Clinical experience of consolidative radiotherapy for localized metastatic non-small cell lung cancer who showed favorable tumor response after systemic treatment.

BACKGROUND: Our study has aimed to assess the effects of consolidative high-dose radiotherapy on clinical outcomes in patients with localized metastatic non-small cell lung cancer (NSCLC) who showed favorable tumor response after systemic treatment. METHODS: We retrospectively reviewed the medical records of 83 patients with localized metastatic NSCLC, who received systemic therapy followed by consolidative local radiotherapy at the Korea University Guro Hospital between March 2017 and June 2022. In the current study, we defined localized metastatic disease as the presence of one to three metastatic sites at the time of diagnosis. And patients who showed favorable tumor response after systemic treatment, including oligo-progressive disease at the thoracic site which was amenable to curative high-dose local radiotherapy, were included. The planned total dose and fraction size mainly depended on the location of lesions. RESULTS: The median follow-up time after consolidative radiotherapy was 16 months (range: 5-52 months). The overall 2-year progression-free survival rates were 81.4%. Of 83 patients, only four (4.3%), treated with intensity-modulated radiation therapy, showed an in-field local recurrence. Interestingly, only one patient experienced a local failure among the 20 patients who showed an oligo-progressive disease at the thoracic site on the tumor response evaluation after systemic treatment. Regarding treatment-related pulmonary toxicity, three patients with grade-3 and one patient with grade-4 radiation pneumonitis were presented. CONCLUSIONS: If the disease is sufficiently controlled and localized by systemic therapy, local consolidative radiotherapy is thought to improves local control rates with acceptable treatment-related toxicities in patients with localized metastatic NSCLC, especially those with oligo-progressive disease.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer.

Importance: Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. Objective: To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. Design, Setting, and Participants: This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). Main Outcomes and Measures: The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. Results: A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). Conclusions and Relevance: In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Survival Outcomes in Premenopausal Patients With Invasive Lobular Carcinoma.

Importance: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient. Objective: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases. Design, Setting, and Participants: This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023. Main Outcomes and Measures: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors. Results: A total of 225 938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant. Conclusions and Relevance: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.

Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease.

BACKGROUND: We aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy. METHODS: We retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS: The median follow-up duration was 15 months (range: 3-47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09-347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group. CONCLUSIONS: This study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.

Survival After Development of Contralateral Breast Cancer in Korean Patients With Breast Cancer.

Importance: Contralateral breast cancer (CBC) is the most frequently diagnosed primary cancer in patients with breast cancer. Although many studies have reported survival after the development of CBC, results have been inconsistent. Objective: To investigate whether the development of CBC is associated with survival among patients with breast cancer. Design, Setting, and Participants: This cohort study was conducted at the Asan Medical Center, Korea, among patients who were diagnosed with primary unilateral, nonmetastatic, stage 0 to III breast cancer between 1999 and 2013 and followed up through 2018. The median (IQR) follow-up was 107 (75-143) months. Patients were categorized into CBC and no-CBC groups by whether they developed CBC during the follow-up period. Data were analyzed from November 2021 to March 2023. Exposure: Development of CBC. Main outcomes and measures: Survival rates of CBC and no-CBC groups were compared using a time-dependent Cox proportional hazard model in the entire study population and in subgroup analyses by interval of CBC development and subtype of the primary breast cancer. Results: Among 16 251 patients with breast cancer (all Asian, specifically Korean; mean [SD] age, 48.61 [10.06] years), 418 patients developed CBC. There was no significant difference in overall survival between CBC and no-CBC groups (hazard ratio, 1.166; 95% CI, 0.820-1.657). Patients who developed CBC within 1.5 years after the surgery of the primary breast cancer had a higher risk for overall death during the study period (hazard ratio, 2.014; 95% CI, 1.044-3.886), and those who developed CBC after 1.5 years showed no significant difference in survival compared with the no-CBC group. Patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-negative breast cancer had a higher risk for overall death in the CBC group (hazard ratio, 1.882; 95% CI, 1.143-3.098) compared with the no-CBC group. Conclusions and Relevance: This study found that development of CBC in patients with breast cancer was not associated with survival but that early development of CBC after diagnosis of the primary breast cancer or development of CBC in patients with HR-positive/ERBB2-negative breast cancer was associated with survival. These results may provide valuable information for patients seeking advice on opting for contralateral prophylactic mastectomy.

Korean Real-World Data on Patients With Unresectable Stage III NSCLC Treated With Durvalumab After Chemoradiotherapy: PACIFIC-KR.

INTRODUCTION: This study aimed to investigate real-world evidence for efficacy and safety of durvalumab consolidation (DC) after chemoradiotherapy (CRT) in patients with unresectable stage III NSCLC. METHODS: Patients with stage III NSCLC who started DC after CRT between September 2018 and December 2020 and were treated at five tertiary hospitals in the Republic of Korea were included. The primary end point was real-world progression-free survival (rwPFS). Secondary end points were overall survival, objective response rate, and adverse events including radiation pneumonitis (RP) and immune-related adverse events (irAEs). RESULTS: A total of 157 patients were enrolled. At the median follow-up of 19.1 months, median rwPFS of DC was 25.9 months (95% confidence interval: 16.5-35.4) and the 1-, 2-, and 3-year rwPFS rates were 59.4%, 51.8%, and 43.5%, respectively. The median overall survival was not mature, and objective response rate of DC was 51.0%. High programmed death-ligand 1 expression (≥50%) and development of RP requiring steroid treatment were significantly associated with longer (p = 0.043) and shorter rwPFS (p = 0.036), respectively. RP, RP requiring steroid treatment, and irAEs developed in 57 (36.3%), 42 (26.8%), and 53 (33.8%) patients, respectively. Among peripheral blood cell counts at the initiation of DC, a high derived monocyte-to-lymphocyte ratio was the most significant risk factor for the development of RP requiring steroid treatment (OR 44.76, 95% CI: 8.89-225.43, p < 0.001) and irAEs (OR 2.85, 95% CI: 1.27-6.41, p = 0.011). CONCLUSIONS: Compared with the outcome of the PACIFIC trial, these real-world data revealed favorable survival benefits of DC after CRT in patients with unresectable stage III NSCLC. Blood-based biomarkers could predict higher-grade RP and irAEs before the initiation of DC.

Consolidative high-dose thoracic radiotherapy for limited metastatic nonsmall cell lung cancer: Focusing on oligo-progressive disease.

AIM: Prior clinical data have shown a significant survival benefit of consolidative local radiotherapy for patients with limited metastatic non-small cell lung cancer (NSCLC). Therefore, this study aimed to evaluate the impact of consolidative high-dose thoracic radiotherapy on local control rates and survivals in patients with limited metastatic NSCLC, especially focusing on oligo-progressive disease. METHODS: We retrospectively reviewed the medical records of 45 patients with limited metastatic NSCLC who received consolidative high-dose thoracic radiotherapy at the Korea University Guro Hospital between March 2015 and December 2020. In the current study, we included patients who showed partial response, stable disease, or oligo-progressive disease on tumor response evaluation after systemic treatment. All patients underwent stereotactic body radiation therapy (23 patients) or intensity-modulated radiation therapy (IMRT, 22 patients). RESULTS: The median follow-up time was 42 months (range: 5-88 months). The overall 2-year disease-free survival (DFS) and overall survival (OS) rates were 80.7% and 88.4%, respectively. Among the 45 patients, only two patients treated with IMRT showed in-field local recurrence. There was no local failure among the patients who showed oligo-progressive disease after systemic treatment. In addition, the response to systemic treatment was not a significant factor for either DFS or OS rates (p = .471 and p = .414, respectively) in univariate analysis. CONCLUSIONS: Consolidative high-dose thoracic radiotherapy improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC. It is also effective and should be considered in patients with oligo-progressive disease after systemic treatment.

Association of Body Mass Index With 21-Gene Recurrence Score Among Women With Estrogen Receptor-Positive, ERBB2-Negative Breast Cancer.

Importance: Body mass index (BMI) may affect the 21-gene recurrence score (RS) in patients with ER-positive, ERBB2-negative breast cancer. If high BMI increases genomic risk in ER-positive, ERBB2-negative breast cancer, weight control will become more important. Objective: To assess the association between RS and BMI according to age groups and address BMI as a factor associated with high RS. Design, Setting, and Participants: This cohort study included 2295 patients with ER-positive, ERBB2-negative breast cancer who had undergone a multigene assay between March 29, 2010, and December 31, 2020, in 2 hospitals. All of the study patients were Korean women, and the median follow-up period was 45 months (range, 1-40 months). The correlations between continuous RS and BMI were investigated. A high BMI was defined as a body mass index greater than or equal to 25. In the younger age group (age ≤45 years), a high RS was defined as an RS of greater than 20. Exposures: Body mass index. Main Outcomes and Measures: The Pearson correlation coefficient was used to estimate the association between RS and BMI. A multivariable binary logistic model was used to identify high RS. Results: Among the 2295 women included (mean [SD] age, 49.8 [4.00] years; range, 22-81 years), 776 were aged 45 years or younger; RS and BMI were weakly correlated (correlation coefficient, 0.119; P < .001) in this younger group. Among them, the proportion of patients with an RS greater than 20 was significantly higher in the high BMI group than in the normal BMI group (45.5% [46 of 101] vs 27.3% [184 of 675]; P < .001). In the multivariable analysis, high BMI was an associated factor for high RS (odds ratio, 2.06; 95% CI, 1.28-3.32; P = .003). The 21-gene multigene assay-guided chemotherapy rate was significantly higher in patients with high BMI (30.7% [31 of 101] vs 20.2% [136 of 674]; P = .02). Conclusions and Relevance: In this cohort study of women aged 45 years or younger, high BMI was associated with higher RS in those with ER-positive, ERBB2-negative breast cancer; further studies are necessary to examine the underlying mechanisms.

Clinical Outcomes of Stereotactic Ablative Radiotherapy for All Stages of Non-Small Cell Lung Cancer; Definitive versus Consolidative.

Background and Objectives: Stereotactic ablative radiotherapy (SABR) is not confined to early stage non-small cell lung cancer (NSCLC) and has a potential role in stage IV disease. We aimed to evaluate the effect of SABR on local control rates and survival outcomes in patients with all stages of NSCLC according to the treatment aim. Materials and Methods: We retrospectively reviewed the medical records of 88 patients with NSCLC who received SABR at the Korea University Guro Hospital between January 2015 and March 2021. Among these, 64 patients with stage I-II NSCLC ineligible for surgery were treated with a definitive aim. Twenty-four patients with stage IV limited metastatic NSCLC showing a favorable response to prior systemic therapy were treated with a consolidative aim. Results: The median follow-up time was 34 (range: 5-88) months. Thirty-one patients developed recurrence (35.2%), with distant metastasis being the most common (25/31, 80.6%). In-field local recurrence occurred in four patients (4/88 patients, 4.5%). For patients treated with definitive SABR, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 91.8% and 58.6%, respectively. In patients treated with consolidative SABR, the 3-year OS and DFS rates were 86.7% and 53.8%, respectively. With respect to treatment-related pulmonary toxicity, grade 3 radiation pneumonitis incidence requiring hospitalization was 2.3% (2/88). Conclusions: Definitive SABR is appropriate for medically inoperable or high surgical risk patients with early stage NSCLC with acceptable treatment-related toxicities. Consolidative SABR improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC.

Is the pathologic tumor size associated with survival in early cervical cancer treated with radical hysterectomy and adjuvant radiotherapy?

OBJECTIVE: In 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system of uterine cervix cancer, size criteria of primary tumor has been revised. This study aimed to evaluate the validity of this new size criteria (<2, 2-4, and ≧4 cm) in patients who underwent radical hysterectomy and adjuvant radiation therapy (RT) for early cervical cancer. MATERIALS AND METHODS: We retrospectively examined 312 patients who underwent radical hysterectomy and adjuvant RT for early cervical cancer (IB-IIA) from 2001 to 2014. The effects of clinical and pathological factors on disease-free survival (DFS) and overall survival (OS) were evaluated in univariate and multivariate analyses. RESULTS: After a median follow-up of 71.5 months, the 5-year DFS and OS rates were 89.5% and 94.7%, respectively. The primary tumor size was not a significant factor for DFS (p = 0.382) or OS (p = 0.725) in all patients. CONCLUSION: Primary tumor size was not a significant factor for survival in patients who received hysterectomy and adjuvant RT for early cervical cancer. Adequacy of new tumor size criteria (<2, 2-4, and ≧4 cm) in new 2018 FIGO stage needs to be validated in further studies.

Improvement of survival in Korean breast cancer patients over a 14-year period: A large-scale single-center study.

PURPOSE: The aim of this study was to evaluate the chronological changes over 14 years in the survival of Korean patients with breast cancer. We also sought to investigate the factors that may have influenced the changes in survival rate. MATERIALS AND METHODS: We retrospectively analyzed 17,776 breast cancer patients who were treated at Asan Medical Center between January 2000 and December 2013. Patient information was collected from the Asan database, including age at diagnosis, clinical manifestation, pathology report, types of treatment and modality, types of recurrence, and follow-up period. We classified the patients into two cohorts according to the year of their surgery (P1: 2000-2007 and P2: 2008-2013) and compared survival and recurrence between both cohorts. RESULTS: We observed that patients treated more recently had better survival outcomes. The 5-year breast cancer-specific survival increased from 94.0% in P1 to 96.6% in P2 (p<0.001), and the 5-year disease-free survival increased from 87.9% in P1 to 91.2% in P2 (p<0.001). When analyzed by type of recurrence, distant metastasis-free survival increased to a significant degree. In subgroup analysis by the subtypes of breast cancer, the survival rates improved in all of the subtypes except triple negative breast cancer, and the improvement was more prominent in subtypes with overexpressed human epidermal growth factor receptor 2. CONCLUSION: This study showed improvement in breast cancer survival over the succeeding years, which is consistent with the advancement in systemic therapy.

Survival Outcomes of Patients With Breast Cancer Diagnosed Using Vacuum-Assisted Biopsy: A Nationwide Study From the Korean Breast Cancer Society.

PURPOSE: Breast cancer is mainly diagnosed using core needle biopsy (CNB), although other biopsy methods, including vacuum-assisted biopsy (VAB), may also be used. We compared differences in clinical characteristics and prognoses of patients with breast cancer according to biopsy methods used for diagnosis. METHODS: A total of 98,457 patients who underwent various biopsy methods (CNB, fine-needle aspiration [FNA], VAB, and excisional biopsy) for diagnosing breast cancer were recruited. Using CNB as a reference, related clinicopathological factors and prognostic differences between biopsy methods were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society Registration System. The associations between biopsy methods and clinicopathological factors were compared using multinomial logistic regression analysis, and the prognoses of patients undergoing the different biopsy methods, as breast cancer-specific survival (BCSS) and overall survival (OS), were compared using the Kaplan-Meier method and Cox proportional hazard model. RESULTS: Univariate and multivariate analyses showed that unlike FNA, both VAB and excisional biopsy were significantly associated with tumor size, palpability, tumor stage, and histologic grade as relatively good prognostic factors compared to CNB. In particular, VAB showed lower odds ratios for these factors than excisional biopsy. In the univariate analysis, the prognosis of patients undergoing VAB was better than that of those undergoing CNB with respect to BCSS (hazard ratio [HR], 0.188, p < 0.001) and OS (HR, 0.359; p < 0.001). However, in the multivariate analysis, there were no significant prognostic differences from CNB in both BCSS and OS; differences were only evident for FNA. CONCLUSION: In this study, we showed that the characteristics of breast cancer differed according to various biopsy methods. Although VAB is not a standard method for breast cancer diagnosis, it showed no prognostic differences to CNB.

MnTnHex-2-PyP5+, Coupled to Radiation, Suppresses Metastasis of 4T1 and MDA-MB-231 Breast Cancer via AKT/Snail/EMT Pathways.

Tumor migration and invasion induced by the epithelial-to-mesenchymal transition (EMT) are prerequisites for metastasis. Here, we investigated the inhibitory effect of a mimic of superoxide dismutase (SOD), cationic Mn(III) ortho-substituted N-n-hexylpyridylporphyrin (MnTnHex-2-PyP5+, MnHex) on the metastasis of breast cancer in cellular and animal models, focusing on the migration of tumor cells and the factors that modulate this behavior. Wound healing and Transwell migration assays revealed that the migration of mouse mammary carcinoma 4T1 cells was markedly reduced during the concurrent treatment of MnHex and radiation therapy (RT) compared with that of the control and RT alone. Bioluminescence imaging showed that MnHex/RT co-treatment dramatically reduced lung metastasis of 4T1 cells in mice, compared with the sham control and both single treatments. Western blotting and immunofluorescence showed that MnHex treatment of 4T1 cells reversed the RT-induced EMT via inhibiting AKT/GSK-3ß/Snail pathway in vitro, thereby decreasing cell migration and invasion. Consistently, histopathological analyses of 4T1 tumors showed that MnHex/RT reduced Snail expression, blocked EMT, and in turn suppressed metastases. Again, in the human metastatic breast cancer MDA-MB-231 cell line, MnHex inhibited metastatic potential in vitro and in vivo and suppressed the RT-induced Snail expression. In addition to our previous studies showing tumor growth inhibition, this study demonstrated that MnHex carries the ability to minimize the metastatic potential of RT-treated cancers, thus overcoming their radioresistance.

Prognosis according to clinical and pathologic lymph node status in breast cancer patients who underwent sentinel lymph node biopsy alone after neoadjuvant therapy.

This study aimed to evaluate the prognosis of breast cancer patients who received neoadjuvant chemotherapy and underwent sentinel lymph node biopsy (SLNB) alone as axillary surgery regardless of their clinical and pathological lymph node status. We reviewed the records of 1,795 patients from Asan Medical Center who were diagnosed with stage I-III breast cancer and received neoadjuvant chemotherapy during 2003-2014. We selected 760 patients who underwent SLNB alone as axillary surgery and divided these patients into four groups according to their clinical lymph node (cN) and pathological lymph node (pN) status: cN(-)pN(-) (n = 377), cN(-)pN(+) (n = 33), cN(+)pN(-) (n = 242), and cN(+)pN(+) (n = 108). We then compared axillary lymph node recurrence, locoregional recurrence (LRR), distant metastasis-free survival (DMFS), and overall survival (OS) among the four groups using Kaplan-Meier analysis. We compared prognosis between the cN(-)pN(-) and cN(+)pN(-) groups to determine whether SLNB alone is an adequate treatment modality even in patients with cN positive pathology before neoadjuvant therapy but SLNB-negative pathology after NAC. The 5-year axillary recurrence rates in the cN(-)pN(-) and cN(+)pN(-) groups were 1.4% and 2.9%, respectively, and there was no significant difference between the two groups (p = 0.152). The axillary recurrence and LRR rates were significantly different among the four groups, with the pN-negative groups (cN[-]pN[-], cN[+]pN[-]) showing lower recurrence rates. DMFS and OS were also significantly different among the four groups, with the cN negative groups (cN[-]pN[-], cN[-]pN[+]) showing improved survival rates. Our study findings suggest that SLNB alone was associated with lower LRR rates even in patients with cN positive pathology before neoadjuvant therapy but cN negative pathology after SLNB. Moreover, recurrence and survival rates differ significantly according to clinical and pathological lymph node status.

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

BACKGROUND: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. METHODS: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. RESULTS: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively. CONCLUSIONS: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.

Radiofrequency ablation and stereotactic body radiotherapy for hepatocellular carcinoma: should they clash or reconcile?

Until a few decades ago, surgical resection was the only valid option for treating hepatocellular carcinoma (HCC). However, various locoregional modalities including arterial-directed therapy, radiofrequency ablation (RFA), and radiotherapy have been recently shown to be effective. RFA is now established as a standard treatment for small localized HCCs, showing oncological results comparable to those of surgical resection in randomized studies. Stereotactic body radiotherapy (SBRT) is a modern radiotherapeutic modality that targets tumors with precision and delivers high radiation doses over a short period of time; it has particularly attracted clinical interest after its therapeutic efficacy was found to be similar to that of surgery in early-stage lung cancer. Given its potent disease control capability, SBRT has also been applied to early HCCs and demonstrated promising results in recent studies. It has also been noted for its suitability to treat tumors located in anatomical locations where RFA would be challenging. However, since its effectiveness has not been compared to that of RFA in randomized studies of patients eligible for RFA, the use of SBRT has been debated. This review was conducted to guide physicians from all fields involved in the treatment of early HCC. The therapeutic characteristics and indications of both SBRT and RFA are described, and recent comparative studies between the two modalities are discussed. In addition, we examined the factors that should be considered when selecting the appropriate treatments, and offer our recommendations.

Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans.

Background and Objectives: This study aimed to evaluate the effect of a BRCA mutation on survival and failure patterns, focusing on the risk of ipsilateral recurrence and contralateral breast cancer in patients. Materials and Methods: We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between 1 January 2000 and 31 December 2010. Ultimately, clinical outcomes of 273 patients were analyzed. Results: The median follow-up duration was 102 months (range, 1 to 220 months). Patients with BRCA1/2-mutated tumors had a shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, patients with BRCA1/2-mutated tumors showed a higher incidence of contralateral breast cancer than those with non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155; 95% CI: 1.789-9.652; p = 0.001). Korean patients with a BRCA mutation showed inferior DFS compared to those without a BRCA mutation. Conclusions: BRCA mutation status is a strong predictor of recurrence in contralateral breast cancer. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have a BRCA mutation.

Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer.

OBJECTIVE: This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. METHODS: We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. RESULTS: After median follow-up of 58.3 months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P = 0.700 and P = 0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P < 0.001 and P < 0.001). CONCLUSIONS: This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

Significance of the number of high-risk factors in patients with cervical cancer treated with radical hysterectomy and concurrent chemoradiotherapy.

OBJECTIVE: The purpose of this study was to evaluate the impact of high-risk factors on the survival of patients with cervical cancer treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 2000 to 2014, medical records of 897 patients with International Federation of Gynecology and Obstetrics stage IB-IIA disease treated with surgery were retrospectively reviewed. Among them, 483 patients with high-risk factors, including pelvic lymph node metastasis, parametrial invasion, or resection margin involvement, were analyzed. RESULTS: The median follow-up time was 57 months (range, 6-205 months). For patients with single and multiple high-risk factors, the 5-year DFS rates were 80.4% and 65.7%, respectively (p < 0.001), and 5-year OS rates were 87.3% and 75.1%, respectively (p = 0.001). Distant metastasis was the most common pattern of recurrence (86.1%). Furthermore, distant metastasis-free survival significantly differed with the number of high-risk factors present (single 82.7% vs. multiple 68.8%, p < 0.001). In the multivariate analysis, while parametrial invasion and resection margin involvement showed no association, the adenocarcinoma histology, pelvic lymph node metastasis, higher metastatic lymph node ratio, and multiple high-risk factors were independent prognosticators associated with poor DFS and OS. CONCLUSIONS: Patients with early-stage cervical cancer having multiple high-risk factors, adenocarcinoma histologic type, and pelvic lymph node metastasis accompanied by a higher lymph node ratio after surgery are more likely to have occult distant metastasis. Further, consolidation with systemic chemotherapy after adjuvant therapy might be considered to improve the survival outcome in this patient population.

Chemoradiotherapy is not superior to radiotherapy alone after radical surgery for cervical cancer patients with intermediate-risk factor.

OBJECTIVES: There is no consensus on whether giving adjuvant concurrent chemoradiotherapy (CCRT) is more effective than adjuvant radiotherapy (RT) alone in patients with early stage cervical cancer and intermediate-risk factor(s). The purpose of this study was to evaluate survival difference according to adjuvant treatment in the intermediate-risk group. METHODS: From 2000 to 2014, the medical records of patients with stage IB-IIA cervical cancer and a history of radical hysterectomy with pelvic lymph node dissection, followed by pelvic RT at a dose ≥40 Gy were retrospectively reviewed. Among these, 316 patients with one or more intermediate-risk factor(s) and no high-risk factors were included. The criteria defined the intermediate-risk group as those patients with any of the following intermediate-risk factors: lymphovascular space involvement, over one-half stromal invasion, or tumor size ≥4 cm. RESULTS: The median follow-up duration was 70 months (range: 3-203 months). According to adjuvant treatment (adjuvant RT alone vs. adjuvant CCRT), the 5-year recurrence-free survival rates (90.8% vs. 88.9%, p=0.631) and 5-year overall survival rates (95.9% vs. 91.0%, p=0.287) did not show a significant difference in patients with any of the intermediate-risk factors. In multivariate analysis, a distinct survival difference according to adjuvant treatment was not found regardless of the number of risk factors. CONCLUSION: The present study showed that giving RT together with chemotherapy is not more effective than RT alone for stage IB-IIA cervical cancer patients with intermediate-risk factor(s). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01101451.