Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies
Open Access

Carbon-ion Radiotherapy for Oligometastatic Colorectal Cancer in the Liver or Lung

SHINTARO SHIBA, KEI SHIBUYA, MASAHIKO OKAMOTO, NAOKO OKANO, NOBUTERU KUBO, TAKUYA KAMINUMA, HIRO SATO, SHOHEI OKAZAKI, YUHEI MIYASAKA, HIDEMASA KAWAMURA and TATSUYA OHNO
Anticancer Research April 2021, 41 (4) 1997-2005; DOI: https://doi.org/10.21873/anticanres.14967
SHINTARO SHIBA
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
2Gunma University Heavy Ion Medical Center, Gunma, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: shiba4885@yahoo.co.jp
KEI SHIBUYA
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MASAHIKO OKAMOTO
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NAOKO OKANO
2Gunma University Heavy Ion Medical Center, Gunma, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NOBUTERU KUBO
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKUYA KAMINUMA
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HIRO SATO
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHOHEI OKAZAKI
2Gunma University Heavy Ion Medical Center, Gunma, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YUHEI MIYASAKA
2Gunma University Heavy Ion Medical Center, Gunma, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HIDEMASA KAWAMURA
2Gunma University Heavy Ion Medical Center, Gunma, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TATSUYA OHNO
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: We aimed to evaluate the clinical outcomes of oligometastatic colorectal cancer in the liver and lung treated with carbon-ion radiotherapy (C-ion RT). Patients and Methods: Nineteen consecutive patients with oligometastatic colorectal cancer in the liver or lung who received C-ion RT were analyzed. The doses of C-ion RT were 60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, 60.0 Gy (RBE) in 12 fractions, or 64.8 Gy (BRE) in 12 fractions. Results: The median follow-up duration was 19 months. There were 23 tumors in 19 patients. The 2-year overall survival and local control rates for the whole patient cohort were 100% and 67%, respectively. None of the patients developed grade 2 or higher acute or late toxicities. Conclusion: C-ion RT for oligometastatic colorectal cancer in liver and lung provides favorable clinical outcomes. These outcomes suggest C-ion RT is a treatment option for oligometastatic colorectal cancer in liver and lung.

Key Words:
  • Carbon-ion radiotherapy
  • oligometastases
  • colorectal cancer
  • liver metastases
  • lung metastases

Oligometastatic disease is an intermediate state between localization and widespread dissemination (1). Therefore, controlling oligometastatic disease by local treatment may improve survival. Colorectal cancer is one of the cancer types that are characterized by oligometastases of the liver and lung. Local treatment of oligometastatic colorectal cancer, with or without chemotherapy, is performed to improve survival (2-7). In contrast, radiotherapy (RT) is performed as a local treatment approach for patients who are not indicated for surgery due to comorbidity or refusal of surgery (8-15).

Carbon-ion (C-ion) RT is performed to treat various types of cancer, including hepatocellular carcinoma, lung cancer, and oligometastatic disease (16-21). C-ion RT has biological and physical advantages over photon therapy. Owing to its biological properties, C-ion RT has a higher relative biological effectiveness (RBE) due to the high linear energy transfer in the Bragg peak. Furthermore, its physical properties allow administration of high doses while sparing normal tissues because of its higher dose localization ability with distal tail-off enabled by the Bragg peak and sharp lateral penumbra (22). Previous studies have demonstrated a dose distribution advantage, showing that C-ion RT delivered a reduced dose to the normal liver and lung compared with stereotactic body RT (SBRT) and intensity-modulated RT (23-25). The biological and physical advantages may contribute to favorable clinical outcomes. However, research on the clinical outcomes of oligometastatic colorectal cancer treated with C-ion RT is limited. Hence, we aimed to evaluate the clinical outcomes of oligometastatic colorectal cancer in the liver and lung treated with C-ion RT.

Patients and Methods

Patients. We reviewed the medical records of patients with oligometastatic colorectal cancer in the liver or lung treated with C-ion RT at Gunma University Heavy Ion Medical Center between October 2013 and March 2020. We enrolled 19 consecutive patients who met the following criteria: i) Liver or lung metastases from colorectal cancer as confirmed by histology or radiography; ii) curative resection for primary disease and regional lymph nodes, without gross or microscopic residual disease; iii) absence of local primary colorectal lesion and lymph node recurrence; iv) absence or control of extrahepatic or extra-thoracic disease; v) ≤3 synchronous liver or lung metastases at the time of treatment; vi) not indicated or refused surgery for metastatic disease of liver or lung ; vii) radiographically measurable tumor; and viii) performance status ≤3 by the Eastern Cooperative Oncology Group classification. Cases were excluded if they had received prior RT to the target area, had intractable infections in the target area, or had received chemotherapy/molecular targeted therapy within 4 weeks before the initiation of C-ion RT. The treatment protocol was reviewed and approved by the Gunma University Institutional Review Board (approval number: HS2019-130), and all patients signed an informed consent form before the initiation of therapy.

Carbon-ion radiotherapy. A heavy ion accelerator at Gunma University Heavy Ion Medical Center generated C-ion beams, and the beam energy was either 290 MeV/u, 380 MeV/u, or 400 MeV/u according to the tumor depth. The XiO-N system (version 4.47; collaborated product of Elekta AB, Stockholm, Sweden, and Mitsubishi Electric, Tokyo, Japan) was used for treatment planning. This system incorporates a dosing engine for ion beam RT (K2dose) (25). We calculated the clinical radiation dose based on the physical dose multiplied by the RBE of the C-ions. Before C-ion RT, patients were immobilized using tailor-made fixation cushions and thermoplastic shells to allow computed tomography (CT); respiratory-gated and 4-dimensional CT images were acquired. In actual treatment, the gating level for respiratory-gated irradiation was within 30% of the wave height around the peak exhalation. Patients received C-ion RT once daily, 4 days a week (Tuesday to Friday).

The gross tumor volume (GTV) was delineated by the treatment planning CT images, which were merged with the contrast-enhanced CT images, contrast-enhanced magnetic resonance imaging (MRI), with/without 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron-emission tomography (PET)/CT images if necessary. The clinical target volume had 5-10 mm margin around the GTV to include microscopic disease. The internal margin was assessed using 4-dimensional CT images for tumor movement. The planning target volume was defined as the summation of the clinical target volume, internal margin, and setup margin. The prescribed doses were 60 Gy (RBE) in four fractions for cases with peripheral metastatic tumor, 60 Gy (RBE) in 12 fractions for cases with metastatic tumor close to the gastrointestinal tract, and 64.8 Gy (RBE) in 12 fractions for cases with large metastatic tumor (>5 cm). The treatment aim was to cover 95% of the PTV with at least 95% of the prescribed dose. The dose constraints were as follows: Dose to 1 cm3 (D1cc) <40 Gy (RBE) administered to the gastrointestinal tract in standard cases; D1cc <45 Gy (RBE) administered to the gastrointestinal tract in the cases treated with 12 fractions; organ volume that received at least 10% of the administered dose (V10) <55% and V20 <40% administered to the liver; V20 <20% administered to the lung; maximum dose (Dmax) <30 Gy (RBE) administered to the spinal cord; Dmax <52.8 Gy (RBE) administered outside the PTV at the porta hepatis (including the first branch of the portal vein and hepatic duct); Dmax <45 Gy (RBE) administered to the skin in standard cases; and Dmax <50 Gy (RBE) administered to the skin in the cases treated with 12 fractions. Figures 1 and 2 show radiographical images before C-ion RT and typical clinical dose distribution with C-ion RT of patients with oligometastatic colorectal cancer in the liver and lung.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

A 65-year-old female with oligometastic sigmoid colon cancer in the liver treated with carbon-ion radiotherapy. A: Contrast-enhanced magnetic resonance imaging in hepatocyte phase before treatment. Yellow arrow shows the tumor with tumor washout. B: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron-emission tomography before treatment. Yellow arrow shows the tumor with abnormal FDG uptake. C: Dose distribution on axial computed tomographic images. The area within the red outline is the gross tumor volume. The 95% (red), 90% (orange), 80% (yellow), 65% (green), 50% (blue), and 20% (purple) isodose curves are highlighted (100% was 60 Gy relative biological effectiveness). D: Contrast-enhanced magnetic resonance imaging in hepatic phase 3 months after treatment. Contrast-enhanced deterioration is observed at the site of the carbon-ion beam path and no recurrence or residual tumor evident (green arrow). E: FDG positron-emission tomography 12 months after treatment. FDG uptake was reduced compared to that before treatment (green arrow).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

A 58-year-old male with oligometastic colorectal cancer in lung treated with carbon-ion radiotherapy. A: Plain computed tomography (CT) before treatment. Yellow arrow shows the tumor with contrast enhancement. B: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron-emission tomography before treatment. Yellow arrow shows the tumor with abnormal FDG uptake. C: Dose distribution on axial CT images. The area within the red outline is the gross tumor volume. The 95% (red), 90% (orange), 80% (yellow), 65% (green), 50% (blue), and 20% (purple) isodose curves are highlighted [100% was 60 Gy (relative biological effectiveness)]. D: Plain CT 12 months after treatment. No recurrence or residual tumor evident (green arrow). E: FDG positron-emission tomography 12 months after treatment. FDG uptake was reduced compared to that before treatment (green arrow).

Evaluation during follow-up. Patients were followed-up for 1 month after the completion of C-ion RT and every 3 months thereafter. Follow-up examinations comprised routine testing of blood cell counts and chemistry and diagnostic imaging using CT, MRI, or FDG-PET. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events (version 4.0) of the National Cancer Institute (27). Acute and late toxicities were evaluated as the highest grade of toxicity that occurred within 3 months and after 3 months of initiating C-ion RT, respectively.

Dose–volume histogram analysis. Dose–volume histogram (DVH) analysis was used to evaluate the dose of C-ion RT to normal liver and normal lung (i.e. total liver or lung volume minus GTV). We assessed the mean liver or lung dose, and the percentage of the normal liver or lung that received at least 5, 10, 15, 20, 25, 30, 40, and 50 Gy (RBE) (V5, V10, V15, V20, V25, V30, V40, and V50) based on the DVH.

Statistical analysis. All statistical analyses were performed using the Statistical Package for the Social Sciences software (version 25.0; IBM Inc., Armonk, NY, USA). Survival was measured from the date of C-ion RT initiation to death or the most recent follow-up. Local control (LC) was defined as no evidence of local recurrence without an increase in tumor size on CT or MRI and no increase in FDG uptake on PET. Progression-free survival (PFS) was defined as the absence of progression of both local and distant metastases. PFS was measured from the date of initiation of C-ion RT to the date of tumor progression or death from any cause. The probabilities of overall survival (OS), LC, and PFS rates were calculated using the Kaplan–Meier method. Next, we evaluated the potential prognostic effect of sex (male or female), age (<65 or ≥65 years), performance score (0 or 1), primary tumor site (rectum or colon), tumor location (liver or lung), tumor size (<3 or ≥3 cm), GTV volume (<10 cm3 or ≥10 cm3), clinical target volume (<40 or ≥40 cm3), serum carcinoembryonic antigen level (<5.0 or ≥5.0 ng/ml), duration between surgery and C-ion RT (<27 or ≥27 months), and surgical indication (not indicated or refused) in OS and LC using the log-rank test.

Results

Patient characteristics. The clinical characteristics of the 19 patients are summarized in Table I. The median follow-up duration after the initiation of C-ion RT was 19 months (range=4-55 months). The median age at the time of registration for C-ion RT was 65 years (range=47-86 years). Four patients had two metastatic tumors that received C-ion RT. The number of oligometastatic tumors in the liver and lung was 14 in 11 patients and nine in eight patients, respectively. The median tumor size of 23 lesions was 2.6 cm (range=1.1-6.5 cm) in maximum diameter, in two cases larger than 5 cm. At the time of C-ion RT, six patients had chemoresistant disease or were unable to continue chemotherapy due to toxicities; 11 patients were unsuitable due to comorbidity and age, or refused chemotherapy. In patients who received chemotherapy before C-ion RT, the median duration from the initiation of chemotherapy for oligometastatic disease to the initiation of C-ion RT was 10 months (range=5-28 months). All patients with liver metastases had Child–Pugh class A and had no liver cirrhosis, and no patients with lung metastases had chronic lung disease or interstitial pneumonia. The dose-fractionation schedules for liver metastases were as follows: Nine lesions received 60 Gy (RBE) in four fractions, one lesion received 60 Gy (RBE) in 12 fractions, and four lesions received 64.8 Gy (RBE) in 12 fractions. For lung metastases, there were nine lesions, which received 60 Gy (RBE) in four fractions. Three patients did not achieve dose coverage of the 95% PTV with at least 95% of the prescribed dose as priority was given to the dose constraint of normal organs such as the gastrointestinal tract or skin.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Patient characteristics.

Clinical outcomes. Figures 1D and 1E, and 2D and 2E show typical radiographic images after C-ion RT. The estimated 2-year OS, LC, and PFS rates for the cohort overall were 100%, 67%, and 35%, respectively; for those with liver metastases, the corresponding rates were 100%, 61%, and 27%; and for those with lung metastases, the rates were 100%, 83%, and 48%, respectively (Figure 3).

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Kaplan–Meier curves of overall survival (OS) (A), local control (LC) (B) and progression-free survival (C) for the whole patient cohort, patients with liver metastases, and those with lung metastases.

Four out of 14 lesions (29%) in the liver and one out of nine lesions (11%) in the lung developed local recurrence after C-ion RT. Two locally recurrent lesions in the liver received 64.8 Gy (RBE) in 12 fractions, and the other two received 60.0 Gy (RBE) in four fractions. A local recurrence in the lung received 60.0 Gy (RBE) in four fractions. All local recurrences were central tumor recurrences. All patients with local recurrence also developed distant or lymph node metastases. Twelve patients developed distant or lymph node metastases. Three patients died of colorectal cancer.

The observed cases of acute and late toxicities are shown in Table II. None of the patients developed grade 2 or higher acute and late toxicities. No patients developed radiation-induced liver disease (RILD) or Child–Pugh class decline. Table III lists DVH parameters. Analysis did not reveal any significant prognostic factors for OS and LC (Table IV).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Acute and late toxicities according to Common Terminology Criteria for Adverse Events, version 4.0 (27) (N=19).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Dose–volume histogram parameters.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

Univariate analysis of overall survival (OS) and local control (LC).

Discussion

Surgery for oligometastatic colorectal cancer in the liver and lung is well established, and previous studies have reported 5-year survival of 30-61% (2-7). These results suggest that local treatment for oligometastatic colorectal cancer improves survival. Another local treatment approach is SBRT, which is indicated for patients who are unsuitable for surgery or refuse surgery. Previous reports of SBRT for oligometastatic colorectal cancer showed that the 2-year OS and LC were 57-75% and 36-91%, respectively, for patients with liver metastases and 68-89% and 58-80%, respectively, for those with lung metastases, with grade 3-4 toxicities developing in 0-9% of patients (8-15). These results suggest that SBRT is an effective local treatment approach and might improve OS in oligometastatic colorectal cancer. In our study, C-ion RT was performed in patients with oligometastatic colorectal cancer who were unsuitable for surgery or refused surgery. The OS and LC rates were 100% and 61%, respectively, for those with liver metastases, and 100% and 83%, respectively, for those with lung metastases, with no grade 2 or higher toxicities. These outcomes are comparable to those in previous reports of SBRT. Additionally, we included patients with inoperable disease and those difficult to treat with chemotherapy; hence, local treatment with C-ion RT might improve OS, underscoring the value of C-ion RT.

We performed DVH analysis for the normal liver. A previous report investigating the relationship between normal liver DVH parameters and liver function after photon therapy found that a mean liver dose >23 Gy, V5 >86%, V10 >68%, V15 >59%, V20 >49%, V25 >35%, V30 >28%, and V40 >20% were risk factors of RILD (28). Another study on SBRT showed that V25 >32% was a risk factor for Child– Pugh class decline in patients with hepatocellular carcinoma (29). In the present study, V25-V40 DVH parameters of liver were exceeded in a few patients with multiple or tumors of 3 cm or larger. However, none of the patients developed RILD and Child–Pugh class decline. In previous studies, a risk factor of RILD and Child–Pugh class decline was liver cirrhosis in patients with hepatocellular carcinoma. However, we did not include patients with liver cirrhosis in our cohort, which explains the absence of RILD and Child–Pugh class decline in our study. The DVH analysis for normal lung in previous studies showed that risk factors for grade 2 or higher radiation-induced pneumonitis were a mean lung dose of >5 Gy and V20 >7% in those treated with SBRT and V30 >15% in C-ion those treated with RT (30, 31). In the present study, V30 did not exceeded 15% in any of the patients, and in only a few patients with multiple or large tumors (≥3 cm) did the mean Iung dose exceed >5 Gy and V20 exceed 7%. However, none of the patients developed grade 2 or higher radiation-induced pneumonitis. These clinical results and DVH parameters suggest that the use of C-ion RT for oligometastatic colorectal cancer in patients with single 3-cm or smaller tumors in liver and lung is a safe treatment approach, and in those with multiple tumors or 3 cm or larger tumor might be safe considering the liver or lung background.

The improvement of LC might trigger more interest in C-ion RT for oligometastatic colorectal cancer. In a previous report of C-ion RT for oligometastatic colorectal cancer in the liver, 3-year LC rates were 82% in those receiving single-fraction doses of 53 Gy (RBE) or higher and 28% in those receiving 48 Gy (RBE) or lower (p=0.01) (21). Additionally, 3-year LC was 86-93% after the administration of 70 Gy (RBE) in 16 fractions or higher in patients with pelvic recurrence of colorectal cancer (32, 33). In the present study, all cases with local recurrence had central recurrence after administration of 60 Gy (RBE) in four fractions or 64.8 Gy (RBE) in 12 fractions. These results suggest a dose deficiency with the prescribed dose in our study. Higher dose irradiation such as 53 Gy (RBE) in a single fraction or 70 Gy (RBE) in 16 fractions without exceeding the tolerable dose with DVH in normal liver or lung might improve LC. In the present study, we considered that increasing the prescribed dose might be safe for small and single tumors.

Research on particle therapy, including proton beam therapy and C-ion RT, for oligometastatic colorectal cancer in the liver or lung is limited (21, 34, 35). All reports showed favorable and similar results to those using SBRT. Our findings are also favorable and comparable to the SBRT results and previous particle therapy.

Our study had several limitations. Firstly, this was a single-institutional retrospective analysis with a small number of patients and a short follow-up duration. Secondly, the patient backgrounds were heterogeneous. Thirdly, analyses of DVH and toxicities for C-ion RT were few, and the threshold risk value in the incidence of toxicities is unknown. Despite these limitations, this study confirmed the safety of C-ion RT. Our study offers useful information on the treatment of oligometastatic colorectal cancer, especially in patients who are unsuitable for surgery.

In conclusion, C-ion RT is a favorable treatment approach for oligometastatic colorectal cancer in the liver and lungs and has comparable clinical outcomes to SBRT. Additionally, C-ion RT might be a safe treatment option, as exemplified by the absence of RILD and radiation-induced pneumonitis. Therefore, C-ion RT can be used in patients with oligometastatic colorectal cancer in the liver and lungs who are unsuitable for surgery.

Acknowledgements

The Authors would like to thank all the patients who were involved in this study, our colleagues at Gunma University Heavy Ion Medical Center and Department of Radiation Oncology Gunma University Graduate School of Medicine, and Editage (www.editage.com) for English language editing.

Footnotes

  • Authors’ Contributions

    Conceptualization, S.S., T.O.; methodology, S.S., K.S., O.M., H.K., T.O; validation, S.S.; formal analysis, S.S.; investigation, S.S., K.S., M.O., H.K.; resources, S.S., K.S., M.O., H.K.; data curation, S.S.; writing–original draft preparation, S.S.; writing–review and editing, K.S., M.O., N.O., N.K., T.K., H.S., S.O., Y.M., H.K., T.O.; visualization, S.S.; supervision, T.O.; project administration, T.O.; funding acquisition, T.O. All Authors read and approved the final article.

  • This article is freely accessible online.

  • Conflicts of Interest

    The Authors declare no conflicts of interest in regard to this study.

  • Received February 4, 2021.
  • Revision received February 24, 2021.
  • Accepted February 25, 2021.

This is an open access article distributed under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

References

  1. ↵
    1. Hellman S and
    2. Weichselbaum RR
    : Oligometastases. J Clin Oncol 13(1): 8-10, 1995. PMID: 7799047. DOI: 10.1200/JCO.1995.13.1.8
    OpenUrlFREE Full Text
  2. ↵
    1. Rees M,
    2. Tekkis PP,
    3. Welsh FK,
    4. O’Rourke T and
    5. John TG
    : Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: A multifactorial model of 929 patients. Ann Surg 247(1): 125-135, 2008. PMID: 18156932. DOI: 10.1097/SLA.0b013e31815aa2c2
    OpenUrlCrossRefPubMed
    1. Elias D,
    2. Liberale G,
    3. Vernerey D,
    4. Pocard M,
    5. Ducreux M,
    6. Boige V,
    7. Malka D,
    8. Pignon JP and
    9. Lasser P
    : Hepatic and extrahepatic colorectal metastases: When resectable, their localization does not matter, but their total number has a prognostic effect. Ann Surg Oncol 12(11): 900-909, 2005. PMID: 16184442. DOI: 10.1245/ASO.2005.01.010
    OpenUrlCrossRefPubMed
    1. Inoue M,
    2. Ohta M,
    3. Iuchi K,
    4. Matsumura A,
    5. Ideguchi K,
    6. Yasumitsu T,
    7. Nakagawa K,
    8. Fukuhara K,
    9. Maeda H,
    10. Takeda S,
    11. Minami M,
    12. Ohno Y,
    13. Matsuda H and Thoracic Surgery Study Group of Osaka University.
    : Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 78(1): 238-244, 2004. PMID: 15223436. DOI: 10.1016/j.athoracsur.2004.02.017
    OpenUrlCrossRefPubMed
    1. Pfannschmidt J,
    2. Dienemann H and
    3. Hoffmann H
    : Surgical resection of pulmonary metastases from colorectal cancer: A systematic review of published series. Ann Thorac Surg 84(1): 324-338, 2007. PMID: 17588454. DOI: 10.1016/j.athoracsur.2007.02.093
    OpenUrlCrossRefPubMed
    1. Kopetz S,
    2. Chang GJ,
    3. Overman MJ,
    4. Eng C,
    5. Sargent DJ,
    6. Larson DW,
    7. Grothey A,
    8. Vauthey JN,
    9. Nagorney DM and
    10. McWilliams RR
    : Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 27(22): 3677-3683, 2009. PMID: 19470929. DOI: 10.1200/JCO.2008.20.5278
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Salah S,
    2. Watanabe K,
    3. Welter S,
    4. Park JS,
    5. Park JW,
    6. Zabaleta J,
    7. Ardissone F,
    8. Kim J,
    9. Riquet M,
    10. Nojiri K,
    11. Gisabella M,
    12. Kim SY,
    13. Tanaka K and
    14. Al-Haj Ali B
    : Colorectal cancer pulmonary oligometastases: Pooled analysis and construction of a clinical lung metastasectomy prognostic model. Ann Oncol 23(10): 2649-2655, 2012. PMID: 22547539. DOI: 10.1093/annonc/mds100
    OpenUrlCrossRefPubMed
  4. ↵
    1. Petrelli F,
    2. Comito T,
    3. Barni S,
    4. Pancera G,
    5. Scorsetti M,
    6. Ghidini A and SBRT for CRC liver metastases.
    : Stereotactic body radiotherapy for colorectal cancer liver metastases: A systematic review. Radiother Oncol 129(3): 427-434, 2018. PMID: 29997034. DOI: 10.1016/j.radonc.2018.06.035
    OpenUrlCrossRefPubMed
    1. Comito T,
    2. Cozzi L,
    3. Clerici E,
    4. Campisi MC,
    5. Liardo RL,
    6. Navarria P,
    7. Ascolese A,
    8. Tozzi A,
    9. Iftode C,
    10. De Rose F,
    11. Villa E,
    12. Personeni N,
    13. Rimassa L,
    14. Santoro A,
    15. Fogliata A,
    16. Mancosu P,
    17. Tomatis S and
    18. Scorsetti M
    : Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: A safe and effective approach. BMC Cancer 14: 619, 2014. PMID: 25163798. DOI: 10.1186/1471-2407-14-619
    OpenUrlCrossRefPubMed
    1. Habermehl D,
    2. Herfarth KK,
    3. Bermejo JL,
    4. Hof H,
    5. Rieken S,
    6. Kuhn S,
    7. Welzel T,
    8. Debus J and
    9. Combs SE
    : Single-dose radiosurgical treatment for hepatic metastases—therapeutic outcome of 138 treated lesions from a single institution. Radiat Oncol 8: 175, 2013. PMID: 23837905. DOI: 10.1186/1748-717X-8-175
    OpenUrlCrossRefPubMed
    1. Joo JH,
    2. Park JH,
    3. Kim JC,
    4. Yu CS,
    5. Lim SB,
    6. Park IJ,
    7. Kim TW,
    8. Hong YS,
    9. Kim KP,
    10. Yoon SM,
    11. Park J and
    12. Kim JH
    : Local control outcomes using stereotactic body radiation therapy for liver metastases from colorectal cancer. Int J Radiat Oncol Biol Phys 99(4): 876-883, 2017. PMID: 29063852. DOI: 10.1016/j.ijrobp.2017.07.030
    OpenUrlCrossRefPubMed
    1. Jingu K,
    2. Matsushita H,
    3. Yamamoto T,
    4. Umezawa R,
    5. Ishikawa Y,
    6. Takahashi N,
    7. Katagiri Y,
    8. Takeda K and
    9. Kadoya N
    : Stereotactic radiotherapy for pulmonary oligometastases from colorectal cancer: A systematic review and meta-analysis. Technol Cancer Res Treat 17: 1533033818794936, 2018. PMID: 30145943. DOI: 10.1177/1533033818794936
    OpenUrlCrossRef
    1. Agolli L,
    2. Bracci S,
    3. Nicosia L,
    4. Valeriani M,
    5. De Sanctis V and
    6. Osti MF
    : Lung metastases treated with stereotactic ablative radiation therapy in oligometastatic colorectal cancer patients: Outcomes and prognostic factors after long-term follow-up. Clin Colorectal Cancer 16(1): 58-64, 2017. PMID: 27522627. DOI: 10.1016/j.clcc.2016.07.004
    OpenUrlCrossRefPubMed
    1. Kinj R,
    2. Bondiau PY,
    3. François E,
    4. Gérard JP,
    5. Naghavi AO,
    6. Leysalle A,
    7. Chamorey E,
    8. Evesque L,
    9. Padovani B,
    10. Ianessi A,
    11. Benezery K and
    12. Doyen J
    : Radiosensitivity of colon and rectal lung oligometastasis treated with stereotactic ablative radiotherapy. Clin Colorectal Cancer 16(3): e211-e220, 2017. PMID: 27670890. DOI: 10.1016/j.clcc.2016.08.003
    OpenUrlCrossRefPubMed
  5. ↵
    1. Kobayashi N,
    2. Abe T,
    3. Noda SE,
    4. Kumazaki YU,
    5. Hirai R,
    6. Igari M,
    7. Aoshika T,
    8. Saito S,
    9. Ryuno Y and
    10. Kato S
    : Stereotactic body radiotherapy for pulmonary oligometastasis from colorectal cancer. In Vivo 34(5): 2991-2996, 2020. PMID: 32871842. DOI: 10.21873/invivo.12130
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Shibuya K,
    2. Ohno T,
    3. Terashima K,
    4. Toyama S,
    5. Yasuda S,
    6. Tsuji H,
    7. Okimoto T,
    8. Shioyama Y,
    9. Nemoto K,
    10. Kamada T,
    11. Nakano T and Japan Carbon Ion Radiotherapy Study Group.
    : Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi-institutional retrospective study. Liver Int 38(12): 2239-2247, 2018. PMID: 30240527. DOI: 10.1111/liv.13969
    OpenUrlCrossRefPubMed
    1. Shiba S,
    2. Shibuya K,
    3. Okamoto M,
    4. Okazaki S,
    5. Komatsu S,
    6. Kubota Y,
    7. Nakano T and
    8. Ohno T
    : Clinical impact of hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma. Radiat Oncol 15(1): 195, 2020. PMID: 32795340. DOI: 10.1186/s13014-020-01634-z
    OpenUrlCrossRefPubMed
    1. Saitoh JI,
    2. Shirai K,
    3. Mizukami T,
    4. Abe T,
    5. Ebara T,
    6. Ohno T,
    7. Minato K,
    8. Saito R,
    9. Yamada M and
    10. Nakano T
    : Hypofractionated carbonion radiotherapy for stage I peripheral nonsmall cell lung cancer (GUNMA0701): Prospective phase II study. Cancer Med 8(15): 6644-6650, 2019. PMID: 31532584. DOI: 10.1002/cam4.2561
    OpenUrlCrossRefPubMed
    1. Okonogi N,
    2. Kaminuma T,
    3. Okimoto T,
    4. Shinoto M,
    5. Yamamoto N,
    6. Yamada S,
    7. Murata K,
    8. Ohno T,
    9. Shioyama Y,
    10. Tsuji H,
    11. Nakano T and
    12. Kamada T
    : Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS). Int J Clin Oncol 24(9): 1143-1150, 2019. PMID: 30968270. DOI: 10.1007/s10147-019-01440-y
    OpenUrlCrossRefPubMed
    1. Shiba S,
    2. Okonogi N,
    3. Kato S,
    4. Wakatsuki M,
    5. Kobayashi D,
    6. Kiyohara H,
    7. Ohno T,
    8. Karasawa K,
    9. Nakano T and
    10. Kamada T
    : Clinical impact of re-irradiation with carbon-ion radiotherapy for lymph node recurrence of gynecological cancers. Anticancer Res 37(10): 5577-5583, 2017. PMID: 28982873. DOI: 10.21873/anticanres.11991
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Makishima H,
    2. Yasuda S,
    3. Isozaki Y,
    4. Kasuya G,
    5. Okada N,
    6. Miyazaki M,
    7. Mohamad O,
    8. Matsufuji N,
    9. Yamada S,
    10. Tsuji H,
    11. Kamada T and Liver Cancer Working Group.
    : Single fraction carbon ion radiotherapy for colorectal cancer liver metastasis: A dose escalation study. Cancer Sci 110(1): 303-309, 2019. PMID: 30417485. DOI: 10.1111/cas.13872
    OpenUrlCrossRefPubMed
  8. ↵
    1. Kanai T,
    2. Endo M,
    3. Minohara S,
    4. Miyahara N,
    5. Koyama-ito H,
    6. Tomura H,
    7. Matsufuji N,
    8. Futami Y,
    9. Fukumura A,
    10. Hiraoka T,
    11. Furusawa Y,
    12. Ando K,
    13. Suzuki M,
    14. Soga F and
    15. Kawachi K
    : Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy. Int J Radiat Oncol Biol Phys 44(1): 201-210, 1999. PMID: 10219815. DOI: 10.1016/s0360-3016(98)00544-6
    OpenUrlCrossRefPubMed
  9. ↵
    1. Abe T,
    2. Saitoh J,
    3. Kobayashi D,
    4. Shibuya K,
    5. Koyama Y,
    6. Shimada H,
    7. Shirai K,
    8. Ohno T and
    9. Nakano T
    : Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma. Radiat Oncol 10: 187, 2015. PMID: 26377092. DOI: 10.1186/s13014-015-0491-8
    OpenUrlCrossRefPubMed
    1. Shiba S,
    2. Shibuya K,
    3. Kawashima M,
    4. Okano N,
    5. Kaminuma T,
    6. Okamoto M,
    7. Kubota Y,
    8. Nakano T and
    9. Ohno T
    : Comparison of dose distributions when using carbon ion radiotherapy versus intensity-modulated radiotherapy for hepatocellular carcinoma with macroscopic vascular invasion: A retrospective analysis. Anticancer Res 40(1): 459-464, 2020. PMID: 31892601. DOI: 10.21873/anticanres.13974
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Ebara T,
    2. Shimada H,
    3. Kawamura H,
    4. Shirai K,
    5. Saito J,
    6. Kawashima M,
    7. Tashiro M,
    8. Ohno T,
    9. Kanai T and
    10. Nakano T
    : Dosimetric analysis between carbon ion radiotherapy and stereotactic body radiotherapy in stage I lung cancer. Anticancer Res 34(9): 5099-5104, 2014. PMID: 25202098.
    OpenUrlAbstract/FREE Full Text
    1. Inaniwa T,
    2. Kanematsu N,
    3. Matsufuji N,
    4. Kanai T,
    5. Shirai T,
    6. Noda K,
    7. Tsuji H,
    8. Kamada T and
    9. Tsujii H
    : Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan. Phys Med Biol 60(8): 3271-3286, 2015. PMID: 25826534. DOI: 10.1088/0031-9155/60/8/3271
    OpenUrlCrossRefPubMed
  11. ↵
    NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. National Institutes of Health, National Cancer Institute, Bethesda, MA, USA, 2009. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf [Last accessed on February 24, 2021]
  12. ↵
    1. Liang SX,
    2. Zhu XD,
    3. Xu ZY,
    4. Zhu J,
    5. Zhao JD,
    6. Lu HJ,
    7. Yang YL,
    8. Chen L,
    9. Wang AY,
    10. Fu XL and
    11. Jiang GL
    : Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 65(2): 426-434, 2006. PMID: 16690430. DOI: 10.1016/j.ijrobp.2005.12.031
    OpenUrlCrossRefPubMed
  13. ↵
    1. Dyk P,
    2. Weiner A,
    3. Badiyan S,
    4. Myerson R,
    5. Parikh P and
    6. Olsen J
    : Effect of high-dose stereotactic body radiation therapy on liver function in the treatment of primary and metastatic liver malignancies using the Child-Pugh score classification system. Pract Radiat Oncol 5(3): 176-182, 2015. PMID: 25423889. DOI: 10.1016/j.prro.2014.09.007
    OpenUrlCrossRefPubMed
  14. ↵
    1. Barriger RB,
    2. Forquer JA,
    3. Brabham JG,
    4. Andolino DL,
    5. Shapiro RH,
    6. Henderson MA,
    7. Johnstone PA and
    8. Fakiris AJ
    : A dose-volume analysis of radiation pneumonitis in non-small cell lung cancer patients treated with stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 82(1): 457-462, 2012. PMID: 21035956. DOI: 10.1016/j.ijrobp.2010.08.056
    OpenUrlCrossRefPubMed
  15. ↵
    1. Hayashi K,
    2. Yamamoto N,
    3. Karube M,
    4. Nakajima M,
    5. Matsufuji N,
    6. Tsuji H,
    7. Ogawa K and
    8. Kamada T
    : Prognostic analysis of radiation pneumonitis: Carbon-ion radiotherapy in patients with locally advanced lung cancer. Radiat Oncol 12(1): 91, 2017. PMID: 28558766. DOI: 10.1186/s13014-017-0830-z
    OpenUrlCrossRefPubMed
  16. ↵
    1. Shiba S,
    2. Okamoto M,
    3. Kiyohara H,
    4. Ohno T,
    5. Kaminuma T,
    6. Asao T,
    7. Ojima H,
    8. Shirabe K,
    9. Kuwano H and
    10. Nakano T
    : Prospective observational study of high-dose carbon-ion radiotherapy for pelvic recurrence of rectal cancer (GUNMA 0801). Front Oncol 9: 702, 2019. PMID: 31417874. DOI: 10.3389/fonc.2019.00702
    OpenUrlCrossRefPubMed
  17. ↵
    1. Shinoto M,
    2. Yamada S,
    3. Okamoto M,
    4. Shioyama Y,
    5. Ohno T,
    6. Nakano T,
    7. Nemoto K,
    8. Isozaki Y,
    9. Kawashiro S,
    10. Tsuji H and
    11. Kamada T
    : Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1404 Rectum. Radiother Oncol 132: 236-240, 2019. PMID: 30360998. DOI: 10.1016/j.radonc.2018.10.007
    OpenUrlCrossRefPubMed
  18. ↵
    1. Takahashi W,
    2. Nakajima M,
    3. Yamamoto N,
    4. Yamada S,
    5. Yamashita H,
    6. Nakagawa K,
    7. Tsuji H and
    8. Kamada T
    : Carbon ion radiotherapy for oligo-recurrent lung metastases from colorectal cancer: a feasibility study. Radiat Oncol 9: 68, 2014. PMID: 24581481. DOI: 10.1186/1748-717X-9-68
    OpenUrlCrossRefPubMed
  19. ↵
    1. Fukumitsu N,
    2. Okumura T,
    3. Takizawa D,
    4. Makishima H,
    5. Numajiri H,
    6. Murofushi K,
    7. Ohnishi K,
    8. Mizumoto M,
    9. Aihara T,
    10. Ishikawa H,
    11. Tsuboi K and
    12. Sakurai H
    : Proton beam therapy for metastatic liver tumors. Radiother Oncol 117(2): 322-327, 2015. PMID: 26385268. DOI: 10.1016/j.radonc.2015.09.011
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Anticancer Research: 41 (4)
Anticancer Research
Vol. 41, Issue 4
April 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Carbon-ion Radiotherapy for Oligometastatic Colorectal Cancer in the Liver or Lung
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 3 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Carbon-ion Radiotherapy for Oligometastatic Colorectal Cancer in the Liver or Lung
SHINTARO SHIBA, KEI SHIBUYA, MASAHIKO OKAMOTO, NAOKO OKANO, NOBUTERU KUBO, TAKUYA KAMINUMA, HIRO SATO, SHOHEI OKAZAKI, YUHEI MIYASAKA, HIDEMASA KAWAMURA, TATSUYA OHNO
Anticancer Research Apr 2021, 41 (4) 1997-2005; DOI: 10.21873/anticanres.14967

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Carbon-ion Radiotherapy for Oligometastatic Colorectal Cancer in the Liver or Lung
SHINTARO SHIBA, KEI SHIBUYA, MASAHIKO OKAMOTO, NAOKO OKANO, NOBUTERU KUBO, TAKUYA KAMINUMA, HIRO SATO, SHOHEI OKAZAKI, YUHEI MIYASAKA, HIDEMASA KAWAMURA, TATSUYA OHNO
Anticancer Research Apr 2021, 41 (4) 1997-2005; DOI: 10.21873/anticanres.14967
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Patients and Methods
    • Results
    • Discussion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Four Different Artificial Intelligence Models Versus Logistic Regression to Enhance the Diagnostic Accuracy of Fecal Immunochemical Test in the Detection of Colorectal Carcinoma in a Screening Setting
  • In-hospital Outcomes Between Total Parenteral Nutrition and Enteral Feeding in Esophageal and Gastric Cancer: A Nationwide Analysis
  • Phase II Study of the Effectiveness of the Germinated Wheat-derived Rigenase Plus Polyhexanide in the Prophylaxis for Hypofractionated Radiation-induced Acute Skin Toxicity in Breast Cancer
Show more Clinical Studies

Similar Articles

Keywords

  • Carbon-ion radiotherapy
  • oligometastases
  • colorectal cancer
  • liver metastases
  • lung metastases
Anticancer Research

© 2025 Anticancer Research

Powered by HighWire