Reduced Risk of Severe Radiation-Induced Lymphopenia in Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer: A Comparative Analysis of Carbon Versus Photon Therapy.

PURPOSE: Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated. MATERIALS AND METHODS: This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 109 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis. RESULTS: After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A. CONCLUSIONS: CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes.

Feasibility of Intraoperative Radiotherapy Tumor Bed Boost in Patients with Breast Cancer after Neoadjuvant Chemotherapy.

PURPOSE: This study aimed to assess the feasibility and safety of administering intraoperative radiotherapy (IORT) as a boost during breast-conserving surgery (BCS) following neoadjuvant chemotherapy for patients at high risk of breast cancer recurrence. MATERIALS AND METHODS: Patients who underwent neoadjuvant chemotherapy received a single 20-Gy dose of IORT during BCS, followed by external beam radiotherapy 4-6 weeks after surgery. RESULTS: The median follow-up duration was 31.0 months (range, 18.0-59.0 months). Initial tumor sizes had a median of 2.6 cm (range: 0.8-5.3 cm), reducing to 0.3 cm (range: 0-4.0 cm) after neoadjuvant chemotherapy. The most common neoadjuvant chemotherapy regimen was doxorubicin and cyclophosphamide, followed by paclitaxel (n=42, 73.7%). Among 57 patients who received neoadjuvant chemotherapy before BCS and IORT, 2 patients (3.5%) required secondary surgery to achieve negative resection margins due to initially positive margins. Regional lymph node irradiation was performed in 37 (64.9%) patients. There was no grade 3 or higher adverse events, with 4 patients (7.0%) experiencing grade 2 acute radiation dermatitis and 3 (5.3%) having less than grade 2 breast edema. Binary correlation analysis did not reveal statistically significant associations between applicator size or radiation therapy modality and the risk of treatment-related toxicity. Furthermore, chi-square analysis showed that the grade of treatment-related toxicity was not associated with the fractionated regimen (p=0.375). CONCLUSION: Most patients successfully received IORT as a tumor bed boost after neoadjuvant chemotherapy. Thus, IORT may be a safe and feasible option for patients with advanced-stage breast cancer receiving neoadjuvant chemotherapy.

Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma.

PURPOSE: This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma. MATERIALS AND METHODS: Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included. RESULTS: In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively. CONCLUSION: Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.

Active involvement of patients, radiation oncologists, and surgeons in a multidisciplinary team approach: Guiding local therapy in recurrent, metastatic rectal cancer.

BACKGROUND: Despite the extensive implementation of an organized multidisciplinary team (MDT) approach in cancer treatment, there is little evidence regarding the optimal format of MDT. We aimed to investigate the impact of patient participation in MDT care on the actual application rate of metastasis-directed local therapy. METHODS: We identified all 1211 patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy at a single institution from 2006 to 2018. Practice patterns, tumor burden and OMD state were analyzed in recurrent, metastatic cases. RESULTS: With a median follow-up of 60.7 months, 281 patients developed metastases, and 96 (34.2%), 92 (32.7%), and 93 (33.1%) patients had 1, 2-5, and >5 lesions, respectively. In our study, 27.1% were managed in the MDT clinic that mandated the participation of at least four to five board-certified multidisciplinary experts and patients in decision-making processes, while the rest were managed through diverse MDT approaches such as conferences, tumor board meetings, and discussions conducted via phone calls or email. Management in MDT clinic was significantly associated with more use of radiotherapy (p = 0.003) and more sessions of local therapy (p < 0.001). At the time of MDT clinic, the number of lesions was 1, 2-5, and >5 in 9 (13.6%), 35 (53.1%), and 19 (28.8%) patients, respectively. The most common states were repeat OMD (28.8%) and de novo OMD (27.3%), followed by oligoprogression (15%) and induced OMD (10.6%). CONCLUSION: Our findings suggest that active involvement of patients and radiation oncologists, and surgeons in MDT care has boosted the probability of using local therapies for various types of OMD throughout the course of the disease.

Risk of on-treatment lymphopenia is associated with treatment outcome and efficacy of consolidation immunotherapy in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND AND PURPOSE: The ability of the effective dose to immune cells (EDIC) and the pre-radiotherapy (RT) absolute lymphocyte count (ALC) to predict lymphopenia during RT, treatment outcomes, and efficacy of consolidation immunotherapy in patients with locally advanced non-small cell lung cancer was investigated. METHODS AND MATERIALS: Among 517 patients treated with concurrent chemoradiotherapy, EDIC was calculated using the mean doses to the lungs, heart, and total body. The patients were grouped according to high and low EDIC and pre-RT ALC, and the correlations with radiation-induced lymphopenia and survival outcomes were determined. RESULTS: Altogether, 195 patients (37.7%) received consolidation immunotherapy. The cutoff values of EDIC and pre-RT ALC for predicting severe lymphopenia were 2.89 Gy and 2.03 × 109 cells/L, respectively. The high-risk group was defined as EDIC ≥ 2.89 Gy and pre-RT ALC < 2.03 × 109 cells/L, while the low-risk group as EDIC < 2.89 Gy and pre-RT ALC ≥ 2.03 × 109 cells/L, and the rest of the patients as the intermediate-risk group. The incidences of severe lymphopenia during RT in the high-, intermediate-, and low-risk groups were 90.1%, 77.1%, and 52.3%, respectively (P < 0.001). The risk groups could independently predict both progression-free (P < 0.001) and overall survival (P < 0.001). The high-risk group showed a higher incidence of locoregional and distant recurrence (P < 0.001). Consolidation immunotherapy showed significant survival benefit in the low- and intermediate-risk groups but not in the high-risk group. CONCLUSIONS: The combination of EDIC and pre-RT ALC predicted severe lymphopenia, recurrence, and survival. It may potentially serve as a biomarker for consolidation immunotherapy.

Study protocol for prospective multi-institutional phase III trial of standard of care therapy with or without stereotactic ablative radiation therapy for recurrent ovarian cancer (SABR-ROC).

BACKGROUND: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision. METHODS: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews. DISCUSSION: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.

Clinical Outcomes of Thymic Carcinoma: The Role of Radiotherapy Combined with Multimodal Treatments.

INTRODUCTION: We aimed to identify the role of radiotherapy (RT) in the treatment of thymic carcinoma as well as the optimal RT target volume. MATERIALS AND METHODS: This single-institution retrospective study included 116 patients diagnosed with thymic carcinoma between November 2006 and December 2021 who received multimodal treatment including RT with or without surgery or chemotherapy. Seventy-nine patients (68.1%) were treated with postoperative RT, 17 patients (14.7%) with preoperative RT, 11 patients (9.5%) with definitive RT, and nine patients (7.8%) with palliative RT. The target volume was defined as the tumor bed or gross tumor with margin, and selective irradiation of the regional nodal area was performed when involved. RESULTS: With a median follow-up of 37.0 (range, 6.7-174.3) months, the 5-year overall survival (OS), progression-free survival, and local recurrence-free survival rates were 75.2%, 47.7% and 94.7%, respectively. The 5-year OS was 51.9% in patients with unresectable disease. Overall, 53 recurrences were observed, of which distant metastasis was the most common pattern of failure (n = 32, 60.4%) after RT. No isolated infield or marginal failures were observed. Thirty patients (25.8%) who had lymph node metastases at the initial diagnosis had regional nodal areas irradiated. There was no lymph node failure inside the RT field. A tumor dimension of ≥5.7 cm (hazard ratio [HR] 3.01; 95% confidence interval [CI] 1.25-7.26; p = 0.030) and postoperative RT (HR 0.20; 95% CI 0.08-0.52; p = 0.001) were independently associated with OS. Intensity-modulated-RT-treated patients developed less overall toxicity (p < 0.001) and esophagitis (p < 0.021) than three-dimensional-conformal-RT-treated patients. CONCLUSIONS: A high local control rate was achieved with RT in the primary tumor sites and involved lymph node area in the treatment of thymic carcinoma. A target volume confined to the tumor bed or gross tumor plus margin with the involved lymph node stations seems reasonable. The advanced RT techniques with intensity-modulated RT have led to reduced RT-related toxicity.

Association of Sinoatrial Node Radiation Dose With Atrial Fibrillation and Mortality in Patients With Lung Cancer.

Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. Design, Setting, and Participants: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main Outcomes and Measures: Main outcomes were AF and overall survival. Results: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmax significantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P < .001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P = .008). However, SAN Dmax was not associated with non-AF cardiac events. Increased SAN Dmax was significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P < .001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P < .001). Conclusions and Relevance: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

Association of neutrophil-to-lymphocyte ratio, radiotherapy fractionation/technique, and risk of development of distant metastasis among patients with locally advanced rectal cancer.

BACKGROUND: We investigated the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced rectal cancer (LARC) and whether modifiable factors in radiotherapy (RT) influenced the NLR. METHODS: Data of 1386 patients who were treated with neoadjuvant RT and concurrent or sequential chemotherapy for LARC between 2006 and 2019 were evaluated. Most patients (97.8%) were treated with long-course RT (LCRT; 50-50.4 Gy in 25-28 fractions) using three-dimensional conformal radiotherapy (3D-CRT) (n = 851) or helical tomotherapy (n = 504), and 30 patients underwent short-course RT (SCRT; 25 Gy in 5 fractions, followed by XELOX administration for 6 weeks). Absolute neutrophil and lymphocyte counts were obtained at initial diagnosis, before and during the preoperative RT course, and after preoperative concurrent chemoradiotherapy. The primary endpoint was distant metastasis-free survival (DMFS). RESULTS: The median follow-up time was 61.3 (4.1-173.7) months; the 5-year DMFS was 80.1% and was significantly associated with the NLR after RT but not before. A post-RT NLR ≥ 4 independently correlated with worse DMFS (hazard ratio, 1.42; 95% confidence interval, 1.12-1.80), along with higher ypT and ypN stages. Post-RT NLR (≥ 4) more frequently increased following LCRT (vs. SCRT, odds ratio [OR] 2.77, p = 0.012) or helical tomotherapy (vs. 3D-CRT, OR 1.29, p < 0.001). CONCLUSIONS: Increased NLR after neoadjuvant RT is associated with increased distant metastasis risk and poor survival outcome in patients with LARC. Moreover, high NLR following RT is directly related to RT fractionation, delivery modality, and tumor characteristics. These results are hypothesis-generating only, and confirmatory studies are required.

Synthetic contrast-enhanced computed tomography generation using a deep convolutional neural network for cardiac substructure delineation in breast cancer radiation therapy: a feasibility study.

BACKGROUND: Adjuvant radiation therapy improves the overall survival and loco-regional control in patients with breast cancer. However, radiation-induced heart disease, which occurs after treatment from incidental radiation exposure to the cardiac organ, is an emerging challenge. This study aimed to generate synthetic contrast-enhanced computed tomography (SCECT) from non-contrast CT (NCT) using deep learning (DL) and investigate its role in contouring cardiac substructures. We also aimed to determine its applicability for a retrospective study on the substructure volume-dose relationship for predicting radiation-induced heart disease. METHODS: We prepared NCT-CECT cardiac scan pairs of 59 patients. Of these, 35, 4, and 20 pairs were used for training, validation, and testing, respectively. We adopted conditional generative adversarial network as a framework to generate SCECT. SCECT was validated in the following three stages: (1) The similarity between SCECT and CECT was evaluated; (2) Manual contouring was performed on SCECT and CECT with sufficient intervals and based on this, the geometric similarity of cardiac substructures was measured between them; (3) The treatment plan was quantitatively analyzed based on the contours of SCECT and CECT. RESULTS: While the mean values (± standard deviation) of the mean absolute error, peak signal-to-noise ratio, and structural similarity index measure between SCECT and CECT were 20.66 ± 5.29, 21.57 ± 1.85, and 0.77 ± 0.06, those were 23.95 ± 6.98, 20.67 ± 2.34, and 0.76 ± 0.07 between NCT and CECT, respectively. The Dice similarity coefficients and mean surface distance between the contours of SCECT and CECT were 0.81 ± 0.06 and 2.44 ± 0.72, respectively. The dosimetry analysis displayed error rates of 0.13 ± 0.27 Gy and 0.71 ± 1.34% for the mean heart dose and V5Gy, respectively. CONCLUSION: Our findings displayed the feasibility of SCECT generation from NCT and its potential for cardiac substructure delineation in patients who underwent breast radiation therapy.

Heart-Sparing Capability and Positional Reproducibility of Continuous Positive Airway Pressure in Left-Sided Breast Radiation Therapy.

PURPOSE: Our purpose was to investigate the interfraction and intrafraction reproducibility and practical applicability of continuous positive airway pressure (CPAP) for left breast volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Interfraction reproducibility of the position of the heart was evaluated by measuring the heart-to-target distance on 20 planning computed tomography (CT) and 300 daily cone beam CT of 20 patients with left breast cancer treated with a 15-fraction VMAT. The dosimetric metrics of the whole heart and its substructures were compared between CPAP and free-breathing based VMAT plans. Intrafraction reproducibility was evaluated by measuring the motions of the breast target and diaphragm in 4-dimensional CT of 20 female patients with nonbreast cancer. Lastly, we analyzed the CPAP compliance data of 237 consecutive patients with left-sided breast cancer with and without internal mammary node irradiation (IMNI). RESULTS: The heart position was reproducible as evidenced by an absolute average heart-to-target distance error of 2.0 ± 2.0 mm. Compared with free-breathing, CPAP significantly reduced the mean heart dose and the dose to the left ventricle and left anterior descending artery. The average intrafraction position variation of the breast target was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm in the mediolateral, craniocaudal, and anteroposterior directions, respectively. CPAP was successfully applied in 221 patients (93%), with a mean heart dose of 1.6 ± 0.7 Gy (IMNI: 2.0 Gy and no IMNI: 1.1 Gy). CONCLUSIONS: CPAP has adequate heart-sparing capability and sufficient reproducibility in VMAT for left-sided breast cancer treatment, with a high compliance rate. Thus, CPAP is applicable in routine practice for left-sided breast cancer radiation therapy.

Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer.

INTRODUCTION: Some patients with cancer may present with progressive or persistent disease at a limited number of sites following a period of treatment response. We evaluated the safety and effectiveness of metastasis-directed radiotherapy (MRT) for oligoprogressive or oligopersistent disease in patients receiving systemic treatment for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who received 5-fluorouracil, leucovorin, and oxaliplatin; 5-fluorouracil, leucovorin, and irinotecan; and/or capecitabine chemotherapy between 2011 and 2020 at a single institution were identified. Then, those who underwent MRT for five or fewer lesion sites while receiving systemic treatment for other metastases were categorized. The primary endpoint was time to change to systemic therapy. Secondary endpoints included MRT-related toxicity, overall survival, and local control. RESULTS: Among 4157 patients included, 91 (2%) received MRT to limited lesion sites (55 oligoprogressive and 36 oligopersistent) during systemic treatment following a period of treatment response. The median time to change to next-line systemic therapy was 5 months in the overall cohort (measured from the current chemotherapy session) and 9.5 (range, 6.0-40.6) months in the MRT group (measured from the MRT session). No severe toxicity or systemic treatment interruption was observed following MRT. The 1-year local control and overall survival rates were 69% and 99%, respectively. CONCLUSION: In patients with oligoprogressive or oligopersistent mCRC, MRT may be performed safely in conjunction with systemic treatment to maximize the benefit of systemic therapy and to prolong the time to change to systemic therapy. Further prospective studies should confirm these findings.

Patterns of Locoregional Recurrence after Radical Cystectomy for Stage T3-4 Bladder Cancer: A Radiation Oncologist's Point of View.

PURPOSE: Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. MATERIALS AND METHODS: We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. RESULTS: Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2-3 patients than in pN0-1 patients (15.2% vs. 4.4%, p=0.04). CONCLUSION: Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Post-mastectomy radiation therapy in breast reconstruction: a patterns of care study of the Korean Radiation Oncology Group.

PURPOSE: The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. MATERIALS AND METHODS: We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. RESULTS: Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. CONCLUSION: Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.

Radiotherapy for initial clinically positive internal mammary nodes in breast cancer.

PURPOSE: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.