Dose–volume comparison of intensity modulated proton therapy and volumetric modulated arc therapy for cervical esophageal cancer


      Proton therapy for cervical esophageal cancer has many issues to be considered, such as the physiological curvature of the spine and the large range change from the neck to the trunk. We clarified the dosimetric characteristics of intensity modulated proton therapy (IMPT) for cervical esophageal cancer by comparing with volumetric modulated arc therapy (VMAT). Ten patients with cervical esophageal cancer were retrospectively planned for VMAT, 2-field IMPT (2F-IMPT), and 3-field IMPT (3F-IMPT). All plans were optimized to reach clinically acceptable levels. For planning target volume (PTV) coverage, 95% of the PTV should be covered by 95% of the prescription dose, unless the spinal cord limit is violated. The organs at risk included the lung, spinal cord, larynx, skin, and whole body. The prescription dose was 60 Gy relative biological effectiveness (RBE) in 30 fractions to the PTV. We compared the results according to dose–volume metrics. Significant dose reductions were achieved at lung doses, especially at low dose volumes of 20 Gy RBE or less in IMPT plans compared with VMAT plans (p < 0.05). Although the spinal cord PRV was below the tolerance level, the results were also significantly higher in VMAT plans than in IMPT plans (p < 0.001). Spinal cord PRV Dmean was significantly higher in 3F-IMPT than in 2F-IMPT (p < 0.001). In addition, it was confirmed that the integral whole body dose can be dramatically reduced in IMPT plans compared with VMAT plans. Both of 2F-IMPT and 3F-IMPT could effectively reduce spinal cord dose, as well as low integral whole body dose to a certain extent, while maintaining similar target coverage compared to VMAT. IMPT could be a promising treatment technique for patients with cervical esophageal cancer.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Medical Dosimetry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Fitzmaurice C
        • Dicker D
        • Pain A
        • et al.
        The global burden of cancer 2013.
        JAMA Oncol. 2015; 1: 505-527
        • Xu C
        • Lin SH
        Esophageal cancer: comparative effectiveness of treatment options.
        Comp Eff Res. 2016; 2106: 1-12
        • Lee DJ
        • Harris A
        • Gillette A
        • et al.
        Carcinoma of the cervical esophagus: diagnosis, management, and results.
        South Med J. 1984; 77: 1365-1367
        • Laterza E
        • Mosciaro O
        • Urso US
        • et al.
        Primary carcinoma of the hypopharynx and cervical esophagus: evolution of surgical therapy.
        Hepatogastroenterology. 1994; 41: 278-282
        • Fenkell L
        • Kaminsky I
        • Breen S
        • et al.
        Dosimetric comparison of IMRT vs. 3D conformal radiotherapy in the treatment of cancer of the cervical esophagus.
        Radiother Oncol. 2008; 89: 287-291
        • Gong Y
        • Wang S
        • Zhou L
        • et al.
        Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer.
        Radiat Oncol. 2010; 5: 65
        • Yin Y
        • Chen J
        • Xing L
        • et al.
        Applications of IMAT in cervical esophageal cancer radiotherapy: A comparison with fixed-field IMRT in dosimetry and implementation.
        J Appl Clin Med Phys. 2011; 12: 3343
        • Jin X
        • Yi J
        • Zhou Y
        • et al.
        CRT combined with a sequential VMAT boost in the treatment of upper thoracic esophageal cancer.
        J Appl Clin Med Phys. 2013; 14: 153-161
        • Ma P
        • Wang X
        • Xu Y
        • et al.
        Applying the technique of volume-modulated arc radiotherapy to upper esophageal carcinoma.
        J Appl Clin Med Phys. 2014; 15: 4732
        • Zhang W
        • Lin Z
        • Yang Z
        • et al.
        Evaluation of the dosimetric impact of applying flattening filter-free beams in intensity-modulated radiotherapy for early-stage upper thoracic carcinoma of oesophagus.
        J Med Radiat Sci. 2015; 62: 108-113
        • Song W
        • Lu H
        • Liu J
        • et al.
        Fixed-jaw technique to improve IMRT plan quality for the treatment of cervical and upper thoracic esophageal cancer.
        J Appl Clin Med Phys. 2019; 20: 24-32
        • Zhou Y
        • Xiang X
        • Xiong J
        • et al.
        Comprehensive comparison of progressive optimization algorithm based automatic plan and manually planned treatment technique for cervical-thoracic esophageal cancers.
        Technol Cancer Res Treat. 2020; 191533033820973283
        • Vivekanandan N
        • Sriram P
        • Kumar SA
        • et al.
        Volumetric modulated arc radiotherapy for esophageal cancer.
        Med Dosim. 2012; 37: 108-113
        • Van Benthuysen L
        • Hales L
        • Podgorsak MB
        Volumetric modulated arc therapy vs. IMRT for the treatment of distal esophageal cancer.
        Med Dosim. 2011; 36: 404-409
        • Isacsson U
        • Lennernäs B
        • Grusell E
        • et al.
        Comparative treatment planning between proton and x-ray therapy in esophageal cancer.
        Int J Radiat Oncol Biol Phys. 1998; 41: 441-450
        • Welsh J
        • Gomez D
        • Palmer MB
        • et al.
        Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: A dosimetric study.
        Int J Radiat Oncol Biol Phys. 2011; 81: 1336-1342
        • Ling TC
        • Slater JM
        • Nookala P
        • et al.
        Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.
        Cancers (Basel). 2014; 6: 2356-2368
        • Prayongrat A
        • Xu C
        • Li H
        • et al.
        Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience.
        Adv Radiat Oncol. 2017; 2: 301-307
        • Shiraishi Y
        • Xu C
        • Yang J
        • et al.
        Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy.
        Radiother Oncol. 2017; 125: 48-54
        • Liu C
        • Bhangoo RS
        • Sio TT
        • et al.
        Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies.
        J Appl Clin Med Phys. 2019; 20: 15-27
        • Ono T
        • Wada H
        • Ishikawa H
        • et al.
        Clinical results of proton beam therapy for esophageal cancer: Multicenter retrospective study in Japan.
        Cancers (Basel). 2019; 11: 993
        • Bhangoo RS
        • DeWees TA
        • Yu NY
        • et al.
        Acute toxicities and short-term patient outcomes after intensity-modulated proton beam radiation therapy or intensity-modulated photon radiation therapy for esophageal carcinoma: A mayo clinic experience.
        Adv Radiat Oncol. 2020; 5: 871-879
        • Celik E
        • Baus W
        • Baues C
        • et al.
        Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer.
        Radiat Oncol. 2020; 15: 120
        • Vanetti E
        • Clivio A
        • Nicolini G
        • et al.
        Volumetric modulated arc radiotherapy for carcinomas of the oro-pharynx, hypo-pharynx and larynx: a treatment planning comparison with fixed field IMRT.
        Radiother Oncol. 2009; 92: 111-117
        • Zenda S
        • Kojima T
        • Kato K
        • et al.
        Multicenter Phase 2 study of cisplatin and 5-fluorouracil with concurrent radiation therapy as an organ preservation approach in patients with squamous cell carcinoma of the cervical esophagus.
        Int J Radiat Oncol Biol Phys. 2016; 96: 976-984
        • Langner UW
        • Eley JG
        • Dong L
        • et al.
        Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data.
        J Appl Clin Med Phys. 2017; 18: 96-107
        • Tanabe S
        • Myojin M
        • Shimizu S
        • et al.
        Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields.
        J Radiat Res. 2013; 54: 1085-1094
        • Shaikh T
        • Churilla TM
        • Monpara P
        • et al.
        Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.
        Pract Radiat Oncol. 2016; 6: 388-394
        • Narayana A
        • Vaughan AT
        • Fisher SG
        • et al.
        Second primary tumors in laryngeal cancer: results of long-term follow-up.
        Int J Radiat Oncol Biol Phys. 1998; 42: 557-562
        • Hofmaier J
        • Dedes G
        • Carlson DJ
        • et al.
        Variance-based sensitivity analysis for uncertainties in proton therapy: A framework to assess the effect of simultaneous uncertainties in range, positioning, and RBE model predictions on RBE-weighted dose distributions.
        Med Phys. 2021; 48: 805-818
        • Nomura K
        • Iwata H
        • Toshito T
        • et al.
        Biological effects of passive scattering and spot scanning proton beams at the distal end of the spread-out Bragg peak in single cells and multicell spheroids.
        Int J Radiat Biol. 2021; 97: 695-703
        • Kumar S
        • Juresic E
        • Barton M
        • et al.
        Management of skin toxicity during radiation therapy: A review of the evidence.
        J Med Imaging Radiat Oncol. 2010; 54: 264-279
        • Yang W
        • Yang Z
        • Zhao T
        • et al.
        A technique to reduce skin toxicity in radiotherapy treatment planning for esophageal cancer.
        J Appl Clin Med Phys. 2020; 21: 67-72
        • Hall EJ
        Intensity-modulated radiation therapy, protons, and the risk of second cancers.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1-7
        • Schena M
        • Battaglia AF
        • Munoz F
        Esophageal cancer developed in a radiated field: can we reduce the risk of a poor prognosis cancer?.
        J Thorac Dis. 2017; 9: 1767-1771
        • Vogel J
        • Lin L
        • Litzky LA
        • et al.
        Predicted rate of secondary malignancies following adjuvant proton versus photon radiation therapy for thymoma.
        Int J Radiat Oncol Biol Phys. 2017; 99: 427-433
        • Gu W
        • Ruan D
        • O'Connor D
        • et al.
        Robust optimization for intensity-modulated proton therapy with soft spot sensitivity regularization.
        Med Phys. 2019; 46: 1408-1425
        • Gu W
        • Neph R
        • Ruan D
        • et al.
        Robust beam orientation optimization for intensity-modulated proton therapy.
        Med Phys. 2019; 46: 3356-3370