Long-Term Toxicities among Wilms Tumor Survivors

Successive trials conducted by the National Wilms Tumor Study have resulted in very high cure rates for children with Wilms tumor (WT). These trials have also significantly reduced the indications for doxorubicin and higher doses of RT in WT. Late toxicities after multimodality treatment especially RT, continues to be a major problem among WT survivors. Higher doses of RT is the most important factor responsible for the many late effects including congestive heart failure, secondary malignant neoplasms, hypogonadism, infertility and pregnancy complications, pulmonary disease, musculoskeletal effects, renal failure and diabetes mellitus. The potential for novel RT techniques like IMRT and proton therapy to reduce the incidence of these toxicities is discussed. The surveillance recommendations for WT survivors are mainly derived from the COG long-term follow-up guidelines. The future directions in late effects research include novel research to improve current knowledge of association between RT doses to target organs and late effects, discovery of novel biomarkers, and identification of predictive genetic biomarkers. Despite all these advances, there are significant challenges facing the global health care community that need to be overcome before the benefits of these innovations in late effects research can be translated to individual cancer survivors

Clinical management of supratentorial non-skull sase meningiomas

Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management and the rationale underlying specific approaches including observation, surgery, radiation, and investigational systemic therapies is covered in detail. Future directions for probable advances in the near and intermediate term are reviewed

Surgical protocol violations in children with renal tumors provides an opportunity to improve pediatric cancer care: a report from the Children’s Oncology Group

BackgroundThe purpose of this study was to evaluate the frequency and characteristics of surgical protocol violations (SPVs) among children undergoing surgery for renal tumors who were enrolled on the Children’s Oncology Group (COG) renal tumor biology and classification study AREN03B2.MethodsAREN03B2 was opened in February 2006, and as on March 31, 2013, there were 3,664 eligible patients. The surgical review forms for 3,536 patients with unilateral disease were centrally reviewed for SPVs. The frequency, type, number of violations, institutional prevalence, and quartiles for SPVs were assessed.ResultsOf the 3,536 patients, there were a total of 505 with at least one SPV (564 total SPVs reported), for an overall incidence of 14.28%. The types of SPVs included a lack of lymph node sampling in 365 (64.7%), avoidable spill in 61 (10.8%), biopsy immediately before nephrectomy in 89 (15.8%), an incorrect abdominal incision in 32 (5.7%), and unnecessary resection of organs in 17 (3.0%). The SPVs occurred in 163 of 215 participating institutions (75.8%). For centers with at least one SPV, the mean number of SPVs reported was 3.10 ± 2.39 (mean ± standard deviation). The incidence of protocol violation per institution ranged from 0 to 67%. Centers with an average of ≤1 case/year had an incidence of SPVs of 12.2 ± 3.8%, those with an average of >1 to 0.05).ConclusionsSPVs that potentially result in additional exposure to chemotherapy and radiation therapy are not uncommon in children undergoing resection of renal malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134088/1/pbc26083.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134088/2/pbc26083_am.pd

Results of Treatment for Patients With Multicentric or Bilaterally Predisposed Unilateral Wilms Tumor (AREN0534): A report from the Children’s Oncology Group

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156248/2/cncr32958_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156248/1/cncr32958.pd

Outcome of patients with intracranial relapse enrolled on national Wilms Tumor Study Group clinical trials.

BACKGROUND: The occurrence of brain metastases (at diagnosis or at relapse) in patients with Wilms tumor is very rare. METHODS: We retrospectively reviewed the clinical characteristics of patients with Wilms tumor and relapse to the brain enrolled on the National Wilms Tumor Studies (NWTSs) 1-5. RESULTS: Intracranial relapse was documented in 47 patients (0.5%). Of the 45 patients with adequate data, 26 (58%) patients were male. Thirty-eight (84%) patients had favorable histology Wilms tumor. In 30 patients (67%), the appearance of intracranial disease was preceded by relapse at another site. Ten patients did not have any disease-directed therapy. Surgical resection was attempted in 15 patients; gross total resection was achieved in 11 patients. Twenty-nine patients received brain irradiation; the median dose was 3,000 cGy (range 1,080-4,000 cGy). Twenty-seven patients received chemotherapy. The 5-year overall survival from the time of intracranial relapse was 28.7% (95% confidence interval: 14.4-43.1%). Nine patients (all favorable histology Wilms tumor) were alive with a median follow-up from brain relapse of 140 months (range 35-381 months). All nine survivors received radiation therapy, eight received chemotherapy, and four underwent surgery (two gross total resection, two partial resection). The overall survival after brain metastases of the NWTS-5 patients was significantly higher than the overall survival of the NWTS 1-4 patients (P value = 0.029, log-rank test). CONCLUSIONS: Patients with Wilms tumor recurrence involving the brain may have durable survival, particularly those treated in recent years. Multimodality therapy including radiation and chemotherapy should be considered for these patients

Adaptability and Resilience of Academic Radiation Oncology Personnel and Procedures during COVID-19 Pandemic

Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. Methods: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. Results: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits. Conclusions: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe

The effects of palbociclib in combination with radiation in preclinical models of aggressive meningioma.

BackgroundMeningiomas are the most common tumor arising within the cranium of adults. Despite surgical resection and radiotherapy, many meningiomas invade the brain, and many recur, often repeatedly. To date, no chemotherapy has proven effective against such tumors. Thus, there is an urgent need for chemotherapeutic options for treating meningiomas, especially those that enhance radiotherapy. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to enhance radiotherapy in preclinical models of other cancers, is well-tolerated in patients, and is used to treat malignancies elsewhere in the body. We, therefore, sought to determine its therapeutic potential in preclinical models of meningioma.MethodsPatient-derived meningioma cells were tested in vitro and in vivo with combinations of palbociclib and radiation. Outputs included cell viability, apoptosis, clonogenicity, engrafted mouse survival, and analysis of engrafted tumor tissues after therapy.ResultsWe found that palbociclib was highly potent against p16-deficient, Rb-intact CH157 and IOMM-Lee meningioma cells in vitro, but was ineffective against p16-intact, Rb-deficient SF8295 meningioma cells. Palbociclib also enhanced the in vitro efficacy of radiotherapy when used against p16-deficient meningioma, as indicated by cell viability and clonogenic assays. In vivo, the combination of palbociclib and radiation extended the survival of mice bearing orthotopic p16 deficient meningioma xenografts, relative to each as a monotherapy.ConclusionsThese data suggest that palbociclib could be repurposed to treat patients with p16-deficient, Rb-intact meningiomas, and that a clinical trial in combination with radiation therapy merits consideration