraint (p<.001) from their partner than AC. Conclusions YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long term QoL problems than survivors diagnosed at a later age.
Summary BACKGROUND Plexiform neurofibromas (PN) are slow growing chemoradiotherapy resistant tumours arising in patients with neurofibromatosis type I (NF1). Currently there are no viable therapeutic options for patients whose life-threatening plexiform neurofibromas cannot be surgically removed due to proximity to vital body structures. Based on identification of molecular targets in genetic mouse models of human NF1 tumours, we hypothesized that the oral kinase inhibitor, imatinib mesylate, may be effective in targeted treatment of these chemoradiotherapy-refractory tumours. METHODS An open-label pilot Phase II clinical trial was designed to test whether treatment with imatinib mesylate can decrease volume burden of clinically significant plexiform neurofibromas in NF1 patients. The entry criteria require patients only to have NF1 and a clinically significant plexiform neurofibroma with the specified age limitations (age 3–65). Patients were treated with daily oral imatinib at 440 mg/m2/day for children and 800 mg/day for adults divided twice daily for 6 months. The primary endpoint measure of significant response was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data was analyzed on an intent to treat basis, however to determine the activity of imatinib on NF1-related plexiform tumours, patients able to take imatinib for 6 months were evaluated for their response. Secondary outcomes included evaluation of safety of imatinib mesylate in this group of patients. The trial is registered at http://clinicaltrials.gov/; study number 0512-25. The trial currently is closed to enrollment, however there is a single patient that continues to respond and remains on study. FINDINGS On an intent to treat basis, 6 out of 36 patients or 17% (95% CI: 6 – 33%) experienced objective response to imatinib mesylate. In the evaluable study population of patients (n=23) who received drug for at least six months, six patients (26%; 95% CI: 10 – 48%) experienced ≥ 20% decrease in volume of one or more plexiform tumours and 30% of study patients had symptomatic improvement. We noted significant inter-patient and intra-patient heterogeneity of plexiform neurofibroma response. Toxicity of drug was comparable to previous reports in patients with chronic myelogenous leukemia. The most common adverse events were reversible skin rash (5 patients) and edema with weight gain (6 patients). More serious adverse events included reversible grade 3 neutropenia (2 patients) and grade 4 transaminitis (one patient). INTERPRETATION Imatinib mesylate caused disease regression in 26% of evaluable patients with clinically significant plexiform neurofibromas due to neurofibromatosis type 1. These results warrant confirmation in a larger multi-institutional clinical trial aimed at this patient population. These findings provide the first demonstration of radiographic volumetric tumour reduction in response to medical therapy in patients with NF1 plexiform neurofibromas using imatinib mesylate based on studies...
Adolescents have unique developmental needs that should be considered at EOL. Timing of EOL discussions occurred very close to death for a significant number of adolescents, allowing very little time to psychologically prepare for death.
Purpose To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL). Experimental Design A retrospective series of children and adolescents with PCNSL was assembled from ten cancer centers in three countries. Results Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 1. Front line therapy consisted of chemotherapy (CT) only in twenty patients (69%), while 9 (31%) had CT plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (CR 69%, PR 17%). The 2 year PFS and OS rates were 61% and 86%, respectively; the 3 year OS was 82%. Univariate analyses were conducted for age (≤ 14 vs > 14 years), PS (0 or 1 vs >1), deep brain lesions, MTX dose, primary treatment with CT alone, intrathecal chemotherapy and high-dose therapy. Primary treatment with CT alone was associated with better overall response rates with an OR of 0.125 (p=0.02). There was a marginally significant relationship between higher doses of MTX and response (OR =1.5, p = 0.06). ECOG-PS of 0–1 was the only factor associated with better outcome with hazard ratios of 0.136 (p = 0.017) and 0.073(p = 0.033) for PFS and OS, respectively. Conclusion This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents appears to be better than in adults. PS of 0–1 is associated with better survival.
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