Timothy Malouff

Role for the epidermal growth factor receptor in chemotherapy-induced alopecia.

Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla condensation and decreased follicular proliferation, but did not progress to telogen as did Egfr wild type follicles. Egfr mutant follicles responded with less proliferation, apoptosis, and fewer p53-positive cells after cyclophosphamide. Treatment of control mice with the EGFR inhibitors erlotinib or gefitinib similarly suppressed alopecia and catagen progression by cyclophosphamide. Secondary analysis of clinical trials utilizing EGFR-targeted therapies and alopecia-inducing chemotherapy also revealed evidence for involvement of EGFR in chemotherapy-induced alopecia. Taken together, our results demonstrated the involvement of EGFR signaling in chemotherapy-induced alopecia, which will help in the design of novel therapeutic regimens to minimize chemotherapy-induced alopecia.

A comparison of clinical and radiologic outcomes between frame-based and frameless stereotactic radiosurgery for brain metastases

PURPOSE Modern experiences in stereotactic radiosurgery (SRS) report noninvasive frameless techniques as an effective alternative to frame-based SRS. Frameless techniques potentially increase positional uncertainty and planning target volume margins are frequently used. Here, we compare rates of local control and radiation necrosis in frameless versus frame-based SRS. METHODS AND MATERIALS Ninety-eight patients (170 lesions) with radiologic and clinical follow-up were analyzed. Group 1 contained 34 patients (61 lesions) immobilized with an invasive stereotactic frame. Group 2 had 64 patients (109 lesions) immobilized with a frameless SRS mask. Patient, tumor, and treatment characteristics were recorded, as were intervals to local recurrence and radiation necrosis (asymptomatic and symptomatic). RESULTS Median patient age was 59 years (range, 25-89), and Karnofsky performance scale was 80 (range, 50-100). Median radiologic and clinical follow-up was 6.5 months (range, 0.7-44.3) and 7 months (range, 0.7-45.7). A median of 2 tumors were treated per course (range, 1-5) with a median dose of 18 Gy (range, 13-24 Gy). The median time to local failure was not reached, and Kaplan-Meier estimates of local failure were not statistically significant between groups (P = .303). Actuarial 6-month local failure rates were 7.2% in group 1 and 12.6% in group 2 (P = .295), with 12-month local failure rates of 14.5% and 26.8% (P = .185), respectively. There was no statistically significant difference in symptomatic (P = .391) or asymptomatic (P = .149) radiation necrosis. Six-month radiation necrosis was 0% in group 1 and 1.6% in group 2 (P = .311) with 12-month rates of 20.2% and 3.8%, respectively (P = .059). Median time to necrosis was not reached in group 1, but was 44 months in group 2. CONCLUSIONS Frameless SRS demonstrates clinical outcomes comparable to frame-based techniques with respect to local failure and radiation necrosis.

Osteosarcoma of the larynx: treatment outcomes and patterns of failure analysis

The incidence of laryngeal sarcoma is exceedingly low with osteosarcomas of the larynx being rarer still, comprising less than 1% of all associated malignancies. To date, only 32 cases have been reported since this pathologic entity was first described in 1942. In this article, we discuss the most recent case of laryngeal osteosarcoma in a patient presenting with respiratory distress found to be due to a tumor mass arising from her cricoid cartilage. We further summarize current knowledge regarding the epidemiology, presentation, and diagnosis of this uncommon disease. Lastly, we synthesize all available information regarding treatment and outcomes of the 32 previously described cases of osteosarcoma of the larynx as well as the presently described case in an attempt to offer some insight regarding optimal treatment in future cases.

Trends in the use of radiation therapy for stage IIA prostate cancer from 2004 to 2013: a retrospective analysis using the National Cancer Database

Background:Recent studies have shown a decrease in the overall use of radiation therapy in the treatment of prostate cancer over the past several decades, as well as a more conservative overall treatment approach. We aim to determine whether this trend continued from 2004 to 2013, and to determine whether there were changes in utilization for various types of radiation.Methods:We conducted this retrospective study using the National Cancer Database. We identified 706 877 patients with sufficient treatment information diagnosed with stage IIA prostate cancer between 2004 and 2013. Logistic regression models were used to evaluate the yearly trend in radiation therapy utilization.Results:There was a significant decline in the use of radiation therapy from 2004 to 2013, from 54.4% in 2004 to 34.5% in 2013 compared with all the other treatments. The use of external beam radiation therapy (EBRT) declined from 27.1% in 2004 to 25.0% in 2013, brachytherapy declined from 19.7% in 2004 to 6.1% in 2013, and combination therapy declined from 6.8% in 2004 to 2.6% in 2013. However, when considering only patients receiving radiation treatments, the use of EBRT steadily increased from 50.6% in 2004 to 74.0% in 2013, whereas the use of brachytherapy declined from 36.7% in 2004 to 18.2% in 2013. Finally, although the proportion of patients receiving combination radiation therapy initially declined from 2004 to 2009 (from 12.7 to 8.3%), there was little change in utilization from 2009 to 2013 (8.3 to 8.5%).Conclusions:There has been a significant decline in the use of overall radiation therapy, as well as for each radiotherapy modality, for the treatment of prostate cancer since 2004. For patients that are receiving radiation, the use of EBRT has increased while brachytherapy use has decreased. These data serve to encourage further analysis as to the causes of these trends and how they affect patient care.

Which Prognostic Index Is Most Appropriate in the Setting of Delayed Stereotactic Radiosurgery for Brain Metastases

Objectives To determine if five commonly used prognostic indices (PIs) – recursive partitioning analysis (RPA), Score Index for Radiosurgery (SIR), Basic Score for Brain Metastases (BSBM), graded prognostic assessment (GPA), and the diagnosis-specific GPA – are valid following delay between diagnosis and treatment of brain metastases. Methods In a single-institutional cohort, records of patients who underwent stereotactic radiosurgery (SRS) more than 30 days from diagnosis of brain metastases were collected, and five PI scores were calculated for each patient. For each PI, three score-based groupings were made to examine survival differences by means of adjusted log-rank analysis and area under the curve (AUC). Results Of 121 patients with sufficient PI information, 72 underwent SRS more than 30 days after diagnosis. Median age and Karnofsky performance status were 60 years and 80, respectively. Forty-three (60%) patients had lung primaries. Prior to SRS, 38 (52.8%) and 12 (16.7%) patients underwent whole brain radiation therapy (WBRT) and surgery, respectively. Two (2.8%) patients underwent both WBRT and surgery prior to SRS. A median of two lesions were treated per SRS course. Median survival of the cohort was 9.0 months. Using adjusted log-rank analysis for pairwise comparison, BSBM and GPA showed significance between two out of the three prognostic groups, while the other scores showed either one or no significant differences on comparison. AUC demonstrated good applicability for BSBM, RPA, and GPA, although SIR was statistically less prognostic than the other PIs. Conclusion The PIs analyzed in this study were applicable in the setting of delayed SRS. Although these data are hypothesis generating, they serve to encourage further analyses to validate a PI that is most optimal for these patients.

Internal Mammary Node Irradiation During Breast Cancer

@OncologyTimes Stem Cell Transplants Without Using Chemotherapy Researchers at the Stanford University School of Medicine have come up with a way of conducting blood stem cell transplantation that, in mice, dramatically lowers its toxicity (Science Translational Medicine 2016;351:351ra105). If the method eventually proves safe and effective for humans, it potentially could be used to cure autoimmune diseases like lupus, juvenile diabetes, and multiple sclerosis; fix congenital metabolic disorders like “bubble boy” disease; and treat many more kinds of cancer, as well as make organ transplants safer and more successful. “There is almost no category of disease or organ transplant that is not impacted by this research,” said Irving Weissman, MD, a co-author of the research and Professor of Pathology and of Developmental Biology at Stanford. “The chemotherapy and radiation used for transplant damage DNA and can cause both immediate problems and long-term damage to many tissues in the body,” noted the paper’s senior author Judith Shizuru, MD, PhD, Professor of Medicine. “Among the many known toxic side effects, these treatments can cause damage to the liver, reproductive organs and brain, potentially causing seizures and impairing neurological development and growth in children.” For these reasons, blood stem cell transplantation is used only when the risks of serious disease outweigh the complications from the transplant. To avoid these side effects, the Stanford researchers composed a symphony of biological instruments that clear the way for blood stem cell transplantation without the use of chemotherapy or radiotherapy.