Deep learning-based synthetic CT generation for MR-only radiotherapy of prostate cancer patients with 0.35T MRI linear accelerator.

PURPOSE: To develop a deep learning model to generate synthetic CT for MR-only radiotherapy of prostate cancer patients treated with 0.35 T MRI linear accelerator. MATERIALS AND METHODS: A U-NET convolutional neural network was developed to translate 0.35 T TRUFI MRI into electron density map using a novel cost function equalizing the contribution of various tissue types including fat, muscle, bone, and background air in training. The impact of training time, dataset size, image standardization, and data augmentation approaches was also quantified. Mean absolute error (MAE) between synthetic and planning CTs was calculated to measure the goodness of the model. RESULTS: With 20 patients in training, our U-NET model has the potential to generate synthetic CT with a MAE of about 29.68 ± 4.41, 16.34 ± 2.67, 23.36 ± 2.85, and 105.90 ± 22.80 HU over the entire body, fat, muscle, and bone tissues, respectively. As expected, we found that the number of patients used for training and MAE are nonlinearly correlated. Data augmentation and our proposed loss function were effective to improve MAE by ~9% and ~18% in bony voxels, respectively. Increasing the training time and image standardization did not improve the accuracy of the model. CONCLUSION: A U-NET model has been developed and tested numerically to generate synthetic CT from 0.35T TRUFI MRI for MR-only radiotherapy of prostate cancer patients. Dosimetric evaluation using a large and independent dataset warrants the validity of the proposed model and the actual number of patients needed for the safe usage of the model in routine clinical workflow.

Quantifying the impact of SpaceOAR hydrogel on inter-fractional rectal and bladder dose during 0.35 T MR-guided prostate adaptive radiotherapy.

PURPOSE: To investigate the impact of rectal spacing on inter-fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing SBRT with a 0.35 T MRI-Linac. MATERIALS AND METHODS: We evaluated and compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI-Linac. Each group consisted of 10 randomly selected patients that received prostate SBRT to a total dose of 36.25 Gy in five fractions. Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified. We also assessed whether adaptive planning was needed to meet constraints for each fraction. RESULTS: On average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p < 0.001). We also found that D3cc received by the rectum could be 12 Gy higher in patients who did not have rectal spacer (p < 9E-7). In addition, the results show that a rectal spacer can reduce the maximum dose and D15cc to the bladder wall by more than 1 (p < 0.004) and 8 (p < 0.009) Gy, respectively. Our study also shows that using a rectal spacer could reduce the necessity for adaptive planning. The incidence of dose constraint violation was observed in almost 91% of the fractions in patients without the rectal spacer and 52% in patients with implanted spacer. CONCLUSION: Inter-fractional changes in rectal and bladder dose were quantified in patients who underwent SBRT with/without rectal SpaceOAR hydrogel. Rectal spacer does not eliminate the need for adaptive planning but reduces its necessity.

Dose to craniofacial region through portal imaging of pediatric brain tumors.

The purpose of this study was to determine dose to the planning target volume (PTV) and organs at risk (OARs) from portal imaging (PI) of the craniofacial region in pediatric brain tumor patients treated with intensity-modulated radiation therapy (IMRT). Twenty pediatric brain tumor patients were retrospectively studied. Each received portal imaging of treatment fields and orthogonal setup fields in the craniofacial region. The number of PI and monitor units used for PI were documented for each patient. Dose distributions and dose-volume histograms were generated to quantify the maximum, minimum, and mean dose to the PTV, and the mean dose to OARs through PI acquisition. The doses resulting from PI are reported as percentage of prescribed dose. The average maximum, minimum, and mean doses to PTV from PI were 2.9 ± 0.7%, 2.2 ± 1.0%, and 2.5 ± 0.7%, respectively. The mean dose to the OARs from PI were brainstem 2.8 ± 1.1%, optic nerves/chiasm 2.6 ± 0.9%, cochlea 2.6 ± 0.9%, hypothalamus/pituitary 2.4 ± 0.6%, temporal lobes 2.3 ± 0.6%, thyroid 1.6 ± 0.8%, and eyes 2.6 ± 0.9%. The mean number of portal images and the mean number of PI monitor units per patient were 58.8 and 173.3, respectively. The dose from PI while treating pediatric brain tumors using IMRT is significant (2%-3% of the prescribed dose). This may result in exceeding the tolerance limit of many critical structures and lead to unwanted late complications and secondary malignancies. Dose contributions from PI should be considered in the final documented dose. Attempts must be made in PI practices to lower the imaging dose when feasible.

Accelerated intensity-modulated radiotherapy to breast in prone position: dosimetric results.

PURPOSE: To report the physics and dosimetry results of a trial of accelerated intensity-modulated radiotherapy to the whole breast with a concomitant boost to the tumor bed in patients treated in the prone position. METHODS AND MATERIALS: Patients underwent computed tomography planning and treatment in the prone position on a dedicated treatment platform. The platform has an open aperture on the side to allow for the index breast to fall away from the chest wall. Noncontrast computed tomography images were acquired at 2.5- or 3.75-mm-thick intervals, from the level of the mandible to below the diaphragm. A dose of 40.5 Gy was delivered to the entire breast at 2.7-Gy fractions in 15 fractions. An additional dose of 0.5 Gy was delivered as a concomitant boost to the lumpectomy site, with a 1-cm margin, using inverse planning, for a total dose of 48 Gy in 15 fractions. No more than 10% of the heart and lung volume was allowed to receive >18 and >20 Gy, respectively. RESULTS: Between September 2003 and August 2005, 91 patients were enrolled in the study. The median volume of heart that received > or =18 Gy was 0.5%, with a maximal value of 4.7%. The median volume of ipsilateral lung that received > or =20 Gy was 0.8%, with a maximum of 7.2%. CONCLUSION: This technique for whole breast radiotherapy is feasible and enables an accelerated regimen in the prone position while sparing the lung and heart.

The combination of ionizing radiation and peripheral vaccination produces long-term survival of mice bearing established invasive GL261 gliomas.

PURPOSE: High-grade glioma treatment includes ionizing radiation therapy. The high invasiveness of glioma cells precludes their eradication and is responsible for the dismal prognosis. Recently, we reported the down-regulation of MHC class I (MHC-I) products in invading tumor cells in human and mouse GL261 gliomas. Here, we tested the hypothesis that whole-brain radiotherapy (WBRT) up-regulates MHC-I expression on GL261 tumors and enhances the effectiveness of immunotherapy. EXPERIMENTAL DESIGN: MHC-I molecule expression on GL261 cells was analyzed in vitro and in vivo by flow cytometry and immunohistochemistry, respectively. To test the response of established GL261 gliomas to treatment, mice with measurable (at CT imaging) brain tumors were randomly assigned to four groups receiving (a) no treatment, (b) WBRT in two fractions of 4 Gy, (c) vaccination with irradiated GL261 cells secreting granulocyte-macrophage colony-stimulating factor, or (d) WBRT and vaccination. Endpoints were tumor response and survival. RESULTS: An ionizing radiation dose of 4 Gy maximally up-regulated MHC-I molecules on GL261 cells in vitro. In vivo, WBRT induced the expression of the beta2-microglobulin light chain subunit of the MHC class I complex on glioma cells invading normal brain and increased CD4+ and CD8+ T cell infiltration. However, the survival advantage obtained with WBRT or vaccination alone was minimal. In contrast, WBRT in combination with vaccination increased long-term survival to 40% to 80%, compared with 0% to 10% in the other groups (P < 0.002). Surviving animals showed antitumor immunity by rejecting challenge tumors. CONCLUSION: Ionizing radiation can be successfully combined with peripheral vaccination for the treatment of established high-grade gliomas.

Prospective Randomized Trial of Prone Accelerated Intensity Modulated Breast Radiation Therapy With a Daily Versus Weekly Boost to the Tumor Bed.

PURPOSE: To report the results of a prospective randomized trial comparing a daily versus weekly boost to the tumor cavity during the course of accelerated radiation to the breast with patients in the prone position. METHODS AND MATERIALS: From 2009 to 2012, 400 patients with stage 0 to II breast cancer who had undergone segmental mastectomy participated in an institutional review board-approved trial testing prone breast radiation therapy to 40.5 Gy in 15 fractions 5 d/wk to the whole breast, after randomization to a concomitant daily boost to the tumor bed of 0.5 Gy, or a weekly boost of 2 Gy, on Friday. The present noninferiority trial tested the primary hypothesis that a weekly boost produced no more acute toxicity than did a daily boost. The recurrence-free survival was estimated for both treatment arms using the Kaplan-Meier method; the relative risk of recurrence or death was estimated, and the 2 arms were compared using the log-rank test. RESULTS: At a median follow-up period of 45 months, no deaths related to breast cancer had occurred. The weekly boost regimen produced no more grade ≥2 acute toxicity than did the daily boost regimen (8.1% vs 10.4%; noninferiority Z = -2.52; P=.006). No statistically significant difference was found in the cumulative incidence of long-term fibrosis or telangiectasia of grade ≥2 between the 2 arms (log-rank P=.923). Two local and two distant recurrences developed in the daily treatment arm and three local and one distant developed in the weekly arm. The 4-year recurrence-free survival rate was not different between the 2 treatment arms (98% for both arms). CONCLUSIONS: A tumor bed boost delivered either daily or weekly was tolerated similarly during accelerated prone breast radiation therapy, with excellent control of disease and comparable cosmetic results.

Use of a Flexible Inflatable Multi-Channel Applicator for Vaginal Brachytherapy in the Management of Gynecologic Cancer.

INTRODUCTION: Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage achievable by single-channel applicator (SC) and comparable to Syed plan simulation. MATERIALS AND METHODS: Twenty-eight plans were evaluated from four patients with primary or recurrent gynecologic cancer in the vagina. Each received whole pelvis radiation, followed by three weekly treatments using HDR brachytherapy with a 13-channel MC. Upper vagina was treated to 5 mm depth to 1500 cGy/3 fractions with a simultaneous integrated boost totaling 2100 cGy/3 fractions to tumor. Modeling of SC and Syed plans was performed using MC scans for each patient. Dosimetry for MC and SC plans was evaluated for PTV700 cGy coverage, maximum dose to 2 cm(3) to bladder, rectum, as well as mucosal surface points. Dosimetry for Syed plans was calculated for PTV700 cGy coverage. Patients were followed for treatment response and toxicity. RESULTS: Dosimetric analysis between MC and SC plans demonstrated increased tumor coverage (PTV700 cGy), with decreased rectal, bladder, and contralateral vaginal mucosa dose in favor of MC. These differences were significant (p < 0.05). Comparison of MC and Syed plans demonstrated increased tumor coverage in favor of Syed plans which were not significant (p = 0.71). Patients treated with MC had no cancer recurrence or ≥grade 3 toxicity. CONCLUSION: Use of MC was efficacious and safe, providing superior coverage of tumor volumes ≤1 cm depth compared to SC and comparable to Syed implant. MC avoids excess dose to surrounding organs compared to SC, and potentially less morbidity than Syed implants. For tumors extending ≤1 cm depth, use of MC represents an alternative to an interstitial implant.

Prone accelerated partial breast irradiation after breast-conserving surgery: preliminary clinical results and dose-volume histogram analysis.

PURPOSE: To report the clinical and dose-volume histogram results of the first 47 patients accrued to a protocol of accelerated partial breast irradiation. Patients were treated in the prone position with three-dimensional conformal radiotherapy after breast-conserving surgery. METHODS AND MATERIALS: Postmenopausal women with Stage T1N0 breast cancer were eligible only after they had first refused to undergo 6 weeks of standard radiotherapy. Planning CT in the prone position was performed on a dedicated table. The postoperative cavity was defined as the clinical target volume, with a 1.5-cm margin added to determine the planning target volume. A total dose of 30 Gy at 6 Gy/fraction was delivered in five fractions within 10 days. RESULTS: The median age of the patients was 67.5 years (range, 51-88 years). The median tumor diameter was 9 mm (range, 1.3-19 mm). In all patients, the prescribed dose encompassed the planning target volume. The mean volume of the ipsilateral breast receiving 100% of the prescription dose was 26% (range, 10-45%), and the mean volume contained within the 50% isodose surface was 47% (range, 23-75%). The lung and heart were spared by treating in the prone position. Acute toxicity was modest, limited mainly to Grade 1-2 erythema. With a median follow-up of 18 months, only Grade 1 late toxicity occurred, and no patient developed local recurrence. CONCLUSION: These data suggest that this approach is well tolerated, with only mild acute side effects and sparing of the heart and lung.

Procedure for unmasking localization information from ProstaScint scans for prostate radiation therapy treatment planning.

PURPOSE: To demonstrate a method to extract the meaningful biologic information from (111)In-radiolabeled capromab pendetide (ProstaScint) SPECT scans for use in radiation therapy treatment planning by removing that component of the (111)In SPECT images associated with normal structures. METHODS AND MATERIALS: We examined 20 of more than 80 patients who underwent simultaneous (99m)Tc/(111)In SPECT scans, which were subsequently registered to the corresponding CT/MRI scans.A thresholding algorithm was used to identify (99m)Tc uptake associated with blood vessels and CT electron density associated with bone marrow. Corresponding voxels were removed from the (111)In image set. RESULTS: No single threshold value was found to be associated with the (99m)Tc uptake that corresponded to the blood vessels. Intensity values were normalized to a global maximum and, as such, were dependent upon the quantity of (99m)Tc pooled in the bladder. The reduced ProstaScint volume sets were segmented by use of a thresholding feature of the planning system and superimposed on the CT/MRI scans. CONCLUSIONS: ProstaScint images are now closer to becoming a biologically and therapeutically useful and accurate image set. After known sources of normal intensity are stripped away, the remaining areas that demonstrate uptake may be segmented and superimposed on the treatment-planning CT/MRI volume.

Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy.

PURPOSE: Limited information is available comparing toxicity of accelerated radiotherapy (RT) to that of standard fractionation RT for early stage breast cancer. We report early and late toxicities of two prone regimens of accelerated intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a sequential electron boost. METHODS: From 2/2003 to 12/2007, 169 consecutive patients with Stage I-II breast cancer were offered the choice to undergo prone RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.25 Gy in 25 fx (5wCB); or a 3-week protocol of 40.5 Gy to WB with an IMRT CB of 7.5 Gy in 15 fx (3wCB). These regimens were estimated as biologically equivalent, based on alpha/beta = 4 for tumor control. Toxicities were reported using RTOG and LENT/SOMA scoring. RESULTS: 51/169 patients chose standard 6wSB, 28 selected 5wCB, and 90 enrolled in 3wCB protocol. Maximum acute toxicity was Grade 3 dermatitis in 4% of the patients in the 6wSB compared 1% in 3wCB. In general, acute complications (breast pain, fatigue, and dermatitis) were significantly less in the 3wCB than in the other schedules (P < 0.05). With a median follow-up of 61 months, the only Grade 3 late toxicity was telangiectasia in two patients: one in 3wCB and one in 5wCB group. Notably, fibrosis was comparable among the three groups (P = NS). CONCLUSION: These preliminary data suggest that accelerated regimens of breast RT over 3 or 5 weeks in the prone position, with an IMRT tumor bed CB, result in comparable late toxicity to standard fractionation with a sequential tumor boost delivered over 6 weeks. As predicted by radiobiological modeling the shorter regimen was associated with less acute effects.

Prone accelerated partial breast irradiation after breast-conserving surgery: five-year results of 100 patients.

PURPOSE: To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. METHODS AND MATERIALS: Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. RESULTS: One hundred patients were enrolled in this institutional review board-approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation, and another patient elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients were evaluable for toxicity, and, in 1 case, both breasts were treated with partial breast irradiation. Median patient age was 68 years (range, 53-88 years); in 55% of patients the tumor size was <1 cm. All patients had hormone receptor-positive cancers: 87% of patients underwent adjuvant antihormone therapy. At a median follow-up of 64 months (range, 2-125 months), there was one local recurrence (1% ipsilateral breast failure) and one contralateral breast cancer (1% contralateral breast failure). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (one breast edema, one transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36 months follow-up. CONCLUSIONS: Five-year efficacy and toxicity of 3D-CRT delivered in prone partial breast irradiation are comparable to other experiences with similar follow-up.

Prone accelerated partial breast irradiation after breast-conserving surgery: compliance to the dosimetry requirements of RTOG-0413.

PURPOSE: The dosimetric results from our institution's trials of prone accelerated partial breast irradiation are compared with the dosimetric requirements of RTOG-0413. METHODS AND MATERIALS: Trial 1 and Trial 2 are 2 consecutive trials of prone-accelerated partial breast irradiation. Eligible for both trials were stage I breast cancer patients with negative margins after breast-conserving surgery. The planning target tumor volume (PTV) was created by extending the surgical cavity 2.0 cm for Trial 1 and 1.5 cm for Trial 2, respectively. Contralateral breast, heart, lungs, and thyroid were contoured. Thirty Gray was delivered in five daily fractions of 6 Gy by a three-dimensional conformal radiation therapy technique in Trial 1 and were by image-guided radiation therapy/intensity-modulated radiation therapy in Trial 2. Dosimetric results from the trials are reported and compared with RTOG 0413 requirements. RESULTS: One hundred forty-six consecutive plans were analyzed: 67 left and 79 right breast cancers. The plans from the trials complied with the required>90% of prescribed dose covering 90% of PTV_EVAL (=generated from the PTV by cropping 0.5 cm from the skin edge and excluding the chest wall): V90% was 98.1±3.0% (with V100% and V95%, 89.4±12.8%, 96.4±5.1%, respectively). No significant difference between laterality was found (Student's t test). The dose constraints criteria of the RTOG-0413 protocol for ipsilateral and contralateral lung (V30<15% and Dmax<3%), heart (V5<40%), and thyroid (Dmax<3%) were satisfied because the plans showed an average V5% of 0.6% (range, 0-13.4) for heart, an average V30% of 0.6% (range, 0-9.1%) for ipsilateral lung, and <2% maximum dose to the thyroid. However, our partial breast irradiation plans demonstrated a higher dose to contralateral breast than that defined by RTOG constraints, with a median value of maximum doses of 4.1% (1.2 Gy), possibly as a result of contouring differences. CONCLUSIONS: Our technique for prone accelerated partial breast irradiation generally satisfied RTOG-0413 requirements.

Prospective study of cone-beam computed tomography image-guided radiotherapy for prone accelerated partial breast irradiation.

PURPOSE: To report setup variations during prone accelerated partial breast irradiation (APBI). METHODS: New York University (NYU) 07-582 is an institutional review board-approved protocol of cone-beam computed tomography (CBCT) to deliver image-guided ABPI in the prone position. Eligible are postmenopausal women with pT1 breast cancer excised with negative margins and no nodal involvement. A total dose of 30 Gy in five daily fractions of 6 Gy are delivered to the planning target volume (the tumor cavity with 1.5-cm margin) by image-guided radiotherapy. Patients are set up prone, on a dedicated mattress, used for both simulation and treatment. After positioning with skin marks and lasers, CBCTs are performed and the images are registered to the planning CT. The resulting shifts (setup corrections) are recorded in the three principal directions and applied. Portal images are taken for verification. If they differ from the planning digital reconstructed radiographs, the patient is reset, and a new CBCT is taken. RESULTS: 70 consecutive patients have undergone a total of 343 CBCTs: 7 patients had four of five planned CBCTs performed. Seven CBCTs (2%) required to be repeated because of misalignment in the comparison between portal and digital reconstructed radiograph image after the first CBCT. The mean shifts and standard deviations in the anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions were -0.19 (0.54), -0.02 (0.33), and -0.02 (0.43) cm, respectively. The average root mean squares of the daily shifts were 0.50 (0.28), 0.29 (0.17), and 0.38 (0.20). A conservative margin formula resulted in a recommended margin of 1.26, 0.73, 0.96 cm in the AP, SI, and ML directions. CONCLUSION: CBCTs confirmed that the NYU prone APBI setup and treatment technique are reproducible, with interfraction variation comparable to those reported for supine setup. The currently applied margin (1.5 cm) adequately compensates for the setup variation detected.

TGFß1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo.

PURPOSE: To determine whether inhibition of TGFß signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. EXPERIMENTAL DESIGN: TGFß-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDA-MB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment with LY364947, a small molecule inhibitor of the TGFß type I receptor kinase. The DNA damage response was assessed in irradiated MDA-MB-231 cells pretreated with LY364947 in vitro and LY2109761, a pharmacokinetically stable inhibitor of TGFß signaling, in vivo. The in vitro response of a syngeneic murine tumor, 4T1, was tested using a TGFß neutralizing antibody, 1D11, with single or fractionated radiation doses in vivo. RESULTS: Human breast cancer cell lines pretreated with TGFß small molecule inhibitor were radiosensitized, irrespective of sensitivity to TGFß growth inhibition. Consistent with increased clonogenic cell death, radiation-induced phosphorylation of H2AX and p53 was significantly reduced in MDA-MB-231 triple-negative breast cancer cells when pretreated in vitro or in vivo with a TGFß type I receptor kinase inhibitor. Moreover, TGFß neutralizing antibodies increased radiation sensitivity, blocked γH2AX foci formation, and significantly increased tumor growth delay in 4T1 murine mammary tumors in response to single and fractionated radiation exposures. CONCLUSION: These results show that TGFß inhibition prior to radiation attenuated DNA damage responses, increased clonogenic cell death, and promoted tumor growth delay, and thus may be an effective adjunct in cancer radiotherapy.

Interfraction and intrafraction setup variability for prone breast radiation therapy.

PURPOSE: To report the interfraction and intrafraction setup variation for prone breast radiotherapy and to determine an appropriate clinical tumor volume (CTV) to planning target volume (PTV)_ margin to account for motion and positional uncertainties. METHODS AND MATERIALS: Ten consecutive patients were prospectively enrolled in a protocol of accelerated, hypofractionated prone breast irradiation. Portal images were acquired using an electronic portal imaging device in cine mode. Interfraction setup error was determined by comparing the first image from each fraction with the digitally reconstructed radiograph. The intrafraction motion was determined by evaluating every image acquired during each fraction and measuring the maximum displacement of an external fiducial and the breast surface. Mean values and 95% confidence intervals (CI) were calculated. Based on these results, a CTV to PTV expansion was derived using the equation M = 2.5Sigma(tot) + 0.7sigma(tot.) RESULTS: The mean interfraction setup variability for the fiducial was 0.08 cm (CI: 0.02-0.14) in the anterior to posterior (AP) direction and -0.04 cm (CI: -0.07-0.00) in the superior to inferior (SI) direction. The mean interfraction variability of the breast surface was -0.14 cm (CI: -0.24 to -0.04) in the AP direction. The mean intrafraction displacements of the fiducial and the breast surface were 0.13 cm (CI: 0.12-0.15) and 0.15 cm (CI: 0.14-0.17), respectively. Using the systematic and random errors for the external fiducial, the calculated CTV to PTV expansion was 1.4 cm. CONCLUSIONS: Acceptable interfraction and intrafraction variability were demonstrated. The findings resulted in a CTV to PTV expansion of 1.4 cm.