Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model

Abstract Background The study objective was to establish the local effect model (LEM) rectum constraints for 12-, 8-, and 4-fraction carbon-ion radiotherapy (CIRT) in patients with localized prostate carcinoma (PCA) using microdosimetric kinetic model (MKM)-defined and LEM-defined constraints for 16-fraction CIRT. Methods We analyzed 40 patients with PCA who received 16- or 12-fraction CIRT at our center. Linear-quadratic (LQ) and RBE-conversion models were employed to convert the constraints into various fractionations and biophysical models. Based on them, the MKM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to 12-, 8-, and 4-fraction CIRT using the LQ model. Then, MKM constraints were converted to LEM using the RBE-conversion model. Meanwhile the LEM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to LEM using the RBE-conversion model. Then, LEM constraints were converted from 16-fraction constraints to the rectum constraints for 12-, 8-, and 4-fraction CIRT using the LQ model. The LEM constraints for 16- and 12-fraction CIRT were evaluated using rectum doses and clinical follow-up. To adapt them for the MKM LQ strategy, CNAO LEM constraints were first converted to MKM constraints using the RBE-conversion model. Results The NIRS (i.e. DMKM|v, V-20%, 10%, 5%, and 0%) and CNAO rectum constraints (i.e. DLEM|v, V-10 cc, 5 cc, and 1 cc) were converted for 12-fraction CIRT using the MKM LQ strategy to LEM 37.60, 49.74, 55.27, and 58.01 Gy (RBE), and 45.97, 51.70, and 55.97 Gy (RBE), and using the LEM LQ strategy to 39.55, 53.08, 58.91, and 61.73 Gy (RBE), and 49.14, 55.30, and 59.69 Gy (RBE). We also established LEM constraints for 8- and 4-fraction CIRT. The 10-patient RBE-conversion model was comparable to 30-patient model. Eight patients who received 16-fraction CIRT exceeded the corresponding rectum constraints; the others were within the constraints. After a median follow-up of 10.8 months (7.1–20.8), No ≥ G1 late rectum toxicities were observed. Conclusions The LEM rectum constraints from the MKM LQ strategy were more conservative and might serve as the reference for hypofractionated CIRT. However, Long-term follow-up plus additional patients is necessary.

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Conversion and Validation of Rectal Constraints for Prostate Carcinoma Receiving Hypofractionated Carbon-ion Radiotherapy With a Local Effect Model

10.21203/rs.3.rs-120631/v1 ◽

2020 ◽

Author(s):

Weiwei Wang ◽

Ping Li ◽

Yinxiangzi Sheng ◽

Zhijie Huang ◽

Jingfang Zhao ◽

...

Keyword(s):

Kinetic Model ◽

Prostate Carcinoma ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Study Objective ◽

Carbon Ion ◽

Conversion Model ◽

Biophysical Models ◽

Effect Model

Abstract Purpose: The study objective was to convert the microdosimetric kinetic model (MKM) rectum constraints for 16-fraction carbon-ion radiotherapy (CIRT) to local effect model (LEM) constraints for 12-fraction, 8-fraction, and 4-fraction CIRT for prostate carcinoma patients (PCAs).Methods: Two strategies were employed. To understand the fractionation effects, MKM linear-quadric (LQ) strategy first converted MKM rectum constraints for 16-fraction CIRT to 12-fraction, 8-fraction, and 4-fraction CIRT. To examine the differences in the biophysical models, MKM constraints were converted to LEM constraints using an RBE-conversion model. The LEM LQ strategy first converted MKM rectum constraints for 16-fraction CIRT to LEM constraints using the RBE-conversion model. Then, the LEM constraints converted the 16-fraction constraints to the rectum constraints for 12-fraction, 8-fraction, and 4-fraction CIRT using the LQ model. The LEM rectum constraints for 16 and 12-fraction CIRTs were compared to the rectum doses and the clinical follow-ups in 40 patients.Results: The 16-fraction NIRS rectum constraint Dmax < 60.8 Gy(RBE) and CNAO rectum constraint D1cc < 66.00 Gy(RBE) were converted by MKM LQ strategy to LEM constraints 58.01 and 55.97 Gy(RBE) (12fx), 45.47 and 43.97 Gy(RBE) (8fx), and 29.64 and 28.67 Gy(RBE) (4fx) and by LEM LQ strategy to 61.73 and 59.69 Gy(RBE) (12fx), 53.03 and 51.33 Gy(RBE) (8fx), and 40.10 and 38.88 Gy(RBE) (4fx). Differences of 36.13% were found. No late rectum complications were reported.Conclusions: The LEM rectum constraints from MKM LQ strategy were more conservative and can be used as the reference constraints for starting the hypofractionated CIRT.

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RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model

10.21203/rs.3.rs-31228/v1 ◽

2020 ◽

Author(s):

Liwen Zhang ◽

Weiwei Wang ◽

Jiyi Hu ◽

Jiade Lu ◽

Lin Kong

Keyword(s):

Nasopharyngeal Carcinoma ◽

Kinetic Model ◽

Target Volume ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Effect Model ◽

Target Volumes ◽

Treatment Plans ◽

Recurrent Nasopharyngeal Carcinoma

Abstract Background We sought to establish a conversion curve to convert the local effect model I (LEM) based RBE-weighted doses (LEM doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the microdosimetric kinetic model (MKM) based RBE-weighted dose (MKM doses) model. We also converted the relevant organ at risk (OAR) constraints based on this curve. Methods Data from 13 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. Clinical target volume CTV1(GTV+5mm)was given 63 Gy (RBE) in 21 fractions. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of the ratio of LEM dose to MKM dose was obtained as the conversion factor to obtain the conversion curve by using an isovolumetric dose method. Using prescriptions and OAR, constraints were converted to MKM doses with this curve. Results Conversion factors (LEM dose/MKM dose) from 1.37±0.02 to 3.09±0.09 corresponded to the LEM fractionated doses from 0.24 Gy (RBE) to 2.86 Gy (RBE), including the doses constraining upon OARs. LEM doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM doses of 16.64 Gy (RBE) and 30.98 Gy (RBE) in 16 fractions. Conclusions This conversion curve could be used to convert LEM doses to MKM doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.

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RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model

10.21203/rs.3.rs-31228/v3 ◽

2020 ◽

Author(s):

Liwen Zhang ◽

Weiwei Wang ◽

Jiyi Hu ◽

Jiade Lu ◽

Lin Kong

Keyword(s):

Spinal Cord ◽

Nasopharyngeal Carcinoma ◽

Kinetic Model ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Conversion Factors ◽

Carbon Ion ◽

Effect Model ◽

Recurrent Nasopharyngeal Carcinoma ◽

Dose Constraints

Abstract Background: We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve.Methods: Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1（GTV+5mm）was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve. Results: For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95％ 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37(CI 95％ 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions. Conclusions: This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.

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RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model

Radiation Oncology ◽

10.1186/s13014-020-01723-z ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Liwen Zhang ◽

Weiwei Wang ◽

Jiyi Hu ◽

Jiade Lu ◽

Lin Kong

Keyword(s):

Spinal Cord ◽

Nasopharyngeal Carcinoma ◽

Kinetic Model ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Conversion Factors ◽

Carbon Ion ◽

Effect Model ◽

Recurrent Nasopharyngeal Carcinoma ◽

Dose Constraints

Abstract Background We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve. Methods Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1 (GTV + 5 mm) was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve. Results For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95% 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37 (CI 95% 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions. Conclusions This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.

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A single institutional experience of carbon-ion radiotherapy for locally advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.461 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 461-461

Author(s):

Makoto Shinoto ◽

Yoshiyuki Shioyama ◽

Hiroaki Suefuji ◽

Shingo Toyama ◽

Keiji Matsumoto

Keyword(s):

Pancreatic Cancer ◽

Survival Rate ◽

Fdg Pet ◽

Locally Advanced ◽

Tumor Resection ◽

Advanced Pancreatic Cancer ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Carbon Ion

461 Background: Carbon-ion radiotherapy (C-ion RT) has the potential advantages in terms of improved dose localization and enhanced biological effectiveness compared to conventional radiotherapy or proton therapy. C-ion RT is expected to contribute to the prolongation of survival in patients with pancreatic ductal adenocarcinoma (PDAC). We started C-ion RT for pancreatic cancer at SAGA HIMAT since April 2014. The aim of this study is to evaluate the clinical results of C-ion RT for locally advanced PDAC. Methods: From April 2014 to May 2016, 76 patients with pancreatic cancer were treated with definitive C-ion RT. 44 patients who were confirmed as unresectable locally advanced PDAC were included in this retrospective analysis. 32 patients were excluded because of resectable disease (n = 8), borderline disease (n = 6), without pathological confirmation (n = 20). C-ion RT was performed with 55.2 Gy (RBE) at 12 fractions in 3 weeks. The anti-tumor effect was evaluating using CT and FDG-PET according to RECIST ver. 4.0. Results: The median follow-up period was 12.8 (range 3.4-27.5) months from the initiation of C-ion RT. In all patients, planned C-ion RT was completed. Induction chemotherapy was performed in 35 (80%) and the median duration time was 3 (range 1-19) months. Forty patients (91%) underwent concurrent chemotherapy with gemcitabine or S-1. Local effect using CT criteria was CR in 2, PR in 5, and SD in 37. The evaluation adding FDG-PET criteria was CR in 25, PR in 6, and SD in 13. Five patients (11%) experienced local recurrence during follow-up period. Two patients who had SD by CT and CR by FDG-PET performed tumor resection and were revealed pathological CR. One and two-year survival rate from C-ion RT were 82% and 66%, respectively. The two-year survival rate from initial treatment was 75%. Only three patients (7%) experienced grade 3 toxicities that were leukopenia, anorexia, and gastric ulcer. There was no grade 4 or 5 toxicity. Conclusions: C-ion RT for locally advanced PDAC was effective and well tolerated. FDG-PET was useful for the evaluation of local effect after C-ion RT.

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Carbon Ion Dose Constraints in the Head and Neck and Skull Base: Review of MedAustron Institutional Protocols

International Journal of Particle Therapy ◽

10.14338/ijpt-20-00093.1 ◽

2021 ◽

Vol 8 (1) ◽

pp. 25-35

Author(s):

Piero Fossati ◽

Ana Perpar ◽

Markus Stock ◽

Petra Georg ◽

Antonio Carlino ◽

...

Keyword(s):

Head And Neck ◽

Local Effect ◽

Brain Parenchyma ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Effect Model ◽

Dose Volume ◽

Ion Therapy ◽

Dose Constraints ◽

Fractionation Schedules

Abstract Background Dose constraints are of paramount importance for the outcome of any radiotherapy treatment. In this article, we report dose-volume constraints as well as currently used fractionation schedules for carbon ion radiotherapy as applied in MedAustron (Wiener Neustadt, Austria). Materials and Methods For fractionation schedules, both German and Japanese regimes were used. From the clinical experience of National Institute of Radiological Sciences (Chiba, Japan) and Heidelberg Ion Therapy (Heidelberg, Germany; formerly GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) and the work by colleagues in Centro Nazionale Adroterapia Oncologica (Pavia, Italy) recalculating the dose from the microdosimetric kinetic model to the local effect model, we have set the dose constraints for critical organs of the head and neck area. Where no clinical data was available, an educated guess was made, based on data available from photon and proton series. Results We report the constraints for the optic nerve and chiasm, brainstem, spinal cord, cochlea, brain parenchyma, salivary gland, eye and adnexa, and mandibular/maxillary bone; constraints are grouped based on a fractionation scheme (German versus Japanese) and the risk of toxicity (safe, low to middle, and middle to high). Conclusion We think validation of dose constraints should present a relevant part of the activity of any carbon ion radiotherapy facility, and we anticipate future multicentric, joint evaluations.

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RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model

10.21203/rs.3.rs-31228/v2 ◽

2020 ◽

Author(s):

Liwen Zhang ◽

Weiwei Wang ◽

Jiyi Hu ◽

Jiade Lu ◽

Lin Kong

Keyword(s):

Spinal Cord ◽

Nasopharyngeal Carcinoma ◽

Kinetic Model ◽

Local Effect ◽

Carbon Ion Radiotherapy ◽

Conversion Factors ◽

Carbon Ion ◽

Effect Model ◽

Recurrent Nasopharyngeal Carcinoma ◽

Dose Constraints

Abstract Background We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve. Methods Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1（GTV+5mm）was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve. Results For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95％ 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37(CI 95％ 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions. Conclusions This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.

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Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽

10.1186/s12894-021-00871-y ◽

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.

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

10.21203/rs.3.rs-32254/v1 ◽

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.

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

PLoS ONE ◽

10.1371/journal.pone.0241636 ◽

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.

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