Long-term clinical outcomes of patients receiving proton beam therapy for caudate lobe hepatocellular carcinoma

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P < 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.     

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery

We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1–10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery.     

Capacity of proton beams in preserving normal liver tissue during proton beam therapy for hepatocellular carcinoma

Unirradiated liver volume (ULV) preservation rate is an important factor associated with radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) undergoing proton beam therapy (PBT). The purpose of this study is to identify the predictors for ULV preservation and quantify the capacity of proton beams in normal liver sparing during PBT. We reviewed planning data of 92 patients with single intrahepatic HCC tumors undergoing PBT. The potential clinical and planning factors that may affect ULV preservation were involved in multiple linear regression for ULV preservation rate. The significant factors were determined to be predictors and their influences were quantified. The median ULV preservation rate was 62.08%. All the assessed clinical factors showed significant effects on ULV preservation rate: clinical target volume (CTV), P < 0.001; portal vein tumor thrombosis (PVTT), P = 0.010; left lobe tumor, P = 0.010. In contrast, none of the planning factors demonstrated significance. The coefficients of significant factors in multiple linear regression were 60.85 for intercept, −0.02 for CTV, −9.01 for PVTT and 8.31 for left lobe tumors. The capacity of proton beams to spare normal liver tissue during PBT for HCC is mainly affected by clinical factors. The baseline of the ULV preservation rate is 60.85%, decreasing 0.02% with each milliliter of CTV increase and 9.01% for tumors with PVTT, and increasing 8.31% for tumors limited to the left lobe. Further clinical studies should be carried out to correlate our dosimetric findings with clinical outcomes.     

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood

Background: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. Methods: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. Results: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Conclusions: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer''s standpoint.     

Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study

In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivary gland tumor cell line, HSG, was irradiated with clinical proton beams (accelerated by 190 MeV/u) and examined at different depths in the distal part and the center of the SOBP. Surviving fractions were analyzed with the colony formation assay. Cell survival curves and the survival parameters were obtained by fitting with the linear–quadratic (LQ) model. The RBE at each depth of the proton SOBP compared with that for X-rays was calculated by the biological equivalent dose, and the biological dose distribution was calculated from the RBE and the absorbed dose at each position. Although the physical dose distribution was flat in the SOBP, the RBE values calculated by the equivalent dose were significantly higher (up to 1.56 times) at the distal end than at the center of the SOBP. Additionally, the range of the isoeffective dose was extended beyond the range of the SOBP (up to 4.1 mm). From a clinical point of view, this may cause unexpected side effects to normal tissues at the distal position of the beam. It is important that the beam design and treatment planning take into consideration the biological dose distribution.     

Working memory and processing speed among pediatric brain tumor patients treated with photon or proton beam radiation therapy

Improved medical technology has enabled many pediatric patients with brain tumors to live longer and enjoy a better quality of life. Medical advances, such as proton beam radiation therapy (PBRT), spares more healthy tissue than traditional radiation (RT) and is thought to result in fewer cognitive late effects. However, PBRT is more expensive, and questions remain whether the cost is justified in terms of short- and long-term health improvements. This study aimed to determine whether working memory and processing speed differed across time in pediatric brain tumor patients treated with RT(n = 17) or PBRT (n = 22). The acute neurocognitive effects of RT and PBRT were examined by comparing neuropsychological test performance on the WISC-IV at treatment initiation (Time 1) and approximately 2-years post-treatment initiation (Time 2). Statistical analysis showed that regardless of treatment type, working memory and processing speed decreased over time. Further, results revealed that gender and age, but not tumor location, impacted working memory scores. Decline in processing speed was not associated with any of these medical or demographic variables. Despite the small sample size and limited power, results support the importance of comprehensive evaluations in this population, which may lead to better educational and vocational outcomes.     

单病种付费对前列腺增生患者住院费用及医疗服务满意度的影响

目的 评估单病种付费对前列腺增生患者住院费用和医疗服务满意度的影响。方法 本院2015年6月—2018年6月主要诊断为前列腺增生的出院患者,按是否采用单病种付费将其分为实验组和对照组。采用典型抽样法,对2组患者进行医疗服务满意度问卷调查。比较分析2组患者住院费用、主要诊断符合率、治愈率、并发症发生率、治疗效果和医疗服务满意度评分。结果 采用单病种付费方式患者较未采用的患者住院时间有所缩短,治疗费用显著降低,其中化验费、检查费、药费和麻醉费减少明显,差异有统计学意义(P<0.01)。而2组主要诊断符合率、治愈率、并发症发生率和满意度评分差异无统计学意义(P>0.05)。结论 单病种付费在保障医疗安全和服务质量的基础上,明显降低了患者医疗费用,费用结构趋于合理,但也需要进一步完善相关配套政策,以更有效地发挥其作用。     

Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.     

Outcomes of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Nasopharyngeal cancer shows a good response to intensity-modulated radiotherapy. However, there is no clear evidence for the benefits of routine use of image-guided radiotherapy. The purpose of this study was to perform a retrospective investigation of the treatment outcomes, treatment-related complications and prognostic factors for nasopharyngeal cancer treated with intensity-modulated radiotherapy and image-guided radiotherapy techniques. Retrospective analysis was performed on 326 consecutive nasopharyngeal cancer patients treated between 2004 and 2015. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. The 5-year overall survival and disease-free survival rates of these patients were 77.9% and 70.5%, respectively. Age, AJCC (American Joint Committee on Cancer) stage, retropharyngeal lymphadenopathy, treatment interruption and body mass index were independent prognostic factors for overall survival. Age, AJCC stage, retropharyngeal lymphadenopathy, image-guided radiotherapy and body mass index were independent prognostic factors for disease-free survival. In conclusion, intensity-modulated radiotherapy significantly improves the treatment outcomes of nasopharyngeal cancer. With the aid of image-guided radiotherapy, the advantage of intensity-modulated radiotherapy might be further amplified.     

Impact of early radiological response evaluation on radiotherapeutic outcomes in the patients with nasal cavity and paranasal sinus malignancies

We analyzed the correlation between primary tumor response within 6 months after radiation therapy (RT) including proton beam therapy (PBT) and progression free survival rate (PFS) in patients with nasal cavity and paranasal sinus malignancies to clarify the impact of early radiological evaluation of treatment response on prognosis. Sixty-five patients treated between January 1998 and December 2008, and whose follow-up duration was more than 2 years were included. The Response Evaluation Criteria in Solid Tumors (version 1.1) was used for the evaluation of treatment. Median age was 59 years (range 21–83 years). Olfactory neuroblastoma (n = 20, 30%) and squamous cell carcinoma (n = 15, 23%) were the major pathological tumor types. The median follow-up duration was 51.6 months. Radiological response evaluation within 6 months after treatment demonstrated that 15% of the patients achieved complete response (CR), and 3-year progression free survival rates of all patients was 49.2%. The 3-year PFS rates according to response for the treatment were 55.6% in the patients with CR and 46.4% in those with non-CR, respectively (P = 0.643). However, the 3-year PFS rates were 80.% in the patients with CR and 10.% in those with non-CR (P = 0.051) in the patients with squamous cell carcinoma (SCC) histology. Radiological response evaluation within 6 months did not have a significant impact on prognosis when analysis included all histology, although early radiological response within 6 months after RT had a borderline significant impact on treatment outcomes for the patients with nasal and paranasal SCC.     

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2–135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.     

Clinical results of external beam radiotherapy alone with a concomitant boost program or with conventional fractionation for cervical cancer patients who did not receive intracavitary brachytherapy

A combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) is well established as the standard radical radiotherapy (RT) for cervical cancer. However, it is sometimes necessary to perform EBRT alone for patients where ICBT is not feasible. For these patients, we initiated EBRT alone with three-dimensional conformal radiotherapy (3DCRT). The purpose of this study is to evaluate the results of EBRT alone without ICBT for patients with cervical cancer. Sixteen patients were treated with EBRT alone between 2002 and 2009. There were three stage IIB, six stage IIIB and seven patients with stage IVA disease. A total of 10 patients were treated with a median dose of 66 Gy with a median overall treatment time (OTT) of 40 days delivered by a concomitant boost (CCB), and a median dose of 60 Gy with a median OTT of 47 days was administered for six patients by conventional fractionation (CF). The 3-year overall survival (OAS) and local control (LC) rates were 43.8% and 75.0%, respectively. The 3-year LC rate was 90.0% for the CCB group, 50.0% for the CF group (P = 0.0692); 100% for OTT ≤42 days, 42.9% for OTT ≥43 days (P = 0.0095). No severe acute and late adverse effects were encountered for any of the patients. These outcomes suggest that EBRT with a CCB program may be a promising radical treatment for cervical cancer that provides better LC with minimal complications, especially in cases where ICBT cannot be performed.     

Prediction of proton beam range in phantom with metals based on monochromatic energy CT images

The purpose of the study was to evaluate the accuracy of monochromatic energy (MonoE) computed tomography (CT) images reconstructed by spectral CT in predicting the stopping power ratio of materials in the presence of metal. The CIRS062 phantom was scanned three times using spectral CT. In the first scan, a solid water insert was placed at the center of the phantom . In the second scan, the solid water insert was replaced with a titanium alloy femoral head . The metal artifact reduction (MAR) algorithm was used in the last scan . The MonoE-CT images of 40 keV and 80 keV were reconstructed. Finally, the single-energy CT method (SECT) and the dual-energy CT method (DECT) were used to calculate the . The mean absolute error (MAE) of the of the inner layer inserts calculated by the SECT method were 3.19%, 13.88% and 2.71%, corresponding to , and , respectively. For the outer layer inserts, the MAE of were 3.43%, 5.42% and 2.99%, respectively. Using the DECT method, the MAE of the of the inner layer inserts was 1.30%, 3.69% and 1.46% and the MAE of the outer layer inserts– was 1.34%, 1.36% and 1.05%. The studies shows that, compared with the SECT method, the accuracy of the DECT method in predicting the of a material is more robust to the presence of metal. Using the MAR algorithm when performing CT scans can further improve the accuracy of predicting the SPR of materials in the presence of metal.     

Changes in sexual function and serum testosterone levels in patients with prostate cancer after image-guided proton therapy

Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before and after IGPT. Among patients treated with IGPT with or without combined androgen blockade (CAB) therapy between February 2013 and September 2014, patients who agreed to participate in the study and were followed up for >3 years after IGPT were evaluated. Serum testosterone levels were regularly measured together with prostate-specific antigen (PSA) levels before and after IGPT. The Erection Hardness Score (EHS) and the sexual domain summary, function subscale and bother subscale of the sexual domain in the Expanded Prostate Cancer Index Composite (EPIC) were assessed. There were 38 low-risk, 46 intermediate-risk and 43 high- or very-high-risk patients (NCCN classification). Although serum testosterone levels in low-risk patients did not decrease after IGPT, reductions were observed in the average EHS and the sexual domain summary score of the EPIC. In intermediate-, high- and very-high-risk patients, testosterone and PSA levels both increased following the termination of CAB after IGPT, and the average EHS increased. The sexual domain summary score gradually increased, but not above minimally important differences. In intermediate-risk patients, the function subscale increased from 4.4 to 14.8 (P < 0.05) 12 months after IGPT and reached a plateau after 60 months. The results of the present study would suggest the potential of IGPT, and further prospective studies to directly compare IGPT with other modalities are warranted.     

Current status and outcomes of patients developing PSA recurrence after prostatectomy who were treated with salvage radiotherapy: a JROSG surveillance study

The conditions and outcomes of Japanese patients with prostate cancer who developed PSA failure after radical prostatectomy (RP), and who were treated via salvage radiotherapy (S-RT), were surveyed. Clinical data on S-RT were gathered in questionnaires completed by facilities participating in the Japanese Radiation Oncology Study Group. S-RT was defined as external-beam radiotherapy delivered to the prostate beds of patients with prostate cancer who had eventually developed PSA failure, although their PSA values had at one stage attained levels <0.2 ng/ml following RP. Hormonal therapy was combined with S-RT in ∼40% of cases. Outcomes were evaluated in 186 cases treated via S-RT alone. The nadir PSA level after RP, and the level upon initiation of S-RT, were 0.0135 ng/ml and 0.292 ng/ml, respectively. The median period between RP and S-RT was 18.6 months. The median follow-up period was 58 months. The 5-year PSA recurrence–free survival (PRFS) and clinical failure–free survival (CFFS) rates were 50.1% (95% CI: 42.8–57.9%) and 90.1% (95% CI: 86.4–95.7%), respectively. PRFS was significantly superior in patients with PSA values ≤0.3 ng/ml upon initiation of S-RT than in those with PSA values >0.3 ng/ml (57.5% vs 40.5%, P = 0.027). In Japan, hormonal therapy is combined with S-RT in ∼40% of cases. The 5-year PRFS and CFFS rates of cases treated via S-RT alone were 50.1% and 90.1%, respectively. A PSA value of 0.3 ng/ml served as a significant cut-off for prediction of PRFS.     

腹式与困难阴式全子宫切除术对子宫良性病变患者的影响对比

目的 探究腹式全子宫切除术(TAH)与困难阴式全子宫切除术(TVH)对子宫良性病变患者术中术后指标及随访情况的影响.方法 选取淮安市妇幼保健院在2015年1至12月期间收治的、符合纳入标准的子宫良性病变患者50例.根据手术方法的不同,分为腹式组(n=12)和阴式组(n=38).阴式组分为3个亚组,即大子宫组(n=20)、多种困难因素并存组(n=13)以及既往盆腔手术史或内膜异位症组(n=5).对比两组术中出血量、手术时间、术后发热、住院时间等术中术后情况;术后随访6个月,记录患者并发症及性生活满意度情况.结果 与腹式组相比,阴式组的术中出血量、手术时间、术中输血例数、术后发热、术后排气时间及住院时间均较低,差异具有统计学意义(t/χ2值分别为11.56、9.13、4.41、8.65、13.40、9.91,均P<0.05).术后随访6个月,两组并发症及性生活满意度比较无明显差异(χ2=0.07,P>0.05).阴式组组间比较发现,大子宫组的子宫重量高于其他两组(F=56.09,P<0.01);多种困难因素并存组的手术时间长于其他两组(F=49.02,P<0.01);3个亚组术中出血量比较无明显差异(F=0.17,P>0.05).结论 改良困难阴式全子宫切除术具有微创、安全、有效等特点,值得临床推广.     

Hypofractionated electron-beam radiation therapy for keloids: retrospective study of 568 cases with 834 lesions

We aimed to analyze the outcomes of hypofractionated high-energy electron beam radiotherapy for the treatment of keloids. From February 1998 to January 2012, 568 patients with a total of 834 keloids underwent radiotherapy: 826 lesions with postoperative radiotherapy, and 36 with skin-grafting. Lesion size was >5 cm in 335 keloids. An electron-beam of 6 or 7 MeV was used, with a total dose of 18 Gy (two fractions with a 1-week interval) covering the lesion with a 1-cm margin. The time between surgery and radiotherapy was 24–48 h. Skin-grafted patients underwent radiotherapy 10–15 days after the operation. The median follow-up was 40 months (range: 12–160 months). The local control rate was 88.25% (736/834). The relapse rate was 9.59% (80/834), and the time to relapse was 6–28 months (median: 12 months). Univariate analyses showed that gender, age, keloid size, keloid site, skin grafting, and operation-to-irradiation interval influenced the local control rate. Multivariate analysis showed that the relapse rate was correlated with gender (P = 0.048), age (P < 0.01), operation-to-irradiation interval (P < 0.01), keloid site (P < 0.01), surgical method (P = 0.04) and keloid size (P < 0.02). Adverse effects were observed in 9.83% (82/834). No radiation-induced cancers were observed. Hypofractionated high-energy electron beam radiotherapy for keloids yielded excellent outcomes, especially in cases without skin grafting. Early postoperative radiotherapy with limited hypofractionation could be a good choice for keloid treatment.     

良性前列腺增生患者生命质量量表QLICD-BPH研制与评价

目的 研制良性前列腺增生患者生命质量测定量表（QLICD-BPH）并对其进行评价。方法 依据慢性病患者生命质量测定量表体系共性模块与特异模块相结合的研究思想,在对文献回顾的基础上,结合中国文化特色,采用量表开发的程序化决策方式研制量表,并通过测试141例良性前列腺增生（BPH）患者的生命质量对量表进行评价。结果 QLICD-BPH量表的重测信度为0.95;Cronbach’s α系数为0.91;分半信度为0.72;相关分析和因子分析显示有较好的结构效度,反应度也尚可;各条目与其所在领域的相关均大于与其他领域的相关,相关系数r值多>0.5。结论 BPH患者QLCID-BPH量表具有较好的信度、效度和反应度,可以作为临床BPH患者的测评工具。     

RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro study at the Proton Medical Research Center at the University of Tsukuba

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBE_plateau) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBE_plateau was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBE_plateau was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBE_plateau or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba.