Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study / Journal of the Korean Cancer Association, 대한암학회지

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.

Radiotherapy for Diffuse Intrinsic Pontine Glioma: Insufficient but Indispensable

Diffuse intrinsic pontine gliomas (DIPGs) account for 10%–20% of all central nervous system tumors in children and are the leading cause of death in children with brain tumors. Although many clinical trials have been conducted over the past decades, the survival outcome has remained unchanged. Over 90% of children die within 2 years of the diagnosis, and radiotherapy remains the standard treatment to date. To improve the prognosis, hyperfractionated and hypofractionated radiotherapy and/or addition of radiosensitizers have been investigated. However, none of the radiotherapy approaches have shown a survival benefit, and the overall survival of patients with DIPG is approximately 11 months.Here, we comprehensively review the management of DIPG with focus on radiotherapy.

The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-institutional Retrospective Study (KROG 18-11) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC). @*Materials and Methods@#A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses. @*Results@#The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003). @*Conclusion@#This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

Treatment outcome of anaplastic ependymoma under the age of 3 treated by intensity-modulated radiotherapy

Purpose@#Intensity-modulated radiotherapy (IMRT) allows for more precise treatment, reducing unwanted radiation to nearby structures. We investigated the safety and feasibility of IMRT for anaplastic ependymoma patients below 3 years of age. @*Materials and Methods@#A total of 9 anaplastic ependymoma patients below 3 years of age, who received IMRT between October 2011 and December 2017 were retrospectively reviewed. The median equivalent dose in 2 Gy fractions was 52.0 Gy (range, 48.0 to 60.0 Gy). Treatment outcomes and neurologic morbidities were reviewed in detail. @*Results@#The median patient age was 20.9 months (range, 12.1 to 31.2 months). All patients underwent surgery. The rates of 5-year overall survival, freedom from local recurrence, and progression-free survival were 40.6%, 53.3%, and 26.7%, respectively. Of the 9 patients, 5 experienced recurrences (3 had local recurrence, 1 had both local recurrence and cerebrospinal fluid [CSF] seeding, and 1 had CSF seeding alone). Five patients died because of disease progression. Assessment of neurologic morbidity revealed motor dysfunction in 3 patients, all of whom presented with hydrocephalus at initial diagnosis because of the location of the tumor and already had neurologic deficits before radiotherapy (RT). @*Conclusion@#Neurologic morbidity is not caused by RT alone but may result from mass effects of the tumor and surgical sequelae. Administration of IMRT to anaplastic ependymoma patients below 3 years of age yielded encouraging local control and tolerable morbidities. High-precision modern RT such as IMRT can be considered for very young patients with anaplastic ependymoma.

Survival, Prognostic Factors, and Volumetric Analysis of Extent of Resection for Anaplastic Gliomas / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification, including extent of resection (EOR) as measured by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) and the T2-weighted MRI. @*Materials and Methods@#The records of 113 patients with anaplastic glioma who were newly diagnosed at our institute between 2000 and 2013 were retrospectively reviewed. There were 62 cases (54.9%) of anaplastic astrocytoma, isocitrate dehydrogenase (IDH) wild-type (AAw), 18 cases (16.0%) of anaplastic astrocytoma, IDH-mutant, and 33 cases (29.2%) of anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted. @*Results@#The median overall survival (OS) was 48.4 months in the whole anaplastic glioma group and 21.5 months in AAw group. In multivariate analysis, age, preoperative Karnofsky Performance Scale score, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative tumor volume, and EOR measured from the T2 MRI sequence were significant prognostic factors. The EOR cut-off point for OS measured in contrast-enhanced T1-weighted MRI and T2-weighted MRI were 99.96% and 85.64%, respectively. @*Conclusions@#We found that complete resection of the contrast-enhanced portion (99.96%) and more than 85.64% resection of the non-enhanced portion of the tumor have prognostic impacts on patient survival from anaplastic glioma.

Radiotherapy for initial clinically positive internal mammary nodes in breast cancer

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

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.

Efficacy of Postoperative Radiotherapy Using Modern Techniques in Patients with Retroperitoneal Soft Tissue Sarcoma

PURPOSE: Local recurrence is the most common cause of failure in retroperitoneal soft tissue sarcoma patients after surgical resection. Postoperative radiotherapy (PORT) is infrequently used due to its high complication risk. We investigated the efficacy of PORT using modern techniques in patients with retroperitoneal soft tissue sarcoma. MATERIALS AND METHODS: Eighty patients, who underwent surgical resection for non-metastatic primary retroperitoneal soft tissue sarcoma at the Yonsei Cancer Center between 1994 and 2015, were retrospectively reviewed. Thirty-eight (47.5%) patients received PORT: three-dimensional conformal radiotherapy in 29 and intensity-modulated radiotherapy in nine patients. Local failure-free survival (LFFS), overall survival (OS), and RT-related toxicities were investigated. RESULTS: Median follow-up was 37.1 months (range, 5.8–207.9). Treatment failure occurred in 47 (58.8%) patients including local recurrence in 33 (41.3%), distant metastasis in eight (10%), and both occurred in six (7.5%) patients. The 2-year and 5-year LFFS rates were 63.9% and 47.9%, respectively. The 2-year and 5-year OS rates were 87.5% and 71.1%. The 5-year LFFS rate was significantly higher in PORT group than in no-PORT group (74.2% vs. 24.3%, p < 0.001). In multivariate analysis, PORT was the only independent prognostic factor for LFFS. However, there was no significant correlation between RT dose and LFFS. OS showed no significant difference between the two groups. Grade ≤2 acute toxicities were observed in 63% of patients, but no acute toxicity ≥grade 3 was observed. CONCLUSION: PORT using modern technique markedly reduced local recurrence in retroperitoneal sarcoma patients, with low toxicity. The optimal RT technique, in terms of RT dose and target volume, should be further investigated.

Patterns of Practice in Radiotherapy for Breast Cancer in Korea / 한국유방암학회지

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

External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence

PURPOSE: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. MATERIALS AND METHODS: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of 10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. RESULTS: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. CONCLUSIONS: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.

Hypofractionated Re-irradiation after Maximal Surgical Resection for Recurrent Glioblastoma: Therapeutic Adequacy and Its Prognosticators of Survival

PURPOSE: To evaluate the adequacy of retreatment, including hypofractionated re-irradiation (HFReRT), after surgery for recurrent glioblastoma (GBM) and related prognosticators of outcomes. MATERIALS AND METHODS: From 2011 to 2014, 25 consecutive patients with recurrent (n=17) or secondary (n=7) disease underwent maximal surgery and subsequent HFReRT after meeting the following conditions: 1) confirmation of recurrent or secondary GBM after salvage surgery; 2) Karnofsky performance score (KPS) ≥60; and 3) interval of ≥12 months between initial radiotherapy and HFReRT. HFReRT was delivered using a simultaneous integrated boost technique, with total dose of 45 Gy in 15 fractions to the gross tumor volume (GTV) and 37.5 Gy in 15 fractions to the clinical target volume. RESULTS: During a median follow-up of 13 months, the median progression-free and overall survival (OS) were 13 and 16 months, respectively. A better KPS (p=0.026), no involvement of the eloquent area at recurrence (p=0.030), and a smaller GTV (p=0.005) were associated with better OS. Additionally, OS differed significantly between risk groups stratified by the National Institutes of Health Recurrent GBM Scale (low-risk vs. high-risk, p=0.025). Radiologically suspected radiation necrosis (RN) was observed in 16 patients (64%) at a median of 9 months after HFReRT, and 8 patients developed grade 3 RN requiring hospitalization. CONCLUSION: HFReRT after maximal surgery prolonged survival in selected patients with recurrent GBM, especially those with small-sized recurrences in non-eloquent areas and good performance.

Selective Radiation Therapy for Ductal Carcinoma In Situ Following Breast-Conserving Surgery According to Age and Margin Width: Korean Radiation Oncology Group 11-04 and 16-02 Studies / 한국유방암학회지

PURPOSE: The optimal indications for omitting adjuvant radiation therapy (RT) after breast-conserving surgery are still controversial in ductal carcinoma in situ (DCIS) of the breast. The purpose of this study was to validate the role of postoperative RT in DCIS patients aged ≤50 years and with tumor margin widths of <1 cm, both of which have been proven to be high-risk features for recurrence in cohorts not receiving RT. METHODS: Using two multicenter retrospective studies on DCIS, a pooled analysis was performed among patients aged ≤50 years and with margin widths < 1 cm. All patients underwent breast-conserving surgery. Two hundred thirty-two patients received postoperative RT, while 54 did not. The median follow-up period was 77 months (range, 2–190 months) and 70 months (range, 5–166 months) in the patients who received RT and those who did not, respectively. RESULTS: The patients who received RT had larger tumors (p < 0.001), higher nuclear grade (p < 0.001), closer margin width (p < 0.001), and negative estrogen receptor expression (p=0.010) compared with those who did not receive RT. During the follow-up period, there were 17 ipsilateral breast tumor recurrences (IBTRs) as follows: invasive carcinoma in 10 patients and DCIS in seven. In the univariate analysis, the treatment with RT and human epidermal growth factor receptor 2 (HER2) status were significant risk factors for IBTR. The 7-year IBTR rates with and without postoperative RT were 3.6% and 13.1%, respectively (p=0.008). HER2-positive tumors had a higher IBTR rate than the HER2-negative tumors (7-year rate, 13.6% vs. 3.9%; p=0.003). CONCLUSION: Postoperative RT following breast-conserving surgery significantly reduced the 7-year IBTR rate in the DCIS patients aged ≤50 years and with margin widths < 1 cm. HER2 positivity was associated with increased IBTR in these patients.

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study

PURPOSE: To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. MATERIALS AND METHODS: Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). RESULTS: The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). CONCLUSIONS: Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs. MATERIALS AND METHODS: The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared. RESULTS: Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS. CONCLUSION: NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.

Re-Irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors

PURPOSE: The aim of this study was to evaluate the efficacy of re-irradiation in patients with recurrent gliomas and to identify subgroups for whom re-irradiation for recurrent gliomas is most beneficial. MATERIALS AND METHODS: We retrospectively reviewed 36 patients with recurrent or progressive gliomas who received re-irradiation between January 1996 and December 2011. Re-irradiation was offered to recurrent glioma patients with good performance or at least 6 months had passed after initial radiotherapy (RT), with few exceptions. RESULTS: Median doses of re-irradiation and initial RT were 45.0 Gy and 59.4 Gy, respectively. The median time interval between initial RT and re-irradiation was 30.5 months. Median overall survival (OS) and the 12-month OS rate were 11 months and 41.7%, respectively. In univariate analysis, Karnofsky performance status (KPS) ≥70 (p<0.001), re-irradiation dose ≥45 Gy (p=0.040), and longer time interval between initial RT and re-irradiation (p=0.040) were associated with improved OS. In multivariate analysis, KPS (p=0.030) and length of time interval between initial RT and re-irradiation (p=0.048) were important predictors of OS. A radiographically suspected mixture of radiation necrosis and progression after re-irradiation was seen in 5 patients. CONCLUSION: Re-irradiation in conjunction with surgery could be a salvage treatment for selected recurrent glioma patients with good performance status and recurrence over a long time.