No abstract

Fertility-related perceptions varied among survivors, but the majority never underwent fertility testing. Uncertainty or concerns differed by current circumstances (e.g., wanting children and relationship status). Providers should routinely discuss potential infertility and offer testing throughout survivorship. A negative impact on romantic relationships may seem small, but should be considered for survivors who desire children and may discover they are infertile in the future.

Purpose This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl –tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. Methods Patients received mifamurtide 2 mg/m2 intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. Results The study began therapy in January 2008; the last patient completed therapy in October 2012. 205 patients were enrolled; median age was 16.5 years and 143/204 (72%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a loglinear manner 2–6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m2 mifamurtide across the age range. Patients reported 3,415 IRAE after 7,122 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills+fever or headache+fatigue symptom clusters. One and two year OS was 70.6% and 41.4%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N=40) had similar 2-year OS (38.8%) as the entire cohort (41.4%) Conclusions Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 41.4%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Over the last 30 years, it has become apparent that oncology patients ages 15 to 39 have not reaped the same rewards of improved survival that we have seen in younger and older patients. As a result, in 2006 the Adolescent and Young Adult (AYA) Oncology Progress Review Group convened and examined the factors that impact the care of the 70,000 new cases per year (approximately 7% of all new cases) in the United States and published their findings. The reasons for inferior survival gains are of course multiple and include the settings in which patients are cared for, clinical trial enrollment, insurance coverage, varied treatment of sarcomas, varied treatment of acute lymphoblastic leukemia, the psychosocial impact of cancer and cancer survivorship. A new area of a yet-to-be completely defined subspecialty was born out of this meeting: AYA oncology. As a medical community we realized that these patients do not fit neatly into the pediatric nor adult world and, therefore, require a unique approach which many individuals, oncology centers, advocacy groups, and cooperative trial groups have started to address. This group of dedicated providers and advocates has made strides but there is still much work to be done on the local, national, and international level to make up for shortcomings in the medical system and improve outcomes. We review key components of AYA cancer care in 2015 that all providers should be aware of, how far we have come, where this movement is headed, and the obstacles that continue to stand in the way of better cure rates and quality of life after cure for this unique group of patients. Like an adolescent maturing into adulthood, this movement has learned from the past and is focused on moving into the future to achieve its goals.

Seprehvir (HSV1716) is an oncolytic herpes simplex virus-1 (HSV-1) previously demonstrated to be well tolerated in pediatric patients when administered intratumorally. To determine the safety of administering Seprehvir systemically, we conducted the first-inhuman phase I trial of intravenous injection in young patients with relapsed or refractory extra-cranial solid cancers. We delivered a single dose of 5 Â 10 4 infectious units (iu)/kg (maximum dose of 2 Â 10 6) or 2.5 Â 10 5 iu/kg (maximum dose of 1 Â 10 7 iu) of Seprehvir via the peripheral vein, monitored adverse events, and measured tumor responses by imaging. We monitored HSV-1 serology as well as viremia and shedding by PCR and culture. We administered a single dose of Seprehvir to seven patients and multiple doses to two patients. We did not observe any dose-limiting toxicities. All five HSV-1 seronegative patients seroconverted by day 28. Four of nine patients had detectable HSV-1 genomes in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had stable disease in response to Seprehvir. Intravenous Seprehvir is well tolerated without viral shedding in children and young adults with late-stage cancer. Viremia consistent with virus replication holds promise for future Seprehvir studies at higher doses and/or in combination with other anti-neoplastic therapies.

, and CD45RO+ lymphocytic infiltrates. We evaluated several tumors from a single patient, observing trends of increasing immunogenicity over time, even with disease progression. We observed similarly immunogenic profiles for malignant peripheral nerve sheath tumors (MPNST) and nodular and plexiform neurofibromas, contrasting with diffuse neurofibromas. These studies suggest that while immunotherapies may offer some benefit for MPNST and nodular and plexiform neurofibromas, tumor heterogeneity might pose a significant clinical challenge to this novel therapeutic approach.

Infertility is a common and distressing late effect of cancer treatment among male survivors. Investigators examined desire for parenthood, prioritization of fertility compared to other life goals, and reports of fertility-related discussions among a cohort of male adolescent and young adult survivors. Eighty percent desired a biological child, yet only 31% ranked having a child among their "top 3" life goals. Only 40% reported fertility-related discussions with their health care providers in survivorship. Given the importance of biological children among this cohort, future guidelines should encourage a more proactive approach to providing fertility counseling and offering testing, to mitigate distress and prevent unplanned pregnancies.

We present a 9-month-old male with mosaic trisomy 18 with a right hepatic lobe mass. The tumor was completely resected and identified as pure fetal histology hepatoblastoma but contained increased mitotic activity. Adjuvant chemotherapy consisted of cisplatin, vincristine, and 5-fluorouracil. After the first and fourth cycles of chemotherapy, recurrent tumor developed. The patient underwent rescue orthotopic liver transplantation, and is currently alive without evidence of hepatoblastoma 28 months after transplantation. This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma.