Intramedullary Metastases to Conus Medullaris: A Review of the Literature with a Case Illustration.

Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes.

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Background: Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease.

Methods: Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART).

MicroRNA-570 targets the HSP chaperone network, increases proteotoxic stress and inhibits mammary tumor cell migration.

The dynamic network of chaperone interactions known as the chaperome contributes significantly to the proteotoxic cell response and the malignant phenotype. To bypass the inherent redundancy in the network, we have used a microRNA (mir) approach to target multiple members of the chaperome simultaneously. We identified a potent microRNA, miR-570 that could bind the 3'untranslated regions of multiple HSP mRNAs and inhibit HSP synthesis.

Development and validation of a pancreatic cancer risk model for the general population using electronic health records: An observational study.

Aim: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at a late, incurable stage. We sought to determine whether individuals at high risk of developing PDAC could be identified early using routinely collected data.

Methods: Electronic health record (EHR) databases from two independent hospitals in Boston, Massachusetts, providing inpatient, outpatient, and emergency care, from 1979 through 2017, were used with case-control matching.

Genotoxic stress induces Sca-1-expressing metastatic mammary cancer cells.

We describe a cell damage-induced phenotype in mammary carcinoma cells involving acquisition of enhanced migratory and metastatic properties. Induction of this state by radiation required increased activity of the Ptgs2 gene product cyclooxygenase 2 (Cox2), secretion of its bioactive lipid product prostaglandin E2 (PGE2), and the activity of the PGE2 receptor EP4. Although largely transient, decaying to low levels in a few days to a week, this phenotype was cumulative with damage and levels of cell markers Sca-1 and ALDH1 increased with treatment dose.

Reduced Mortality Risk in the Recent Era in Early-Stage Hodgkin Lymphoma Patients Treated With Radiation Therapy With or Without Chemotherapy.

Purpose: To determine the effect of treatment changes over time on all-cause mortality risk in patients with early-stage Hodgkin lymphoma (HL) after radiation therapy. The long-term survivorship of those with HL necessitates quantification of the late risk of mortality from HL and other causes.

Methods And Materials: An institutional review board-approved retrospective study was conducted using a multi-institutional database of 1541 stage I and II HL patients treated from 1968 to 2007 with radiation therapy alone or combined-modality treatment.

Bending the cost curve: a unique collaboration between radiation oncologists and Blue Cross Blue Shield of Massachusetts to optimize the use of advanced technology.

Purpose: Intensity-modulated radiation therapy (IMRT) limits the dose of radiation to critical normal tissue structures and can be applied to the management of most cancers treated with radiation therapy. Because of increased treatment planning time and quality assurance, IMRT is costly. Blue Cross Blue Shield of Massachusetts (BCBSMA) and the Massachusetts Radiation Oncology Physicians Advisory Council (PAC) developed a strategy to develop standards for the appropriate use of IMRT.

Thyroid malignancies in survivors of Hodgkin lymphoma.

Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes.

Methods And Materials: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model.

Cellular and molecular chaperone fusion vaccines: targeting resistant cancer cell populations.

Molecular chaperone-based vaccines offer a number of advantages for cancer treatment. We have discussed the deployment of a vaccine prepared by gentle isolation of Hsp70 from tumour dendritic cell fusions (Hsp70 fusion vaccine). The vaccine was highly effective in triggering specific T cell immunity and in the treatment of tumour-bearing mice and the preparation was shown to retain an increased amount of tumour antigens compared to other chaperone-based isolates.

Heat shock proteins, autoimmunity, and cancer treatment.

Heat shock proteins (HSPs) have been linked to the therapy of both cancer and inflammatory diseases, approaches that utilize contrasting immune properties of these proteins. It would appear that HSP family members Hsp60 and Hsp70, whether from external sources or induced locally during inflammation, can be processed by antigen-presenting cells and that HSP-derived epitopes then activate regulatory T cells and suppress inflammatory diseases. These effects also extend to the HSP-rich environments of cancer cells where elevated HSP concentrations may participate in the immunosuppressive tumor milieu.

Frameless angiogram-based stereotactic radiosurgery for treatment of arteriovenous malformations.

Purpose: Stereotactic radiosurgery (SRS) is an effective alternative to microsurgical resection or embolization for definitive treatment of arteriovenous malformations (AVMs). Digital subtraction angiography (DSA) is the gold standard for pretreatment diagnosis and characterization of vascular anatomy, but requires rigid frame (skull) immobilization when used in combination with SRS. With the advent of advanced proton and image-guided photon delivery systems, SRS treatment is increasingly migrating to frameless platforms, which are incompatible with frame-based DSA.

Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come.

Molecular chaperone-peptide complexes extracted from tumors (heat shock protein [HSP] vaccines) have been intensively studied in the preceding two decades, proving to be safe and effective in treating a number of malignant diseases. They offer personalized therapy and target a cross-section of antigens expressed in patients' tumors. Future advances may rely on understanding the molecular underpinnings of this approach to immunotherapy.

The role of heat shock factors in stress-induced transcription.

Heat shock proteins (HSPs) are rapidly induced after stresses, such as heat shock, and accumulate at high concentrations in cells. HSP induction involves a family of heat shock transcription factors that bind the heat shock elements of the HSP genes and mediate transcription in trans. We discuss methods for the study of HSP binding to HSP promoters and the consequent increases in HSP gene expression in vitro and in vivo.

Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation.

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation.

Early-stage, lymphocyte-predominant Hodgkin's lymphoma: patient outcomes from a large, single-institution series with long follow-up.

PURPOSE The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution.

Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy.

Purpose: There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters.

Patients And Methods: Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007.

A prospective study of salivary gland function in lymphoma patients receiving head and neck irradiation.

Purpose: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients with lymphoma receiving radiation therapy (RT) to the head and neck (H&N).

Methods And Materials: We conducted a prospective study on salivary-gland function in lymphoma patients receiving RT to the H&N. Fifteen patients were enrolled on the study.

Targeting the oncogene and kinome chaperone CDC37.

CDC37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncoprotein that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on increased CDC37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit CDC37.

Targeting Cdc37 inhibits multiple signaling pathways and induces growth arrest in prostate cancer cells.

Members of the 90-kDa heat shock protein (HSP90) family are known to bind and stabilize intermediates in a wide variety of cell signaling pathways and contribute to their dysregulation in cancer. An important intracellular cofactor for HSP90 is Cdc37, a protein with a broad role in fostering the activities of protein kinases. By targeting Cdc37 using RNA interference, we have shown that the loss of Cdc37 function induces irreversible growth arrest in androgen receptor-positive and -negative prostate carcinoma cells.

Mechanisms for Hsp70 secretion: crossing membranes without a leader.

Heat shock protein 70 (Hsp70) is released from cells of many types and plays a significant signaling role, particularly in the inflammatory and immune responses. However, Hsp70 does not contain a consensus secretory signal and thus cannot traverse the plasma membrane by conventional mechanisms. However, Hsp70 can be released from cells by active mechanism that are independent of de novo Hsp70 synthesis or cell death.

Academic career selection and retention in radiation oncology: the Joint Center for Radiation Therapy experience.

Purpose: The United States healthcare system has witnessed declining reimbursement and increasing documentation requirements for longer than 10 years. These have decreased the time available to academic faculty for teaching and mentorship. The impact of these changes on the career choices of residents is unknown.

Persistent viral shedding during asymptomatic Aleutian mink disease parvoviral infection in a ferret.

A 2-year-old domestic ferret that appeared clinically healthy was repeatedly seropositive for Aleutian mink disease parvovirus (ADV) over a 2-year observation period. Antibody titers, determined by counter-immunoelectrophoresis, ranged from 1024 to 4096. Viral DNA also was identified in serum, urine, feces, and blood cell fractions by polymerase chain reaction analysis.

Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy.

Purpose: To analyze long-term outcomes and causes of death in patients receiving radiation therapy (RT) for localized, low-grade follicular lymphoma.

Methods And Materials: Between 1972 and 2000, 106 patients with Stage I-II, Grade 1-2 follicular lymphoma received RT alone or radiation and chemotherapy (RT/CT). Seventy-four percent had Stage I, and 26% had Stage II disease.

Anemia, tumor hypoxemia, and the cancer patient.

Purpose: To review the impact of anemia/tumor hypoxemia on the quality of life and survival in cancer patients, and to assess the problems associated with the correction of this difficulty.

Methods: MEDLINE searches were performed to find relevant literature regarding anemia and/or tumor hypoxia in cancer patients. Articles were evaluated in order to assess the epidemiology, adverse patient effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer cell growth and/or therapeutic resistance.