A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). @*Materials and Methods@#Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. @*Results@#Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. @*Conclusion@#The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Gene Expression Analyses of Mutant Flammulina velutipes (Enokitake Mushroom) with Clogging Phenomenon

Regulation of proper gene expression is important for cellular and organismal survival, maintenance, and growth. Abnormal gene expression, even for a single critical gene, can thwart cellular integrity and normal physiology to cause diseases, aging, and death. Therefore, gene expression profiling serves as a powerful tool to understand the pathology of diseases and to cure them. In this study, the difference in gene expression in Flammulina velutipes was compared between the wild type (WT) mushroom and the mutant one with clogging phenomenon. Differentially expressed transcripts were screened to identify the candidate genes responsible for the mutant phenotype using the DNA microarray analysis. A total of 88 genes including 60 upregulated and 28 downregulated genes were validated using the realtime quantitative PCR analysis. In addition, proteomic differences between the WT and mutant mushroom were analyzed using two–dimensional gel electrophoresis and matrixassisted laser desorption/ionization-time of flight (MALDI-TOF). Interestingly, the genes identified by these genomic and proteomic analyses were involved in stress response, translation, and energy/sugar metabolism, including HSP70, elongation factor 2, and pyruvate kinase. Together, our data suggest that the aberrant expression of these genes attributes to the mutant clogging phenotype. We propose that these genes can be targeted to foster normal growth in F. velutipes.

Prognosis of patients with axillary lymph node metastases from occult breast cancer: analysis of multicenter data

Purpose@#This study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). @*Materials and Methods@#Data of 53 patients with OBC who received axillary lymph node dissection (ALND) positiveegative (+/–) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35). @*Results@#The median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient’s age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. @*Conclusion@#Patients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS.

Impact of Breast Reconstruction on Biophysical Parameters of Mammary Skin in Patients Receiving Postmastectomy Radiotherapy for Breast Cancer / 한국유방암학회지

Purpose@#In this study, we examined the impact of reconstruction using tissue expander insertion (TEI) on the risk of radiation dermatitis in patients undergoing postmastectomy radiotherapy (PMRT). @*Methods@#Between August 2015 and March 2019, patients with breast cancer who had received systemic chemotherapy and PMRT were prospectively included. Skin parameters, including melanin, erythema, hydration, sebum, and elasticity, were measured using a multiprobe instrument at 6 time points: before the initiation of radiotherapy (pre-RT), at weeks 1, 3, and 5 during radiotherapy (weeks 1–5), and 1 and 3-month after radiotherapy (post-RT-1m and post-RT-3m). Patient-reported outcomes (PROs) were assessed at each time point.Changes in biophysical parameters and PRO were compared between patients with and without TEI (TEI+ vs. TEI−). @*Results@#Thirty-eight patients, including 18 with TEI+ and 20 with TEI-, were analyzed. The pattern of time-course changes in biophysical parameters and PRO did not differ between TEI+ and TEI− patients. The melanin index was highest at post-RT-1m, while the erythema index was highest at week 5. At post-RT-3m, TEI+ patients presented higher melanin values than TEI- patients, with no statistical significance (coefficient, 47.9 vs. 14.2%; p = 0.07). In all patients, water content decreased throughout the measurement period. At post-RT-3m, TEI+ patients demonstrated a further decrease in water content, while the TEI- group nearly recovered the water content to pre-RT status (coefficient, −17.1, −2.5; p = 0.11). The sebum and elasticity levels were not altered by TEI. @*Conclusion@#In patients undergoing PMRT, TEI did not significantly affect the changing patterns of skin biophysical parameters and PRO during radiotherapy.

Prognosis of patients with axillary lymph node metastases from occult breast cancer: analysis of multicenter data

Purpose@#This study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). @*Materials and Methods@#Data of 53 patients with OBC who received axillary lymph node dissection (ALND) positiveegative (+/–) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35). @*Results@#The median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient’s age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. @*Conclusion@#Patients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS.

Impact of Breast Reconstruction on Biophysical Parameters of Mammary Skin in Patients Receiving Postmastectomy Radiotherapy for Breast Cancer / 한국유방암학회지

Purpose@#In this study, we examined the impact of reconstruction using tissue expander insertion (TEI) on the risk of radiation dermatitis in patients undergoing postmastectomy radiotherapy (PMRT). @*Methods@#Between August 2015 and March 2019, patients with breast cancer who had received systemic chemotherapy and PMRT were prospectively included. Skin parameters, including melanin, erythema, hydration, sebum, and elasticity, were measured using a multiprobe instrument at 6 time points: before the initiation of radiotherapy (pre-RT), at weeks 1, 3, and 5 during radiotherapy (weeks 1–5), and 1 and 3-month after radiotherapy (post-RT-1m and post-RT-3m). Patient-reported outcomes (PROs) were assessed at each time point.Changes in biophysical parameters and PRO were compared between patients with and without TEI (TEI+ vs. TEI−). @*Results@#Thirty-eight patients, including 18 with TEI+ and 20 with TEI-, were analyzed. The pattern of time-course changes in biophysical parameters and PRO did not differ between TEI+ and TEI− patients. The melanin index was highest at post-RT-1m, while the erythema index was highest at week 5. At post-RT-3m, TEI+ patients presented higher melanin values than TEI- patients, with no statistical significance (coefficient, 47.9 vs. 14.2%; p = 0.07). In all patients, water content decreased throughout the measurement period. At post-RT-3m, TEI+ patients demonstrated a further decrease in water content, while the TEI- group nearly recovered the water content to pre-RT status (coefficient, −17.1, −2.5; p = 0.11). The sebum and elasticity levels were not altered by TEI. @*Conclusion@#In patients undergoing PMRT, TEI did not significantly affect the changing patterns of skin biophysical parameters and PRO during radiotherapy.

Penicillium ulleungdoense sp. nov. from Ulleung Island in Korea

In a study of the fungal diversity on Ulleung Island in Korea, three novel strains of Penicillium were isolated. Different sites on Ulleung Island were selected for collecting endophytic fungi, and three endophytic fungal strains showed unique morphological characteristics. DNA sequence of the internal transcribed spacer, β-tubulin, calmodulin, and RNA polymerase II second largest subunit regions of the strains were analyzed and they showed unique taxonomic position from the other species of Penicillium section Sclerotiora. The new strains were named Penicillium ulleungdoense sp. nov. As the novel endophytic Penicillium taxa were discovered in a unique environment, the data could be meaningful for understanding the geographical distribution of Ascomycetes on Ulleung Island.

Survival and Prognostic Factors for Breast Cancer Patients with Regional Oligo-Recurrence / 한국유방암학회지

Methods@#In the breast cancer registry of our institution, 18,790 patients received curative surgery for stage I–III breast cancer between January 1995 and June 2016. Of those patients, only 87 (0.5%)underwent salvage local treatment for isolated nodal recurrence on the axillary lymph nodes (ALNs) (n = 58), supraclavicular lymph nodes (SCNs) (n = 17), or internal mammary lymph nodes (IMNs) (n = 12). @*Results@#The median follow-up duration after regional oligo-recurrence was 49 months (range: 6–194 months). For patients with recurrence of ALN, SCN, or IMN, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 40.0%, 32.1%, and 25.0%, respectively (p = 0.3) and 62.7%, 70.0%, and 58.3%, respectively(p = 0.97). In the multivariable analysis for PFS, age at recurrence ≥ 65 years, disease-free interval 1 RF (p 1 RF, the 5-year PFS rates were 7.3% in the ALN group and 7.1% in the SCN/IMN group (p = 1.00). @*Conclusion@#In breast cancer patients with regional oligo-recurrence, clinical outcomes after salvage treatment were favorable in patients with ≤ 1 RF, while patients with > 1 RF had poor prognoses irrespective of the location of recurrence.

Survival and Prognostic Factors for Breast Cancer Patients with Regional Oligo-Recurrence / 한국유방암학회지

Methods@#In the breast cancer registry of our institution, 18,790 patients received curative surgery for stage I–III breast cancer between January 1995 and June 2016. Of those patients, only 87 (0.5%)underwent salvage local treatment for isolated nodal recurrence on the axillary lymph nodes (ALNs) (n = 58), supraclavicular lymph nodes (SCNs) (n = 17), or internal mammary lymph nodes (IMNs) (n = 12). @*Results@#The median follow-up duration after regional oligo-recurrence was 49 months (range: 6–194 months). For patients with recurrence of ALN, SCN, or IMN, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 40.0%, 32.1%, and 25.0%, respectively (p = 0.3) and 62.7%, 70.0%, and 58.3%, respectively(p = 0.97). In the multivariable analysis for PFS, age at recurrence ≥ 65 years, disease-free interval 1 RF (p 1 RF, the 5-year PFS rates were 7.3% in the ALN group and 7.1% in the SCN/IMN group (p = 1.00). @*Conclusion@#In breast cancer patients with regional oligo-recurrence, clinical outcomes after salvage treatment were favorable in patients with ≤ 1 RF, while patients with > 1 RF had poor prognoses irrespective of the location of recurrence.

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

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.

Carcinoembryonic Antigen Improves the Performance of MagneticResonance Imaging in the Prediction of Pathologic Response afterNeoadjuvant Chemoradiation for Patients with Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levelsin improving the performance of magnetic resonance imaging (MRI) for the predictionof pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectalcancer. @*Materials and Methods@#We retrospectively reviewed the medical records of 524 rectal cancer patients who underwentNCRT and total mesorectal excision between January 2009 and December 2014. Theperformances of MRI with or without CEA parameters (initial CEA and CEA dynamics) forprediction of pathologic tumor response grade (pTRG) were compared by receiver-operatingcharacteristic analysis with DeLong’s method. Cox regression was used to identify the independentfactors associated to pTRG and disease-free survival (DFS) after NCRT. @*Results@#The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis,poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) andthe mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed associationwith poor pTRG. The mrTRG plus CEA parameters showed significantly improved performancesin the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEAwere also identified as independent factors associated with DFS. The initial CEA further discriminatedDFS in the subgroups with good mrTRG or that without mrMFI. @*Conclusion@#The CEA parameters significantly improved the performance of MRI in the prediction ofpTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initialCEA level in the groups with favorable MRI parameters.

Gastric Complications after Adjuvant Radiotherapy for Breast Cancer / 한국유방암학회지

PURPOSE: In some patients who receive adjuvant radiotherapy (RT) for the left breast, the stomach is located inside the RT field. This study investigates the incidence of gastric complications following adjuvant RT for breast cancer using data of the Health Insurance Review and Assessment Service in South Korea. METHODS: We identified 37,966 women who underwent surgery and received adjuvant RT for breast cancer. The cumulative incidence rate of gastric hemorrhage and gastric cancer was calculated and compared for left and right breast cancers. RESULTS: Among 37,966 patients, 19,531 (51.4%) and 18,435 (48.6%) had right and left breast cancers, respectively. After a median follow-up duration of 6.3 years, the cumulative incidence of gastric cancer and gastric hemorrhage did not differ between right and left breast cancers (p = 0.414 and p = 0.166, respectively). The multivariable analysis revealed that old age was the only factor associated with the development of gastric cancer (p < 0.001) and gastric hemorrhage (p < 0.001). The incidence of gastric cancer and hemorrhage did not differ between patients who received adjuvant RT for right and left breast cancers. CONCLUSION: Irradiation-related chronic complications of the stomach in patients with breast cancer are minimal. A study with a longer follow-up duration might be needed to assess the risk of gastric cancer.

The Benefit of Post-Mastectomy Radiotherapy in ypN0 Patients after Neoadjuvant Chemotherapy According to Molecular Subtypes / 한국유방암학회지

PURPOSE: The benefit of post-mastectomy radiation therapy (PMRT) in patients with breast cancer who achieve ypN0 following neoadjuvant chemotherapy (NAC) has not yet been established. This study aimed to identify the role of PMRT in patients who achieve ypN0 according to molecular subtype. METHODS: We identified patients initially suspected with axillary disease who achieved ypN0 following NAC. From 13 institutions of the Korean Radiation Oncology Group between 2005 and 2011, a total of 189 patients were included in the analysis. Effects of PMRT on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) were evaluated for different molecular subtypes. RESULTS: In all patients, the prognostic effect of PMRT on LRC, DFS, or OS was not significant. Subgroups analysis showed that the effect of PMRT on LRC was different according to molecular subtype (p for interaction = 0.019). PMRT was associated with greater LRC in the luminal subtype (p = 0.046), but not in other subtypes. CONCLUSION: In patients who achieve ypN0 following NAC and mastectomy, PMRT shows no additional survival benefits for any molecular subtype.

Risk factors for locoregional recurrence in patients with pathologic T3N0 rectal cancer with negative resection margin treated by surgery alone

PURPOSE: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. MATERIALS AND METHODS: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. RESULTS: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06–47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. CONCLUSION: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.

Central Nervous System Failure in Korean Breast Cancer Patients with HER2-Enriched Subtype: Korean Radiation Oncology Group 16-15 Multicenter Retrospective Study / 한국유방암학회지

PURPOSE: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). METHODS: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). RESULTS: The median follow-up duration was 84 (range, 8–171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076–4.746; p = 0.031). CONCLUSION: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

Korean First Prospective Phase II Study, Feasibility of Prone Position in Postoperative Whole Breast Radiotherapy: A Dosimetric Comparison / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This first Korean prospective study is to evaluate the feasibility of prone breast radiotherapy after breast conserving surgery for left breast cancer patients who have relatively small breast size and we present dosimetric comparison between prone and supine positions. MATERIALS AND METHODS: Fifty patients underwent two computed tomography (CT) simulations in supine and prone positions. Whole breast, ipsilateral lung, heart, and left-anterior-descending coronary artery were contoured on each simulation CT images. Tangential-fields treatment plan in each position was designed with total 50 Gy in 2-Gy fractions, and then one of the positions was designated for the treatment by comparing target coverage and dose to normal organs. Also, interfractional and intrafractional motion was evaluated using portal images. RESULTS: In total 50 patients, 32 cases were decided as prone-position–beneficial group and 18 cases as supine-position–beneficial group based on dosimetric advantage. Target dose homogeneity was comparable, but target conformity in prone position was closer to optimal than in supine position. For both group, prone position significantly increased lung volume. However, heart volumewas decreased by prone position for prone-position–beneficial group but was comparable between two positions for supine-position–beneficial group. Lung and heart doses were significantly decreased by prone position for prone-position–beneficial group. However, prone position for supine-position–beneficial group increased heart dose while decreasing lung dose. Prone position showed larger interfractional motion but smaller intra-fractional motion than supine position. CONCLUSION: Prone breast radiotherapy could be beneficial to a subset of small breast patients since it substantially spared normal organs while achieving adequate target coverage.

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) / Journal of the Korean Cancer Association, 대한암학회지

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.

Comparison of Breast Conserving Surgery Followed by Radiation Therapy with Mastectomy Alone for Pathologic N1 Breast Cancer Patients in the Era of Anthracycline Plus Taxane-Based Chemotherapy: A Multicenter Retrospective Study (KROG 1418) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups. RESULTS: The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly. CONCLUSION: There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III.

Breast Conservation Therapy Versus Mastectomy in Patients with T1-2N1 Triple-Negative Breast Cancer: Pooled Analysis of KROG 14-18 and 14-23 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study is to compare the treatment outcomes of breast conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients with pT1-2N1 triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Using two multicenter retrospective studies on breast cancer, a pooled analysis was performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS (n=212) receivedwhole breast RTwith orwithoutregional nodal RT,while nonewho underwent mastectomy (n=108)received it. All patients received taxane-based adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT group, and 74 months in the mastectomy group. RESULTS: The median age of all patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher number of involved lymph node (p=0.028), and higher nodal ratio ≥ 0.2 (p=0.037). Other characteristics were not significantly different between the two groups. The 5-year locoregionalrecurrence-free, disease-free, and overall survivalrates of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus 80.4%, and 95.0% versus 87.8%, respectively, and the differences were statistically significant after adjusting for covariates (p=0.010, p=0.006, and p=0.005, respectively). CONCLUSION: In pT1-2N1 TNBC, breast conservation therapy achieved better locoregional recurrencefree, disease-free, and overall survival rates compared with mastectomy.

Which Patients with Left Breast Cancer Should be Candidates for Heart-Sparing Radiotherapy? / 한국유방암학회지

PURPOSE: This study aimed to identify risk factors that have significant interaction with radiation exposure to the heart, and thus to determine candidates for heart-sparing radiotherapy (RT) among women with left breast cancer. METHODS: We identified 4,333 patients who received adjuvant RT following breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer from 1996 to 2010. Incidence rates of cardiovascular disease were compared between left-sided and right-sided RT, and stratified by age and risk factors such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes, administration of anthracycline, and trastuzumab. RESULTS: In all patients, the cumulative incidence of cardiovascular disease was greater in patients treated with left-sided RT than in those treated with right-sided RT, but the difference was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence interval [CI], 2.109–17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI, 3.235–9.580; p<0.001) were the most powerful risk factors for cardiovascular disease. There was no significant factor that further increased the risk of cardiovascular disease after left breast RT compared to right breast RT. CONCLUSION: Although hyperlipidemia and smoking are risk factors for cardiovascular disease, they have not been proven to increase the risk of RT-related cardiovascular disease in Korean women.