Byung Kiu Park

Craniospinal Irradiation Techniques: A Dosimetric Comparison of Proton Beams With Standard and Advanced Photon Radiotherapy

PURPOSE To evaluate the dosimetric benefits of advanced radiotherapy techniques for craniospinal irradiation in cancer in children. METHODS AND MATERIALS Craniospinal irradiation (CSI) using three-dimensional conformal radiotherapy (3D-CRT), tomotherapy (TOMO), and proton beam treatment (PBT) in the scattering mode was planned for each of 10 patients at our institution. Dosimetric benefits and organ-specific radiation-induced cancer risks were based on comparisons of dose-volume histograms (DVHs) and on the application of organ equivalent doses (OEDs), respectively. RESULTS When we analyzed the organ-at-risk volumes that received 30%, 60%, and 90% of the prescribed dose (PD), we found that PBT was superior to TOMO and 3D-CRT. On average, the doses delivered by PBT to the esophagus, stomach, liver, lung, pancreas, and kidney were 19.4 Gy, 0.6 Gy, 0.3 Gy, 2.5 Gy, 0.2 Gy, and 2.2 Gy for the PD of 36 Gy, respectively, which were significantly lower than the doses delivered by TOMO (22.9 Gy, 4.5 Gy, 6.1 Gy, 4.0 Gy, 13.3 Gy, and 4.9 Gy, respectively) and 3D-CRT (34.6 Gy, 3.6 Gy, 8.0 Gy, 4.6 Gy, 22.9 Gy, and 4.3 Gy, respectively). Although the average doses delivered by PBT to the chest and abdomen were significantly lower than those of 3D-CRT or TOMO, these differences were reduced in the head-and-neck region. OED calculations showed that the risk of secondary cancers in organs such as the stomach, lungs, thyroid, and pancreas was much higher when 3D-CRT or TOMO was used than when PBT was used. CONCLUSIONS Compared with photon techniques, PBT showed improvements in most dosimetric parameters for CSI patients, with lower OEDs to organs at risk.

Statistics of hematologic malignancies in Korea: incidence, prevalence and survival rates from 1999 to 2008

Background The nationwide statistical analysis of hematologic malignancies in Korea has not been reported yet. Methods The Korea Central Cancer Registry and the Korean Society of Hematology jointly investigated domestic incidence rates and prevalence of hematologic malignancies occurred between 1999 and 2008, and analyzed survival rates of patients who were diagnosed between 1993 and 2008. Data of hematologic malignancies from 1993 to 2008 were obtained from the Korean National Cancer Incidence Data base. The crude incidence rates, age-specific incidence rates, age-standardized incidence rates, annual percentage change of incidence, and prevalence from 1999-2008 were calculated. Survival rates for patients diagnosed in 1993-2008 were estimated. Results In 2008, a total of 8,006 cases of hematologic malignancies were occurred, which comprised 4.5% of all malignancies. In all genders, non-Hodgkin lymphoma, myeloid leukemia, and multiple myeloma were most frequent diseases. In terms of age, ages between 60 and 69 were most prevalent. From 1999 to 2008, the age-standardized incidence rates increased from 10.2 to 13.7, and the annual percentage change was 3.9%. The 5-year survival rate increased from 38.2% during 1993-1995 to 55.2% during 2004-2008. As of January 2009, number of patients with 10-year prevalence was 33,130, and with 5- to 10-year prevalence was 10,515. Conclusion This is the first nationwide statistical report of hematologic malignancies in Korea. It could be used as the basic information to help investigate epidemiologic characteristics, evaluate progress during the past years, and establish future strategies for hematologic malignancies. Periodic statistical analysis of hematologic malignancies in Korea should be continued.

Cancer Incidence and Survival among Adolescents and Young Adults in Korea

Background In Korea, cancer is the third leading cause of death among adolescents and young adults (AYAs). However, cancer incidence and survival trends among AYAs (15–29 years) have never been studied in Korea. Therefore, this study aimed to investigate the incidence and relative survival rates and their trends among AYAs in Korea. Materials and Methods Cancer incidence data from 1999–2010 were obtained from the Korea Central Cancer Registry (KCCR). Each cancer was classified into subgroups according to the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) AYA site recode. Percent distributions, age-specific incidence rates, age-standardized incidence rates per million, and annual percent changes (APCs) were calculated for AYAs according to sex. Five-year relative survival rates were estimated for cases diagnosed between 1993 and 2010 and followed up to 2011. Results The age-standardized incidence rates of all cancers combined were 196.4 and 367.8 per million for males and females, respectively (male-to-female (M/F) ratio: 0.5). The age-standardized incidence rates increased from 208.7 per million in 1999 to 396.4 per million in 2010, and the APC was 6.3% (P<0.001). The five most common cancers among AYAs were thyroid carcinoma, non-Hodgkin lymphoma, stomach carcinoma, breast carcinoma, and acute myeloid leukemia. In males, the 5-year relative survival rate improved, from 46.5% in 1993–1995 to 75.9% in 2006–2010. In females, the 5-year relative survival rate also improved, from 66.7% in 1993–1995 to 89.1% in 2006–2010. Conclusions Our study showed increases in cancer incidence and improvements in the 5-year relative survival rate among Korean AYAs. This study also provides additional data regarding temporal and geographic trends in cancer that may enhance future efforts to identify factors affecting cancer incidence and responses to treatment among AYAs.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO−), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO+). The 5-year overall survival (OS) rates in the SS, MS-RO−, and MS-RO+ groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ⩽2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO+ patients and reduce reactivation in younger patients with MS involvement.

Current status of pediatric umbilical cord blood transplantation in Korea: A multicenter retrospective analysis of 236 cases

We report the outcome of 236 pediatric umbilical cord blood transplantations (UCBT) performed in Korea. Given that the sources of the grafts were mostly unrelated donors (n = 226; 95.8%), only the results of unrelated UCBT were included for all statistics. The most frequent primary disease was acute leukemia (n = 167). In total, 91.7% of recipients were seropositive for cytomegalovirus (CMV). The median doses of nucleated cells and CD34+ cells were 4.84 × 107/kg and 2.00 × 105/kg, respectively. The median times to neutrophil (>0.5 × 109/L) and platelet recovery (>20 × 109/L) were 18 and 45 days, respectively. Grade 2–4 acute graft‐versus‐host‐disease (GVHD) and chronic GVHD developed in 41.1 and 36.1% of cases, respectively. Forty‐five patients developed CMV disease. The 5‐year overall and event‐free survival were 47.5 and 36.9%, respectively. Multivariate analysis revealed that adverse factors for survival of the whole cohort were total body irradiation‐based conditioning (P = 0.007), salvage transplant (P = 0.001), failure to achieve early complete chimerism (P < 0.0005), and CMV disease (P = 0.001). The outcomes of the single‐ and double‐unit UCBT (n = 64) were similar, while double‐unit recipients were heavier (P < 0.0005) and older (P < 0.0005). We conclude that double‐unit UCBT is a reasonable option for older or heavier children and that the thorough surveillance of CMV infection and the development of an effective CMV therapeutic strategy may be especially important for Korean children, whose CMV seroprevalence exceeds 90%. Am. J. Hematol., 2011.

Incidence and Survival of Childhood Cancer in Korea

Purpose An epidemiologic study of childhood cancer would provide useful information on cancer etiology and development of management guidelines. Materials and Methods Data from the Korea National Cancer Incidence Database were used to examine the incidence and survival of cancer in patients aged 0-14 years. Patients were grouped according to the International Classification of Childhood Cancer, 3rd edition. Age-specific and age-standardized incidences per million and estimated annual percentage change (APC) were calculated by sex and age. Five-year relative survival was calculated for four periods from 1993 to 2011. Results The study comprised 15,113 patients with malignant neoplasms. Age-standardized incidence rates for all cancers were 134.9 per million children in 1999-2011 and 144.0 and 124.9 per million for males and females, respectively (M/F ratio, 1.2; p < 0.05). The highest incidences were observed for ‘leukemias, myeloproliferative diseases, and myelodysplastic diseases’ (group I) (46.4), ‘central nervous system neoplasms’ (group III) (18.3), and ‘lymphomas and reticuloendothelial neoplasms’ (group II) (13.4). Age-standardized incidence increased from 117.9 in 1999 to 155.3 in 2011, with an APC of 2.4% (95% confidence interval, 2.1 to 2.7). There was a significant increase of APC in ‘neuroblastoma and other peripheral nervous cell tumors’ (group IV) (5.6%) and ‘other malignant epithelial neoplasms and malignant melanomas’ (group XI) (5.6%). The 5-year relative survival rate for all childhood cancers improved significantly from 56.2% (1993-1995) to 78.2% (2007-2011) (males, 56.7% to 77.7%; females, 55.5% to 78.8%). Conclusion This study provides reliable information on incidence and survival trends for childhood cancer in Korea.

Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.

Nationwide statistical analysis of myeloid malignancies in Korea: incidence and survival rate from 1999 to 2012

Background Large-scale epidemiologic analysis for hematologic malignancies will be helpful to understand the trends in incidence and survival. Methods The Korea Central Cancer Registry (KCCR) updated the nationwide analysis on the incidence and survival of myeloid malignancies, from the Korean National Cancer Incidence Database between 1999 and 2012. Myeloid malignancies were classified based on the International Classification of Diseases for Oncology 3rd edition (ICD-O-3). Results Overall 3,771 cases of myeloid diseases, which was 1.7% of all cancers, were identified in 2012. The highest incidence of myeloid malignancies was observed in age 70s and male predominance was noted (1.3:1). Acute myeloid leukemia (AML) was the most frequent subtype, followed by myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and MDS/MPN: age-standardized incidence rates (ASR) in 2012 for each disease were 2.02, 1.95, 1.13, and 0.12 per 100,000 persons, respectively. The ASR for all myeloid malignancies was increased from 3.31 in 1999 to 5.70 in 2012 with the annual percentage change (APC) of 5.4 %. Five-year relative survival rate (RS) for myeloid malignancies has gradually improved for decades. RS changed from 26.3% to 34.8% in AML, specifically from 51.6% to 69.6% in acute promyelocytic leukemia (APL) and from 23.8% to 29.9% in non-APL AML, between 1996-2000 and 2008-2012. RS also increased from 81.8% to 87.1% in MPN, with a significant improvement in CML (from 74.5% to 85.5%), and from 27.3% to 31.7% in MDS/MPN between 2001-2005 and 2008-2012. However, there was no survival improvement in MDS during the study period (45.6% in 2001-2005 to 44.4% in 2008-2012). Conclusion This report updated the nationwide statistical analysis on myeloid malignancies since 2008, showing increasing incidence and improving trends in survival.

The impact of HLA matching on unrelated donor hematopoietic stem cell transplantation in Korean children

Background The impact of HLA matching on outcomes of unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) varies in different racial or ethnic groups. Since little is known about the impact of such matching on URD HSCT in Korean children, we analyzed this issue. Methods We analyzed the outcomes of 142 patients who underwent URD HSCT at 4 Korean medical centers. All patient donor pairs were fully typed for HLA-A, -B, -C, and -DR alleles. Results At a median follow-up of 22 months, 3-year survival rates for patients with 8, 7, and ≤6 matched alleles were 88.4%, 70.7%, and 53.6%, respectively. A single mismatch (Mm) at HLA-B or -C was associated with lower survival compared with that associated with 8 matched alleles. No significant differences were observed between single-allele and single-antigen Mms with respect to survival rate or acute graft-versus-host disease (aGVHD) incidence rates. HLA disparity had a greater impact on the survival of patients with high-risk malignancy than of those with low-risk malignancy. Among pairs with a single Mm, only locus A showed a significant association and higher risk of grade III-IV aGVHD compared to those in patients with 8 matched alleles. Conclusion Disparity in HLA class I, regardless of antigen or allele Mm, adversely affected both survival and grade III-IV aGVHD development. An increased number of HLA Mms was associated with a higher risk of post-transplantation complications. Further investigations using larger cohorts are required to confirm the effects of HLA mismatching on URD HSCT patient outcomes.

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5–18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.