Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided High Dose Rate brachytherapy boost

PURPOSE: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. RESULTS: Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. CONCLUSION: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive

Absorbing customer knowledge: how customer involvement enables service design success

Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change

Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies

Abstract Background Cytokines may be elevated in tumor and normal tissues following irradiation. Cytokine expression in these tissues may predict for toxicity or tumor control. The purpose of this pilot study was to determine the feasibility of measuring local salivary cytokine levels using buccal sponges in patients receiving chemo-radiation for head and neck malignancies. Patients and methods 11 patients with epithelial malignancies of the head and neck were recruiting to this study. All patients received radiotherapy to the head and neck region with doses ranging between 60 – 67.5 Gy. Chemotherapy was delivered concurrently with radiation in all patients. Salivary samples were obtained from high dose and low dose regions prior to treatment and at three intervals during treatment for assessment of cytokine levels (IL-4, IL-6, IL-8, IL-10, EGF, MCP-1, TNF-α, and VEGF). Results Cytokine levels were detectable in the salivary samples. Salivary cytokine levels of IL-4, IL-6, IL-8, EGF, MCP-1, TNF- α , and VEGF were higher in the high dose region compared to the low dose region at all time points (p  Conclusion Assessment of salivary cytokine levels may provide a novel method to follow local cytokine levels during radiotherapy and may provide a mechanism to study cytokine levels in a regional manner.</p

Pattern of failure in prostate cancer previously treated with radical prostatectomy and post-operative radiotherapy: a secondary analysis of two prospective studies using novel molecular imaging techniques

Abstract Background Prostate Membrane Specific Antigen (PSMA) positron emission tomography (PET) and multiparametric MRI (mpMRI) have shown high accuracy in identifying recurrent lesions after definitive treatment in prostate cancer (PCa). In this study, we aimed to outline patterns of failure in a group of post-prostatectomy patients who received adjuvant or salvage radiation therapy (PORT) and subsequently experienced biochemical recurrence, using 18F-PSMA PET/CT and mpMRI. Methods PCa patients with biochemical failure post-prostatectomy, and no evident site of recurrence on conventional imaging, were enrolled on two prospective trials of first and second generation 18F-PSMA PET agents (18F-DCFBC and 18F-DCFPyL) in combination with MRI between October 2014 and December 2018. The primary aim of our study is to characterize these lesions with respect to their location relative to previous PORT field and received dose. Results A total of 34 participants underwent 18F-PSMA PET imaging for biochemical recurrence after radical prostatectomy and PORT, with 32/34 found to have 18F-PSMA avid lesions. On 18F-PSMA, 17/32 patients (53.1%) had metastatic disease, 8/32 (25.0%) patients had locoregional recurrences, and 7/32 (21.9%) had local failure in the prostate fossa. On further exploration, we noted 6/7 (86%) of prostate fossa recurrences were in-field and were encompassed by 100% isodose lines, receiving 64.8–72 Gy. One patient had marginal failure encompassed by the 49 Gy isodose. Conclusions 18F-PSMA PET imaging demonstrates promise in identifying occult PCa recurrence after PORT. Although distant recurrence was the predominant pattern of failure, in-field recurrence was noted in approximately 1/5th of patients. This should be considered in tailoring radiotherapy practice after prostatectomy. Trial registration www.clinicaltrials.gov , NCT02190279 and NCT03181867. Registered July 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02190279 and June 8 2017, https://clinicaltrials.gov/ct2/show/NCT03181867

Assessment of Aortoiliac Atherosclerotic Plaque on CT in Prostate Cancer Patients Undergoing Treatment

Traditionally, atherosclerotic risk factors for cardiovascular disease and cancer are assessed using coronary artery calcium scoring. However, this neglects the impact of atherosclerotic disease more proximal to the cancer site. This study assesses whether aortoiliac atherosclerotic plaque is associated with prostate cancer. The dataset consisted of abdominopelvic CT of 93 patients with prostate cancer and 186 asymptomatic patients who underwent CT colonography as an age- and gender-matched control group. Agatston scores were measured in the abdominal aorta, common iliac, and internal iliac arteries. The scores were evaluated for associations with age, Framingham risk score, and prostate cancer-related biomarkers, including prostate-specific antigen, Gleason score, tumor location, prostatectomy, androgen deprivation therapy, mortality, and bone metastasis. The atherosclerotic plaque of prostate cancer patients did not differ from the control group (p = 0.22) and was not correlated with any of the prostate cancer-related biomarkers (p &gt; 0.05). However, Agatston scores of abdominal plaques correlated well with age (p &lt; 0.001) and Framingham risk scores (p = 0.002)

Hyperpolarized [1-(13)C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer in vivo predicts efficacy of targeting the Warburg effect

PURPOSE: To evaluate the potential of hyperpolarized [1-(13)C]-pyruvate magnetic resonance spectroscopic imaging (MRSI) of prostate cancer as a predictive biomarker for targeting the Warburg effect. EXPERIMENTAL DESIGN: Two human prostate cancer cell lines (DU145 and PC3) were grown as xenografts. The conversion of pyruvate to lactate in xenografts was measured with hyperpolarized [1-(13)C]-pyruvate MRSI after systemic delivery of [1-(13)C] pyruvic acid. Steady state metabolomic analysis of xenograft tumors was performed with mass spectrometry and steady state lactate concentrations were measured with proton ((1)H) MRS. Perfusion and oxygenation of xenografts was measured with electron paramagnetic resonance (EPR) imaging with OX063. Tumor growth was assessed after lactate dehydrogenase (LDH) inhibition with FX-11 (42 microg/mouse/day for 5 days x 2 weekly cycles). Lactate production, pyruvate uptake, extracellular acidification rates and oxygen consumption of the prostate cancer cell lines was analyzed in vitro. LDH activity was assessed in tumor homogenates. RESULTS: DU145 tumors demonstrated an enhanced conversion of pyruvate to lactate with hyperpolarized [1-(13)C]-pyruvate MRSI compared to PC3, and a corresponding greater sensitivity to LDH inhibition. No difference was observed between PC3 and DU145 xenografts in steady state measures of pyruvate fermentation, oxygenation, or perfusion. The two cell lines exhibited similar sensitivity to FX-11 in vitro. LDH activity correlated to FX-11 sensitivity. CONCLUSIONS: Hyperpolarized [1-(13)C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect