Prostate bed localization with image-guided approach using on-board imaging: reporting acute toxicity and implications for radiation therapy planning following prostatectomy.

OBJECTIVES: To report our experience using Image-Guided Radiation Therapy (IGRT) in patients undergoing post-prostatectomy irradiation. METHODS: Twenty-six patients were treated with radiotherapy following radical prostatectomy using Intensity Modulated Radiation Therapy (IMRT). Prostate bed localization was done using image guidance to align surgical clips relative to the reference isocenter on the planning digitally reconstructed radiographs. Assuming surgical clips to be surrogate for prostate bed, daily shifts in their position were calculated after aligning with the bony anatomy. Shifts were recorded in three dimensions. The acute toxicity was measured during and after completion of treatment. RESULTS: The average (standard deviation) prostate bed motion in anterior-posterior, superior-inferior and left-right directions were: 2.7mm (2.1), 2.4mm (2.1) and 1.0mm (1.7), respectively. The majority of patients experienced only grade 1 symptoms, two patients had grade 2 symptoms and none had grade 3 or higher acute toxicity. CONCLUSIONS: Daily IGRT is recommended for accurate target localization during radiation delivery to improve efficacy of treatment and enhance therapeutic ratio. Larger studies with longer follow-up are necessary to make definitive recommendations regarding magnitude of margin reduction around clinical target volume.

Potential attenuation of disease progression in recurrent prostate cancer with plant-based diet and stress reduction.

A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic. While hormonal therapy may slightly extend survival in a minority of patients, it is not curative and produces side effects including hot flashes, decreased libido, and loss of bone mass. Alternatively, dietary modification may offer an important tool for clinical management. Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment. Conversely, many elements of plant-based diets have been associated with reduced risk of progression. However, dietary modification can be stressful and difficult to implement. We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet, reinforced by stress management training, could attenuate the rate of further PSA rise. Urologists at the University of California, San Diego, and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer. A pre-post design was employed in which each patient served as his own control. Rates of PSA rise were ascertained for each patient for the following periods: from the time of posttreatment recurrence up to the start of the study (prestudy) and from the time immediately preceding the intervention (baseline) to the end of the intervention (0-6 months). There was a significant decrease in the rate of PSA rise from prestudy to 0 to 6 months (P < .01). Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study. Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times. Median PSA doubling time increased from 11.9 months (prestudy) to 112.3 months (intervention). These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer.

Minimally invasive sentinel lymph node mapping of the pig colon with Lymphoseek.

BACKGROUND: Minimally invasive surgery and sentinel node mapping are being utilized increasingly in colon cancer surgery. Making these techniques efficient and easy to perform will be essential for the future of this and other gastrointestinal operations. The purpose of this study was to test a new laparoscopic gamma detection probe for minimally invasive sentinel node mapping of the colon, while utilizing Lymphoseek, a radiopharmaceutical specifically designed for sentinel lymph node (SLN) detection. METHODS: Eight anesthetized pigs received an endoscopic co-injection of Lymphoseek and Isosulfan Blue in the colon. The laparoscopic gamma detector, inserted via a 12-mm trocar, was used to identify radioactive sentinel lymph nodes. The reliability of the side-viewing probe was tested using a radioactive source. All blue and radioactive lymph nodes were excised and the signal-to-background ratio (S/B) and percent of injected dose (%ID) were measured. RESULTS: The probe was easy to maneuver and led to efficient visualization of the radioactive node. The side port allowed for better distinction between injection site scatter and sentinel node activity. The reliability of the probe was validated by an identification rate of 97%. At least one SLN was detected for each pig; two SLNs were detected in two pigs. All SLNs were stained blue. The SLN S/B ranged from 38 to 315 and the %ID ranged from 0.06% to 2.01%. Sentinel nodes were found within 10 minutes. CONCLUSIONS: Minimally invasive sentinel node mapping with the radiopharmaceutical Lymphoseek and a side-viewing gamma detector yielded high S/B and directionality for accurate mapping of gastrointestinal sentinel lymph nodes within minutes of radiotracer administration.

A preclinical study of prostate sentinel lymph node mapping with [99mTC]diethylenetetramine pentaacetic acid-mannosyl-dextran.

PURPOSE: SLN identification could improve the pathological staging of prostate cancer. Prior SLN studies have been compromised by delayed radiotracer uptake rates and significant diffusion rates out of the sentinel nodes. Lymphoseek is a new radiopharmaceutical specifically designed for SLN mapping. It shows rapid and sustained SLN uptake. MATERIALS AND METHODS: We investigated the use of Lymphoseek for prostate SLN mapping by measuring SLN uptake in 12 anesthetized pigs. The prostate was injected with 0.05 ml of a 1:1 volume per volume mixture of Lymphazurin and 1.0 mCi Lymphoseek (1 nmole). Within 5 to 19 minutes the pelvic lymph nodes were dissected and assayed with a gamma probe. A lymph node was considered a sentinel node if it had count rates that exceeded 10 times the background count. We calculated the percent of injected dose of each lymph node excised and the prostate gland. RESULTS: A total of 35 SLNs were identified in the 12 studies. Of the SLNs 81% were located outside of the obturator fossa in this pig model. The SLN percent of injected dose was 0.05% to 7.75% (mean +/- 1 SD 1.74% +/- 1.92%). The mean percent of injected dose in the prostate was 27% +/- 12%. There was no correlation between the side of SLN and the lobe injected. CONCLUSIONS: After prostate administration of Lymphoseek pelvic SLNs attain high signal-to-background ratios within 10 minutes. This property should permit intraoperative injection and SLN mapping without significantly adding to the duration of prostatectomy. A phase I clinical trial has been initiated, which will later incorporate minimally invasive techniques.

Identification of DNA methylation differences during tumorigenesis by methylation-sensitive arbitrarily primed polymerase chain reaction.

The ability to detect methylation changes associated with oncogenic transformation is of critical importance in understanding how DNA methylation may contribute to tumorigenesis. We have developed a simple and reproducible fingerprinting method called methylation-sensitive arbitrarily primed polymerase chain reaction (AP-PCR) to screen for DNA methylation changes. This technique relies on digesting genomic DNA with methylation-sensitive and -insensitive restriction enzymes (e.g., HpaII and MspI) prior to AP-PCR amplification. Matched normal and tumor DNAs were compared to identify differential methylation. After the PCR products were resolved on high-resolution polyacrylamide gels, regions of genomic DNA that showed hypo- and hypermethylation associated with tumors were detected. These fragments were then isolated, cloned, and sequenced. Novel CpG islands were found to be frequently hypermethylated in bladder and colon tumors. We have demonstrated that this technique is a rapid and efficient method that can be used to screen for altered methylation patterns in genomic DNA and to isolate specific sequences associated with these changes.