A Phase II Trial of Bevacizumab in Patients with Recurrent/Progressive Solid Tumor Brain Metastases That Have Progressed Following Whole-Brain Radiation Therapy.

Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.

Immunotherapy for Solitary Fibrous Tumor (Hemangiopericytoma): A Unique Treatment Approach for a Rare Central Nervous System Tumor.

INTRODUCTION: Solitary fibrous tumors (SFTs) of the central nervous system represent a unique entity with limited data on best treatment practices. CASE REPORT: Here, we present a case of multiply recurrent central nervous system SFT treated with radiation and immunotherapy. Immunotherapy was chosen based on mutations of genes encoding DNA repair enzymes detected through next-generation sequencing of the tumor, DNA polymerase epsilon catalytic subunit ( POLE ) and mutL homolog 1. The use of radiation and immunotherapy led to slight shrinkage and no recurrence of the tumor for over 2 years. CONCLUSION: The presence of somatic DNA repair enzyme gene mutations in SFT may suggest a benefit from a combination of radiotherapy and immunotherapy. This may serve as a biomarker for guiding management in patients with this rare tumor.

Differential Diagnosis of Tumor-like Brain Lesions.

Purpose of Review: Tumor-like brain lesions are rare and commonly suggest a neoplastic etiology. Failure to rapidly identify non-neoplastic causes can lead to increased morbidity and mortality. In this review, we describe 10 patients who presented with atypical, non-neoplastic tumor-like brain lesions in which brain biopsy was essential for a correct diagnosis and treatment. Recent Findings: There has been increasing recognition of autoimmune conditions affecting the nervous system, and many of those diseases can cause tumor-like brain lesions. Currently available reports of non-neoplastic tumor-like brain lesions are scarce. Most case series focus on tumefactive demyelinating lesions, and a comprehensive review including other neuroimmunological conditions such as CNS vasculitis, neurosarcoidosis, histiocytic and infectious etiologies is lacking. Summary: We review the literature on tumor-like brain lesions intending to increase the awareness and differential diagnosis of non-neoplastic brain tumor mimics. We advocate for earlier brain biopsies, which, in our case series, significantly changed diagnosis, management, and outcomes.

Neuro-Oncology in Women: Clinical Considerations.

Sex differences play a large role in oncology. It has long been discussed that the incidence of different types of tumors varies by sex, and this holds in neuro-oncology. There are also profound survival sex differences, biologic factors, and treatment effects. This review aims to summarize some of the main sex differences observed in primary brain tumors and goes on to focus specifically on gliomas and meningiomas, as these are two commonly encountered primary brain tumors in clinical practice. Additionally, considerations unique to female individuals, including pregnancy and breastfeeding, are explored. This review sheds light on many of the unique attributes that must be considered when diagnosing and treating female patients with primary brain tumors in clinical practice.

The impact of the molecular classification of glioblastoma on the interpretation of therapeutic clinical trial results.

In 2016, the World Health Organization (WHO) released the most recent update to the classification of central nervous system tumors. This update has led to the reshaping of tumor identification and subsequently changed current understanding of treatment options for patients. Moreover, the restructuring of the classification of central nervous system tumors to include molecular markers has led to the need to re-evaluate how to interpret pivotal trials. These trials originally enrolled patients purely based upon histologic diagnoses without the use of adjunctive, and frequently diagnostic molecular testing. With this new paradigm also comes the need to assess how one should incorporate molecular markers into current trials as well as shape future trials. First, we will discuss updates on the molecular classification of glioblastoma (GBM) (and its histologic mimics). This will be followed by a review of key pivotal trials which have defined our standard of care for glioblastoma within the context of molecular classification of their study populations. This will be followed by preliminary results of ongoing phase 3 cooperative group trials for high-grade gliomas that were initiated prior to routine molecular classification of tumors and how one could interpret these results in light of advances in molecular classification. Finally, we will end with suggestions for future clinical trial design with a focus on enrollment based upon molecular diagnostics.

Updates on Molecular Targeted Therapies for Intraparenchymal CNS Metastases.

Central nervous system (CNS) metastases can occur in a high percentage of systemic cancer patients and is a major cause of morbidity and mortality in these patients. Almost any histology can find its way to the brain, but lung, breast, and melanoma are the most common pathologies seen in the CNS from metastatic disease. Identification of many key targets in the tumorigenesis pathway has been crucial to the development of a number of drugs that have demonstrated successful penetration of the blood-brain, blood-cerebrospinal fluid, and blood-tumor barriers. Targeted therapy and immunotherapy have dramatically revolutionized the field with treatment options that can provide successful and durable control of even CNS disease. In this review, we discuss major targets with successful treatment options as demonstrated in clinical trials. These include tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates. We also provide an update on the state of the field and highlight key upcoming trials. Patient-specific molecular information combined with novel therapeutic approaches and new agents has demonstrated and continues to promise significant progress in the management of patients with CNS metastases.

Margins in breast conserving surgery: The financial cost & potential savings associated with the new margin guidelines.

INTRODUCTION: In this study, we compare the indications for re-excision, the findings of additional tumor in the re-excision specimen as they relate to margin status, and costs associated with re-excision based on recent new consensus statements. MATERIALS AND METHODS: A retrospective analysis was performed on 462 patients with invasive breast carcinoma who underwent at least one lumpectomy between January 2011 and December 2013. Postoperative data was analyzed based on where additional disease was found, as it relates to the margin status of the initial lumpectomy and the additional direct costs associated with additional procedures. RESULTS: Of the 462 patients sampled, 149 underwent a re-excision surgery (32.2%). Four patients underwent mastectomy as their second operation. In the 40 patients with additional disease found on re-excision, 36 (90.0%) of them had a positive margin on their initial lumpectomy. None of the four mastectomy patients had residual disease. The mean cost of the initial lumpectomy for all 462 patients was $2118.01 plus an additional $1801.92 for those who underwent re-excision. DISCUSSION: A positive margin was most predictive of finding residual tumor on re-excision as would be expected. Using old criteria only 0.07% (4/61) of patients who had undergone re-excision with a 'clear' margin, had additional tumor found, at a total cost of $106,354.11. Thus, the new consensus guidelines will lead to less overall cost, at no clinical risk to patients while reducing a patient's surgical risk and essentially eliminating delays in adjuvant care.

Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars.

UNLABELLED: The aim of this study was to compare the effects of the pulsed-dye laser (PDL) at a wavelength of 585 nm with those at 595 nm in the treatment of post-surgical scars, starting on the day of suture removal. The study was a prospective, non-randomized, double-blind, controlled, clinical trial, set in an outpatient clinic. Fifteen outpatients with 21 post-operative scars at least 3 cm long were recruited, and 14 patients with 19 scars completed the study. Scars were divided into three equal portions. Each outer portion was randomly allocated to PDL at 585 nm or at 595 nm (3.5 J/cm(2), 450 micros, 10 mm spot size), and the center was an untreated control; treatment was composed of three laser sessions at 4-week intervals. A blinded examiner evaluated the three scar sections using the Vancouver scar scale for pigmentation, vascularity, pliability, and height. Cosmetic appearance was evaluated with a visual analog scale. Punch biopsies of three randomly selected scars were evaluated. Pigmentation: more scars after laser treatments were of normal color than in the control, but the difference was not statistically significant. Vascularity: after treatment, more scars had normal vascularity in all three groups than at baseline (P < 0.05); the largest increase was with a wavelength of 585 nm (10.5-94.7%), then 595 nm (15.8-78.9%), then control (5.2-36.6%). Pliability: there was more normal pliability in all three groups than at baseline (P < 0.05), with greater improvements in the laser-treated groups. Height: significantly more flat scars after 585 nm PDL (63.2%) than at baseline (21.1%) (P < 0.05). We observed a slight but non-significant decrease in the scar heights with 595 nm PDL in comparison with the control. HISTOLOGY: after laser irradiation, the treated sections were more similar to a non-scarring process than the control. Cosmetic outcome: visual analog scales increased in all groups (P < 0.05), but the greatest increases were observed in the 585 nm and 595 nm laser-treated groups (50% and 60%, respectively) compared with controls (30%). There were significantly higher scores with the lasers than for the control (P < 0.001) at each visit after baseline. Both the 585 nm and 595 nm PDL treatments were effective in improving the appearance and normalizing the vascularity and pliability of post-operative scars. Both wavelengths improved the scars' visual appearance more than controls. We found that 585 nm appears to be the preferred wavelength, as it substantially normalized the height in addition to the vascularity and pliability in a significant number of scars.

Magnetic resonance imaging for axillary staging in patients with breast cancer.

PURPOSE: To determine the utility of MRI for assessing axillary lymph node status in patients with breast cancer. MATERIALS AND METHODS: A consecutive series of patients who underwent breast MR before surgical management of breast cancer with axillary sampling between 2005 and 2007 were identified. MRs were evaluated for the number of nodes, contrast kinetics, nodal area, and number of nodes with no fatty hilum. Data were analyzed in the context of final breast pathology, sentinel lymph node status, and axillary nodal status. Correlations were analyzed using Kendall's tau-b test. Reported P values are one-sided. RESULTS: Fifty-six females (median = 58 years) were studied. Sentinel lymph nodes (SLN) were positive in 15/56 patients (27%). All SLN + patients (n = 15) had completion axillary dissection. Extent of nodal disease was 1 (n = 3), 2 (n = 4), >2 (n = 8). Presence of any axillary lymph node with no fatty hilum and the number of nodes with no fatty hilum on MR significantly correlated with pathologic node positivity (P = 0.04); while kinetics, node number, and node size did not correlate. CONCLUSION: Breast MR may be useful in the assessment of axillary nodes in patients with breast cancer.

Effect of the 1,450 nm diode non-ablative laser on collagen expression in an artificial skin model.

BACKGROUND AND OBJECTIVE: The 1,450-nm Smoothbeam Laser is a diode laser equipped with a cryogen cooling spray. Primary objectives were to evaluate the effects of this non-ablative laser on Apligraf (bioengineered skin-substitute) and to document its use as a model for non-ablative procedures. We also measured the effects of laser fluence levels on collagen and elastin expression. STUDY DESIGN/MATERIALS AND METHODS: Three sheets of Apligraf were used for this study. Each received six separate laser applications at 4J, 6J, 8J, 10 J, 12J, and 14J. The sheets were then incubated with 10% CO(2) at 37 degrees C and samples were collected and analyzed 3 days later, using RT-PCR and immunofluorescent staining. RESULTS: Collagen III expressions significantly increased in both mRNA and protein levels at approximately 12 J. CONCLUSIONS: There appears to be a threshold effect where there is very little increased collagen III mRNA and protein expression until the laser fluence reaches around 12J.