Carryn M. Anderson

Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

Development of an implantable artificial lung : Challenges and progress

Unlike dialysis, which functions as a bridge to renal transplantation, or a ventricular assist device, which serves as a bridge to cardiac transplantation, no suitable bridge to lung transplantation exists. Our goal is to design and build an ambulatory artificial lung that can be perfused entirely by the right ventricle and completely support the metabolic O2 and CO2 requirements of an adult. Such a device could realize a substantial clinical impact as a bridge to lung transplantation, as a support device immediately post-lung transplant, and as a rescue and/or supplement to mechanical ventilation during the treatment of severe respiratory failure. Research on the artificial lung has focused on the design, mode of attachment to the pulmonary circulation, and intracorporeal versus paracorporeal placement of the device.

Adjuvant therapy for resected extrahepatic cholangiocarcinoma: A review of the literature and future directions

Cholangiocarcinoma is a rare neoplasm originating from the intra- or extrahepatic bile duct epithelium. Incidence has been increasing worldwide in the last three decades. Complete surgical resection provides the only possibility of cure, but even with resection 5-yr survival can be as low as 11%. Adjuvant therapy has the potential to play a crucial role in prolonging survival and local control. Retrospective series have suggested benefit to adjuvant radiation, chemotherapy or concurrent chemo-radiation. The scarce prospective data has not shown a survival benefit to adjuvant therapy. In this article we review and summarize the published data regarding adjuvant therapy for resected extrahepatic cholangiocarcinoma. Prospective, multi-institutional randomized trials are needed to clarify the role of adjuvant therapy in this disease.

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PURPOSE To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. METHODS AND MATERIALS Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. RESULTS After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. CONCLUSION Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.

Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system.

PURPOSE To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd(2)O(2)S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to which the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. METHODS A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision(TM) image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. RESULTS For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10(- 8)), 1.64 (p < 10(- 13)), 2.66 (p < 10(- 9)), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. CONCLUSIONS Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.

Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial

Adenoid cystic carcinomas (ACCs) are malignant salivary gland tumors noteworthy for high rates of late failure with limited salvage therapy options. We have previously shown increased Akt signaling is common in ACC and the human immunodeficiency virus (HIV) protease inhibitor nelfinavir (NFV) inhibits in vitro tumor growth by suppressing Akt signaling. This phase II trial was conducted to determine progression‐free survival in response to NFV in patients with recurrent/endstage ACC who have failed standard therapies.

Change of maximum standardized uptake value slope in dynamic triphasic [18F]-fluorodeoxyglucose positron emission tomography/computed tomography distinguishes malignancy from postradiation inflammation in head-and-neck squamous cell carcinoma: a prospective trial.

PURPOSE To evaluate dynamic [(18)F]-fluorodeoxyglucose (FDG) uptake methodology as a post-radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG-positron emission tomography/computed tomography (FDG-PET/CT). METHODS AND MATERIALS We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV(max)) of regions of interest were measured at 60, 90, and 120 minutes. The SUV(max) slope between 60 and 120 minutes and change of SUV(max) slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up. RESULTS A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV(max) slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV(max) ≥2.5 (P=.02). CONCLUSIONS The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV(max) slope, accurately distinguishing tumor from inflammation on positive and equivocal scans.

Low Dose Irradiation for Diffuse Choroidal Hemangioma

Sturge-Weber Syndrome is a nonheritable congenital syndrome characterized by a “port-wine stain” on the face and angioma of the meninges. Ocular findings include diffuse choroidal hemangioma, retinal detachment, and various types of glaucoma. Management of diffuse choroidal hemangioma is aimed at preserving the affected eye and preventing glaucoma. In the past this has been challenging. Herein, we describe a case of Sturge-Weber Syndrome with diffuse choroidal hemangioma which was successfully treated with low dose lens-sparing external beam radiotherapy.

Influence of body composition on survival in patients with head and neck cancer

Recent evidence has suggested links between obesity and outcomes for various types of cancer. This study investigates the impact that body composition has on survival in patients with head and neck cancer.

Laryngeal Chloroma Heralding Relapse of Acute Myeloid Leukemia

Introduction Granulocytic sarcomas, also referred to as chloromas or myeloid sarcomas, are extramedullary neoplasms that are composed of immature myeloidcells.Thetermchloromareferstothegreencolorthat is imparted to the tissues as a result of the high concentration of myeloperoxidase foundwithinthetumorcells. These tumors typicallyoccur inassociation with nonlymphocytic leukemias or myelodysplastic syndromes, and their development may precede or coincide with relapse of systemic disease. Although the exact incidence is unknown, they are relatively uncommon, occurring in less than 10% of cases of acute myeloid leukemia (AML). Despite the facts that granulocytic sarcomas can occur in almost any organ and the head and neck are frequently reported sites, laryngeal involvement has rarely been cited in the medical literature. Here we report the unusual clinical presentation and management of a laryngeal granulocytic sarcoma that heralded relapse of AML.