Patterns of intrafractional motion and uncertainties of treatment setup reference systems in accelerated partial breast irradiation for right- and left-sided breast cancer

PurposeThis study investigated the patterns of intrafractional motion and accuracy of treatment setup strategies in 3-dimensional conformal radiation therapy of accelerated partial breast irradiation (APBI) for right- and left-sided breast cancers.Methods and MaterialsSixteen right-sided and 17 left-sided breast cancer patients were enrolled in an institutional APBI trial in which gold fiducial markers were strategically sutured to the surgical cavity walls. Daily pre- and postradiation therapy kV imaging were performed and were matched to digitally reconstructed radiographs based on bony anatomy and fiducial markers, respectively, to determine the intrafractional motion. The positioning differences of the laser-tattoo and the bony anatomy-based setups with respect to the marker-based setup (benchmark) were determined to evaluate their accuracy.ResultsStatistical differences were found between the right- and left-sided APBI treatments in vector directions of intrafractional motion and treatment setup errors in the reference systems, but less in their overall magnitudes. The directional difference was more pronounced in the lateral direction. It was found that the intrafractional motion and setup reference systems tended to deviate in the right direction for the right-sided breast treatments and in the left direction for the left-sided breast treatments.ConclusionsIt appears that the fiducial markers placed in the seroma cavity exhibit side dependent directional intrafractional motion, although additional data may be needed to further validate the conclusion. The bony anatomy-based treatment setup improves the accuracy over laser-tattoo. But it is inadequate to rely on bony anatomy to assess intrafractional target motion in both magnitude and direction.     

Factors influencing intrafractional target shifts in lung stereotactic body radiation therapy

PurposeThe objective of this study is to investigate the influence of tumor size, location, and patient characteristics on the intrafractional target shift in lung stereotactic body radiation therapy (SBRT).Methods and MaterialsSixty-nine stage I lung cancer patients with partial upper body fixation who received SBRT in our center were included in this study. The patients had pre- and post-radiation therapy cone-beam computed tomography (CBCT) at each fraction for target alignment during radiation therapy setup. The 3-dimensional (3D), intrafractional shift and on-couch time for each fraction were recorded with soft tissue matching. Statistical correlations of these shifts with the characteristics of the tumor (volume, location in upper vs lower, central vs peripheral, right vs left, and internal motion) and the patient (age, sex, performance status, pulmonary function, body mass index, and on-couch time) were determined.ResultsOverall, 470 intrafractional shifts were measured on the 69 patients. The median 3D shift was 2.4 mm (range, 0-15 mm) and the median on-couch time was 17 minutes (range, 10-55 minutes). On 55 occasions (11.7%), 3D shifts larger than 5 mm were observed. The tumor volume, tumor location (upper vs lower thorax), and the patient motion tendency were significantly associated with the probability of larger intrafractional shifts (3D shift > 5 mm). Linear regression model analysis indicated male sex (P = .039), larger tumor volume (P = .019), and a motion tendency (P = .0006) are predictors for patients with a large intrafractional shift. No other factors were good predictors of large intrafractional target shifts in lung SBRT.ConclusionsIn lung SBRT patients with large tumor size, being male and large motion tendency are prone to having a > 5 mm intrafractional target shift determined from the CBCT soft tissue matching system. Prior knowledge of these factors would be beneficial in selecting a customized immobilization system for the lung SBRT patients with the specific conditions.     

Practical Safety Considerations for Integration of Magnetic Resonance Imaging in Radiation Therapy

Interest in integrating magnetic resonance imaging (MRI) in radiation therapy (RT) practice has increased dramatically in recent years owing to its unique advantages such as excellent soft tissue contrast and capability of measuring biological properties. Continuous real-time imaging for intrafractional motion tracking without ionizing radiation serves as a particularly attractive feature for applications in RT. Despite its many advantages, the integration of MRI in RT workflows is not straightforward, with many unmet needs. MR safety remains one of the key challenges and concerns in the clinical implementation of MR simulators and MR-guided radiation therapy systems in radiation oncology. Most RT staff are not accustomed to working in an environment with a strong magnetic field. There are specific requirements in RT that are different from diagnostic applications. A large variety of implants and devices used in routine RT practice do not have clear MR safety labels. RT-specific imaging pulse sequences focusing on fast acquisition, high spatial integrity, and continuous, real-time acquisition require additional MR safety testing and evaluation. This article provides an overview of MR safety tailored toward RT staff, followed by discussions on specific requirements and challenges associated with MR safety in the RT environment. Strategies and techniques for developing an MR safety program specific to RT are presented and discussed.     

Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

PurposeFiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT.MethodsAn institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers.ResultsWe identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present post-treatment imaging at a median of 107 days (range, 33-471 days) after implantation.ConclusionsEUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques.     

Optimal control of set-up margins and internal margins for intra- and extracranial radiotherapy using stereoscopic kilovoltage imaging.

In this paper the clinical introduction of stereoscopic kV-imaging in combination with a 6 degrees-of-freedom (6 DOF) robotics system and breathing synchronized irradiation will be discussed in view of optimally reducing interfractional as well as intrafractional geometric uncertainties in conformal radiation therapy. Extracranial cases represent approximately 70% of the patient population on the NOVALIS treatment machine (BrainLAB A.G., Germany) at the AZ-VUB, which is largely due to the efficiency of the real-time positioning features of the kV-imaging system. The prostate case will be used as an example of those target volumes showing considerable changes in position from day-to-day, yet with negligible motion during the actual course of the treatment. As such it will be used to illustrate the on-line target localization using kV-imaging and 6 DOF patient adjustment with and without implanted radio-opaque markers prior to treatment. Small lung lesion will be used to illustrate the system's potential to synchronize the irradiation with breathing in coping with intrafractional organ motion.     

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial,SweBCG 91 RT

BackgroundBreast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients.Patients and methodsA total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program.ResultsAfter 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P < 0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P = 0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P = 0.68, nor was breast cancer–specific mortality significantly higher.ConclusionsRT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.     

Bilateral Regional Nodal Irradiation Using Volumetric Modulated Arc Therapy: Dosimetric Analysis and Feasibility

PurposeDosimetric and technical challenges often limit radiation therapy (RT) target coverage for patients with breast cancer who require bilateral breast/chest wall and regional nodal irradiation (RNI). We evaluated the feasibility of using volumetric modulated arc therapy (VMAT) to administer bilateral comprehensive RNI including the internal mammary nodes.Methods and MaterialsWe analyzed all patients treated at our institution with bilateral RNI using VMAT between 2017 and 2020. Medical records were reviewed to ascertain clinicopathologic features, radiotherapeutic parameters, and treatment-related adverse events.ResultsThe cohort was comprised of 12 patients who underwent VMAT for bilateral RNI, with a median follow-up time of 14.5 months. Median volume of the lung receiving 5 Gy (V₅) for the bilateral lungs was 96.1% (range, 84.5%-99.8%), and median volume of the lung receiving 20 Gy for each lung was 27.5% (range, 14.9%-38.1%). The cardiac mean dose was a median of 699 cGy (range, 527-1117 cGy). Five patients (41%) developed grade 1 cough/dyspnea, with one patient developing grade 3 dyspnea. Of note, 3 of these patients (60%) were current or former smokers. No patient received glucocorticoid therapy or required respiratory intervention, and none developed longer-term pulmonary complaints. A decline in ejection fraction occurred in one patient with a preexisting cardiac condition who also received anthracycline-based chemotherapy and trastuzumab. Only one patient experienced a locoregional recurrence with synchronous distant progression, and subsequently succumbed to the disease. No secondary cancers have been noted to date.ConclusionsVMAT appears to be a feasible and tolerable RT modality for patients with breast cancer who require bilateral comprehensive adjuvant RT with RNI to obtain excellent target coverage. No patients required medical intervention for pulmonary complaints despite a median bilateral V₅ approaching 100%, providing further evidence that V₅ is not predictive for complications.     

The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects

BackgroundRadiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients:1. Does guideline-adherent RT improve primary breast cancer patient survival?2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters?3. Does adjuvant RT compensate for an incomplete tumor resection (R1)?Patients and methodsIn this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines.ResultsThe patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613].ConclusionOur study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.     

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy

BackgroundWhole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate.Patients and MethodsThe National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors.ResultsA total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001).ConclusionsSFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.     

Radiation dose and contralateral breast cancer risk associated with megavoltage cone-beam computed tomographic image verification in breast radiation therapy

PurposeTo measure and compare organ doses from a standard tangential breast radiation therapy treatment (50 Gy delivered in 25 fractions) and a megavoltage cone-beam computed tomography (MV-CBCT), taken for weekly image verification, and assess the risk of radiation-induced contralateral breast cancer.Methods and MaterialsOrgan doses were measured with thermoluminescent dosimeters placed strategically within a female anthropomorphic phantom. The risk of radiation-induced secondary cancer of the contralateral breast was estimated from these values using excess absolute risk and excess relative risk models.ResultsThe effective dose from a MV-CBCT (8-monitor units) was 35.9 ± 0.2 mSv. Weekly MV-CBCT imaging verification contributes 0.5% and 17% to the total ipsilateral and contralateral breast dose, respectively. For a woman irradiated at age 50 years, the 10-year postirradiation excess relative risk was estimated to be 0.8 and 0.9 for treatment alone and treatment plus weekly MV-CBCT imaging, respectively. The 10-year postirradiation excess absolute risk was estimated to be 4.7 and 5.6 per 10,000 women-years.ConclusionsThe increased dose and consequent radiation-induced second cancer risk as calculated by this study introduced by the imaging verification protocols utilizing MV-CBCT in breast radiation therapy must be weighed against the benefits of more accurate treatment. As additional image verification becomes more common, it is important that data be collected in regard to long-term malignancy risk.     

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline

PurposeWith the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling.MethodsThe American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.ResultsThe task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy.ConclusionsThese recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.     

T1-2N0M0 Triple-Negative Breast Cancer Treated With Breast-Conserving Therapy Has Better Survival Compared to Mastectomy: A SEER Population-Based Retrospective Analysis

BackgroundFor early-stage breast cancer, the two current mainstay treatments are breast-conserving therapy (BCT; lumpectomy followed by radiotherapy [RT] and BCT) and mastectomy. Generally, triple-negative breast cancer (TNBC) is more aggressive compared to hormone receptor–positive breast cancer. We sought to investigate the effect of BCT compared to mastectomy on overall survival (OS) and breast cancer–specific survival (BCSS) in T1-2N0M0 TNBC.Patients and MethodsA population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into 3 groups according to surgical modality and RT: BCT, mastectomy alone, and mastectomy with RT. The survival end points were OS and BCSS, and survival analysis was performed by the Kaplan-Meier method and the log-rank test among treatment types.ResultsA total of 14,910 female subjects with T1-2N0M0 TNBC diagnosed between 2010 and 2014 were included. A total of 7381 patients had BCT; 6967 had mastectomy alone, and 562 had mastectomy with RT. Patients treated with BCT had better OS (log-rank P < .05) and BCSS (log-rank P < .05) than those receiving mastectomy with or without RT. The 5-year OS was 88.6% for BCT, 83.0% for mastectomy alone, and 79.6% for mastectomy with RT. The 5-year BCSS was 94.3% for BCT, 93.3% for mastectomy alone, and 83.7% for mastectomy with RT.ConclusionIn patients with T1-2N0M0 TNBC, BCT was associated with superior OS and BCSS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT.     

Radiation Therapy for Cervical Cancer: Executive Summary of an ASTRO Clinical Practice Guideline

PurposeThis guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer.MethodsThe American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT in definitive and postoperative management of cervical cancer. These questions included the indications for postoperative and definitive RT, the use of chemotherapy in sequence or concurrent with RT, the use of intensity modulated radiation therapy (IMRT), and the indications and techniques of brachytherapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.ResultsThe guideline recommends postoperative RT for those with intermediate risk factors, and chemoradiation for those with high-risk factors. In the definitive setting, chemoradiation is recommended for stages IB3-IVA, and RT or chemoradiation is conditionally recommended for stages IA1-IB2 if medically inoperable. IMRT is recommended for postoperative RT and conditionally recommended for definitive RT, for the purposes of reducing acute and late toxicity. Brachytherapy is strongly recommended for all women receiving definitive RT, and several recommendations are made for target dose and fractionation, the use of intraoperative imaging, volume-based planning, and recommendations for doses limits for organs at risk.ConclusionsThere is strong evidence supporting the use of RT with or without chemotherapy in both definitive and postoperative settings. Brachytherapy is an essential part of definitive management and volumetric planning is recommended. IMRT may be used for the reduction of acute and late toxicity. The use of radiation remains an essential component for women with cervical cancer to achieve cure.     

Feasibility of Breast-Conservation Therapy and Hypofractionated Radiation in the Setting of Prior Breast Augmentation

PurposeCosmetic outcomes and rate of implant loss are poorly characterized among patients with breast cancer with previous breast augmentation (BA) who undergo breast-conservation therapy (BCT). Here we determine capsular contracture and implant loss frequency after BCT among patients receiving contemporary whole-breast radiation therapy (RT).Methods and MaterialsPatients with breast cancer with a history of BA presenting to our institution from January 2006 to January 2017 who elected for BCT were included. Seventy-one breast cancers in 70 patients with a history of BA electing for BCT were retrospectively identified. Clinicopathologic, treatment, and outcome variables were examined. Whole-breast RT included conventional and hypofractionated schedules with and without a boost. Rates of implant loss and cosmetic outcomes among patients who did and did not develop a new/worse contracture based on physician assessment were compared.ResultsIn the study, 54.9% of patients received radiation using hypofractionated whole-breast tangents; 81.7% received a boost. In addition, 18 out of 71 cases (25.4%) developed a new/worse contracture after BCT with a mean follow-up of 1.9 years. Furthermore, 9 out of 71 cases (12.7%) were referred to a plastic surgeon for revisional surgery. There were no implant-loss cases. On univariate analysis, implant location, time from implant placement to diagnosis, RT type, RT boost, body mass index, and tumor size were not associated with new/worse contracture. Of 12 patients with existing contracture, only 2 developed worsening contracture. Physician assessment of cosmetic outcome after BCT was noted to be excellent or good for 87.4% of patients.ConclusionsBCT for breast cancer patients with prior history of BA has a low risk of implant loss. Hypofractionated RT does not adversely affect implant outcomes. Patients should be counseled regarding risk for capsular contracture, but the majority have good/excellent outcome; BA does not represent a contraindication to BCT.     

The Impact of Locoregional Treatment on Survival in Patients With Metastatic Breast Cancer: A National Cancer Database Analysis

BackgroundAlthough systemic therapy is the standard treatment for metastatic breast cancer, the value of locoregional treatment (LRT) of the primary tumor and its impact on survival is controversial. This study evaluates survival outcomes in patients with metastatic breast cancer after receiving LRT (surgery and/or radiation therapy) of the primary tumor.Materials and MethodsThe National Cancer Database was used to identify 16,128 qualifying cases of metastatic breast cancer who received systemic therapy with or without LRT from 2004 to 2013. Treatment modality was divided into surgery (Sx), radiation therapy (RT), surgery followed by RT (Sx + RT), and no LRT. The median survival and 3-year actuarial survival rates (OS) were analyzed for each treatment group. On multivariate analyses, adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox regression modeling to adjust for patient and clinicopathologic characteristics.ResultsOverall, the median follow-up was 28.3 months, and the median survival for all patients was 37.2 months. With 9761 deaths reported, the estimated 3-year OS was 51.3%. The Sx + RT group (n = 2166) had the highest 3-year OS of 69.4%, followed by the Sx group (n = 4293) with 57.6%, the no LRT group (n = 8955) with 44.3%, and the RT group (n = 714) with 41.5% (P < .0001). On multivariate analysis, compared with the no LRT group, a decreased HR was noted in patients receiving Sx (adjusted HR, 0.68; 95% CI, 0.65-0.71; P < .0001) and Sx + RT (adjusted HR, 0.46; 95% CI, 0.43-0.49; P < .0001).ConclusionLRT, especially surgery followed by RT, in addition to systemic therapy, was associated with improved survival in patients with metastatic breast cancer.     

Triggered Imaging With Auto Beam Hold and Pre-/Posttreatment CBCT During Prostate SABR: Analysis of Time Efficiency,Target Coverage,and Normal Volume Changes

PurposeOur purpose was to investigate time efficiency and target coverage for prostate stereotactic ablative radiation therapy (SABR) using triggered imaging (TI) and auto beam hold.Methods and MaterialsA total of 20 patients were treated with volumetric modulated arc–based SABR. Treatment verification consisted of pre- and post-radiation therapy cone beam computed tomography (CBCT) with gold marker-based TI every 3 seconds. In case of ≥3 mm (deviation limit) displacement, the treatment was interrupted and imaging-based correction was performed. Beam interruptions, intrafractional shifts, and treatment times were recorded. Prostate, rectum, and bladder were delineated on each CBCT. Target coverage was evaluated by comparing the individual prostate delineations with 98% isodose contour volumes (% of the evaluated volumes exceeding the reference). Both inter- and intrafractional changes of bladder and rectal volumes were assessed.ResultsThe average overall treatment time (±standard deviation) was 18 ± 11 min, with a radiation delivery time of 6 ± 3 min if no intrafractional CBCT acquisitions were necessary (91% of fractions). On average, 1.2 beam interruptions per fraction were required with 0/1 correction in 71% of the fractions. The mean residual 3-dimensional shift was 1.6 mm, exceeding the deviation limit in 8%. In the case of intrafractional CBCT and/or ≥2 corrections the treatment time dramatically increased. The 98% isodose lines did not encompass the prostate in only 8/180 (4%) evaluations in 6 different patients, leading to a loss of D98 between 0.1%-6% as a worst case scenario. The bladder volumes showed significant increases during treatment (P < .01) while rectal volumes were stable.ConclusionsTime efficiency of TI + auto beam hold with 3 mm/3 sec threshold during prostate SABR is comparable with competitive techniques, resulting in minimal 3-dimensional residual errors with maintained target coverage. Technical developments are necessary to further reduce radiation delivery time. Use of CBCT allowed full control of rectal volumes, while bladder volumes showed significant increases over time.     

Spontaneous Rib Fractures After Breast Cancer Treatment Based on Bone Scans: Comparison Of Conventional Versus Hypofractionated Radiotherapy

BackgroundSpontaneous rib fractures (SRFs) are defined as fractures without apparent blunt force trauma. This study evaluated the incidence and risk factors of SRFs after treatment of patients with breast cancer based on bone scans. In addition, we analyzed radiation-associated SRFs and identified radiotherapy (RT) factors related to SRF.Patients and MethodsWe retrospectively reviewed 1265 patients with breast cancer who underwent surgery in 2015 at our institution, and were followed-up with at least 3 bone scans. Bone scans were conducted approximately every 12 months after breast cancer treatment. The endpoint was SRF detected by bone scan. In this study, 754 (60%) patients were treated with chemotherapy, 867 (69%) with RT, and 946 (75%) with anti-hormone therapy.ResultsThe median follow-up duration was 37.5 months. A total of 209 (16.5%) patients experienced SRFs during follow-up. The incidence of SRFs increased sharply during the 3-year follow-up period after completion of treatment. In multivariate analyses, abnormal bone density, chemotherapy, and RT were significant risk factors for SRFs. In patients treated with RT (n = 867), 159 (18%) rib fractures occurred: 127 (80%) in the ipsilateral breast and 32 (20%) in the contralateral breast. Among the patients with ipsilateral SRFs who received tumor bed boost (n = 84), the SRF occurred inside the boost field in 80 (95%) cases. Multivariate analysis of RT subgroups showed that hypofractionated RT increased the rate of SRFs (P = .002).ConclusionsMost of the rib fractures that occurred after treatment were spontaneous. Hypofractionated RT increased the risk of ipsilateral rib fractures in RT-treated patients.     

Clinical Intensity Modulated Proton Therapy for Hodgkin Lymphoma: Which Patients Benefit the Most?

PurposeRadiation therapy (RT) improves control of Hodgkin lymphoma (HL), but patients who undergo RT are at risk for late effects, including cardiovascular disease and second cancers, because of radiation doses to organs at risk (OARs). Proton therapy (PT) can reduce OAR doses compared with conventional photon RT. However, access to PT is currently limited, so referrals must be appropriately selective. We aimed to identify subgroups of patients with HL who could benefit the most dosimetrically from RT with PT based on the prechemotherapy disease characteristics.Methods and materialsNormal tissue radiation doses were calculated for 21 patients with HL who were treated with deep-inspiration breath-hold pencil-beam scanning (PBS) PT and compared with doses from 3-dimensional conformal (3D-CRT) and partial arc volumetric modulated (PartArc) photon RT. Prechemotherapy disease characteristics associated with significant dosimetric benefits from PBS compared with photon RT were identified.ResultsTreatment with PBS was well tolerated and provided with good local control. PBS provided dosimetric advantages for patients whose clinical treatment volume extended below the seventh thoracic level and for female patients with axillary disease. In addition, an increasing dosimetric benefit for some OARs was observed for increasing target volume. PBS significantly reduced the mean dose to the heart, breast, lungs, spinal cord, and esophagus. Dose homogeneity and conformity within the target volume were also superior with PBS, but some high-dose measures and hot spots were increased with PBS compared with partial arc volumetric modulated photon RT.ConclusionsPBS gives good target coverage and local control while providing reductions in radiation dose to OARs for individuals who receive RT for HL compared with advanced photon RT. Our findings highlight groups of patients who would be expected to gain more dosimetric benefit from PBS. These findings facilitate the selection of patients who should be considered a priority for PT.     

Omission of radiotherapy in elderly patients with early breast cancer: 15-Year results of a prospective non-randomised trial

BackgroundWhether radiotherapy (RT) is beneficial in elderly (⩾70 years) patients undergoing conservative surgery for early breast cancer has long been controversial. Recent randomised trials show that most elderly patients do not benefit from RT. We started a prospective non-randomised trial to address this issue in 1987 and now present results for the 627 consecutive pT1/2cN0 patients recruited, and treated by conservative surgery (quadrantectomy) and tamoxifen, and assigned non-randomly to RT or no RT.MethodsWe used multivariate competing risks models to estimate 15-crude cumulative incidence (CCI) of ipsilateral breast tumour recurrence (IBTR), distant metastasis and breast cancer mortality. The models incorporated a propensity score as a measure of probability of receiving RT based on baseline characteristics, to account for the lack of randomisation.ResultsFor pT1 patients, 15-year CCIs of IBTR, distant metastasis and breast cancer death were indistinguishable in the RT and no RT groups. For pT2 patients, 15-year CCI of IBTR was much higher in those not given RT (14.6% versus 0.8%, p = 0.004), although breast cancer mortality and distant metastasis did not differ significantly between RT and no RT.ConclusionsConsistent with the findings of recent randomised trials, our long-term data indicate that most elderly, ER-positive patients with pT1 cN0 breast cancer treated by quadrantectomy do not benefit from RT. The 14.6% CCI of IBTR in our pT2 patients is an additional finding not presented in the trials and suggests that RT should be administered to elderly patients with pT2 disease.     

Intrafractional tumor motion: lung and liver

Three-dimensional (3D) dose distribution has been improved by 3D conformation and intensity modulation in external radiotherapy. Interfractional uncertainty has been reduced by image-guided setup techniques. Reduction of ambiguity because of intrafractional target motion is the next step forward. Respiratory organ motion is known to be the largest intrafractional organ motion. Radiotherapy techniques controlling, gating, or tracking respiratory motion are under investigation to use smaller safety margins and higher doses for moving tumors. However, data on intrafractional tumor motion are sparse. We developed a fluoroscopic real-time tracking system and implantation techniques of fiducial markers for moving organs and have been accumulating knowledge about internal tumor motion. We also found the importance of 4-dimensional treatment planning to account for tumor motion in precision radiotherapy. This article reviews the current basic knowledge on respiratory physiology and summarizes the accumulating knowledge on internal motion of lung and liver tumors.