Stereotactic body radiotherapy for bone oligometastatic disease in prostate cancer

Patel, Priyanka; Chaw, C.L.; Tree, A.; Sharabiani, Mansour T. A.; As, Nicholas van

doi:10.1007/s00345-019-02873-w

Cited by 31 publications

(25 citation statements)

References 27 publications

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“…Grade 3 adverse events were observed in one patient (3%) [21]. Muldermans et al reported LC at 2 years of 82% after treating 69 patients with 81 metastases-88% received SFRS with a median dose of 16 Gy (range: [16][17][18][19][20][21][22][23][24] [37]. Seventy percent of patients were staged with choline PET/ CT.…”

Section: Plos Onementioning

confidence: 99%

“…One-year local control (LC) rates reported after fractionated stereotactic body radiotherapy (fSBRT) for patients with oligometastatic prostate cancer vary from 93-100%. Besides, no grade �3 adverse events have been observed [18][19][20]. In this regard, single fraction radiosurgery (SFRS) is particularly attractive, since LC rates seem to be equally effective but treatment is delivered in a single session [21].…”

Section: Introductionmentioning

confidence: 99%

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68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

et al. 2020

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Background Androgen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated. Methods Patients with �5 metastases from OMPC, with/without ADT treated with PSMA-PET/CTbased SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS). Results Fifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients,

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Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

et al. 2020

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“…The cellular response of tumour cells to DNA damage treatment can be related to an underlying genetic background and can itself markedly alter gene expression to effect differential phenotypic behaviour ( 5 , 6 ). Crucially, RT is no longer restricted to use in the treatment of local disease but is becoming a viable therapeutic option for advanced disease, with clinical trials currently evaluating the potential use of stereotactic RT to treat oligometastatic CaP ( 7–9 ). The extended deployment of radiation as an intervention across the continuum of the clinical landscape accentuates the requirement to optimize this treatment modality.…”

Section: Introductionmentioning

confidence: 99%

Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

et al. 2020

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Abstract Functional impairment of the tumour suppressor PTEN is common in primary prostate cancer and has been linked to relapse post-radiotherapy (post-RT). Pre-clinical modelling supports elevated CXC chemokine signalling as a critical mediator of PTEN-depleted disease progression and therapeutic resistance. We assessed the correlation of PTEN deficiency with CXC chemokine signalling and its association with clinical outcomes. Gene expression analysis characterized a PTENLOW/CXCR1HIGH/CXCR2HIGH cluster of tumours that associates with earlier time to biochemical recurrence [hazard ratio (HR) 5.87 and 2.65, respectively] and development of systemic metastasis (HR 3.51). In vitro, CXCL signalling was further amplified following exposure of PTEN-deficient prostate cancer cell lines to ionizing radiation (IR). Inhibition of CXCR1/2 signalling in PTEN-depleted cell-based models increased IR sensitivity. In vivo, administration of a CXCR1/2-targeted pepducin (x1/2pal-i3), or CXCR2-specific antagonist (AZD5069), in combination with IR to PTEN-deficient xenografts attenuated tumour growth and progression compared to control or IR alone. Post-mortem analysis confirmed that x1/2pal-i3 administration attenuated IR-induced CXCL signalling and anti-apoptotic protein expression. Interventions targeting CXC chemokine signalling may provide an effective strategy to combine with RT in locally advanced prostate cancer patients with known presence of PTEN-deficient foci.

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“…The cellular response of tumor cells to DNA-damage treatment can be related to an underlying genetic background and can itself markedly alter gene expression to effect differential phenotypic behaviour (Kumareswaran, Ludkovski et al, 2012, Taiakina, Dal Pra et al, 2014). Crucially, RT is no longer restricted to use in the treatment of local disease but is becoming a viable therapeutic option for advanced disease, with clinical trials currently evaluating the potential use of stereotactic RT to treat oligometastatic CaP (Muldermans, Romak et al, 2016, Ost, Jereczek-Fossa et al, 2016, Patel, Chaw et al, 2019). The extended deployment of radiation as an intervention across the continuum of the clinical landscape accentuates the requirement to optimize this treatment modality.…”

Section: Introductionmentioning

confidence: 99%

Targeting CXCR1 and CXCR2 to overcome radiotherapy resistance in PTEN-deficient prostate carcinoma

Ong

et al. 2020

Preprint

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Functional impairment of the tumour-suppressor PTEN is common in primaryprostate cancer and has been linked to relapse post-radiotherapy (RT). Pre-clinical modelling supports elevated CXC-chemokine signaling as a critical mediator of PTEN-depleted disease progression and therapeutic resistance. We assessed the correlation of PTEN-deficiency with CXC-chemokine signaling and its association with clinical outcomes. Gene expression analysis characterized a PTEN LOW /CXCR1 HIGH /CXCR2 HIGH cluster of tumors that associates with earlier timeto-biochemical recurrence (HR 5.87 and HR 2.65 respectively) and development of systemic metastasis (HR 3.51). In vitro, CXCL-signaling was further amplified following exposure of PTEN-deficient prostate cancer cell lines to ionizing radiation (IR). Inhibition of CXCR1/2-signaling in PTEN-depleted cell-based models increased IR-sensitivity. In vivo, administration of a CXCR1/2-targeted pepducin (x1/2pal-i3), orCXCR2-specific antagonist (AZD5069), in combination with IR to PTEN-deficient xenografts attenuated tumor growth and progression compared to control or IR alone. Post-mortem analysis confirmed that x1/2pal-i3 administration attenuated IRinduced CXCL-signaling and anti-apoptotic protein expression. Interventions targeting CXC-chemokine signaling may provide an effective strategy to combine with radiotherapy, in both locally-advanced and oligometastatic-prostate cancers, with known presence of PTEN-deficient foci.Thus, we adopted the hypothesis that exposure to ionizing radiation (IR) would similarly induce chemokine-signaling and that this would have a profound impact in modulating the sensitivity of PTEN-deficient tumors to radiation.The objective of this comprehensive study, employing clinical datasets and established in vitro and in vivo models, was to characterize whether stress-induced potentiation of CXCR1/2-signaling may underpin the adverse response of PTENdeficient prostate cancer to radiation and to potentially explain biological mechanisms related to increased clinical relapse reported in PTEN-deficient tumors. MATERIALS AND METHODS Cell cultureAuthenticated DU145, LNCaP, C42, C42B, PC3 and 22Rv1 CaP cells were obtained from ATCC. DU145 cells were manipulated as previously described to generate isogenic PTEN-expressing NT01 cells and PTEN-deficient sh11.02 cells (Maxwell et al., 2013). PC3 were manipulated as previously described so that PTEN-expression can be reconstituted following exposure to tetracycline (Maxwell et al., 2013). PTENdepleted 22RV1 cells were generated following lentiviral transfection of HuSh-29 pre-designed PTEN shRNA pGFP-V-RS constructs (Origene, Rockville, MD, USA), and selected under puromycin selection pressure at a final concentration of 0.5 μg/ml. Cell line authenticity was confirmed by STR genotyping (July 2019) and mycoplasma testing was performed every 4-6 weeks (MycoAlert, Lonza). ELISACells were plated into six-well plates at a density of 5 x 10 5 cells per well and allowed to adhere overnight. After 24H, cells were irradiated and med...

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Stereotactic body radiotherapy for bone oligometastatic disease in prostate cancer

Cited by 31 publications

References 27 publications

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

Targeting CXCR1 and CXCR2 to overcome radiotherapy resistance in PTEN-deficient prostate carcinoma

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