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This retrospective study is to assess the performance of 18 F-Fluciclovine PET/CT in prostate cancer (PC) patients with multiple treatment failures and prostate-specific antigen (PSA) ≤ 0.5 ng/mL. PC patients with multiple treatment failures who had PSA level within 2-week interval of 18 F-Fluciclovine PET/CT (PSA PET ) ≤ 0.5 ng/mL were identified in retrospective review of our institution's database (n=28). Patient, tumor, treatment, PSA and castration characteristics as well as findings on 18 F-Fluciclovine PET/CT were collected and compared between positive and negative 18 F-Fluciclovine PET/CT subgroups by using Fisher's exact test. The overall detection rate of 18 F-Fluciclovine PET/CT was 7 of 28 studies (25%). PSA PET > 0.2 ng/mL was associated with higher detection rates in all (33.3 vs 10%, P =0.172), castration-resistant (CR) (50 vs 20%, P =0.343) and castration-sensitive (CS) (28.6 vs 0%, P =0.179) patients. Sites of recurrence were local 42.9% (3/7), nodal 42.9% (3/7) and bone metastases 14.3% (1/7). Higher Gleason score (GS 8-10) (33.3 vs 14.5%, P =0.396), advanced tumor stage (T3-T4) (35.7 vs 20%, P =0.653), second-line androgen deprivation therapy (ADT) uses (66.7 vs 20%, P =0.145), chemotherapy uses (50 vs 23.1%, P =0.444) and CRPC (33.3 vs 21.1%, P =0.483) related to positivity of 18 F-Fluciclovine PET/CT but none reached statistical significance. Performance of 18 F-Fluciclovine PET/CT in prostate cancer patients with multiple treatment failures and PSA PET ≤ 0.5 ng/mL was acceptable particularly in patients with PSA PET ≥ 0.3 ng/mL, CRPC, initial GS ≥ 8 or T3-T4., Competing Interests: None., (AJNMMI Copyright © 2021.)

Precision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.gov: NCT02152254), and 69 patients met the criteria for randomization. Tumor board and multidisciplinary review of molecular alterations optimized treatment selection. From 5/2014 to 4/2017, 320 patients (median age, 63 years; men, 47%) had tumor molecular aberrations, and 213 (66.56%) received anticancer therapy. The most frequently mutated genes were TP53 (42%), KRAS (16%), PIK3CA (12%), and CDKN2A (11%). The median OS was 10.9 months (95% CI, 8.8-12.9). OS was shorter in patients with higher tumor mutational burden. Independent factors associated with shorter OS were age ≥60 years, liver metastases, low albumin levels, high LDH levels, and KRAS and TP53 mutations. Outcomes for randomized patients will be reported after completion of the study.

When we aspire to cure cancer, we may need to search no further than a curable cancer, such as Germ Cell Tumor of the Testis (TGCT). After all, a germ cell is a primordial stem cell. Importantly, TGCT provides a classic stem cell model of cancer that teaches us some invaluable lessons about curing other intractable solid tumors. The intrinsic intratumoral heterogeneity of TGCT alludes to its stem-ness origin and nature. Which implicates the existence of putative lethal TGCT subtypes-the identification and detection of which may further enhance the cure rate and improve the therapeutic ratio of TGCT. In this Mini review, we discuss about the role of biologic insights, clinical lessons, and therapeutic strategies in drug and therapy development. We illustrate some clinical pearls and perils when it concerns drug versus therapy development in the cure and care of patients with TGCT. In many respects, we have cured more TGCT patients when we apply multimodal therapy rather than targeted therapy and integrated medicine rather than precision medicine. In principle and in practice, this is the implication of therapy versus drug development in improving the overall outcome and cure rate of patients with cancer.

Renal cell carcinoma bone metastases (RCCBM) are typically osteolytic. We previously showed that BIGH3 (beta Ig-h3/TGFBI), secreted by 786-O renal cell carcinoma, plays a role in osteolytic bone lesion in RCCBM through inhibition of osteoblast (OSB) differentiation. To study this interaction, we employed three-dimensional (3D) hydrogels to coculture bone-derived 786-O (Bo-786) renal cell carcinoma cells with MC3T3-E1 pre-OSBs. Culturing pre-OSBs in the 3D hydrogels preserved their ability to differentiate into mature OSB; however, this process was decreased when pre-OSBs were cocultured with Bo-786 cells. Knockdown of BIGH3 in Bo-786 cells recovered OSB differentiation. Furthermore, treatment with bone morphogenetic protein 4, which stimulates OSB differentiation, or cabozantinib (CBZ), which inhibits VEGFR1 and MET tyrosine kinase activities, also increased OSB differentiation in the coculture. CBZ also inhibited pre-osteoclast RAW264.7 cell differentiation. Using RCCBM mouse models, we showed that CBZ inhibited Bo-786 tumor growth in bone. CBZ treatment also increased bone volume and OSB number, and decreased osteoclast number and blood vessel density. When tested in SN12PM6 renal cell carcinoma cells that have been transduced to overexpress BIGH3, CBZ also inhibited SN12PM6 tumor growth in bone. These observations suggest that enhancing OSB differentiation could be one of the therapeutic strategies for treating RCCBM that exhibit OSB inhibition characteristics, and that this 3D coculture system is an effective tool for screening osteoanabolic agents for further in vivo studies., (©2020 American Association for Cancer Research.)

Purpose: The aim of this study was to investigate the imaging diagnostic performance of F-fluciclovine PET/CT and pelvic multiparametric MRI (mpMRI) for prostate cancer in the setting of rising PSA after initial treatment, with a focus on detection of recurrent and metastatic prostate cancer in the pelvis., Methods: Patients with prostate cancer who had fluciclovine PET and pelvic mpMRI between October 2017 and October 2018 in our center were retrospectively reviewed. Patients were included if they had fluciclovine PET/CT and mpMRI within a 3-month interval. Patients were excluded if they had separate concurrent cancer or if the PSA were more than 2-fold difference with an absolute difference more than 1 ng/mL between the 2 image studies. For each eligible patient, we compared all abnormal lesions identified on either scan. The findings were verified by pathology or other imaging techniques within minimal 10-month clinical follow-up., Results: A total of 129 patients with 129 paired tests were included in this study. Fluciclovine PET/CT and pelvic MRI had a high degree of concordance (121/129, 93.8%). The sensitivity, specificity, positive predictive value, and negative predictive value for fluciclovine PET/CT and mpMRI were 96.6%, 94.3%, 93.4%, and 97%, and 91.5%, 95.7%, 94.7%, and 93%, respectively. There were no statistical significant differences in diagnostic performance between the 2 imaging tests. Among the 8/129 discordant cases, although fluciclovine PET/CT provided definitive diagnosis when mpMRI was equivocal due to paramagnetic artifacts from fiducial markers and detected normal-sized regional lymph nodes, mpMRI detected subcentimeter periurethral recurrence and clarified physiological urinary artifacts that was not appreciated on fluciclovine PET/CT., Conclusions: Our single-center study demonstrated that fluciclovine PET/CT has similar diagnostic performance with pelvic mpMRI in detecting recurrent/metastatic prostate disease in the pelvis in the setting of rising PSA after initial treatment. Moreover, fluciclovine PET/CT and mpMRI have different implications in different clinical scenario; each test has its own limitation and pitfalls, but can be complementary to each other.

Introduction: Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment., Patients and Methods: Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution. We assessed absolute neutrophil count recovery, incidence of neutropenia, neutropenic fever, antibiotic usage, treatment delays or discontinuation, dose reduction, and hospitalization with pegfilgrastim administration. Radiologists blinded to therapy reviewed computed tomography scans to detect urinary tract inflammation., Results: The median patient age was 69 years (range, 41-88 years); 78% of patients were white, and 54% had a Gleason score ≥ 9. Median overall survival was 9 months (95% confidence interval, 8-11 months). One patient (< 1%) had neutropenia; 38 patients (25%) had infection. During cycle 1, a significantly higher proportion of patients receiving pegfilgrastim after 24 hours developed infection than did those receiving pegfilgrastim the same day (26% vs. 6%; P = .01)., Conclusion: Same-day pegfilgrastim administration after cabazitaxel treatment with or without carboplatin in patients with mCRPC is feasible. The urinary tract inflammation rate (21%) was higher than that reported anecdotally. Results need to be prospectively validated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Acute care is usually associated with disease progression, treatments for cancer, and medical comorbidities. Patients with cancer may develop sudden functional deficits that require rehabilitation. Some of these patients benefit from acute rehabilitation, others benefit from subacute rehabilitation. After acute rehabilitation, continuous care for these patients has not been well described. Three studies are presented to demonstrate that cancer rehabilitation is a continuous process. Rehabilitation professionals should know how to detect fall risk, monitor symptoms, and render symptom management. Patients with cancer often require rehabilitation services during their entire disease trajectory., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: About 10% of tumors derived from nongynecologic, noncoelomic tissues react with the OC125 antibody. Some patients with advanced prostate cancer were found to have elevated serum CA-125 level., Materials and Methods: We examined the clinical history of 11 patients with castration resistant prostate cancer and an elevated serum CA-125 level. Pathological review and immunohistochemical staining were performed on tumors from eight of these patients., Results: Patients with advanced prostate cancer and an elevated serum CA-125 level responded to androgen ablative therapy (median duration, 27 months). They were predisposed to develop persistent or recurrent urinary symptoms and visceral metastases. Eight of 11 patients had a low or undetectable serum prostate-specific antigen level (≤ 4 ng/mL) or an elevated serum carcinoembryonic antigen level (> 6 ng/mL). In 3 of 7 patients whose specimens were available for further review, the tumors contained histologic features compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate., Conclusions: Patients with prostate cancer and an elevated serum CA-125 level have unique clinical and pathologic characteristics. Some of these patients possess tumors compatible with a subtype of prostate cancer known as ductal adenocarcinoma. Additional studies need to be performed to elucidate the biologic basis of the various subtypes of prostate cancer.

Introduction: A small subset of young men die from seminoma. Studying these high risk, clinically atypical seminomas (CASs)-aggressive tumors with visceral metastases and chemotherapy resistance-may provide clues to the nature of drug resistance and the origin of testicular cancers. We explored the possibility that these seminomas are a unique clinical and biologic entity with intrinsic yolk sac tumor (YST) features., Materials and Methods: We assayed available archived tissue samples (n = 22) for chemotherapy-resistance markers found in YSTs. Specifically, we analyzed tissues and clinical histories from patients with CASs (those who had visceral metastases and recurrent disease), classical seminomas, and mixed germ-cell tumors containing YST. By using immunohistochemical testing, we evaluated the expression of bone morphogenetic protein 2, alpha fetoprotein, and glutathione S-transferase (pi) [GST (pi)]., Results: GST (pi) expression significantly predicted for overall survival (p = .036). In addition, according to the results of GST (pi) immunohistochemical staining, the CASs appeared to resemble YSTs more than they did classical seminomas (p = 0.043). Less-advanced tumors, both those that expressed GST (pi) and those that were negative for GST (pi), were more amenable to local therapies, and the patients who had those tumors had better clinical outcomes., Conclusions: Results from this exploratory study suggest that certain CASs that express GST (pi) are more similar to YST than they are to classical seminomas, and that GST (pi) expression may be able to be used as a prognosticator of disease-specific survival. Such CASs thus may have a unique biologic origin that differs from that of classical seminomas. Additional studies are needed to determine the natural history and therapeutic implications of these CASs.

Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.

Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy.

Prostate cancer is the most common cancer among men in the United States. Advanced prostate cancer has a particular propensity to metastasize to bone, where it produces predominantly osteoblastic lesions and local bone formation. The tropism for bone is thought to be due in part to specific interactions between the prostate cancer cells and cells present in the bone environment, particularly the bone marrow endothelial cells and osteoblasts. Such interactions involve numerous signaling pathways that could serve as targets for new therapeutic agents. Because androgen directly influences the proliferation and metastasis of prostate cancer cells, the current first-line treatment for metastatic prostate cancer is androgen deprivation therapy. Subsequent therapies include chemotherapy and radiation therapy. New molecular therapies are being developed to target specific steps in the metastatic process. However, as yet none of these therapies has radically improved survival. Nonetheless, it is hoped that with better understanding of the biology of the disease, combination therapy that addresses multiple pathways that support the progression of prostate cancer in bone could significantly improve the survival and quality of life of men with prostate cancer.

Prostate cancer (PCa) is the most common malignancy in men. Although mortality from PCa has been declining over the past decade, metastasis can substantially shorten survival time and remains a major challenge in maintaining quality of life for survivors. PCa cells preferentially metastasize to bone and typically result in osteoblastic lesions. In the late stages of disease, however, osteolytic lesions are observed. The mechanisms of PCa bone metastasis are still unclear, but relationships between the PCa cells and the bone tissue elements are suspected of being more complex than initially thought. Far from being an innocent bystander, the bone participates actively in the metastatic process and provides the cancer cells with growth factors and a fertile environment. Among the various cells in the bone environment, osteoblasts have a central role through their bidirectional interactions with the PCa cells. This review discusses the possible mechanisms of PCa bone metastasis and highlights the essential role of osteoblasts in the metastasis of PCa to bone.