Loose versus stranded seeds in permanent prostate brachytherapy: Dosimetric comparison of intraoperative plans

PurposeTo compare target volume coverage and critical organ dosimetry of intraoperative treatment plans for loose seed (LS) and stranded seed (SS) ¹²⁵I permanent implants for low and intermediate risk prostate cancer.MethodsTwo hundred and five patients who underwent permanent seed brachytherapy were included in the study. For prostate dosimetry V90, V100, V150, V200, D90 and COIN were used. The dose to urethra and rectum was determined by the maximal dose and relative doses that cover specified volumes. Means and standard deviations were calculated and statistically compared.ResultsOn average, 54 (range, 30–78) and 48 (range, 31–67) seeds were implanted in the prostate with individual median activities of 0.62 U (range, 0.52–0.70 U) and 0.71 U (range, 0.65–0.71 U) for LS and SS technique, respectively. The target coverage was slightly better with SS (V100: 98% vs. 96%, p < 0.05; D90: 172 Gy vs. 166 Gy, p < 0.05), but more conformal dose distributions were observed with LS (COIN: 0.70 vs. 0.63, p < 0.05). The dose homogeneity did not differ significantly between the two groups. Regarding the dose to urethra and rectum all dose parameters were significantly lower with LS.ConclusionsLS resulted in less dose to the urethra and rectum compared to SS in intraoperative dosimetry. A slightly better target volume coverage with decreased conformity of dose distribution is reported with SS. More studies are necessary to determine how these results will affect postoperative dosimetry, and ultimately, clinical outcome.     

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy

PurposeRetrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy.Materials and methodsBetween 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120−130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0).ResultsAt a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding).ConclusionSalvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.     

Volumetric modulated arc therapy for prostate cancer patients with hip prosthesis

Aim

To study the use of RapidArc techniques in the treatment of prostate cancer patients with hip prosthesis.

Background

An important aspect of treatment planning is to achieve dose homogeneity inside the planning target volume (PTV). Especially for those patients presenting with hip prosthesis, it becomes a challenging task to achieve dose uniformity inside the PTV.

Materials and methods

Five prostate patients presenting with hip prosthesis who had undergone radical radiotherapy were selected for this study. Depending on the composition of prosthesis, a predefined set of Hounsfield values were assigned to each study set. RapidArc plans were generated on an Eclipse treatment planning system. Two arcs that include clockwise and counter-clockwise arcs were used in all these cases. To avoid beams passing through the prosthesis, a simple structure was defined around it with 1 cm margin and a strict dose constraint applied to the block during VMAT optimization.

Results

The mean D2/D98 ratio of PTV for all the patients was 1.06 ± 0.01. The mean percentage rectum volume receiving 50 Gy, 60 Gy, 70 Gy and 75 Gy for all the patients were 33.1 ± 5.9, 21.7 ± 5.5, 13.8 ± 4.4 and 9.5 ± 3.0, respectively.

Conclusions

This study shows that using a double arc RapidArc technique is a simple and effective treatment method of treating prostate cancer in patients presenting with a hip prosthesis. The definition of a beam avoidance structure encompassing the prosthesis and applying strict dose constraints to it reduces the beam contribution to the prosthesis     

Empirical estimation of beam-on time for prostate cancer patients treated on Tomotherapy

Background and aim

This study proposed a method to estimate the beam-on time for prostate cancer patients treated on Tomotherapy when FW (field width), PF (pitch factor), modulation factor (MF) and treatment length (TL) were given.

Material and methods

The study was divided into two parts: building and verifying the model. To build a model, 160 treatment plans were created for 10 patients. The plans differed in combination of FW, PF and MF. For all plans a graph of beam-on time as a function of TL was created and a linear trend function was fitted. Equation for each trend line was determined and used in a correlation model. Finally, 62 plans verified the treatment time computation model – the real execution time was compared with our estimation and irradiation time calculated based on the equation provided by the manufacturer.

Results

A linear trend function was drawn and the coefficient of determination R² and the Pearson correlation coefficient r were calculated for each of the 8 trend lines corresponding to the adequate treatment plan. An equation to correct the model was determined to estimate more accurately the beam-on time for different MFs. From 62 verification treatment plans, only 5 disagreed by more than 60 s with the real time from the HT software. Whereas, for the equation provided by the manufacturer the discrepancy was observed in 16 cases.

Conclusions

Our study showed that the model can well predict the treatment time for a given TL, MF, FW and it can be used in clinical practice.     

Preliminary clinical outcomes of patients treated with vaginal brachytherapy alone using multi-channel vaginal brachytherapy applicator in operated early-stage endometrial cancer

BackgroundRecommendations for adjuvant treatment for postoperative, early-stage endometrial cancer varies from observation through vaginal brachytherapy alone to pelvic radiation. While observation alone can lead to recurrence, external radiotherapy has increased morbidity. The aim of this study is to show our results with vaginal brachytherapy alone using a multichannel applicator for treatment of early-stage endometrial cancer.Materials and methodsConsecutive patients undergoing vaginal brachytherapy alone following surgery for early-stage endometrial cancer were examined. A Miami multichannel vaginal brachytherapy applicator was used to deliver HDR brachytherapy in 62 patients from May 2013 to June 2018. CT scan-based images guided planning. A dose of 5.5–6.5 Gy × 4 fractions was prescribed 5 mm from the surface of the applicator.ResultsAt a median follow up of 19 months (6–48 months), 93% of patients treated were alive with no recurrence. Two patients had only local recurrence, and 1 was salvaged with external radiotherapy and chemotherapy. There was only one nodal failure and 2 distant failures. There was no grade 2 or higher vaginal, gastrointestinal or genitourinary toxicity.ConclusionVaginal brachytherapy alone using a multichannel applicator can be considered for early-stage endometrial cancers without compromising outcomes.     

前列腺钙化灶的超声显像诊断与分型的临床研究

目的：探究超声显像诊断前列腺钙化灶（PFC）的临床实用价值和超声分型。方法：对1284倒经腹部超声显像诊断为PFC的临床资料进行回顾性分析,并根据超声所见进行分型。结果：超声显像诊断PFC1,284例,单发768倒（59．81％）。多发516例（40．19％）;钙化灶直径2-36mm;Ⅰ度542例（42．21％）,Ⅱ度460例（35．83％）,Ⅲ度282例（21．96％）;孤立型412例（32．09％）,散在型319例（24．84％）,聚集型395例（30．76％）,条索型158例（12-31％）。内腺435例（33．88％）、外腺348例（（27．10％）、内外腺交界处351例（27．34％）、后尿道周围150例（11．68％）。单纯性钙化520例（40．50％）,合并前列腺增生597例（46．50％）、前列腺炎129例（10．05％）、前列腺囊肿36例（2．80％）、前列腺癌2例（0．16％）。结论：PFC是男性泌尿生殖系统常见疾病,其程度和类型与年龄密切相关,近半数与前列腺增生并存,可能与组织退变、增生、炎症、钙磷代谢紊乱等因素有关。超声显像是诊断PFC最可靠、最简便的方法,具有重要的l陆床实用价值。     

Design and optimizing a novel ocular plaque brachytherapy with dual-core of 103Pd and 106Ru

In recent decades, eye plaques of brachytherapy have been extensively used as primary treatment as well as a complementary treatment for ocular cancer. The purpose of this study is the development of the eye plaque brachytherapy throughout a new design of eye plaque by combining the COMS plaque and the CCB BEBIG plaque loaded by IRA1-¹⁰³Pd and ¹⁰⁶Ru, respectively. A new dual-core plaque with a diameter of 20 mm was designed in the way that the BEBIG plaque with a diameter of 20 mm loaded by ¹⁰⁶Ru plate is attached to the COMS plaque with a diameter of 20 mm loaded by 24 of IRA1-¹⁰³Pd seeds. Dose calculations for the new plaque were performed by using the MCNP5 code. Dose calculations of dual-core plaque including ¹⁰³Pd seeds (gamma) and ¹⁰⁶Ru plate (beta) were separately done for the sake of MCNP constraints in gamma and beta particle transfer simultaneously. The new dual-core plaque delivers a much higher dose rate to the tumor compared with every single plaque, while the dose rate reached to healthy tissues is slightly higher than each plaque separately. Of course, this is acceptable because the treatment time reduces and subsequently the error in radiation therapy reduces.     

前列腺钙化灶的超声显像诊断与分型的临床研究

目的:探究超声显像诊断前列腺钙化灶(PFC)的临床实用价值和超声分型。方法:对1284例经腹部超声显像诊断为PFC的临床资料进行回顾性分析,并根据超声所见进行分型。结果:超声显像诊断PFC 1,284例,单发768例(59.81%),多发516例(40.19%);钙化灶直径2~36mm;Ⅰ度542例(42.21%),Ⅱ度460例(35.83%),Ⅲ度282例(21.96%);孤立型412例(32.09%),散在型319例(24.84%),聚集型395例(30.76%),条索型158例(12.31%)。内腺435例(33.88%)、外腺348例((27.10%)、内外腺交界处351例(27.34%)、后尿道周围150例(11.68%)。单纯性钙化520例(40.50%),合并前列腺增生597例(46.50%)、前列腺炎129例(10.05%)、前列腺囊肿36例(2.80%)、前列腺癌2例(0.16%)。结论:PFC是男性泌尿生殖系统常见疾病,其程度和类型与年龄密切相关,近半数与前列腺增生并存,可能与组织退变、增生、炎症、钙磷代谢紊乱等因素有关。超声显像是诊断PFC最可靠、最简便的方法,具有重要的临床实用价值。     

Effect of accounting for interfractional CTV shape variations in PTV margins on prostate cancer radiation treatment plans

PurposeThe aim of this study was to account for interfractional clinical target volume (CTV) shape variation and apply this to the planning target volume (PTV) margin for prostate cancer radiation treatment plans.MethodsInterfractional CTV shape variations were estimated from weekly cone-beam computed tomography (CBCT) images using statistical point distribution models. The interfractional CTV shape variation was taken into account in the van Herk’s margin formula. The PTV margins without and with the CTV shape variation, i.e., standard (PTV_ori) and new (PTV_shape) margins, were applied to 10 clinical cases that had weekly CBCT images acquired during their treatment sessions. Each patient was replanned for low-, intermediate-, and high-risk CTVs, using both margins. The dose indices (D98 and V70) of treatment plans with the two margins were compared on weekly pseudo-planning computed tomography (PCT) images, which were defined as PCT images registered using a deformable image registration technique with weekly CBCT images, including contours of the CTV, rectum, and bladder.ResultsThe percentage of treatment fractions of patients who received CTV D98 greater than 95% of a prescribed dose increased from 80.3 (PTV_ori) to 81.8% (PTV_shape) for low-risk CTVs, 78.8 (PTV_ori) to 87.9% (PTV_shape) for intermediate-risk CTVs, and 80.3 (PTV_ori) to 87.9% (PTV_shape) for high-risk CTVs. In most cases, the dose indices of the rectum and bladder were acceptable in clinical practice.ConclusionThe results of this study suggest that interfractional CTV shape variations should be taken into account when determining PTV margins to increase CTV coverages.     

Dose to pelvic lymph nodes in image based high dose rate brachytherapy of carcinoma cervix

AimThe aim of this study is to analyse the dosimetry to the pelvic lymph nodes and its correlation to point B using CT based high dose rate brachytherapy of carcinoma cervix.BackgroundConventionally, dose to pelvic lymph nodes from intracavitary brachytherapy was reported by point B and by the reference points of the lymphatic trapezoid.Materials and methods30 consecutive CT based high dose rate applications were reviewed between February and March 2016. The high risk clinical target volume and the organs at risk and the pelvic nodal groups were contoured. DVH parameters for the right and left obturator nodal group, right and left external iliac nodal group and right and left internal iliac nodal group were recorded. Right and left point B doses were also recorded.ResultsOn analysis of the combined dose, it was found that all the DVH parameters were significantly different from point B, except the D100 obturator and D2cc internal iliac lymph node. There was a significant correlation between all DVH parameters and point B, except D2cc, D1cc and D0.1cc of external iliac. The obturator group received the highest dose contribution from brachytherapy. The mean D90 dose received per fraction for the obturator, external iliac and internal iliac nodes was 2.7 Gy, 1.17 Gy and 1.41 Gy, respectively.ConclusionsThere is a significant dose contribution to the pelvic lymph nodal groups during intracavitary brachytherapy. There is a low degree of correlation between point B dose and dosimetric parameters of the individual nodal groups. Hence, it is important to analyse the dose delivered to individual nodal groups during intracavitary brachytherapy, at least in patients with enlarged lymph nodes to calculate the cumulative dose delivered.     

白藜芦醇对大鼠局灶性脑缺血再灌注的治疗作用

目的:观察白藜芦醇对大鼠局灶性脑缺血再灌注损伤的治疗作用及可能的机制。方法:将SD大鼠随机分为2组:对照组(n=16),白藜芦醇组(n=16)。对照组再灌注即刻腹腔给予0.5 ml生理盐水,白藜芦醇组再灌注即刻腹腔给予20 mg/kg白藜芦醇。再灌注22小时后,进行神经功能学评分、脑梗死容积测定,用分光光度仪测定脑组织溶浆中SOD、MDA和MPO的含量。结果:再灌注22小时后,白藜芦醇治疗组可以改善大鼠神经功能学评分和降低脑梗死面积(P<0.05),同时可以增加脑组织溶浆中SOD的活性,降低MDA和MPO的含量。结论:白藜芦醇通过减轻白细胞的浸润、提高自由基的清除率对大鼠局灶性脑缺血再灌注损伤发挥治疗作用。     

Long term results of HDR brachytherapy in men older than 75 with localized carcinoma of the prostate

Background

Prostate cancer is an illness with a high incidence, especially among older men. The choice of a treatment option among men above 75 years is, however, not clear. Radical prostatectomy in this age group is connected with a relatively high morbidity. A further possibility of curative treatment is radiotherapy which can be administered in the form of external beam or in combination with high dose rate (HDR) brachytherapy.

Aim

The aim of our work was to evaluate how HDR brachytherapy is tolerated among men older than 75 and how associated diseases can influence the tolerance to this treatment. Of interest to us were the treatment results and mortality from other diseases.

Materials and methods

We analyzed a sample of 20 men above 75 years old (median 77 years) who were undergoing treatment by a combination of external radiotherapy and brachytherapy. Sixteen (80%) of them had prostate cancer with an intermediate and high risk of recurrence, four had low risk prostate cancer. Most patients, 14 (70%), had less than two comorbidities.

Results

The median observation period was 57 months. No perioperative complications were recorded. Acute genitourinary toxicity (GU) to a maximum grade of 1–2 manifested in 60% of cases. Acute gastrointestinal toxicity (GIT) was observed only at grade 1 and in 25% of cases. Late GU toxicity occurred in 35% of patients, with only one showing grade 3; late GIT toxicity was recorded at grade 1 only in 3 patients (15%). 70% of the men lived longer than 3 years after treatment, at present, 50% lived more than 5 years. Long-term biochemical remission was achieved in 18 patients (90%).

Conclusions

HDR BRT is possible and well-tolerated in older men above 75 years in good condition and without serious intercurrence.Well-selected older patients with higher-risk tumours and without serious comorbidities undoubtedly benefit from radical treatment when compared with watchful waiting.     

Biochemical failure and toxicity in treatment with brachytherapy and external beam radiotherapy compared with radical prostatectomy in localized prostate cancer

BackgroundLocalized prostate cancer (T1–3N0M0) has therapeutic options such as radical prostatectomy (RP), external beam radiation therapy (EBRT) and brachytherapy (BT). However, the evidence of the outcome of these treatments is limited and no studies have been conducted comparing biochemical failure (BF) and toxicity associated with surgical treatment and EBRT + high-dose brachytherapy (HDBT) in the region.Materials and methodsRetrospective cohort study, clinical records of patients diagnosed with localized prostate cancer between 2014 and 2018 were reviewed at one of the main private neoplasm centers in Lima, Peru; Cox regression was used for both the BF outcome and the grade 2 toxicity outcome, calculating the hazard ratio (HR) with 95% confodence interval (CI).ResultsOf 549 patients, 76.3% (419) received RP as primary treatment, and 72% were between 50 and 70 years old at the time of diagnosis. The patients treated with EBRT + HDBT presented worse characteristics. The EBRT + HDBT group had a 40% lower risk of presenting BF (HR = 0.6; 95% CI: 0.4–0.9), and also a 50% greater risk of presenting toxicity greater than or equal to grade 2 (HR = 1.5; 95% CI: 1.0–2.0) than the group treated with RP.ConclusionOur results show that when comparing patients treated with EBRT + HDBT and RP, BF was greater in RP, and post-treatment toxicity was greater in EBRT + HDBT.     

Treatment planning systems dosimetry auditing project in Portugal

Background and purposeThe Medical Physics Division of the Portuguese Physics Society (DFM_SPF) in collaboration with the IAEA, carried out a national auditing project in radiotherapy, between September 2011 and April 2012. The objective of this audit was to ensure the optimal usage of treatment planning systems. The national results are presented in this paper.Material and methodsThe audit methodology simulated all steps of external beam radiotherapy workflow, from image acquisition to treatment planning and dose delivery. A thorax CIRS phantom lend by IAEA was used in 8 planning test-cases for photon beams corresponding to 15 measuring points (33 point dose results, including individual fields in multi-field test cases and 5 sum results) in different phantom materials covering a set of typical clinical delivery techniques in 3D Conformal Radiotherapy.ResultsAll 24 radiotherapy centers in Portugal have participated. 50 photon beams with energies 4–18 MV have been audited using 25 linear accelerators and 32 calculation algorithms.In general a very good consistency was observed for the same type of algorithm in all centres and for each beam quality.ConclusionsThe overall results confirmed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy is generally acceptable with no major causes for concern. This project contributed to the strengthening of the cooperation between the centres and professionals, paving the way to further national collaborations.     

Dermatofibrosarcoma protuberans of the upper eyelid treated with surface mould high-dose-rate brachytherapy

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumor, comprising less than 0.1% of all malignant neoplasms. The trunk is the most commonly affected area, followed by the extremities and the head and neck. Of the latter cases, involvement of the periorbital area has been infrequently reported. Surgery is the cornerstone of treatment but is associated with a high rate of recurrence if margins remain close or positive. This rate has been shown to be considerably decreased by the use of adjuvant radiotherapy. However, most reported cases utilize external beam radiation therapy (EBRT ) in the treatment of DFSP, including those with primary periorbital locations. We report a case of a 40-year-old male, presenting with a small nodule on the right upper eyelid, diagnosed as DFSP with positive margins post-surgery and treated with adjuvant customized surface mould high-dose-rate (HDR) brachytherapy in a low-resource setting.     

Comparative dosimetrical analysis of intensity-modulated arc therapy,CyberKnife therapy and image-guided interstitial HDR and LDR brachytherapy of low risk prostate cancer

BackgroundThe objective of the study was to dosimetrically compare the intensity-modulated-arc-therapy (IMAT), Cyber-Knife therapy (CK), single fraction interstitial high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy (BT) in low-risk prostate cancer.Materials and methodsTreatment plans of ten patients treated with CK were selected and additional plans using IMAT, HDR and LDR BT were created on the same CT images. The prescribed dose was 2.5/70 Gy in IMAT, 8/40 Gy in CK, 21 Gy in HDR and 145 Gy in LDR BT to the prostate gland. EQD2 dose-volume parameters were calculated for each technique and compared.ResultsEQD2 total dose of the prostate was significantly lower with IMAT and CK than with HDR and LDR BT, D90 was 79.5 Gy, 116.4 Gy, 169.2 Gy and 157.9 Gy (p < 0.001). However, teletherapy plans were more conformal than BT, COIN was 0.84, 0.82, 0.76 and 0.76 (p < 0.001), respectively. The D₂ to the rectum and bladder were lower with HDR BT than with IMAT, CK and LDR BT, it was 66.7 Gy, 68.1 Gy, 36.0 Gy and 68.0 Gy (p = 0.0427), and 68.4 Gy, 78.9 Gy, 51.4 Gy and 70.3 Gy (p = 0.0091) in IMAT, CK, HDR and LDR BT plans, while D_0.1 to the urethra was lower with both IMAT and CK than with BTs: 79.9 Gy, 88.0 Gy, 132.7 Gy and 170.6 Gy (p < 0.001). D₂ to the hips was higher with IMAT and CK, than with BTs: 13.4 Gy, 20.7 Gy, 0.4 Gy and 1.5 Gy (p < 0.001), while D₂ to the sigmoid, bowel bag, testicles and penile bulb was higher with CK than with the other techniques.ConclusionsHDR monotherapy yields the most advantageous dosimetrical plans, except for the dose to the urethra, where IMAT seems to be the optimal modality in the radiotherapy of low-risk prostate cancer.     

Techniques for adaptive prostate radiotherapy

Variations in the position and shape of the prostate make accurate setup and treatment challenging. Adaptive radiation therapy (ART) techniques seek to alter the treatment plan, at one or more points throughout the treatment course, in response to changes in patient anatomy observed between planning and pre-treatment images. This article reviews existing and developing ART techniques for prostate cancer along with an overview of supporting in-room imaging technologies. Challenges to the clinical implementation of adaptive radiotherapy are also discussed.     

Integration of rotatable tandem applicator to conventional ovoid applicator toward complete framework of intensity modulated brachytherapy (IMBT) for cervical cancer

A new tandem applicator with tungsten shield for Ir-192 radiation source used in intra-cavitary brachytherapy (ICBT) enabled intensity modulated brachytherapy (IMBT) in cervical cancer treatment through fluence-modulation by rotating shield. Our previous work employed group-wise and element-wise sparsity constraints for plan optimization of tandem applicator to minimizes the number of activated angles and source dwell points for delivery efficiency. It, however, did not incorporate the ovoid applicators into the optimizing process, which is generally used to prevent cancer recurrence. To integrate ovoid applicators to the new tandem applicator, this work proposed a comprehensive framework that modifies 1) dose deposition matrix for inverse planning, and 2) plan optimizing algorithm. The dose deposition matrix was newly formulated by the Monte-Carlo simulated dose distribution for 10 positions of ovoid applicators, followed by combining those with tandem-associated dose deposition matrix. The plan optimizing algorithm decomposed entire elements into tandem and ovoid applicators, which were governed by different constraints adaptive to specified plan objectives. The integrated framework was compared against conventional ICBT, and IMBT with tandem only for three patients with asymmetric dose distributions. Integrated IMBT framework resulted in the most optimal plans. Including fluence-modulation by rotating-shield outperformed conventional ICBT in dose sparing to critical organs. Adopting ovoid applicators to the optimization yielded more conformal dose distribution around inferior, laterally expanded region of target volume. The resulting plans reduced D_5cc and D_2cc by 30.9% and 27.8% for critical organs over conventional ICBT, and by 20.6% and 21.5% for target volume over IMBT with tandem only.