Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

BACKGROUND: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. METHODS: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. RESULTS: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. CONCLUSIONS: In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study.

PURPOSE: This multicenter retrospective study aimed to investigate clinical, radiologic, and treatment-related factors affecting survival in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) treated with radiotherapy. MATERIALS AND METHODS: Patients aged <30 years who underwent radiotherapy as an initial treatment for DIPG between 2000 and 2018 were included; patients who did not undergo magnetic resonance imaging at diagnosis and those with pathologically diagnosed grade I glioma were excluded. We examined medical records of 162 patients collected from 10 participating centers in Korea. The patients' clinical, radiological, molecular, and histopathologic characteristics, and treatment responses were evaluated to identify the prognosticators for DIPG and estimate survival outcomes. RESULTS: The median follow-up period was 10.8 months (interquartile range, 7.5 to 18.1). The 1- and 2-year overall survival (OS) rates were 53.5% and 19.0%, respectively, with a median OS of 13.1 months. Long-term survival rate (≥ 2 years) was 16.7%, and median OS was 43.6 months. Age (< 10 years), poor performance status, treatment before 2010, and post-radiotherapy necrosis were independently associated with poor OS in multivariate analysis. In patients with increased post-radiotherapy necrosis, the median OS estimates were 13.3 months and 11.4 months with and without bevacizumab, respectively (p=0.138). CONCLUSION: Therapeutic strategy for DIPG has remained unchanged over time, and the associated prognosis remains poor. Our findings suggest that appropriate efforts are needed to reduce the occurrence of post-radiotherapy necrosis. Further well-designed clinical trials are recommended to improve the poor prognosis observed in DIPG patients.

Outcomes of intracranial germinoma-A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies.

BACKGROUND: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes. METHODS: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken. RESULTS: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had ß-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%). CONCLUSIONS: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease.

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer.

PURPOSE: To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. MATERIALS AND METHODS: From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50-70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. RESULTS: The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3-5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. CONCLUSION: HFRT with 50-70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.

The role of postoperative radiotherapy after primary tumor resection in patients with de novo stage IV breast cancer.

AIM: This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post-breast conserving radiotherapy (PBCRT) and post-mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR). METHODS: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS). RESULTS: At a median follow-up of 48.9 months (range, 3.5-183.4 months), the median OS was 54.9 months (range, 5.3-185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively CONCLUSIONS: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment.

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years.

PURPOSE: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years. MATERIALS AND METHODS: A search of medical records from seven centers was performed between January 2005 and December 2016. RESULTS: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01). CONCLUSION: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.

Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience.

PURPOSE: To analyze the clinical outcomes and long-term toxicity of pediatric patients with Hodgkin lymphoma after combined-modality treatment (CMT) with involved-field or involved-nodal radiotherapy (RT). MATERIALS AND METHODS: We retrospectively reviewed the records of 27 pediatric Hodgkin lymphoma patients who received CMT at a single institution between January 1990 and July 2017. Patients with stage I-III received a heterogeneous chemotherapy regimen depending on their risk group followed by 19.8-36 Gy RT, with the dose based on their response to the chemotherapy before RT. An optional 9-20 Gy boost was delivered to residual sites. The risk group was determined based on the initial stage, the presence of bulky disease, and any B symptoms. We evaluated overall survival, event-free survival, and long-term toxicities. RESULTS: A total of 27 patients completed the CMT. At a median follow-up of 125 months (range, 9 to 337 months), the estimated 5-year event-free survival and overall survival were 88.9% and 96.3%, respectively. Late symptomatic cardiopulmonary toxicity was not observed, and only one patient was positive on a subclinical obstructive pulmonary function test. The incidence of hypothyroidism was 58.3% among 12 patients with an available thyroid function test. There was one papillary thyroid cancer diagnosed 7.2 years after treatment. CONCLUSION: CMT for pediatric Hodgkin lymphoma with involved-field and involved-nodal RT achieved an excellent survival with only modest long-term toxicity. Smaller-field RT seemed to decrease long-term toxicities and had good local control.

Cervical Lymph Node Involvement above the Supraclavicular Fossa in Breast Cancer: Comparison with Stage IIIC (KROG 18-02).

PURPOSE: We aimed to analyze the treatment outcomes of ipsilateral cervical lymph node (CLN)-positive breast cancer without other distant metastasis and compare the outcomes with those of supraclavicular lymph node (SCL)-positive breast cancer. METHODS: Seventy-eight patients with breast cancer and ipsilateral CLN metastasis above the supraclavicular fossa (CLN[+] group) were treated at 7 institutions (2000-2014). Seventy-four patients received systemic chemotherapy and breast surgery followed by locoregional radiotherapy. Outcomes of the CLN(+) group were compared with those of the SCL(+) group, which included 183 patients with SCL involvement. RESULTS: The median follow-up duration was 55.9 months. Twenty-two regional failures were found in 15 patients-axillary lymph node (LN) in 8, SCL in 6, internal mammary LN in 3, previously involved CLN in 4, and previously uninvolved ipsilateral CLN in one patient. The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates were 68.6%, 46.7%, 68.4%, and 57.0%, respectively. Neck dissection did not improve LRRFS and DFS (p = 0.86 and p = 0.26, respectively). Multivariate analysis showed that hormone receptor negativity and the presence of extracapsular extension were prognostic factors for poor DFS. On comparison with stage IIIC using propensity score matching, survival outcomes of the CLN(+) and SCL(+) groups were not different (5-year OS, p = 0.75; DFS, p = 0.88; LRRFS, p = 0.86; and DMFS, p = 0.45). CONCLUSION: The comparable clinical outcomes indicate that patients with breast cancer who have ipsilateral CLN metastasis without other distant metastasis may benefit from locoregional treatment of the ipsilateral breast and systemic therapies, as do those with N3c disease.

Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

Risk stratification system for groups with a low, intermediate, and high risk of subsequent distant metastasis and death following isolated locoregional recurrence of breast cancer.

PURPOSE: This study aimed to identify prognostic factors for long-term outcomes among patients with isolated locoregional recurrence (ILRR) of breast cancer as their first failure event. Many prognostic tools have been developed to inform systemic treatment choices in the adjuvant setting, but tools for predicting post-ILRR prognosis are scarce. METHODS: A total of 495 patients who experienced ILRR after primary surgery at the Asan Medical Center between 1989 and 2008 were included. All patient information and tumor characteristics at the initial surgery were retrieved from our retrospectively collected database, and ILRRs were categorized as local recurrence or regional recurrence (RR). Distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival post-ILRR were calculated. RESULTS: The median follow-up from the ILRR was 65 months (range 1-249 months), and the 5-year post-ILRR DMFS rate was 58.9%. We found three factors-lymph node metastasis, a disease-free interval < 30 months, and RR as the ILRR type-that were independent prognostic factors for both DMFS [hazard ratio (HR) = 2.08, 1.60, and 1.59; P < 0.001, 0.002, and 0.003, respectively] and BCSS (HR = 2.28, 1.99, and 1.48; P < 0.001, < 0.001, and 0.016, respectively) post-ILRR. Patients were classified into four groups according to the presence these three prognostic indicators: the low-, intermediate-, high-, and extremely high-risk groups. The 5-year post-ILRR DMFS rates were 79.4%, 68.1%, 47.6%, and 36.0%, respectively. CONCLUSIONS: This risk stratification system for subsequent distant metastases after ILRR can be used to make more informed decisions regarding prognosis-based local or systemic management strategies.

Aggressive Surgical Excision of Supraclavicular Lymph Node Did Not Improve the Outcomes of Breast Cancer With Supraclavicular Lymph Node Involvement (KROG 16-14).

INTRODUCTION: The purpose of this study was to evaluate the outcomes of upfront surgery followed by radiation therapy (RT) for ipsilateral supraclavicular (SCN) and/or internal mammary (IMN) node-positive breast cancer. MATERIALS AND METHODS: One hundred fifty-eight patients were included; among these, 91 patients were SCN-positive, 54 were IMN-positive, and 13 were SCN- and IMN-positive. Patients underwent breast conserving surgery (n = 74) or mastectomy (n = 84) followed by systemic therapy, and adjuvant RT to whole breast/chest wall with or without regional nodal RT. Regarding regional treatments for SCN and IMN, SCN excision was performed in 59 (37.3%) patients, IMN excision in 10 (6.3%) patients, SCN RT in 143 (90.5%) patients, and IMN RT in 68 (43.0%) patients. RESULTS: The median duration of follow-up was 72 months (range, 7-182 months). There were 20 locoregional recurrences and 45 distant metastases. In-field failure was observed only in SCN (n = 8), and 6 of these patients initially underwent SCN excision. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 87.3%, 71.6%, and 89.7%, respectively. Neither SCN excision nor SCN RT dose ≥ 54 Gy improved locoregional control (P = .927 and P = .693, respectively) or DFS (P = .394 and P = .686, respectively). Having ≥ 10 involved axillary lymph nodes was the only independent prognosticator for DFS after adjusting for covariates (P = .003). CONCLUSION: Regional control rate in initially involved SCN and/or IMN was acceptable in patients treated with upfront surgery followed by systemic therapy plus adjuvant RT. More aggressive regional therapy such as SCN excision did not improve locoregional control or survival.

Prediction of Late Breast Cancer-Specific Mortality in Recurrence-Free Breast Cancer Survivors Treated for Five Years with Tamoxifen.

PURPOSE: The extension of endocrine therapy beyond 5 years for recurrence-free survivors of breast cancer improves survival; however, the issue on how to clinically identify appropriate candidates remains controversial. This study aimed to identify prognostic factors for breast-cancer-specific mortality in patients who have had 5 years of tamoxifen treatment and categorize subgroups based on the risk of death using combinations of these prognostic factors to assist in the clinical decision to perform further endocrine therapy. METHODS: In total, 3,158 patients with breast cancer were enrolled. Breast cancer-specific survival rates after 5 years of tamoxifen treatment were calculated, and associated prognostic factors were analyzed using a Cox proportional-hazards model. RESULTS: An age extreme at diagnosis (i.e., < 40 or ≥ 60 years), tumor size > 2 cm, and positive lymphovascular invasion were robust independent prognostic factors for late breast cancer-specific death in tamoxifen-treated patients (hazard ratio [HR] = 2.162, 1.739, and 1.993; p = 0.001, 0.047, and 0.011, respectively). Lymph node metastasis and progesterone receptor negativity had borderline significance in this regard (HR = 1.741 and 1.638, p = 0.099 and 0.061). The study patients were classified into four groups according to the number of prognostic indicators, i.e., low, intermediate, high, and extremely high risk. The additional 5- and 10-year cumulative risks of breast cancer-specific death were 0.8% and 1.5% in the low-risk group, 0.9% and 3.9% in the intermediate-risk group, 1.3% and 7.3% in the high-risk group, and 4.8% and 13.8% in the extremely high-risk group, respectively. CONCLUSION: This new risk stratification system for late mortality in breast cancer can be used to identify the right candidates for extended endocrine therapy after 5 years of tamoxifen treatment.

Patterns of recurrence after radiation therapy for high-risk neuroblastoma.

PURPOSE: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site. MATERIALS AND METHODS: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14-36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival. RESULTS: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%. CONCLUSION: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

The Characteristics of Local Recurrence After Breast-Conserving Surgery Alone for Malignant and Borderline Phyllodes Tumors of the Breast (KROG 16-08).

BACKGROUND: Despite margin-negative breast-conserving surgery (BCS), phyllodes tumors (PT) of the breast show high local recurrence (LR) rates. In this study we aimed to assess the site and grade of LR to identify high-risk patients after initial treatment of malignant and borderline PT using BCS alone. PATIENTS AND METHODS: From 1981 to 2014, 312 patients with malignant (n = 164) and borderline (n = 148) PT were treated using BCS alone at 10 centers. LR was defined as true recurrence (TR) if < 2 cm from the primary tumor bed and as elsewhere failure (EF) if otherwise. RESULTS: At a median of 21 months, LR occurred in 17.6% (55 of 312), 18.9% (31 of 164) among malignant and 16.2% (24 of 148) among borderline PT (P = .636). Only 1.9% (6 of 312) had EF. Five-year cumulative LR rates were 14.7% and 35.9% after margin-negative and -positive BCS, respectively (P < .001). Positive margin was an independent risk factor for TR (P = .002) and EF (P = .002). In multivariable competing risk regression of patients with negative margins < 1 cm (n = 115), age < 35 years (P = .001), and tumor size ≥ 5 cm (P = .008) independently increased LR risk. Of patients who experienced a LR, 30.9% (17 of 55) had a second or third repeated event. Borderline-to-malignant transformation rates increased at each LR event: 4.1% (6 of 148), 12.5% (3 of 24), and 77.8% (7 of 9) at first, second, and third LR, respectively (P = .006). CONCLUSION: LRs almost always develop near the primary tumor bed. Many patients experience multiple events, with heightened risk of borderline-to-malignant transformation at each subsequent event. For patients with negative margins < 1 cm, younger age and larger tumor size are independent risk factors for increased LR.

Impact of Regional Nodal Irradiation for Breast Cancer Patients with Supraclavicular and/or Internal Mammary Lymph Node Involvement: A Multicenter, Retrospective Study (KROG 16-14).

PURPOSE: The purpose of this study was to evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement. MATERIALS AND METHODS: A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjuvant systemic therapy followed by breast-conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy. RESULTS: The median follow-up duration was 61 months (range, 7 to 173 months). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥ 4, triple-negative subtype, and mastectomy were significant adverse prognosticators for DFS (p=0.022, p=0.001, p=0.001, and p=0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥ 54 Gy was not associated with DFS (5-year rate, 52.9% vs. 50.9%; p=0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-year rate, 56.1% vs. 78.1%; p=0.099) in IMN-involved patients. CONCLUSION: Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients.

Is tumor bed boost necessary in patients who achieved ypCR following neoadjuvant chemotherapy and breast conserving therapy? (KROG 12-05 and 16-16).

PURPOSE: This multi-institutional study intended to investigate the effect of tumor bed boost in patients who achieved pathologic complete response (ypCR) following neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). MATERIALS AND METHODS: We identified 180 patients who initially had lymph node (LN) metastasis and achieved ypCR (ypT0/isN0) following NAC and BCT from the 13 institutions of the Korean Radiation Oncology Group (KROG) 16-16 and KROG 12-05. The effect of tumor bed boost on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates was analyzed. RESULTS: In all patients, five-year LRC, DFS and OS rates were 97.5%, 95.4%, and 99.4%, respectively. Tumor bed boost was performed in 158 (87.8%) patients. Advanced N-stage (cN2-3, p = 0.036), close resection margin (p < 0.001), and sentinel lymph node biopsy (p = 0.040) were unfavorable factors for DFS. Tumor bed boost was not a significant factor for LRC, DFS, and OS. CONCLUSIONS: This study suggests the benefit of tumor bed boost might be minimal in ypCR patients following NAC and BCT. Larger prospective studies are needed to address this issue.

Axillary Lymph Node Dissection Does Not Improve Post-mastectomy Overall or Disease-Free Survival among Breast Cancer Patients with 1-3 Positive Nodes.

PURPOSE: Axillary lymph node dissection (ALND) may be avoidable for breast cancer patients with 1-2 positive lymph nodes (LN) after breast-conserving therapy. However, the effects of ALND after mastectomy remain unclear because radiation is not routinely used. Herein, we compared the benefits of post-mastectomy ALND versus sentinel node biopsy (SNB) alone for breast cancer patients with 1-3 metastatic LNs. MATERIALS AND METHODS: A total of 1,697 patients with pN1 disease who underwent mastectomy during 2000-2015 were identified from an institutional database. Outcomes were compared using the inverse probability of treatment weighted method. RESULTS: Patients who underwent SNB tended to have smaller tumors, a lower histology grade, a lower number of positive LNs, and better immunohistochemical findings. After correcting all confounding factors regarding patient, tumor, and adjuvant treatment, the SNB and ALND groups did not differ in terms of overall survival (OS) and disease-free survival (DFS), distant metastasis and locoregional recurrence. The 10-year DFS and OS rates were 83% and 84%, respectively, during a median follow-up period of 93 months. CONCLUSION: ALND did not improve post-mastectomy survival outcomes among patients with N1 breast cancer, even after adjusting for all histopathologic and treatment-related factors.

Automated Field-In-Field (FIF) Plan Framework Combining Scripting Application Programming Interface and User-Executed Program for Breast Forward IMRT.

PURPOSE: To develop an one-click option on treatment planning system that enables for the automated breast FIF planning by combining the Eclipse Scripting application programming interfaces and user-executed programming in Windows. METHODS: Scripting application programming interfaces were designed to promote automation in clinical workflow associated with radiation oncology. However, scripting cannot provide all functions that users want to perform. Thus, a new framework proposes to integrate the benefits of the scripting application and user-executed programming for the automated field-in-field technique. We adopted the Eclipse Scripting applications, which provide an interface between treatment planning system server and client and enable for running the executed program to create dose clouds and adjust the planning parameters such as multi-leaf collimator placements and monitor unit values. Importantly, all tasks are designed to perform with one-click option on treatment planning system, including the automated pushback of the proposed plan to the treatment planning system. RESULTS: The plans produced from the proposed framework were validated against the manual field-in-field plans with 40 retrospective breast patient cases in planning efficiency and plan quality. The elapsed time for running the framework was less than 1 minute, which significantly reduced the manual multi-leaf collimator/monitor unit adjustment time. It decreased the total planning time by more than 50%, relative to the manual field-in-field planning. In dosimetric aspects, the mean and maximum dose of the heart, lung, and whole breast did not exceed 1% deviation from the manual plans in most patient cases, while maintaining the target dose coverage and homogeneity index inside the target volume. From numerical analysis, the automated plans were demonstrated to be sufficiently close to the manual plans. CONCLUSION: The combination of scripting applications and user-executed programming for automated breast field-in-field planning accomplished a significant enhancement in planning efficiency without degrading the plan quality, relative to the manual field-in-field procedure.

Cyberknife Dosimetric Planning Using a Dose-Limiting Shell Method for Brain Metastases.

OBJECTIVE: We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs). METHODS: We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans (CKoriginal) had been produced using 1 to 3 dose-limiting shells : one at the prescription isodose level (PIDL) for dose conformity and the others at lowisodose levels (10-30% of prescription dose) for dose spillage. In each case, a modified CK plan (CKmodified) was generated using 5 dose-limiting shells : one at the PIDL, another at intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared. RESULTS: There were no differences in the conformity indices among the CKoriginal, CKmodified, and GK plans (mean 1.22, 1.18, and 1.24, respectively; p=0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; p=0.177), whereas the CKmodified plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the CKoriginal plans (p<0.001), with no statistical differences in those volumes compared with GK plans (p=0.345). CONCLUSION: These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.

Patterns of Practice in Radiotherapy for Breast Cancer in Korea.

Adjuvant radiotherapy (RT) is a well-established treatment for breast cancer. However, there is a large degree of variation and controversy in practice patterns. A nationwide survey on the patterns of practice in breast RT was designed by the Division for Breast Cancer of the Korean Radiation Oncology Group. All board-certified members of the Korean Society for Radiation Oncology were sent a questionnaire comprising 39 questions on six domains: hypofractionated whole breast RT, accelerated partial breast RT, postmastectomy RT (PMRT), regional nodal RT, RT for ductal carcinoma in situ, and RT toxicity. Sixty-four radiation oncologists from 54 of 86 (62.8%) hospitals responded. Twenty-three respondents (35.9%) used hypofractionated whole breast RT, and the most common schedule was 43.2 Gy in 16 fractions. Only three (4.7%) used accelerated partial breast RT. Five (7.8%) used hypofractionated PMRT, and 40 (62.5%) had never used boost RT after chest wall irradiation. Indications for regional nodal RT varied; ≥pN2 (n=7) versus ≥pN1 (n=17) versus ≥pN1 with pathologic risk factors (n=40). Selection criteria for internal mammary lymph node (IMN) irradiation also varied; only four (6.3%) always treated IMN when regional nodal RT was administered and 30 (46.9%) treated IMN only if IMN involvement was identified through imaging. Thirty-one (48.4%) considered omission of whole breast RT after breast-conserving surgery for ductal carcinoma in situ based on clinical and pathologic risk factors. Fifty-two (81.3%) used heart-sparing techniques. Overall, there were wide variations in the patterns of practice in breast RT in Korea. Standard guidelines are needed, especially for regional nodal RT and omission of RT for ductal carcinoma in situ.