scholarly journals Carbon Ion Radiotherapy Evokes a Metabolic Reprogramming and Individualized Response in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Renli Ning ◽  
Yulei Pei ◽  
Ping Li ◽  
Wei Hu ◽  
Yong Deng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Principal Component ◽  
Metabolic Reprogramming ◽  
Carbon Ion Radiotherapy ◽  
Arginine Biosynthesis ◽  
Metabolic Pathway Analysis ◽  
Urine Metabolites ◽  
Carbon Ion ◽  
Metabolite Profiles ◽  
The Impact

Introduction: Carbon ion radiotherapy (CIRT) is a novel treatment for prostate cancer (PCa). However, the underlying mechanism for the individualized response to CIRT is still not clear. Metabolic reprogramming is essential for tumor growth and proliferation. Although changes in metabolite profiles have been detected in patients with cancer treated with photon radiotherapy, there is limited data regarding CIRT-induced metabolic changes in PCa. Therefore, the study aimed to investigate the impact of metabolic reprogramming on individualized response to CIRT in patients with PCa.Materials and Methods: Urine samples were collected from pathologically confirmed patients with PCa before and after CIRT. A UPLC-MS/MS system was used for metabolite detection. XCMS online, MetDNA, and MS-DIAL were used for peak detection and identification of metabolites. Statistical analysis and metabolic pathway analysis were performed on MetaboAnalyst.Results: A total of 1,701 metabolites were monitored in this research. Principal component analysis (PCA) revealed a change in the patient's urine metabolite profiles following CIRT. Thirty-five metabolites were significantly altered, with the majority of them being amino acids. The arginine biosynthesis and histidine metabolism pathways were the most significantly altered pathways. Hierarchical cluster analysis (HCA) showed that after CIRT, the patients could be clustered into two groups according to their metabolite profiles. The arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis pathways are the most significantly discriminated pathways.Conclusion: Our preliminary findings indicate that metabolic reprogramming and inhibition are important mechanisms involved in response to CIRT in patients with PCa. Therefore, changes in urine metabolites could be used to timely assess the individualized response to CIRT.

scholarly journals Carbon-ion Evokes Metabolic Reprogramming and Individualized Response in Prostate Cancer

2021 ◽  
Author(s):  
Yulei Pei ◽  
Renli Ning ◽  
Ping Li ◽  
Wei Hu ◽  
Yong Deng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
High Throughput ◽  
Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
Pathway Enrichment Analysis ◽  
Arginine Biosynthesis ◽  
Metabolic Pathway Analysis ◽  
Urine Metabolites ◽  
Carbon Ion

Abstract Background: Carbon ion radiotherapy (CIRT) is a novel and powerful tool for prostate cancer (PCa). However, the underlying mechanism for individualized treatment response after CIRT was not clear, and there was still no effective indicator to timely demonstrate the treatment response. Metabolic reprogramming is one of the main hallmarks of malignancy. Metabolic status might have a high relationship with the radiosensitivity and the individualized radiation response. The significant changes of metabolites profiles were detected after radiotherapy in the serum sample of different malignancies. But there was limited data regarding CIRT induced metabolic changes in prostate cancer. Our aim was to preliminary investigate the carbon-ion induced metabolic reprogramming in PCa patients and the individualized response of PCa patients to carbon ion. Methods: Urine samples collected from 15 pathology confirmed PCa patients before and after CIRT were enrolled into this analysis. High-throughput UPLC-MS/MS system was used for metabolites detection. XCMS online, MetDNA and MSDIAL were used for peak detection and identification of metabolites. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.Results: A total of 1701 metabolites were monitored by high-throughput UPLC-MS/MS and 217 metabolites were identified. The PCA scores plot revealed clear discrimination of the patient’s urine metabolites profiles before (pre-CIRT) and after (pre-CIRT) CIRT treatment. 35 metabolites significantly altered after CIRT, and these metabolites mainly were amino acid. Pathway enrichment analysis further identified these metabolites could be enriched in 8 pathways (FDR<0.05, impact>2), while arginine biosynthesis and histidine metabolism pathways were the most significant. In addition, the HCA shows that after CIRT, the patients can be clustered into two groups according to the metabolites profiles. The discriminatory metabolites after CIRT in patients urine mainly enriched in the pathway of arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis. Conclusion: Metabolic reprogramming and metabolic inhibition seems one of the most important mechanisms of CIRT to cure PCa. Urine metabolites also showed their potentials to timely identify the individualized response of PCa patients to CIRT.

scholarly journals Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhei Miyasaka ◽  
Hidemasa Kawamura ◽  
Hiro Sato ◽  
Nobuteru Kubo ◽  
Tatsuji Mizukami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Therapeutic Benefit ◽  
Carbon Ion Radiotherapy ◽  
Safety And Efficacy ◽  
Carbon Ion ◽  
Grade 3 ◽  
Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

scholarly journals Prostate-Specific Antigen Dynamics After Carbon Ion Radiotherapy for Prostate Cancer

2020 ◽  
Author(s):  
Yosuke Takakusagi ◽  
Takahiro Oike ◽  
Kio Kano ◽  
Wataru Anno ◽  
Keisuke Tsuchida ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Carbon Ion Radiotherapy ◽  
Clinical Recurrence ◽  
Carbon Ion ◽  
Psa Bounce ◽  
Psa Failure ◽  
Risk Prostate Cancer

Abstract Background This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Methods Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria.Results The median patient age was 68 (range, 48–81) years. The median follow-up duration was 33 (range, 20–48) months. The clinical T stage was T1c, T2a, and T2b in 26, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33–19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2–116) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6–30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15–33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age was a significant predictor of PSA bounces and PSA failure. Conclusions The dynamics of PSA levels after CIRT was investigated in the present study. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

scholarly journals Prostate-specific antigen dynamics after neoadjuvant androgen-deprivation therapy and carbon ion radiotherapy for prostate cancer

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241636
Author(s):  
Yosuke Takakusagi ◽  
Takahiro Oike ◽  
Kio Kano ◽  
Wataru Anno ◽  
Keisuke Tsuchida ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion ◽  
Younger Age ◽  
Psa Bounce ◽  
Psa Failure

Background This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Methods Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria. Results The median patient age was 68 (range, 48–81) years. The median follow-up duration was 33 (range, 20–48) months. The clinical T stage was T1c, T2a, and T2b in 27, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33–19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2–117) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6–30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15–33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age and lower T stage were significant predictors of PSA bounce. Younger age was a significant predictor of PSA failure. Conclusions In this study, we identified the significant predictors of the occurrence of PSA bounce and failure. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

scholarly journals Five-year quality of life assessment after carbon ion radiotherapy for prostate cancer

2017 ◽  
Vol 58 (2) ◽  
pp. 260-266 ◽  
Author(s):  
Katsuya Maruyama ◽  
Hiroshi Tsuji ◽  
Takuma Nomiya ◽  
Hiroyuki Katoh ◽  
Hitoshi Ishikawa ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Life Assessment ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion ◽  
Trial Outcome Index ◽  
Related Quality ◽  
Health Related ◽  
Outcome Index

Abstract The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63–66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted.

Advancement in Hypofractionation of Carbon Ion Radiotherapy for Prostate Cancer

2009 ◽  
Vol 75 (3) ◽  
pp. S554
Author(s):  
H. Tsuji ◽  
T. Okada ◽  
S. Sugahara ◽  
T. Kamada ◽  
H. Kato ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion
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