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.

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.

Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08).

PURPOSE: To identify risk factors for local recurrence (LR) and investigate roles of adjuvant local therapy for malignant and borderline phyllodes tumors of the breast. METHODS: From 1981 to 2014, 362 patients with malignant (n = 235) and borderline (n = 127) phyllodes tumors were treated by breast-conserving surgery (BCS) or total mastectomy (TM) at 10 centers. Thirty-one patients received adjuvant radiation therapy (RT), and those who received adjuvant chemotherapy were excluded from the study. RESULTS: Median follow-up was 5 years. LR developed in 60 (16.6%) patients. Regional recurrence occurred in 2 (0.6%) patients and distant metastasis (DM) developed in 19 (5.2%) patients. Patients receiving BCS (p = 0.025) and those not undergoing adjuvant RT (p = 0.041) showed higher LR rates. For malignant subtypes, local control (LC) rates at 5 years for BCS alone, BCS with adjuvant RT, TM alone, and TM with adjuvant RT were 80.7, 93.3, 92.4, and 100%, respectively (p = 0.033). Multivariate analyses revealed BCS alone, tumor size ≥ 5 cm, and positive margins as independent risk factors for LR. Margin-positive BCS alone showed poorest LC regardless of tumor size (62.5%, p = 0.007). For margin-negative BCS alone, 5-year LC rates for tumors ≥ 5 cm versus those < 5 cm were 71.8% versus 89.5% (p = 0.012). For borderline subtypes, only positive margins (p = 0.044) independently increased the risk of LR. DM developed exclusively in malignant subtypes and a prior LR event increased the risk of DM by sixfold (HR 6.2, 95% CI 1.6-16.1, p = 0.001). CONCLUSIONS: Malignant and borderline phyllodes tumors with positive margins after surgery have high LR rates. After treatment by margin-negative BCS alone, patients with large malignant phyllodes tumors ≥ 5 cm also have heightened risk of LR. Thus, such patients should be considered for additional local therapy.

Chest wall recurrence in pT1-2N0-1 breast cancer patients after mastectomy without radiotherapy.

PURPOSE: In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). METHODS: The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N = 1842 and KROG 14-23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. RESULTS: The median follow-up time was 72.2 months (range 0.8-125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. CONCLUSIONS: The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

The effect of escalating the boost dose for patients with involved resection margin after breast-conserving surgery.

BACKGROUND: This study aims to investigate the impact of boost dose escalation on ipsilateral breast tumor recurrence (IBTR) in breast cancer patients with involved resection margins following breast-conserving surgery. METHODS: Between January 1998 and December 2010, 192 patients were treated with a boost dose of over 10 Gy for involved resection margins. We retrospectively analyzed outcomes in 192 patients who underwent whole breast irradiation of 50.4 Gy followed by a median boost dose of 15.0 Gy (range, 12-16 Gy). Boost doses of 12.5 Gy and 15 Gy were delivered to patients with carcinoma in situ and invasive carcinoma, respectively, at the positive margins. We evaluated the impact of the boost dose on the IBTR rate. RESULTS: Median follow-up duration was 6.7 years (0.4-15.6 years). The 5-year cumulative risk of IBTR as a first event was 5.0%. IBTR occurred as a first recurrence in 13 of 192 patients. In-boost-field recurrences were found in 11 patients (85%). Five patients (39%) experienced out-of boost field recurrences, and three experienced both types of recurrences. In multivariate analysis, age (<40 years), pT stage, and positive radial resection margin were prognostic factors for IBTR (P = 0.029, P = 0.024 and P = 0.035, respectively). CONCLUSIONS: A median boost dose of 15 Gy might be insufficient in patients younger than 40 years, with tumor size greater than 2 cm, or with involved radial resection margins. On the other hand, in cases of positive superficial or deep margins, dose-escalated boost or re-excision may not be necessary.

Psychological Distress and Drawing Tests among Women with Breast Cancer.

BACKGROUND: The aim of this study was to evaluate the use of the Diagnostic Drawing Series (DDS) as a screening tool for the breast cancer patients with psychological distress. METHODS: All of 64 patients with breast cancer participated in this study. Patients' depressive and anxiety symptoms were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) when the DDS was applied to the partipicants. RESULTS: Depressed patients used more enclosure in the Feeling drawings (P = 0.002) and tilt in Free drawings (P = 0.048). Patients with anxiety drew a picture over 67% of the paper (P = 0.015) in Tree drawing and more medium pressure (P = 0.049) in Feeling drawings. Thirty four subjects (77.3%) of unstable emotion group used over 67% of the space (P = 0.002). More Landscapes were observed in the Feeling drawings of unstable patients (P = 0.042). CONCLUSION: These results suggested that DDS could be used as a supplemental screening tool for psychological distress in breast cancer patients.

Impact of pathologic diagnosis of internal mammary lymph node metastasis in clinical N2b and N3b breast cancer patients.

PURPOSE: To analyze the prognostic role of pathologic confirmation of internal mammary lymph nodes (IMNs) for breast cancer patients who received neoadjuvant chemotherapy. METHODS: Of the patients who were treated with neoadjuvant chemotherapy, surgery, and radiation therapy between 2009 and 2013, 114 women had suspicious IMNs and FNAB was attempted. Clinical IMN metastasis was diagnosed by 18F-FDG PET/CT positivity or pathologic confirmation (N = 70). Patients were divided into the FNAB(+) or FNAB(-) IMN group. RESULTS: The pathologic confirmation rate was 57% (40 of 70 patients). Rates were 74% in US-positive, 70% in MRI-positive, and 55% in PET-positive patients. Nodal stage was cN2b (6%) or cN3b (94%). Five-year progression-free survival (PFS) was significantly worse in patients with FNAB(+) IMN metastasis than FNAB(-) IMN metastasis (61% vs. 87%, P = 0.03). FNAB(+) IMN patients showed worse distant metastasis and regional recurrence-free survival without statistical significance (69% vs. 86%, P = 0.06, and 81% vs. 96%, P = 0.06). With median follow-up of 50.5 months (13.0-97.0 months), overall survival at 5 years was 77%, and PFS was 72%. CONCLUSIONS: Patients with FNAB-proven IMN metastasis had worse treatment outcomes compared to patients with clinically diagnosed IMN metastasis in cN2b/N3b breast cancer.

Recurrence outcomes after omission of postoperative radiotherapy following breast-conserving surgery for ductal carcinoma in situ of the breast: a multicenter, retrospective study in Korea (KROG 16-02).

PURPOSE: To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS: Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82). The median tumor size was 7 mm (range, 0.01-76). Margin width was <1 cm in 85 patients (27.3%), and nuclear grade was high in 37 patients (11.9%). Two hundred and three patients (65.3%) received tamoxifen. RESULTS: With a median follow-up of 74 months (range, 5-189), there were 11 local recurrences (invasive carcinoma in 6 and DCIS in 5) and 1 regional recurrence. The 7-year LRR rate was 3.8%. On univariate analysis, age and margin width were significant risk factors influencing LRR (p = 0.017 and 0.014, respectively). When age and margin width were combined among 211 patients whose margin width were available, the 7-year LRR rates were as follows (p < 0.001): (1) 0% in patients with age >50 years and any margin width status (n = 64), (2) 1.2% in age ≤50 years and margin width ≥1 cm (n = 93), (3) 13.1% in age ≤50 years and margin width <1 cm (n = 54). CONCLUSIONS: The LRR rate was very low in selected DCIS patients treated with breast-conserving surgery without postoperative RT. However, adjuvant RT should be considered for those with age ≤50 years and margin width <1 cm.

Expression of FOXM1 and related proteins in breast cancer molecular subtypes.

Forkhead box (FOX) proteins constitute an extended family of transcriptional regulators. FOXM1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM1 is associated with poor prognosis in various malignant tumours. FOXM1 and FOXO3a are often transcriptionally antagonistic. FOXO3a plays a critical tumour-suppressive role in breast cancer. FOXO activity is modulated by its acetylation status, which is regulated by class III histone deacetylases (sirtuins; also known as SIRTs). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM1, FOXO3a, SIRT1 and SIRT6 were evaluated in tissue microarray blocks containing 688 consecutive breast cancer samples. Mean expression levels were used to categorize tumours according to the expression of each protein (high or low). High expression of FOXM1 was significantly correlated with high SIRT1 and SIRT6 expression, higher histologic grade and triple-negative breast cancer (TNBC). High expression of nuclear FOXO3a and nuclear SIRT1 was correlated with a lower histologic grade and the hormone receptor-positive/HER2-negative subtype. In survival analysis, FOXM1 was an independent adverse prognostic factor for disease-free and overall survival in the hormone receptor-positive/HER2-negative subtype but not in the HER2-positive subtype or TNBC. In conclusion, although high FOXM1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC. However, it had prognostic significance in the hormone receptor-positive/HER2-negative subtype.

Foam dressing with epidermal growth factor for severe radiation dermatitis in head and neck cancer patients.

This study was conducted to evaluate the effects of foam dressing with human recombinant human epidermal growth factor (rhEGF) on the healing process in head and neck cancer patients who experience radiation-induced dermatitis (RID). Seven patients, including three with oropharyngeal, two with nasopharyngeal and one each with hypopharyngeal and laryngeal carcinoma, who underwent radiotherapy (RT) for head and neck cancer at the Asan Medical Center from March to December 2008 were prospectively included in this study. Patients who showed severe RID (more than wet desquamation) on the supraclavicular fossa or neck areas were treated by wound cleaning and debridement of granulation tissue, followed by daily rhEGF spray and foam dressing. Median time to stop exudates and reepithelialisation was 4 days. Within 14 days (median 8 days), all patients showed complete healing of RID and no longer required dressings. This new method of treatment with dressing containing rhEGF may have the potential to accelerate the healing process in patients with RID. A case-control study is needed to confirm this finding.

Influence of boost radiotherapy in patients with ductal carcinoma in situ breast cancer: a multicenter, retrospective study in Korea (KROG 11-04).

To estimate the effect of boost radiotherapy on local recurrence-free survival (LRFS) in patients with ductal carcinoma in situ (DCIS) breast cancer. We included patients from nine institutions who met the following criteria: having Tis, age 18 years or older, having breast conserving surgery (BCS) and radiotherapy within 12 weeks after surgery. From 1995 through 2006, 728 patients were analyzed retrospectively by the Korean Radiation Oncology Group. All patients received whole-breast radiation therapy (WBRT) after BCS. 232 patients (31.9 %) also received boost radiation therapy (RT) (median 10 Gy). After median follow-up of 82 months, 5-year LRFS was 98.4 % and 10-year LRFS was 95.8 % for all patients. There was no statistically significant difference of LRFS between the boost and no-boost groups. Nineteen (2.6 %) patients had ipsilateral breast recurrences, including 12 of invasive recurrence and 7 DCIS. The presence of the HER2 receptor was associated with more invasive recurrences. Nine (1.2 %) patients developed contralateral breast cancer, including six invasive breast cancer and three DCIS. In the multivariate analysis, only the margin status was a significant prognostic factor for LRFS. Boost RT was not associated with further improvement of local control in DCIS after BCS and WBRT. HER2 receptor-positive patients may need further treatment with the anti-HER2 agents.

Evaluation of effective dose conversion coefficients for Korean adults during medical x-ray examinations up to 150 keV through comparison with ICRP Publication 74 and ICRP Publication 116.

A Monte Carlo program for calculating organ doses for patients undergoing medical x-ray examination (PCXMC) was used to calculate effective dose conversion coefficients for Korean adults. Two sets of effective dose results were calculated based on tissue weighting factors recommended in International Commission on Radiological Protection (ICRP) Publications 60 and 103 for monochromatic energy photons of 10, 15, 20, 30, 40, 50, 60, 70, 80, 100 and 150 keV. The results were obtained for monoenergetic photons, since effective dose conversion coefficients recommended in ICRP Publications 74 and 116 were given for monochromatic energies, thereby enabling the comparison of our result to those suggested by the ICRP publications. The areas of comparison include: to observe effects due to changes in tissue weighting factors, modification within Medical Internal Radiation Dose (MIRD) phantoms and differences in phantom types. The phantom employed in the PCXMC program is a modified version of the phantom used in ICRP Publication 74, with additional organs that were added in order to take into account the updated tissue weighting factors given in ICRP Publication 103. Both use MIRD phantoms but our study modified the phantom size to the average physical condition of Korean adults, while ICRP Publication 74 uses the phantom size of the reference man defined in ICRP Publication 23. On the other hand, the effective dose suggested in ICRP 116 was calculated using an entirely different type of phantom: a voxel phantom with the size of reference man. Although significant differences were observed for certain organ doses in the lateral beam directions, differences in the effective doses were within 5% for the anterior-posterior (AP) and posterior-anterior (PA) directions, and within 16% in lateral directions when tissue weighting factors were applied and the variations were adjusted for all three comparisons. The results show that calculation of effective doses for Korean adults using the PCXMC (Caucasian-based phantom) is acceptable for the AP and PA directions, but care should be taken for lateral directions.

Long-term outcomes and risk profile of cT3N0 breast cancer treated with neoadjuvant chemotherapy and curative surgery.

INTRODUCTION: We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery. METHODS: We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high-risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki-67 labeling index >20%. RESULTS: Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5-month median follow-up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5-year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high-risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001). CONCLUSION: Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence.

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.

Erratum to: Retrospective analysis of treatment outcome of pediatric ependymomas in Korea: analysis of Korean multi-institutional data

The name of the 14th author was incorrect in the original publication. It is correct in this erratum (Young-Shin Ra).

Retrospective analysis of treatment outcome of pediatric ependymomas in Korea: analysis of Korean multi-institutional data.

We analyzed the treatment outcomes of intracranial ependymomas in Korean children aged <18 years. Data for 96 patients were collected from five hospitals. Survival rates were calculated using the Kaplan-Meier method. Log-rank tests for univariate analyses and Cox regression model for multivariate analysis were conducted to identify prognostic factors for survival. The median age of the patients was 4 years (range, 0.3-17.9 years). The median follow-up was 55 months (range, 2-343 months). Age <3 years was an important factor for selecting adjuvant therapy after surgery. Among children aged <3 and ≥ 3 years, adjuvant radiotherapy (RT) was applied to 55 and 84 %, respectively, and adjuvant chemotherapy to 52 and 10 %, respectively. The 5 year local progression-free survival (LPFS), disease-free survival (DFS), and overall survival (OS) rates were 54, 52, and 79 %, respectively. Gross total resection was the most significant prognostic factor for all survival endpoints. Age ≥ 3 years and RT were significant prognostic factors for superior LPFS and DFS. However, the significance of age was lost in multivariate analysis for DFS. LPFS, DFS, and OS were superior in patients who started RT within 44 days after surgery (the median time) than in patients who started RT later in the patients aged ≥ 3 years. Postoperative RT was a strong prognostic factor for intracranial ependymomas. Our results suggest that early use of RT is an essential component of treatment, and should be considered in young children.

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.

Low-dose external beam radiotherapy as a postoperative treatment for patients with diffuse pigmented villonodular synovitis of the knee: 4 recurrences in 23 patients followed for mean 9 years.

BACKGROUND AND PURPOSE: Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder involving synovial membranes, and patients with PVNS have a variable prognosis. We retrospectively analyzed clinical outcomes after synovectomy plus low-dose external beam radiotherapy for diffuse PVNS of the knee. METHODS: We reviewed the medical records of 23 patients who underwent postoperative radiotherapy between 1998 and 2007. 19 patients had primary disease and 4 had recurrent disease with an average of 2.5 prior surgeries. After synovectomy (17 arthroscopic surgeries; 6 open), all 23 patients received 4-MV or 6-MV external beam radiotherapy with a median dose of 20 (12-34) Gy in 10 fractions. RESULTS: At a median follow-up of 9 (0.8-12) years, 4 patients had recurrent disease, with a median disease-free interval of 5 years. Of these 4 patients, 3 received salvage synovectomy and regained local control. Univariate analysis showed that age, sex, history of trauma, and total dose of radiation were not predictive of local control. 22 patients reported excellent or good joint function, and 1 who refused salvage synovectomy had poor joint function. None of the patients experienced grade 3 or higher radiation-related toxicity or radiation-induced secondary malignancies. INTERPRETATION: Postoperative external beam radiotherapy is an effective and acceptable modality to prevent local recurrence and preserve joint function in patients with diffuse PVNS of the knee. Low-dose (20 Gy) radiotherapy appears to be as effective as moderate-dose treatment (around 35 Gy).

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.

Clinical features and course of brain metastases in triple-negative breast cancer: comparison with human epidermal growth factor receptor 2-positive and other type at single institution in Korea.

The incidences and clinical aggressiveness of intracranial metastases have not been as well characterized in patients with triple-negative (TN) breast cancer as in patients with human epidermal growth factor 2-positive (HER2+) breast cancer. Patients diagnosed with brain metastases from primary breast cancer, as determined by computed tomography and/or magnetic resonance imaging, at Asan Medical Center from January 1990 to July 2006 were identified and classified into three subtypes: TN, HER2+, and other. The clinical features and outcomes of these three groups were compared. Of the 7,872 patients diagnosed with primary breast cancer, 198 developed brain metastases; of these, 61 patients with unknown estrogen receptor, progesterone receptor, and HER2 status were excluded. Of the remaining 137 patients, 44 (32%) were classified as TN, 69 (50%) as HER2+, and 24 (18%) as other. Clinical parameters, including performance status and previous adjuvant chemotherapy and/or radiotherapy, were well balanced among groups, except that earlier staged tumors (I and II) were more prevalent in the TN than in the HER2+ and other (59 vs. 36 vs. 38%, P = 0.01). At a median follow-up of 99 months, the median times from initial diagnosis to brain metastasis (20 vs. 32 vs. 45 months, P = 0.01) and to first distant metastasis at any site (16 vs. 23 vs. 23 months, P = 0.005) were significantly shorter in TN than in the HER2+ and other. Median overall survival (OS) from primary cancer diagnosis was significantly shorter in the TN than in the HER2+ and other (31 vs. 39 vs. 57 months, P = 0.02), but survival after brain metastasis was similar (5.9 vs. 5.2 vs. 8.8 months, P = 0.31). Compared with other breast cancer phenotypes, TN breast cancer was characterized by earlier brain and other distant metastases and shorter OS, despite a higher proportion of tumors diagnosed at early stages.