Postoperative Radiotherapy For Breast Cancer Research Articles

Excluding Upper Axillary Level 1 in Regional Nodal Irradiation Does Not Increase Axillary Recurrence Risk in Patients With Breast Cancer

PurposeThe optimal extent of regional nodal irradiation (RNI) in postoperative radiotherapy for breast cancer, particularly regarding axillary level 1 (AXL1), remains uncertain. This study aims to compare clinical outcomes between extensive RNI including the entire axilla and limited RNI excluding the upper AXL1 in patients with breast cancer. MethodsA retrospective analysis included 1,780 women with non-metastatic unilateral breast cancer who underwent RNI during postoperative radiotherapy between 2007 and 2018. Patients were classified into extensive and limited RNI groups based on the upper AXL1 inclusion in the radiation field. Propensity score matching yielded a cohort of 1,020 patients. Non-inferiority of limited RNI compared to extensive RNI was assessed with a defined margin of ≤2% in the 5-year axillary recurrence rate. ResultsAfter a median follow-up of 67.9 months, the 5-year axillary recurrence rates were similar between extensive and limited RNI groups (1.2% vs. 1.6%; Plog-rank=0.790). Limited RNI demonstrated non-inferiority with a 0.4% difference (95% confidence interval, -1.1%–1.9%; Pnon-inferiority=0.019). Disease-free survival (87.9% vs. 91.5%; Plog-rank=0.122) and overall survival (94.1% vs. 96.9%; Plog-rank=0.260) at 5 years were not significantly different between extensive and limited RNI groups. Multivariable analysis revealed that lymphovascular invasion (hazard ratio [HR], 5.17; P=0.02) and negative hormone receptor status (HR, 11.73; P=0.002) were associated with a higher risk of axillary recurrence, while limited RNI showed no significant association (HR, 1.35; P=0.652). Subgroup analysis demonstrated that extensive RNI did not improve axillary control in patients with lymphovascular invasion, hormone receptor negativity, positive lymph node metastasis, or a small number of nodes removed. ConclusionLimited RNI, excluding the upper AXL1 from the radiation field, demonstrated axillary recurrence rates comparable to those of extensive RNI in patients with breast cancer. The study suggests that extensive RNI may not provide additional therapeutic benefits, while limited RNI appears to be a valid option for regional control.

Validation of different automated segmentation models for target volume contouring in postoperative radiotherapy for breast cancer and regional nodal irradiation

IntroductionTarget volume delineation is routinely performed in postoperative radiotherapy (RT) for breast cancer patients, but it is a time-consuming process. The aim of the present study was to validate the quality, clinical usability and institutional-specific implementation of different auto-segmentation tools into clinical routine. MethodsThree different commercially available, artificial intelligence-, ESTRO-guideline-based segmentation models (M1-3) were applied to fifty consecutive reference patients who received postoperative local RT including regional nodal irradiation for breast cancer for the delineation of clinical target volumes: the residual breast, implant or chestwall, axilla levels 1 and 2, the infra- and supraclavicular regions, the interpectoral and internal mammary nodes. Objective evaluation metrics of the created structures were conducted with the Dice similarity index (DICE) and the Hausdorff distance, and a manual evaluation of usability. ResultsThe resulting geometries of the segmentation models were compared to the reference volumes for each patient and required no or only minor corrections in 72 % (M1), 64 % (M2) and 78 % (M3) of the cases. The median DICE and Hausdorff values for the resulting planning target volumes were 0.87–0.88 and 2.96–3.55, respectively. Clinical usability was significantly correlated with the DICE index, with calculated cut-off values used to define no or minor adjustments of 0.82–0.86. Right or left sided target and breathing method (deep inspiration breath hold vs. free breathing) did not impact the quality of the resulting structures. ConclusionArtificial intelligence-based auto-segmentation programs showed high-quality accuracy and provided standardization and efficient support for guideline-based target volume contouring as a precondition for fully automated workflows in radiotherapy treatment planning.

Postoperative Radiotherapy Using VMAT for RNI Including IMN in Breast Cancer: Report of Short-term Follow-up.

The application of volumetric-modulated arc therapy (VMAT) in postoperative radiotherapy for breast cancer has recently garnered considerable interest, especially when regional lymph node irradiation (RNI), is extended to include the internal mammary node (IMN) region, along with whole-breast or chest wall irradiation. This study aimed to assess both acute and late toxicities, as well as breast cancer outcomes, during the observation period. This retrospective study aimed to assess the safety and feasibility of VMAT in postoperative radiotherapy, including the IMN region, for patients with breast cancer at our hospital. We included 33 eligible patients who received postoperative VMAT radiotherapy, including the IMN region, between November 2018 and July 2021. The primary indications for implementing VMAT were the presence of IMN metastases before primary systemic therapy or more than four axillary lymph node metastases. The median prescribed dose for the chest wall or conserved breast and regional lymph nodes was 50 Gy in 25 fractions. In 16 cases, a simultaneous boost (median, 10 Gy) was administered to residual lymph node metastases. VMAT facilitated a reduction in the mid- or high-dose range to organs at risk, exemplified by V20Gy and V40Gy of the ipsilateral lung, which were 24.10% and 6.84%, respectively, while ensuring adequate target dose irradiation, V45Gy=95.23%. No serious adverse events, including symptomatic radiation pneumonitis, occurred during the 15-month median observation period. Our findings demonstrate the safety and effectiveness of postoperative radiotherapy for breast cancer, including the IMN region, when using VMAT.

Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma insitu. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Risk of thoracic soft tissue sarcoma after breast cancer radiotherapy: a population-based cohort study in Osaka, Japan.

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7years (interquartile range, 4.0-8.6years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population.

Quantify the Effect of Air Gap Errors on Skin Dose for Breast Cancer Radiotherapy.

Purpose: Determining the impact of air gap errors on the skin dose in postoperative breast cancer radiotherapy under dynamic intensity-modulated radiation therapy (IMRT) techniques. Methods: This was a retrospective study that involved 55 patients who underwent postoperative radiotherapy following modified radical mastectomy. All plans employed tangential IMRT, with a prescription dose of 50 Gy, and bolus added solely to the chest wall. Simulated air gap depth errors of 2 mm, 3 mm, and 5 mm were introduced at depression or inframammary fold areas on the skin, resulting in the creation of air gaps named Air2, Air3, and Air5. Utilizing a multivariable GEE, the average dose (Dmean) of the local skin was determined to evaluate its relationship with air gap volume and the lateral beam's average angle (AALB). Additionally, an analysis was conducted on the impact of gaps on local skin. Results: When simulating an air gap depth error of 2 mm, the average Dmean in plan2 increased by 0.46 Gy compared to the initial plan (planO) (p < .001). For the 3-mm air gap, the average Dmean of plan3 was 0.51 Gy higher than that of planO (p < .001). When simulating the air gap as 5 mm, the average Dmean of plan5 significantly increased by 0.59 Gy compared to planO (p < .001). The TCP results showed a similar trend to those of Dmean. As the depth of air gap error increases, NTCP values also gradually rise. The linear regression of the multivariable GEE equation indicates that the volume of air gaps and the AALB are strong predictors of Dmean. Conclusion: With small irregular air gap errors simulated in 55 patients, the values of skin's Dmean, TCP, and NTCP increased. A multivariable linear GEE regression model may effectively explain the impact of air gap volume and AALB on the local skin.

Application research on reducing radiation-induced lung injury with a trigger operator based on overlap volume histogram (OVH) in breast cancer postoperative radiotherapy

This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P < 0.01), and in the V5, V10, V20, V30, and V40 of the L-Lung in the SG (P < 0.01). Our findings suggest that the proposed trigger operator can improve plan quality, thereby reducing radiation-induced lung injury in postoperative radiotherapy for breast cancer.

Prior information guided auto-segmentation of clinical target volume of tumor bed in postoperative breast cancer radiotherapy

BackgroundAccurate delineation of clinical target volume of tumor bed (CTV-TB) is important but it is also challenging due to surgical effects and soft tissue contrast. Recently a few auto-segmentation methods were developed to improve the process. However, those methods had comparatively low segmentation accuracy. In this study the prior information was introduced to aid auto-segmentation of CTV-TB based on a deep-learning model.MethodsTo aid the delineation of CTV-TB, the tumor contour on preoperative CT was transformed onto postoperative CT via deformable image registration. Both original and transformed tumor contours were used for prior information in training an auto-segmentation model. Then, the CTV-TB contour on postoperative CT was predicted by the model. 110 pairs of preoperative and postoperative CT images were used with a 5-fold cross-validation strategy. The predicted contour was compared with the clinically approved contour for accuracy evaluation using dice similarity coefficient (DSC) and Hausdorff distance.ResultsThe average DSC of the deep-learning model with prior information was improved than the one without prior information (0.808 vs. 0.734, P < 0.05). The average DSC of the deep-learning model with prior information was higher than that of the traditional method (0.808 vs. 0.622, P < 0.05).ConclusionsThe introduction of prior information in deep-learning model can improve segmentation accuracy of CTV-TB. The proposed method provided an effective way to automatically delineate CTV-TB in postoperative breast cancer radiotherapy.

Does Epigallocatechin Gallate as a Radiation Protective Agent Reduce the Anti-Tumor Effect of Radiotherapy in Postoperative Breast Cancer Radiotherapy?

Based on the previous encouraging results, we further explored whether EGCG would have a protective effect on potential tumor lesions, that is, reduce the efficacy of radiotherapy. We selected patients with stage III breast cancer with or without EGCG. The local control rate, distant metastasis rate, DFS and OS were compared between the two groups. Patients with stage III breast cancer who were treated with EGCG and radiotherapy was selected from a phase II clinical study (ClinicalTrials.gov, No. NCT02580279). Each patient was matched with one control patient without EGCG From the medical database of our hospital matching for age and stage. The control group of stage-and age-matched patients was selected at random from the medical database of our hospital RESULTS: We identified 43 EGCG patients and 43 matched controls. The median age was 45 years (range: 26-67). Between the two groups, there were no obvious differences in the baseline demographic or clinical features. When compared to the placebo group, the mean radiation-induced dermatitis index (RIDI) in the EGCG group was substantially lower (2.56±1.14 vs 3.36±1.16 T = -3.232, P = 0.002). Repeated measures ANOVA indicated the significant differences in the RTOG score during the course of radiotherapy between the two groups (F = 9.611 P = 0.003). The patients mostly experienced RID two or three weeks after starting radiotherapy, although in the EGCG group, it appeared later (3.19±0.91 weeks) than it did in the placebo group (2.67±0.84 weeks), P = 0.008. The median follow-up for patients in the EGCG group at the time of data collection was 50.6 months with 95% confidence interval (CI) from 43.9 to 57.3. While it was 48.6 months (95% CI: 43.4-53.9) for patients in the control group. There was no significant difference in overall survival (OS), disease free-survival (DFS) and freedom from locoregional (LRF) and distant failure (DMF) (P > 0.05). At the data cut-off (December 2021), the 4-year DFS with EGCG was 71.4% compared to 65.4% with conventional therapy, and the 4-year OS was 77.0% compared to 80.3%. The prophylactic use of EGCG solution reduced the RID score of stage III breast cancer patients without negatively impacting the therapeutic effect of radiotherapy on the tumor. EGCG is safe and feasible choice for RID for breast cancer during radiotherapy.

Clinical Application of Individualized 3D-Printed Chest Wall Conformal Device in IMRT for Post-Mastectomy Breast Cancer.

Background Breast cancer is the most common malignant tumour in women. Radical mastectomy with postoperative radiotherapy is now the standard treatment for locally advanced breast cancer. Intensity-modulated radiotherapy (IMRT) has now been developed, which employs linear accelerators to deliver precise radiation to a tumour while minimizing the dose to surrounding normal tissue. It significantly improves the efficacy of breast cancer treatment. However, there are still some flaws that must be addressed. Objective To assess the clinical application of the three-dimensional (3D)-printed chest wall conformal device for breast cancer patients who need to be treated by chest wall intensity modulated radiotherapy (IMRT) after radical mastectomy. Methods The 24 patients were divided into three groups. During a computed tomography (CT) scan, patients in the study group were fixed by a 3D-printed chest wall conformal device, nothing in control group A, and a traditional 1-cm thick silica gel compensatory pad on the chest wall in control group B. The parameters of mean Dmax, Dmean, D2%, D50%, D98%, the conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV) are compared. Results The study group had the best dose uniformity (HI = 0.092) and the highest conformation (CI = 0.97), the worst in control group A (HI = 0.304, CI = 0.84). The mean Dmax, Dmean, and D2% of the study group were lower than control groups A and B (p<0.05). The mean D50% was higher than control group B (p<0.05), while the mean D98% was higher than control groups A and B (p<0.05). The mean Dmax, Dmean, D2%, and HI of control group A were higher than control group B (p<0.05), whereas the mean D98% and CI were lower than control group B (p<0.05). Conclusion By improving the efficacy of postoperative radiotherapy for breast cancer, using 3D-printed chest wall conformal devices may greatly improve the accuracy of repeating position fixation, increase the dose on the skin surface of the chest wall, optimise the dose distribution of the target area, and thus further reduce tumour recurrence and prolong patients' survival.

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer

BackgroundPost-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. MethodsAll patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). ResultsFrom 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7–28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8–20.8 years] compared to 8 years for patients without boost [1.7–28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. DiscussionWe report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance.

A deep learning approach for automatic delineation of clinical target volume in stereotactic partial breast irradiation (S-PBI)

Accurate and efficient delineation of the clinical target volume (CTV) is of utmost significance in post-operative breast cancer radiotherapy. However, CTV delineation is challenging as the exact extent of microscopic disease encompassed by CTV is not visualizable in radiological images and remains uncertain. We proposed to mimic physicians’ contouring practice for CTV segmentation in stereotactic partial breast irradiation (S-PBI) where CTV is derived from tumor bed volume (TBV) via a margin expansion followed by correcting the extensions for anatomical barriers of tumor invasion (e.g. skin, chest wall). We proposed a deep-learning model, where CT images and the corresponding TBV masks formed a multi-channel input for a 3D U-Net based architecture. The design guided the model to encode the location-related image features and directed the network to focus on TBV to initiate CTV segmentation. Gradient weighted class activation map (Grad-CAM) visualizations of the model predictions revealed that the extension rules and geometric/anatomical boundaries were learnt during model training to assist the network to limit the expansion to a certain distance from the chest wall and the skin. We retrospectively collected 175 prone CT images from 35 post-operative breast cancer patients who received 5-fraction partial breast irradiation regimen on GammaPod. The 35 patients were randomly split into training (25), validation (5) and test (5) sets. Our model achieved mean (standard deviation) of 0.94 (±0.02), 2.46 (±0.5) mm, and 0.53 (±0.14) mm for Dice similarity coefficient, 95th percentile Hausdorff distance, and average symmetric surface distance respectively on the test set. The results are promising for improving the efficiency and accuracy of CTV delineation during on-line treatment planning procedure.

Cardiac impacts of postoperative radiotherapy for breast cancer in Japanese patients.

Radiotherapy for breast cancer has attracted attention in Western countries because radiation to the heart can cause cardiac events. The purposes of this study were to evaluate the relationship between radiotherapy after breast-conserving surgery and the frequency of cardiac events in Japanese patients and to investigate the risk factors of cardiac events after postoperative radiotherapy in those patients. Female patients who received postoperative radiotherapy following breast-conserving surgery between 2007 and 2012 at our hospital were evaluated. In this study, we estimated the cumulative incidence of cardiac events including angina pectoris, myocardial infarction, ischemic heart disease, heart failure and cardiomyopathy after radiotherapy. Of 311 eligible patients, 7.1% of the patients had a smoking history, 20.3% of the patients were obese and 22.2% of the patients had hypertension. The median follow-up period was 118months (interquartile range, 102-132months). Twelve patients (3.9%) experienced cardiac events after treatment. The mean time to cardiac events was 126months. The 10-year cumulative incidences of cardiac events after treatment were 4.2% and 4.3% for patients with left-sided and right-sided breast cancer, respectively, without a significant difference. Multivariate analysis showed that only hypertension was a risk factor for cardiac events (hazard ratio = 16.67, P = 0.0003). In conclusion, postoperative radiotherapy for breast cancer did not increase the incidence of cardiac events. Since at least 2007, postoperative radiotherapy for breast cancer has been safely performed without effects on the heart.

Improved treatment robustness of postoperative breast cancer radiotherapy including supraclavicular nodes.

A combination of a three-dimensional conformal radiation therapy (3D-CRT) plan with a dose gradient of the chest wall area and a volumetric modulated arc therapy (VMAT) plan of the supraclavicular area might improve the dose distribution robustness in the junction. To investigate the impact of patient motion on the dose distribution, hybrid 3D-CRT and VMAT plans were recalculated by shifting the isocenter of the VMAT plan. Compared to the nominal plan, the target D98% for high- vs low-dose gradients decreased by 24% vs 12%. Hybrid VMAT with a low-dose gradient 3D-CRT plan was found to be robust towards patient motion.

Feasibility, Tolerance, and Quality of Life for Hypofractionation Versus Conventional Fractionation for Post-mastectomy Radiotherapy in Indian Patients.

Introduction: The international standard for post-operative radiotherapy for breast cancer delivers hypofractionated radiotherapy. However, many centers in India still follow the longer conventional schedule probably because of paucity of large prospective trials in Indian patients on the same and apprehension regarding tolerance of high dose per fraction in the said population. We aimed to test the feasibility of hypofractionation in our setting and compared the toxicities and the quality of life in patients receiving conventional and hypofractionated radiotherapy.Materials and methods: Eighty histopathologically proven women of non-metastatic carcinoma breast who underwent modified radical mastectomy were assigned to receive 50 Gray/25 fractions/five weeks or 40 Gray/15 fractions/three weeks. Patients were assessed for the following toxicities - radiation dermatitis, radiation pneumonitis, dysphagia, skin fibrosis, lymphedema, shoulder stiffness, and brachial plexopathy, during radiation and at treatment completion and then at first, third, and sixth-month follow-up. Health-related quality of life was assessed using the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) and breast cancer-specific quality of life questionnaire (QLQ-BR23) at treatment completion and then at first, third, and sixth-month follow-up.Results and conclusion: We had a mean follow-up of 12.78 months. All the assessed toxicities and quality of life scores were comparable between the two arms at all time points of evaluation (p>0.05); 40 Gray in 15 fractions over three weeks is feasible and as safe as the five-week schedule with comparable quality of life. Hypofractionation can be practiced as a routine for post-mastectomy breast cancer patients as this shorter radiotherapy schedule is convenient and cheaper for the patients with no compromise on normal tissue toxicity or quality of life.

The factors of fiducial marker motions and individual margin assessment in postoperative breast cancer radiotherapy.

As a surrogate for the breast tumor bed, individual fiducial markers frequently move during radiotherapy. This study aimed to classify the motions and calculate the individualized target margin. The mammary basal diameters (D) and heights (H) were measured to represent breast sizes for 15 patients after breast-conserving surgery. The clinical target volume (CTV) was divided into 4 quadrants by a coordinate system with the center of mass of the tumor bed as the origin. The lateral, anteroposterior, and craniocaudal motions of markers were calculated (MLR, MAP, MSI) based on the difference of the setup errors between the spine matching and the fiducial markers matching. The distances between markers and the innermost, foremost, and uppermost borders of CTV (DSLR, DSAP, DSSI) were recorded. In the first quadrant, MAP was strongly correlated with D×H (r>0.80) when D×H <99.89 cm2. Both MLR and MAP were positively linearly related to DSLR, DSAP, DSSI (r>0.85, R2>0.75). MSI was also positively linearly correlated with DSAP and DSLR (r>0.90, R2>0.80). In the fourth quadrant with D×H <90.71 cm2, only MLR and DSLR showed a linear positive correlation (r>0.90, R2>0.75), whereas the others showed linear negative correlations (r>-0.90, R2>0.80). The planning target volume (PTV) margin varied significantly between the first and fourth quadrant (P<0.05), and the largest margin was 12.4 mm in the craniocaudal direction of the first quadrant with D×H ≥99.89 cm2. Fiducial motion is susceptible to breast size and fiducial position, and the individualized PTV margins should take the above factors into account.

Left-sided Breast Cancer Irradiation With Deep Inspiration Breath-hold: Changes in Heart and Lung Dose in Two Periods

Post-operative radiotherapy for breast cancer can increase cardiac disease in a dose-dependent manner. In this study we show the reduction of dose to heart and left anterior descending artery (LAD) which can be achieved by using "Deep inspiration breath-hold" (DIBH) technique.Tangential 3D-planned radiation was delivered to 357 patients with left-sided breast cancer, 159 of them with the DIBH technique. A distinction was made according to fractionation scheme.The mean heart dose was significantly reduced by DIBH from 2.64 Gy to 1.39 Gy (p<0.001). The mean dose to the LAD was significantly reduced from 5.68 Gy to 3.88 Gy (p<0.001). Mean dose and volume receiving 5, 10 and 15 Gy of ipsilateral lung were higher with both hypofractionated schedule and conventional fractionation in the DIBH group.DIBH in left-sided breast irradiation is an effective method of reducing the radiogenic heart dose.

Prior information guided auto-contouring of breast gland for deformable image registration in postoperative breast cancer radiotherapy.

Contouring of breast gland in planning CT is important to postoperative radiotherapy of patients after breast conserving surgery (BCS). However, the contouring task is difficult because of the poorer contrast of breast gland in planning CT. To improve its efficiency and accuracy, prior information was introduced in a 3D U-Net model to predict the contour of breast gland automatically. The preoperative CT was first aligned to the planning CT via affine registration. The resulting transform was then applied to the contour of breast gland in preoperative CT, and the corresponding contour in planning CT was obtained. This transformed contour was a preliminary estimation of breast gland in planning CT and was used as prior information in a 3D U-Net model to obtain a more accurate contour. For evaluation, the dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess the deep learning (DL) model's prediction accuracy. The average DSC and HD of the prediction model were 0.775±0.065 and 44.979±20.565 for breast gland without the input of prior information, while the average values were 0.830±0.038 and 17.896±5.737 with the input of prior information (0.775 vs. 0.830, P=0.0014<0.05; 44.979 vs. 17.896, P=0.002<0.05). The prediction accuracy was increased significantly with the introduction of prior information, which provided valuable geometrical distribution of target for model training. This method provides an effective way to identify low-contrast targets from surrounding tissues in CT and will be useful in other image modalities.

Pneumonitis and fibrosis after breast cancer radiotherapy: occurrence and treatment-related predictors

Background Radiation pneumonitis (RP) and radiation fibrosis (RF) are common side effects after breast cancer (BC) radiotherapy (RT). However, there is a great variation in the frequency of RP and RF. This study presents the occurrence of- and the treatment-related predictors for RP and RF. Further, physician- and patient-reported pulmonary symptoms during the first year after postoperative RT for BC are demonstrated. Materials and methods From 2007 to 2008, 250 BC patients referred for postoperative RT were included in a prospective cohort study and followed during the first year after RT. High-resolution computed tomography of the lungs and symptom registration were performed before RT and 3, 6, and 12 months after RT. Patient-reported symptoms were registered by standard quality of life questionnaires. Logistic regression analyses were applied to estimate treatment-related predictors for radiological RP (rRP), clinical RP (cRP), radiological RF (rRF), and clinical RF (cRF). Results The occurrence of rRP and cRP at three months was 78% and 19%, while 12 months after RT rRF and cRF was 89% and 16%, respectively; all reported as grade 1. In multivariable analyses, mastectomy predicted cRP at three months (OR = 2.48, p = .03) and cRF at six months, ipsilateral lung volume receiving 20 Gray or more (V20), V30, and mean lung dose (MLD) predicted rRP at six months (OR = 1.06, p = .0003; OR = 1.10, p = .001; and OR = 1.03, p = .01, respectively). Endocrine treatment predicted cRF at 12 months (OR = 2.48, p = .02). Physicians reported significant more dyspnea at 3 months (p = .003) and patients reported ‘a little dyspnea’ more at 3 and 12 months compared to baseline (p = .007). Conclusion RP and RF are prevalent in the first year after BC radiation. Mastectomy predicted cRP at three months. V20, V30, D25, and MLD predicted rRP at 6 months, and endocrine treatment predicted cRF at 12 months. Patients and physicians reported dyspnea differently.