Carbon ion radiation therapy for prostate cancer: Results of a prospective phase II study

Several model studies have shown potential clinical advantages with charged particles (protons and light ions) compared with 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in many disease sites. The newly developed intensity-modulated proton therapy (IMPT) often yields superior dose distributions to photon IMRT, with the added advantage of a significant reduction in the volume of healthy normal tissues exposed to low-to-medium doses. Initially, the major emphasis in clinical research for proton and light ion therapy was dose escalation for inherently radioresistant tumors, or for lesions adjacent to critical normal structures that constrained the dose that could be safely delivered with conventional x-ray therapy. Since the advent of IMRT the interest in particle therapy has gradually shifted toward protocols aimed at morbidity reduction. Lately the emphasis has mostly been placed on the potential for reduced risk of radiation-induced carcinogenesis with protons. Compared with 3D-CRT, a 2-fold increase has been theoretically estimated with the use of IMRT due to the larger integral volumes. In the pediatric setting, due to a higher inherent susceptibility of tissues, the risk could be significant, and the benefits of protons have been strongly emphasized in the literature. There is a significant expansion of particle therapy facilities around the world. Increasing public awareness of the potential benefits of particle therapy and wider accessibility for patients require that treating physicians stay abreast of the clinical indications of this radiotherapy modality. The article reviews the available literature for various disease sites in which particle therapy has traditionally been considered to offer clinical advantages and to highlight current lines of clinical research. The issue of radiation-induced second malignancies is examined in the light of the controversial epidemiological evidence available. The cost-effectiveness of particle therapy is also discussed. Cancer 2007;109: 1227-38. 2007 American Cancer Society.KEYWORDS: radiotherapy, proton therapy, light ions, intensity modulated radiotherapy, second cancers. C harged particles (protons and light ions) have a finite range in tissues. The interaction probability to cause ionization increases as they lose velocity traversing through tissues, so that a peak of dose occurs at a depth proportional to the energy of each particle. Beyond this peak no further dose deposition occurs. This phenomenon was described by William Bragg over 100 years ago.1 The dose peak may be 'spread out' to achieve a plateau of uniform dose to precisely cover the target while sparing adjacent normal structures. Passively scattered beams of a certain aperture can be produced by means of range-shifting modulators of variable thickness providing spread-out Bragg peaks (SOBP) for clinical use. The recent introduction of the spot scanning method represents a major advance in particle therapy.2 In this method, small pencil beams of a certain

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“…79 Late grade 2 GI and GU morbidities were 2% and 5%, respectively. No grade 3 toxicities were observed.…”

Section: Light Ionsmentioning

confidence: 97%

Current status of radiotherapy with proton and light ion beams

Greco

Wolden

2007

Cancer

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“…37 The results of this phase II trial also show that the highrisk group initially stratified according to the risk factors in the study should be further divided into two subgroups; namely, an intermediate risk group and a true high risk group. 35 Patients with T3 primary tumor, GS Ն 8, or an iPSA value of Ն20 ng/mL needed a long-term ADT as the true high risk group, whereas C-ion RT combined with a short course of neoadjuvant and concurrent ADT was successfully effective for patients in the intermediate group.…”

Section: Clinical Trials At Nirsmentioning

confidence: 97%

“…9,34 Taking these results into consideration, a phase II clinical study (protocol 9904) was designed to further confirm the effectiveness of C-ion RT for patients with T1-T3 prostate cancer using a fixed dose fractionation schedule of 66 GyE in 20 fractions over 5 weeks. 35 Patients were divided into two groups based on their risk factors, such as T stage, initial PSA value and GS of the tumor. The study was started in April 2000 and closed in October 2003, and 176 patients were registered.…”

Section: Clinical Trials At Nirsmentioning

confidence: 99%

“…Local control was achieved in all but one patient, and Grade 2 GI and GU morbidities in the study were observed in just 2% and 5% of the patients, respectively. 35 To reduce the GI and GU morbidities in C-ion RT, we have made an effort to explore predictive risk factors in this study. Consequently, the use of anticoagulation therapy and dosimetric parameters using a DVH analysis were predictive factors in the occurrence of rectal bleeding, 36 and the use of a long-course of ADT increased Grade 1-2 GU morbidities based on the long-term follow-up results.…”

Section: Clinical Trials At Nirsmentioning

confidence: 99%

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Carbon‐ion radiation therapy for prostate cancer

Ishikawa

Tsuji²,

Kamada³

et al. 2012

Int J of Urology

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104

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Abbreviations & Acronyms ADT = androgen deprivation therapy bNED = biological relapse free C-ion RT = carbon-ion radiotherapy CSS = cause-specific survival CT = computed tomography CTV = clinical target volume 3D-CRT = three-dimensional conformal radiation therapy DVH = dose-volume histogram Fr = fractions GHMC = Gunma Heavy Ion Medical Center GI = gastrointestinal GS = Gleason score GU = genitourinary Gy = gray GyE = gray equivalents HAMT = Highly Advanced Medical Technology HDR = high-dose-rate HIMAC = Heavy-Ion Medical Accelerator in Chiba IMRT = intensity modulated radiotherapy iPSA = initial serum prostate-specific antigen LET = linear energy transfer L/Q = linear-quadratic NIRS = National Institute of Radiological Sciences PSA = prostate-specific antigen PTV1 = initial planning target volume PTV2 = second planning target volume RBE = relative biological effectiveness RT = radiation therapy RTOG = Radiation Therapy Oncology Group SBRT = stereotactic body radiotherapy SOBP = spread-out Bragg peak UICC = Union for International Cancer Control Abstract: In 1994, carbon-ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy-Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon-ion radiotherapy for both early-and advance-stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon-ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon-ion radiotherapy for prostate cancer was approved as "Highly Advanced Medical Technology" from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon-ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon-ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described.

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“…22 Late grade 2 GI and GU morbidities were 2 and 5%, respectively. No grade 3 toxicities were observed.…”

Section: Particle Therapy In Prostate Cancer C Grecomentioning

confidence: 97%

Particle therapy in prostate cancer: a review

Greco

2007

Prostate Cancer Prostatic Dis

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While dose escalation is proving important to achieve satisfactory long-term outcomes in prostate cancer, the optimal radiation modality to deliver the treatment is still a topic of debate. Charged particle beams can offer improved dose distributions to the target volume as compared to conventional 3D-conformal radiotherapy, with better sparing of surrounding healthy tissues. Exquisite dose distributions, with the fulfillment of dose-volume constraints to normal tissues, however, can also be achieved with photon-based intensity-modulated techniques. This review summarizes the literature on the use of particle therapy in prostate cancer and attempts to put in perspective its relative merits compared to current photon-based radiotherapy.

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Carbon ion radiation therapy for prostate cancer: Results of a prospective phase II study

Cited by 104 publications

References 34 publications

Current status of radiotherapy with proton and light ion beams

Current status of radiotherapy with proton and light ion beams

Carbon‐ion radiation therapy for prostate cancer

Particle therapy in prostate cancer: a review

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