Landscape of Carbon Ion Radiotherapy in Prostate Cancer: Clinical Application and Translational Research.
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ABSTRACT:
SUBMITTER: Chen X
PROVIDER: S-EPMC8602827 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Carbon-ion irradiation is an emerging therapeutic option for several tumor entities including lung cancer. Well oxygenated tumor areas compared to a hypoxic environment favor therapeutic photon irradiation efficiency of solid tumors due to increased amounts of DNA damage. The resistance of hypoxic tumor areas towards photon irradiation is enhanced through increased HIF-1 signaling. Here, we compared the effects of oxygen and HIF 1 after photon and carbon-ion irradiation with biological equivalent doses in a human non-small lung cancer model. In hypoxia compared to normoxia, A549 and H1299 cells displayed improved survival after photon irradiation. Knockdown of HIF-1α combined with photon irradiation synergistically delayed tumor growth in vivo. Photon irradiation induced HIF-1α and several of its target genes such as PDK1, GLUT-1, LDHA, and VEGF with subsequent enhanced tumor angiogenesis in vivo, a signaling cascade that was not targeted by carbon-ion irradiation. We present evidence that photons but not carbon-ions induce HIF-1α via mTOR pathway. Importantly, after carbon-ion irradiation in vivo, we observed substantial downregulation of HIF-1α and a drastically delayed tumor growth indicating a considerable higher relative biological effectiveness (RBE) than anticipated from the cell survival data. In sum, our results demonstrate that carbon-ions mediate an improved therapeutic response of tumor treatment compared to photon irradiation that is independent of cell oxygenation and HIF-1 signaling.
2014-04-20 | GSE45403 | GEO
Project description:Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by combining it with cancer immunotherapy. Clinical validation of preclinical findings is necessary to further improve the treatment efficacy of carbon ion radiotherapy.
| S-EPMC4899433 | biostudies-literature
Project description:Carbon-ion irradiation is an emerging therapeutic option for several tumor entities including lung cancer. Well oxygenated tumor areas compared to a hypoxic environment favor therapeutic photon irradiation efficiency of solid tumors due to increased amounts of DNA damage. The resistance of hypoxic tumor areas towards photon irradiation is enhanced through increased HIF-1 signaling. Here, we compared the effects of oxygen and HIF 1 after photon and carbon-ion irradiation with biological equivalent doses in a human non-small lung cancer model. In hypoxia compared to normoxia, A549 and H1299 cells displayed improved survival after photon irradiation. Knockdown of HIF-1M-NM-1 combined with photon irradiation synergistically delayed tumor growth in vivo. Photon irradiation induced HIF-1M-NM-1 and several of its target genes such as PDK1, GLUT-1, LDHA, and VEGF with subsequent enhanced tumor angiogenesis in vivo, a signaling cascade that was not targeted by carbon-ion irradiation. We present evidence that photons but not carbon-ions induce HIF-1M-NM-1 via mTOR pathway. Importantly, after carbon-ion irradiation in vivo, we observed substantial downregulation of HIF-1M-NM-1 and a drastically delayed tumor growth indicating a considerable higher relative biological effectiveness (RBE) than anticipated from the cell survival data. In sum, our results demonstrate that carbon-ions mediate an improved therapeutic response of tumor treatment compared to photon irradiation that is independent of cell oxygenation and HIF-1 signaling. 16 independent cell cultures were used. Each culture was split into an irradiated and a control plate, yieldin a total of 16 paired samples. Paired samples were analysed in 16 two-color hybridizations. Factors time (after irradiation) with levels 1h and 4h and factor radiation quality with levels C12 and X-rays were analyzed. Each of the 2x2 combinations was analyzed in 4 independent experiments.
2014-04-20 | E-GEOD-45403 | biostudies-arrayexpress
Project description:This study aimed to first elucidate prostate-specific antigen (PSA) kinetics in prostate cancer patients treated with carbon ion radiotherapy (CIRT). From 2010 to 2015, 131 patients with prostate adenocarcinoma treated with CIRT (57.6 Gy relative biological effectiveness (RBE) in 16 fractions) alone were recruited. PSA was measured at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post-CIRT. PSA bounce was defined as PSA increase over a cutoff followed by spontaneous decrease to or below the pre-bounce nadir. PSA failure was determined using the Phoenix criteria (nadir + 2.0 ng/mL). As a result, non-failure-associated temporary increase in PSA exhibited two distinct patterns, namely a classical bounce and a surge at one month. PSA bounce of ³0.2 ng/mL was observed in 55.7% of the patients. Bounce amplitude was <2.0 ng/mL in 97.6% of cases. Bounce occurred significantly earlier than PSA failure. Younger age was a significant predictor of bounce occurrence. Bounce positivity was a significant predictor of favorable 5-year PSA failure-free survival. Meanwhile, a PSA surge of ³0.2 ng/mL was observed in 67.9% of patients. Surge amplitude was significantly larger than bounce amplitude. Larger prostate volume was a significant predictor of PSA surge occurrence. PSA surge positivity did not significantly predict PSA failure. In summary, PSA bounce was distinguishable from PSA failure with regard to timing of occurrence and amplitude (earlier and lower for bounce, respectively). These data are useful for post-CIRT surveillance of prostate cancer patients.
| S-EPMC7139713 | biostudies-literature
Project description:Over the past several years, analyses of data from high-throughput studies have elucidated many fundamental insights into prostate cancer biology. These insights include the identification of molecular alterations and subtypes that drive tumour progression, recurrent aberrations in signalling pathways, the existence of substantial intertumoural and intratumoural heterogeneity, Darwinian evolution in response to therapeutic pressures and the complicated multidirectional patterns of spread between primary tumours and metastatic sites. However, these concepts have not yet been fully translated into clinical tools to improve prognostication, prediction and personalization of treatment of patients with prostate cancer. The current and future clinical implications of 'omics' level knowledge is not only revolutionizing our understanding of prostate cancer biology, but is also shaping ongoing, and future clinical investigations and practice. In this Review, we summarize these advances, and the remaining challenges surrounding tumour heterogeneity and the ability to overcome treatment resistance are also described.
| S-EPMC5030163 | biostudies-literature
Project description: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.
| S-EPMC5439371 | biostudies-literature
Project description: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.
| S-EPMC8688694 | biostudies-literature
Project description:BackgroundThis 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).MethodsEighty-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.ResultsThe 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.ConclusionsIn 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.
| S-EPMC7647067 | biostudies-literature
Project description:BackgroundCarbon ion radiotherapy (CIRT) and proton beam therapy (PBT) are promising methods for prostate cancer, however, the consensus of an increasing number of studies has not been reached. We aimed to provide systematic evidence for evaluating the efficacy and safety of CIRT and PBT for prostate cancer by comparing photon radiotherapy.Materials and methodsWe searched for studies focusing on CIRT and PBT for prostate cancer in four online databases until July 2021. Two independent reviewers assessed the quality of included studies and used the GRADE approach to rate the quality of evidence. R 4.0.2 software was used to conduct the meta-analysis. A meta-regression test was performed based on the study design and tumor stage of each study.ResultsA total of 33 studies including 13 CIRT- and 20 PBT-related publications, involving 54,101, participants were included. The quality of the included studies was found to be either low or moderate quality. Random model single-arm meta-analysis showed that both the CIRT and PBT have favorable efficacy and safety, with similar 5-year overall survival (OS) (94 vs 92%), the incidence of grade 2 or greater acute genitourinary (AGU) toxicity (5 vs 13%), late genitourinary (LGU) toxicity (4 vs 5%), acute gastrointestinal (AGI) toxicity (1 vs 1%), and late gastrointestinal (LGI) toxicity (2 vs 4%). However, compared with CIRT and PBT, photon radiotherapy was associated with lower 5-year OS (72-73%) and a higher incidence of grade 2 or greater AGU (28-29%), LGU (13-14%), AGI (14-19%), and LGI toxicity (8-10%). The meta-analysis showed the 3-, 4-, and 5-year local control rate (LCR) of CIRT for prostate cancer was 98, 97, and 99%; the 3-, 4-, 5-, and 8-year biochemical relapse-free rate (BRF) was 92, 91, 89, and 79%. GRADE assessment results indicated that the certainty of the evidence was very low. Meta-regression results did not show a significant relationship based on the variables studied (P<0.05).ConclusionsCurrently available evidence demonstrated that the efficacy and safety of CIRT and PBT for prostate cancer were similar, and they may significantly improve the OS, LCR, and reduce the incidence of GU and GI toxicity compared with photon radiotherapy. However, the quantity and quality of the available evidence are insufficient. More high-quality controlled studies are needed in the future.
| S-EPMC8547329 | biostudies-literature
Project description:BackgroundProstate cancer rates have been steadily increasing in recent years. As high-precision radiation therapy methods, stereotactic body radiation therapy (SBRT) and carbon-ion radiation therapy (CIRT) have unique advantages. Analyzing the dosimetric differences between SBRT and CIRT in the treatment of localized prostate cancer can help provide patients with more accurate, individualized treatment plans.MethodsWe selected computed tomography positioning images and the contours of target volumes of 16 patients with localized prostate cancer who received radiotherapy. We delineated the organs at risk (OARs) on the CyberKnife (CK) treatment planning system (TPS) MultiPlan4.0, which were imported into the CIRT uniform scanning TPS HIMM-1 ci-Plan. Two treatment plans, SBRT and CIRT, were designed for the same patient, and we used SPSS 22.0 for the statistical analysis of data.ResultsBoth SBRT and CIRT plans met the prescribed dose requirements. In terms of target volume exposure dose, D2 (P<0.001), D5 (P<0.001), D50 (P<0.001), D90 (P=0.029), D95 (P<0.001), D98 (P<0.001), and Dmean (P<0.001) under SBRT were significantly higher than those under CIRT; the conformity index (CI) under SBRT was significantly better than that under CIRT (P<0.001); the target volume coverage rate (V95%) and dose homogeneity index (HI) under CIRT were significantly better than those under SBRT (P<0.001). In terms of OAR exposure dosage, the Dmax of the bladder and rectum under SBRT was significantly lower than that under CIRT (P<0.001), but Dmean was in the other direction; the exposure dose of the intestinal tract under CIRT was significantly lower than that under SBRT (P<0.05); Dmax of the femoral head under CIRT was significantly lower than that under SBRT (P<0.05), and there was no statistical difference between them at other doses.ConclusionsIn this study, we found that when CIRT was used for treating localized prostate cancer, the dose distribution in target volume was more homogeneous and the coverage rate was higher; the average dose of OARs was lower. SBRT had a better CI and higher dose in target volume; the dose hotspot was lower in OARs. It is important to comprehensively consider the dose relationship between local tumor and surrounding tissues when selecting treatment plans.
| S-EPMC10585578 | biostudies-literature