RapidArc makes it possible to quickly deliver an advanced image-guided, intensity-modulated radiation therapy (IMRT) treatment with one 360 degree rotation of the treatment machine around the patient. In this case, however, Scarbrough [Todd Scarbrough, M.D., radiation oncologist and director of the Melbourne Internal Medical Associates, Florida --ed.] and his team designed a treatment that was delivered with just half a rotation around the patient.

"The tumor was near the surface of his thigh, so a full arc would have exposed too much of his normal leg to the treatment beam," Scarbrough said.

Scarbrough's team planned the RapidArc treatment using Varian's Eclipse™ treatment planning software, which allowed them to visualize how the dose would be distributed within the patient's leg. "The RapidArc plan gave us a dose distribution that was superior to what we could have achieved with traditional IMRT," Scarbrough said. "Eclipse made it easy to create a plan that would avoid the previously-irradiated tissues. We just superimposed the dose distribution from his earlier treatments onto the new CT scans, created a structure out of that area, and instructed the software to avoid it as if it were a critical organ. It was very easy to do."

Stereotactic body radiotherapy involves delivering higher-than-usual doses of radiation to a tumor over a shorter-than-usual timeframe. It requires great accuracy and precision, both in terms of targeting and in terms of beam shaping, to minimize the exposure of surrounding tissues. MIMA's RapidArc protocol achieves the necessary level of precision. 3-D X-ray images of the targeted area are used to fine-tune patient positioning prior to each treatment. Then, as the treatment machine rotates around the patient, the treatment beam is continually shaped and reshaped to match the dimensions of the tumor.

Press release: MIMA Cancer Center Becomes First in World to Treat Soft Tissue Carcinoma With Stereotactic Body Radiotherapy Using RapidArc™ Radiotherapy Technology...

Product page: RapidArc™ Radiotherapy...

Product brochure (.pdf)...

The kit is based on a technology called chromogenic in situ hybridization (CISH). The test uses a DNA probe for the HER2 gene, which is amplified in 18 to 30 percent of breast cancers and predicts whether a breast cancer patient is a candidate for trastuzumab treatment. Current medical practice requires that all patients who are considered for trastuzumab treatment be tested for HER2 amplification or overexpression. CISH test results are visualized under a standard bright-field microscope, as opposed to fluorescent in situ hybridization tests, in which the results must be visualized using a fluorescent microscope. This specialized microscope frequently requires that the analysis is done at a reference lab. In addition, HER2 CISH test results are quantifiable; removing the subjectivity inherent in tests based on immunohistochemistry (IHC) interpretation schemes.

"The current protocol for assessing HER2 gene status is for labs to initially screen tissue samples with immunohistochemistry to gauge whether there is an overabundance of the HER2 protein, as an indirect measure of gene amplification," said August Sick, vice president and general manager of Invitrogen's Cellular Analysis Business. "In the case of an inconclusive test, the samples are typically sent to an outside lab for confirmation. Because the SPOT-Light(R) HER2 CISH Kit doesn't need specialized equipment, any histology lab can now assess amplification of the HER2 gene while simultaneously examining tissue morphology."

Press release: FDA Grants Invitrogen Premarket Approval of Breast Cancer Test

Flashback: HERmark Breast Cancer Assay Is Now Available

Image courtesy Invitrogen Corp.: SPOT-Light HER2 Probe...

Some of the features from the product page:

Adult and pediatric dosing for FDA-approved and off-label indications

Black box warnings, contraindications, and cautions

Serious and common adverse reactions, and drug interactions organized by clinical category

Pill pictures within the drug monograph showing you and your patients exactly what each drug looks like

Safety and monitoring information, such as pregnancy risk categories, lactation safety ratings, monitoring parameters and therapeutic drug levels

Manufacturer information, approximate retail pricing, and FDA/DEA status

Pharmacology information, including metabolism, excretion (i.e., half-life), drug class, and mechanism of action

Notes section for your personal notes

Press release: Epocrates Drug and Formulary Application on Apple App Store

Product page: Epocrates Rx for iPhone

From a press release by the company:

ERmark is a proprietary diagnostic that accurately quantifies HER2 total protein levels and HER2 homodimerization in patients with breast cancer. HERmark is a CLIA-validated assay that is performed exclusively in Monogram's CAP-certified clinical reference laboratory in South San Francisco. Robust, accurate, sensitive and reproducible measurements of HER2 status are reported to physicians with a turnaround time of 7 days.

With the accurate measurements provided by HERmark, it is expected that as many as 15-20% of patients determined by conventional technologies to be HER2- negative would be reclassified by HERmark.

Key advantages of the HERmark Breast Cancer Assay include:

-- HERmark is highly sensitive and can detect HER2 at levels from 2,500 to over 1 million receptors per cell -- 7 to 10 times more sensitive than IHC.

-- HERmark provides a better measure of HER2 status by measuring the drug target -- the HER2 protein and HER2 homodimers -- rather than the HER2 gene.

-- The HERmark report is simple to interpret and provides a specific quantitative measure of HER2 expression, a HER2 status of "positive", "negative" or "equivocal" and indicates, relative to conventional measurements, how positive or how negative the patient is.

-- Clinical studies demonstrate that HERmark is an accurate method for stratifying patients with metastatic breast cancer who are more likely to respond to Herceptin-containing therapy.

Press release: Monogram Announces Commercial Availability of the HERmark(TM) Breast Cancer Assay...

Product page: HERmark...

Some patients who are potential candidates for balloon therapy are currently excluded because of the location of the lesion and their breast size. Contura’s advanced multi-lumen design may address this issue for certain patients. In addition, the Contura MLB uses vacuum to remove excess seroma and air to enhance conformance of often irregularly shaped lumpectomy cavity walls to the balloon surface in order to deliver precise radiation dosing through multiple radiation source lumens.

“The novel proprietary design of our newest Contura Multi-Lumen Radiation Balloon (MLB) Catheter allows the clinician greater flexibility in appropriately fitting the lumpectomy cavity with a balloon catheter,” said Lloyd Malchow, SenoRx President and Chief Executive Officer. “The new-size Contura balloon may be appropriate for approximately 10 to15 percent of patients where a larger balloon is warranted and will allow us to compete for these cases. The product is currently being evaluated at several clinical sites and is expected to become generally available during the third quarter of 2008. The original Contura is 4 to 5 centimeters in diameter, while the new balloon can be used for larger lumpectomy cavities ranging from 5 to 6 centimeters in diameter.”

Press release: SenoRx Receives Additional 510(k) Clearance for Its Contura MLB...

Product page: Contura ...

The company explains its technology:

Laser opto-acoustic imaging technology combines optics and acoustics with a goal of improving the accuracy of the cancer diagnosis without the use of ionizing radiation (x-ray). The process starts by illuminating the breast with laser light of specific wavelengths. Tumors preferentially absorb the light over normal tissue and become slightly heated. A transient thermoelastic expansion causes a tumor to emit a pressure (acoustic) wave. This acoustic wave is then detected by an array of sensors positioned around the periphery of the breast held within the probe.

Signals from the sensors are analyzed and assembled into high contrast, high-resolution images that present the lesion in striking color. Because image contrast is related to both blood volume and oxygenation status, lesions may be correlated with benign or malignant histopathology. This is because malignant tumors possess increased microvasculature, but deplete oxygen from the blood at a higher rate than benign growths. Deoxygenated blood results in brighter images in the presence of a shorter wavelength than it does in the presence of a longer wavelength.

This technology has the merit of both the high contrast and spectral specificity of optical imaging and the sensitivity and resolution of ultrasonic imaging. It is more than just a combination of the two methods. The goal is to incorporate laser illumination and ultrasonic detection to achieve very high detection sensitivity.

Laser opto-acoustic imaging may permit the identification of tumors as small as 2 mm and has demonstrated the ability to see submillimeter structures. Early detection is important because biologically advanced tumors are more capable of metastasis.

Technology page @ Seno Medical: Laser Opto-Acoustic Imaging...

Press release: Seno Medical Instruments Launches First-Ever Commercially Available Opto-Acoustic Small Animal Imaging Research System...

Flashbacks: Optoacoustic Technology for Early Cancer Detection

So, let us get it straight. Now we have a company that tries to utilize a bacterium responsible for a common food poisoning to fight a common cancer? Indeed, and the reason is the strong T cell mediated immune response that the human body mounds against Listeria, hence the organism could potentially be used as a vaccine vehicle. According to Advaxis, the firm holds the rights to a portfolio of patents based on the work of Dr. Yvonne Paterson from the University of Pennsylvania, protecting its use of Listeria and listerial products in hopes of developing vaccines against a variety of diseases.

Advaxis, on its technology page, explains how it plans to exploit the pathogen:

Listeria has a unique life cycle. It infects Antigen Presenting Cells (APC), which are the cells that activate immune cells and tell them what to attack. Because of this, Listeria becomes perfectly positioned to have the maximum effect on the immune system in terms of directing it against specific targets. Even more unusual is Listeria's ability to stimulate both helper T cells (CD4+) and killer T cells (CD8+), since both are necessary for an antitumor response and it is unusual for a single pathogen to stimulate both in the way Listeria does.

Antigen Processing Cells normally engulf foreign elements to remove them from the body and present them to the immune system.

Following their ingestion, they are encapsulated and digested in a phagolysosome. Fragments of the digested invader are used to stimulate the immune system through the exogenous pathway (exogenous; since the invader came from outside the cell).

This pathway is associated with the formation of MHC class II complexes and the activation of specific CD4+ helper T cells directed against the invader. This is the most common response to a foreign invader.

A certain percentage of Listeria, however, are able to break out of the phagolysosomes and enter into the cytoplasm of the cell, where they are safe from lysosomal destruction. After escaping from the phagolysosome, the bacteria multiply in the cell. Additionally, Listeria is able to migrate into neighboring cells and spread without entering the extracellular space.

Once in the cytoplasm, Listeria is capable of stimulating the immune system via the endogenous pathway (endogenous; because Listeria is now living within the cell). The endogenous pathway is associated with MHC class I complex formation and resultant CD8+ killer T cells.

Listeria also has other effects; such as the maturation of dendritic cells, which is most powerful APC and is essential for a strong antitumor response.

Thus, Listeria has the ability to stimulate multiple limbs of the immune response simultaneously and in an integrated way that serves to bring a number of immune mechanisms together to attack cancer...

The details of Listeria intracellular activity are important for understanding Advaxis technology. Inside the phagolysosome, Listeria produces and secretes the virulence factor listeriolysin O ("LLO"), a protein that generates a hole in the membrane of the phagolysosome and allows the bacteria to escape into the relatively safe cytoplasm. Once in the cytoplasm, however, LLO still retains some activity and is also capable of creating a hole in the cell membrane. This would destroy the host cell, and spill the bacteria back out into the intercellular space where it would be exposed to more immune cell attacks and destruction. To prevent this, a sequence of approximately 30 amino acids is present in the LLO protein, called the PEST sequence (for the predominant amino acids it contains). This PEST sequence is recognized by the host cells and targets the LLO protein for rapid digestion, thus giving LLO a very short life span. The benefit for the Listeria is that the LLO is neutralized and the bacteria can continue to prosper inside the cell, which also remains alive.

Since the activation of the immune system is also dependent upon the digestion of antigens and the creation of small fragments that can be used as recognition sites for an immune attack, Advaxis reasoned that we might use this mechanism that rapidly breaks down LLO to also break down antigens, which are released in both the phagolysosome and in the cytoplasm of the APC. To do so, we created a proprietary method in which we engineer Listeria to secrete a "fusion protein" which is comprised of a specific antigen that we wish to use as the focus for an immune attack fused to a segment of LLO. In this way, we can accelerate the breakdown of antigens into immuno-active fragments because the PEST sequence of the fusion protein is recognized and the secreted antigen fusion protein is routed for rapid degradation, thus accelerating both the rate at which antigen fragments are created and the speed with which they are delivered to the immune system for use in the creation of recognition molecules that activate T cells. Furthermore, the fusion of the antigen to LLO is essential to promote the secretion of the antigen, because the signal sequence needed for LLO secretion is kept intact in the fusion protein.

To read more, head on to Advaxis technology page...

Press release: Advaxis Files Investigational New Drug Application with U.S. Food and Drug Administration...

From the press release:

As a testament to the growing demand to improve patient care while reducing healthcare costs, Toshiba America Medical Systems, Inc. has installed the Aquilion ONE™ dynamic volume CT system at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School in Boston.

"In one of the country's leading medical teaching hospitals, we hope the Aquilion ONE's ability to image an entire organ and show function for the first time will mean faster, more accurate diagnosis, better patient outcomes and ultimately lower healthcare costs for our patients," explained Dr. Vassilios D. Raptopoulos, interim radiologist-in-chief, Department of Radiology and director, CT services, Beth Israel Deaconess Medical Center. "We are grateful to be one of the first teaching hospitals in the United States using this advanced technology."

Toshiba's Aquilion ONE dynamic volume CT system utilizes 320 ultra-high resolution detector rows (0.5 mm in width) to image an entire organ in a single gantry rotation. The result is unparalleled in diagnostic imaging today and produces a 4D clinical video showing up to 16 cm of anatomical coverage, enough to capture the entire brain or heart, and show its movement such as blood flow.

"The Aquilion ONE has the potential to provide a single, comprehensive exam that can replace a variety of duplicative and invasive procedures," added Dr. Raptopoulos. "Its versatility and ability to diagnose disease fast will be used within our radiology department to detect and treat life-threatening conditions, including cancer, heart disease, stroke and other neurovascular conditions."

To get impressed, head on to the Aquilion ONE Clinical Movie Theatre at Toshiba, and check out some of the studies presented there...

Product page: Aquilion ONE...

Here's what Philips says about its Brilliance iCT with Essence technology:

... customers tout the system’s ability to provide greater dimension and depth across a range of clinical areas such as whole brain perfusion, cardiac CT with Step & Shoot technology that images the heart in two beats while reducing dose, head and neck angiography, full field of view lung studies, virtual colonoscopy and abdominal and pelvic imaging. Brilliance iCT with Essence technology offers an impressive combination of speed, power and coverage to improve image quality while incorporating the latest dose reduction technology. Overall patient experience is improved through shorter scan times.

In addition to the 256 slice intelligent Brilliance iCT, the Brilliance 64-channel configuration is also designed with Essence technology. Unique and proprietary to Philips, Essence technology brings advances to the X-ray tube, detector system, and reconstruction engine while offering a scalable platform to enhance image quality and dose efficiencies.

“With Brilliance iCT, the superb image quality aids our clinicians in the diagnosis of complicated health conditions,” said Dr. Nathan Peled, head department of radiology of Carmel Medical Center in Haifa, Israel. “The system has delivered increased rotation speeds and improved image quality and clinical performance for diagnostic confidence in routine and advanced radiological imaging.”

Below you can find the technical backgrounder paper distributed by the company:

Product page: Brilliance iCT...

Press release: Philips accelerates plans to install Brilliance iCT around the world...

The online database brings together data on all the known somatic mutations (tumor derived - tumor specific) in a molecule called epithelial growth factor receptor (EGFR). Somatic mutations in this cell-surface molecule are known to affect treatment with the newer tyrosine kinase inhibitor class of drugs.

"We have known for some time that some EGFR mutations correlate with response to tyrosine kinase inhibitors for lung cancer patients," says Dr. Samuel Murray from Department of Molecular Pathology and Translational Oncology, Metropolitan Hospital, Athens, Greece. "But there have been so many articles published on this topic that we felt that it would be virtually impossible for any given center or individual to interpret the clinical relevance of a given mutation."

"So we worked on the assumption that a comprehensive list of all somatic EGFR mutations coupled with data on the response of non-small-cell lung cancers treated with tyrosine kinase inhibitors (TKIs) would help clinicians determine whether a specific mutation was likely to correlate with clinical benefit."

The database includes cumulative data from thousands of patients. In addition, independent patient data (IPD) for patients who have been treated with tyrosine kinase inhibitors and some who have not, is being added. A total of 12,244 patients are included, of whom 3,381 had somatic mutations in EGFR. The researchers catalogued 254 different mutations.

Ultimately, the database offers a chance to improve treatment for people receiving tyrosine kinase inhibitors. "We believe that for the more common mutations the database allows clinicians to make more robust decisions concerning their treatment options for NSCLC," says Dr. Murray.

EGFR Mutations Database...

Press release: Mutation database helps personalized treatment of lung cancer