Do Hoon Lim

Phase III Trial Comparing Capecitabine Plus Cisplatin Versus Capecitabine Plus Cisplatin With Concurrent Capecitabine Radiotherapy in Completely Resected Gastric Cancer With D2 Lymph Node Dissection: The ARTIST Trial

PURPOSE The ARTIST (Adjuvant Chemoradiation Therapy in Stomach Cancer) trial was the first study to our knowledge to investigate the role of postoperative chemoradiotherapy therapy in patients with curatively resected gastric cancer with D2 lymph node dissection. This trial was designed to compare postoperative treatment with capecitabine plus cisplatin (XP) versus XP plus radiotherapy with capecitabine (XP/XRT/XP). PATIENTS AND METHODS The XP arm received six cycles of XP (capecitabine 2,000 mg/m2 per day on days 1 to 14 and cisplatin 60 mg/m2 on day 1, repeated every 3 weeks) chemotherapy. The XP/XRT/XP arm received two cycles of XP followed by 45-Gy XRT (capecitabine 1,650 mg/m2 per day for 5 weeks) and two cycles of XP. RESULTS Of 458 patients, 228 were randomly assigned to the XP arm and 230 to the XP/XRT/XP arm. Treatment was completed as planned by 75.4% of patients (172 of 228) in the XP arm and 81.7% (188 of 230) in the XP/XRT/XP arm. Overall, the addition of XRT to XP chemotherapy did not significantly prolong disease-free survival (DFS; P = .0862). However, in the subgroup of patients with pathologic lymph node metastasis at the time of surgery (n = 396), patients randomly assigned to the XP/XRT/XP arm experienced superior DFS when compared with those who received XP alone (P = .0365), and the statistical significance was retained at multivariate analysis (estimated hazard ratio, 0.6865; 95% CI, 0.4735 to 0.9952; P = .0471). CONCLUSION The addition of XRT to XP chemotherapy did not significantly reduce recurrence after curative resection and D2 lymph node dissection in gastric cancer. A subsequent trial (ARTIST-II) in patients with lymph node-positive gastric cancer is planned.

Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset Analyses

PURPOSE The Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial tested whether the addition of radiotherapy to adjuvant chemotherapy improved disease-free survival (DFS) in patients with D2-resected gastric cancer (GC). PATIENTS AND METHODS Between November 2004 and April 2008, 458 patients with GC who received gastrectomy with D2 lymph node dissection were randomly assigned to either six cycles of adjuvant chemotherapy with capecitabine and cisplatin (XP) or to two cycles of XP followed by chemoradiotherapy and then two additional cycles of XP (XPRT). This final update contains the first publication of overall survival (OS), together with updated DFS and subset analyses. RESULTS With 7 years of follow-up, DFS remained similar between treatment arms (hazard ratio [HR], 0.740; 95% CI, 0.520 to 1.050; P=.0922). OS also was similar (HR, 1.130; 95% CI, 0.775 to 1.647; P=.5272). The effect of the addition of radiotherapy on DFS and OS differed by Lauren classification (interaction P=.04 for DFS; interaction P=.03 for OS) and lymph node ratio (interaction P<.01 for DFS; interaction P<.01 for OS). Subgroup analyses also showed that chemoradiotherapy significantly improved DFS in patients with node-positive disease and with intestinal-type GC. There was a similar trend for DFS and OS by stage of disease. CONCLUSION In D2-resected GC, both adjuvant chemotherapy and chemoradiotherapy are tolerated and equally beneficial in preventing relapse. Because results suggest a significant DFS effect of chemoradiotherapy in subsets of patients, the ARTIST 2 trial evaluating adjuvant chemotherapy and chemoradiotherapy in patients with node-positive, D2-resected GC is under way.

The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution.

The objective of this retrospective cohort study was to define the efficacy and safety of fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) for the treatment of patients with pituitary adenoma.

Fractionated stereotactic radiation therapy for extracranial head and neck tumors

BACKGROUND This study is to report the clinical experiences of fractionated stereotactic radiation therapy (FSRT) for extracranial head and neck tumors. METHODS AND MATERIALS Between the period of July 1995 and November 1998, 48 patients with extracranial head and neck tumors were given FSRT as a boost and sole modality. Individualized treatment planning was performed using XKnife-3 system with relocatable Gill-Thomas-Cosman frame. In 24 patients, FSRT was applied as a boost technique following the 2-dimensional conventional external radiation therapy (ERT); in 24 patients FSRT was the sole radiotherapy modality. The primary diseases in the boost group consisted of nasopharynx cancer (19), lacrimal gland adenoid cystic carcinoma (3), orbital lymphoma (1), and skull-base recurrence of maxillary sinus adenoid cystic carcinoma (1). The primary diseases in the sole modality group consisted of recurrent nasopharynx cancer (12), orbital pseudotumor (4), skull-base recurrence of maxillary sinus, submandibular gland, and hypopharynx cancers (3), orbital rhabdomyosarcoma (2), orbital lymphoma (1), orbital metastasis of neuroblastoma (1), and nasal cavity melanoma (1). The fractionation schedule was to give 5 treatments per one week and the fractional doses were 2.0-3 Gy depending on the treatment aim and the FSRT volume. The FSRT doses varied depending on the nature of the primary diseases. RESULTS The local tumor response in nasopharynx cancer patients was excellent compared to retrospective data without occurrence of unexpectedly severe complication. FSRT to other regions was well tolerated by the patients and resulted in good to excellent local tumor responses with no unacceptable side effects as expected by the authors. CONCLUSION Based on the current observations, FSRT is a very effective and safe modality in the treatment of extracranial head and neck tumors.

A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea

Aim: To determine the national practice processes of care and outcomes of radiotherapy for hepatocellular carcinoma (HCC) in Korea.

High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor

Single or tandem double high‐dose chemotherapy (HDCT) was used to treat children with newly diagnosed high‐risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor (MB/sPNET) in order to defer or avoid radiotherapy in young children.

Effect of customized small bowel displacement system in pelvic irradiation

PURPOSE Authors designed a customized small bowel displacement system (SBDS) to displace the small bowel out of the pelvic radiation fields and to minimize treatment related bowel morbidity. METHODS AND MATERIALS From August 1995 to May 1996, 55 consecutive patients who received pelvic radiation therapy with the SBDS were included in this study. The SBDS consists of a customized Styrofoam compression device that can displace the small bowel out of the radiation fields and an individualized immobilization abdominal board for easy daily setup of the patient in prone position. After opacifying the small bowel with barium, the patients were laid prone and posterior-anterior (PA) and lateral (LAT) simulation films were taken with and without the SBDS. The volume of the small bowel included in the radiation fields with and without the SBDS were compared. RESULTS Using the SBDS, the mean small bowel volume was reduced by 59% on PA and 51% on LAT films (p = 0.0001). In six patients (6 of 55, 11%), it was possible that no small bowel was included within the treatment fields. The mean upward displacement of the most caudal small bowel was 4.8 cm using the SBDS. Patients treated with the SBDS manifested a significantly lower incidence of diarrhea requiring medication (8 of 55, 15%) vs. those without the SBDS (24 of 39, 62%) (p < 0.05). CONCLUSION The SBDS is a novel method that can be used to displace the small bowel away from the treatment portal effectively and to reduce the radiation therapy morbidity. Compliance with setup is excellent.

Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity.

Purpose:We prospectively evaluated the efficacy and toxicity of early 3-dimensional conformal radiotherapy (3D-CRT) for patients with unresectable hepatocellular carcinoma (HCC) after incomplete transcatheter arterial chemoembolization (TACE). Methods:Patients with unresectable HCC who failed 1 or 2 courses of TACE were eligible for this study. Three dimensional-CRT was added for HCC with incomplete uptake of iodized oil. Between January 2006 and February 2007, 40 patients (43 lesions) were enrolled. TACE was performed by using Lipiodol and adriamycin, followed by Gelfoam embolization. Two cycles of TACE were performed in 24 patients (60%), whereas 16 patients (40%) underwent one cycle. The median dose of 54 Gy (3 Gy daily) was delivered with 3D-CRT. Tumor response was evaluated by changes in tumor size on serial computed tomography scans and toxicity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results:An objective response was achieved in 27 of 43 lesions (62.8%), with a complete response in 9 lesions (20.9%) and partial response in 18 lesions (41.9%). The overall survival rate was 72.0% at 1 year and 45.6% at 2 years. There was no grade 3 or greater acute toxicity. Nine patients (22.5%) showed progression of the disease within the irradiated field during the follow-up and intrahepatic metastases developed in 16 patients (40.0%). Conclusion:Early 3D-CRT for HCC unresponsive to 1 or 2 cycles of TACE resulted in a 62.8% tumor response rate and relatively high complete response rates (20.9%) with acceptable toxicity. This study shows that the application of 3D-CRT could be considered for patients with incomplete TACE.

Liposarcoma: exploration of clinical prognostic factors for risk based stratification of therapy.

BackgroundPrognosis and optimal treatment strategies of liposarcoma have not been fully defined. The purpose of this study is to define the distinctive clinical features of liposarcomas by assessing prognostic factors.MethodsBetween January 1995 and May 2008, 94 liposarcoma patients who underwent surgical resection with curative intent were reviewed.ResultsFifty patients (53.2%) presented with well differentiated, 22 (23.4%) myxoid, 15 (16.0%) dedifferentiated, 5 (5.3%) round cell, and 2 (2.1%) pleomorphic histology. With the median 14 cm sized of tumor burden, about half of the cases were located in the retroperitoneum (46.8%). Seventy two (76.6%) patients remained alive with 78.1%, and 67.5% of the 5- and 10-year overall survival (OS) rates, respectively. Low grade liposarcoma (well differentiated and myxoid) had a significantly prolonged OS and disease free survival (DFS) with adjuvant radiotherapy when compared with those without adjuvant radiotherapy (5-year OS, 100% vs 66.3%, P = 0.03; 1-year DFS, 92.9% vs 50.0%, respectively, P = 0.04). Independent prognostic factors for OS were histologic variant (P = 0.001; HR, 5.1; 95% CI, 2.0 – 12.9), and margin status (P = 0.005; HR, 4.1; 95% CI, 1.6–10.5). We identified three different risk groups: group 1 (n = 66), no adverse factors; group 2, one or two adverse factors (n = 28). The 5-year OS rate for group 1, and 2 were 91.9%, 45.5%, respectively.ConclusionThe histologic subtype, and margin status were independently associated with OS, and adjuvant radiotherapy seems to confer survival benefit in low grade tumors. Our prognostic model for primary liposarcoma demonstrated distinct three groups of patients with good prognostic discrimination.

Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma

Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim DH, Kim K‐M, Park CK. Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 2009; 117: 598–606.