방사선치료 중 오심 및 구토에 대한 그라니세트론의 효과

홍성언,강진오,Hong, Seong-Eon,Kang, Jin-O 대한방사선종양학회 1999 대한방사선종양학회지 Vol.17 No.2

Purpose : Granisetron is a potent, the most selective 5-HT3 receptor antagonist and is reported to b effective in treatment of radiation-induced emesis. The antiemetic efficacy and safety of oral granisteron was evaluated in patients with receiving highly emetogenic treatment by conventional fractionated irradiation. Materials and Methods : Patients with various cancers who were being treated with irradiation were accrued into the present study. The intensity of nausea was evaluated on first 24 hours and on day-7 by patients according to the degree of interference with normal daily life as followings; a) none; b) present but no interference with normal daily life (mild): c) interference with normal daily life (moderate): and d) bedridden because of nausea (severe). Non or mild state was considered to indicate successful treatment. The efficacy of antiemetic treatment was graded as follows; a) complete response; no vomiting, no worse than mild nausea and receive no rescue antiemetic therapy over the 24h period, b) major response; either one episode of vomiting or moderate/severe nausea or had received rescue medication over 24h period, or any combination of these, c) minor response; two to four episodes of vomiting over the 24h period, regardless of nausea and rescue medication, d) failure; more than four medication. The score of the most symptom was recorded and the total score over 24 hours was summarized. The complete or major response was considered to indicate successful treatment. Results : A total of 10 patients were enrolled into this study, and all were assessable for efficacy analysis. Total nausea control was achieved in 90$\%$ (9/10:none=60$\%$ plus mild=30$\%$) of total patients after 7 days. The control of vomiting by granisteron was noted in seven patients (70$\%$) of complete response and three (30$\%$) of major response with a hundred-percent successful treatment over 7 days. The minor response or treatment failure were not observed. No significant adverse events or toxicities from granisetron were recorded in patient receiving granisetron. Conclusion : We concluded that granisetron is a highly effective antiemetic agent in controlling radiotherapy-induced nausea or vomiting with a minimal toxicity profile.

The Combined Effect of Adriamycin and Irradiation on the Small Intestinal Villi of Mice

홍성언,안치열,Hong, Seong-Eon,Ahn, Chi-Yul The Korean Society for Radiation Oncology 1986 Radiation Oncology Journal Vol.4 No.1

방사선 조사와 adriamycin 병용투여가 마우스 소장 소낭선세포의 방사선 감수성에 미치는 영향을 관찰하고 adriamycin의 방사선 증강효과를 측정하기 위하여 $C_3H$계 마우스 120마리를 cobalt-60원 격치료기로 전복부에 조사하였다. 방사선 단독조사군은 1,000rad에서 1,600rad까지, adriamycin병용투여군은 900rad에서 1,400rad까지 각각 100rad씩 증강시켜 조사하였고 adriamycin 10mg/kg을 조사 2시간전과 4시간후에 각각 복강내에 주사하였다. 실험군은 84시간 후에 공장을 절제하고 소낭선 측정법을 이용하여 세포생존곡선을 작성하므로써 adriamycin 병용투여시의 조사효과를 측정하였으며, 주사전자현미경(SEM)으로 소장융모의 형태변화를 관찰하여 다음과 같은 효과를 얻었다. 1) 조사군의 환상면당 소낭선수는 평균 $130{\pm}16$개이었다. 2) 방사선 단독조사 군에서 소낭선세포의 평균 치사선량은 160rad이었으며, 방사선조사 2시간과 4시간후 adriamycin 병용투여군은 모두 170rad이었다. 3) 방사선조사 2시간전과 4시간 후에 adriamycin 투여군의 dose effect factor(DEF)는 1.19와 1.26이었다. 4) 주사전자현미경소견에서 조사선량 증가에 따라 소장융모의 손상이 각각 다른 형태로 뚜렷이 변하였으며, conical collapse형태로 면한 것은 단독조사군의 1,200rad와 adriamycin병용투여군의 1,000rad에서 각각 관찰되었다. 이상의 실험결과로 보아 마우스 소장에서 방사선과 adriamycin 병용투여시 $19{\sim}26%$의 유의한 조사효과 상승이 관찰되었으므로 향후 복부나 골반부에 방사선조사와 항암제를 병용하는 경우에는 방사선 감수성이 높은 장기인 소장에 대한 손상을 고려하여 임상에서 암의 방사선치료에 깊은 배려가 필요하다고 사료된다. In order to clarify the effect of radiation on the mouse jejunal crypt cells by combined administration of administration and radiation and also to evaluate the enhancing effect of adriamycin, the authors performed this study by delivering single irradiation of 1,000 to 1,600 rad to the whole abdomen of mice by cobalt-60 teletherapy unit. In combination with adriyamycin treatment groups, the drug was administered as single dose of 10 mg/kg either 2 hours before or 4 hours after graded single dose,900 to 1,400 rad, of irradiation. The authors studied the quantitative changes of intestinal crypt cells by microcolony survival assay technique and the morphological changes of small intestinal villi by scanning electron microscope in mice following to combined therapy with adriamycin and irradiation, The average number of jejunal crypts per circumference was $130{\pm}16$ in control group. The mean lethal dose(Do) of each irradiation alone and combined therapy groups 2 hours before and 4 hours after irradiation, were 160, 170, and 170 rad in cell survival curves, respectively. The dose effect factor(DEF) of adriamycin in each groups of pre-irradiation and post-irradiation were 1.19 and 1.26, respectively. The conical shaped villi were noted on 1,200 rad in irradiation alone group and 1,000 rad in combined groups. For the proper clinical application we must be careful of the radiation injury to small bowel when the anticancer chemotherapy and radiation therapy to the abdomen and pelvic area are used as combined therapeutic modality.

저분화 성상세포종-수술후 방사선치료가 필수적인가 ?

홍성언,최두호,김태성,임언,Hong Seong Eon,Choi Doo Ho,Kim Tee Sung,Leem Won The Korean Society for Radiation Oncology 1992 대한방사선종양학회지 Vol.10 No.2

The precise role of radiotherapy for low grade gliomas including the optimal radiation dose and timing of treatment remains unclear. The information given by a retrosepctive analysis may be useful in the design of prospective randomized studies looking at radiation dose and time of surgical and radiotherapeutic treatment. The records of 56 patients (M:F = 29:27) with histologically verified cerebral low grade gliomas (47 cases of grade 1 or 2 astrocytomas and 9 oligodendrogliomas) diagnosed between 1979 and 1989 were retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 38 patients ($68\%$) and partial or biopsy only in the remaining 18 patients ($32\%$). Postooperative radiation therapy was given to 36 patients ($64\%$) of the total 56 patients with minimum dose of 5000 cGy (range=1250 to 7220 cGy). The 5-and 10-year survival rates for the total 56 patients were $44\%$ and $32\%$ respectively with a median survival of 4.1 years. According to the histologic grade the 5- and 10-year survivals were $52\%$ and $35\%$ for the 24 patients respectively with grade I astrocytomas compared to $20\%$ and $10\%$ for the 23 patients with grade II astrocytomas. Survival of oligodendroglioma patients was greater than those with astrocytoma ($65\%$ vs $36\%$ at 5 years), and the difference was also remarkable in the long term period of follow up ($54\%$ vs $23\%$ at 10 years). Those who received high-dose radiation therapy ($\geq$5400 cGy) had significant better survival than those who received low-dose radiation (< 5400cGy) or surgery alone (p<0.05). The 5- and 10-year survival rates were, respectively $59\%$ and $46\%$ for the 23 patients receiving high-dose radiation, $36\%$ and $24\%$ for the 13 patients receiving low-dose radiation, and $35\%$ and $26\%$ for the 20 patients with surgery alone. Survival rates by the extent of surgical resection were similar at 5 years ($46\%$ vs $41\%$), but long term survival was quite different (p<0.01) between total/subtotal resection and partial resection/biopsy ($41\%$ and $12\%$, resepctively). Previously published studies have identified important prognostic factors in these tumor: age, extent of surgery, grade, performance status, and duration of symptoms. But in our cases statistical analysis revealed that grade I histology (p<0.025) and young age (p<0.001) were the most significant good prognostic variables.

원저 : 방사선조사에 의한 마우스 구강점막 상피의 급성반응 ( Original Article : An Experimental Study for Acute Reaction of Lip Mucosa of Mice To Irradiation )

홍성언(Seong Eon Hong),안치열(Chi Yul Ahn) 경희대학교 경희의료원 1987 慶熙醫學 Vol.3 No.4

원저 : 방사선 조사와 Adriamycin 병용투여가 마우스 소장에 미치는 영향에 관한 연구 ( Original Article : The Effect of combined adriamycin and Irradiation on the Small Intestine of Mice )

홍성언(Seong Eon Hong),안치열(Chi Yul Ahn) 경희대학교 경희의료원 1986 慶熙醫學 Vol.2 No.1

진행된 성문상부암에서 PCR-SSCP에 의한 p53의 변이 양상과 임상적 의의

홍성언(Seong Eon Hong),강진오(Jin Oh Kang),백형환(Hyung Hwan Baik),윤경식(Kyung Sik Yoon) 대한방사선종양학회 2001 대한방사선종양학회지 Vol.19 No.2

목 적 :진행된 성문 상부암 환자에서 p53 유전자 변이 양상을 파악하고 이의 임상적 예후 인자로서의 관련성을 확인하고자 하였다. 대상 및 방법 :경희대학병원에서 병기 3 또는 4의 진행된 후두암으로 진단 받고 근치적 목적의 전 또는 부분 후두절제술을 시행 받고 4600 cGy 이상의 방사선 치료를 받은 환자 60례 중 적절한 조직을 확보 할 수 있었던 환자 26명을 대상으로 하였다. 조직 일부는 면역 염색을 시행하였고 일부는 p53 유전인자의 exon 5번 부터 8번까지 PCR-SSCP 시행후 PCR-SSCP 상 이상 소견이 있는 환자들의 DNA를 염기 서열 분석하였다. 이 결과를 임상적 소견과 비교 분석하였다. 결 과 :PCR-SSCP 검사 결과 exon 5∼8번에서 전체 26례 중 8례(31%)에서 변이를 나타내었다. 8례 모두 점돌연변이었으며 transition이 전체 8례 중 6례이었다. Exon 5번의 변이가 3례, exon 6번의 변이가 4례, exon 7번의 변이가 1예이었다. 전체 환자의 평균 생존 기간은 67.4개월 이었고 p53 변이가 없는 군이 70.2개월, p53 변이가 있는 군이 61.3개월로 p53 변이가 있는 군의 생존 기간이 감소되어 나타났으나 두 군간의 생존 기간의 통계적인 유의한 차이는 없었다(p=0.596). 환자를 병기 III과 IV로 나누어 SSCP상 변이의 차이를 비교하였는데 병기 III은 양성이 25%이었고 병기 IV는 36%로 나타나 병기 IV 에서 약간 높게 나타났으나 통계적 차이는 없었다(p=0.563). 임파절 음성인 환자 중 SSCP 양성은 25%이었고 임파절 양성인 환자 중 SSCP 양성은 42%이었으나 통계적 차이는 없었다(p=0.437). 결 론 : PCR-SSCP 를 이용한 p53 유전인자 변이의 검색은 생존 기간, 병기, 임파절 전이 등과 관련이 없으며 예후인자로서 유용하지 않은 것으로 판단하였다. Purpose : To determine the prognostic s ignificance of p53 mutations in advanced supraglottic cancer patients . Material and Methods : Twenty- s ix patients with pertinent tissue materials among 60 patients diagnosed as advanced supraglottic cancer in Kyung Hee univers ity hospita l a nd received total or partial laryngectomy followed by radiation therapy were enrolled. Immunohistochemical staining us ing DO7 monoclonal antibody was performed. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by us ing PCR- SSCP analys is followed by DNA sequencing of all variants . Results : p53 mutations were present in 8 cases among 26 patiets . Mutations within exon 5 were 3 cases , exon 6 were 4 cases , and exon 7 was 1 case. Mean survival time was 70.2 months in patients without mutations , 61.3 months with mutations but there was no statistically s ignificant differences (p=0.596). Mutations were 25% in stage III and 36% in stage IV but there was no statistically s ignificant differences (p=0.563). Mutations were 25% in lymph node negative group and 42% in lymph node pos itive group but there was no statistically s ignificant differences (p=0.437). Conclusion : The presence of a p53 mutation detected by PCR- SSCP is not associated with survival, stage and lymph node status.

종설 : 온열요법과 방사선치료 ( Review : Hyperthermia and Radiation Therapy )

홍성언(Seong Eon Hong) 경희대학교 경희의료원 1987 慶熙醫學 Vol.3 No.4

Radiation Therapy In Management Of Primary Non-Hodgkin's Lymphoma Of Central Narvous System

홍성언(Seong Eon Hong) 대한방사선종양학회 1994 대한방사선종양학회지 Vol.12 No.1

1982년부터 1991년까지 경희대학병원 치료방사선과에서 원발성 중추신경계 림프종으로 확진되어 방사선치료를 받은 16명의 환자를 대상으로 치료결과를 후향적으로 분석하였다. 가장 흔한 세포아형은 large, noncleaved cell과 B cell의 immumoblastic 림프종이었으며 측두엽과 심핵부위에 호발하였다. 치료는 환자를 생검 또는 절제술후 전뇌에 40 Gy(range= 30-50 Gy)를 방사선 조사하였으며 원발병소 15-20 Gy를 추가조사하였다. 16명의 환자중 14명은 방사선치료후 2개월에서 49개월 사이에 사망하였으며, 2명은 재발없이 각각 8개월과 22개월째 생존하고 있다. 1년 및 2년생존율은 각각 55.6%와 34.7%이었고, 중간 생존기간은 12개월이었다. 16명의 환자중 재발된 11명을 분석하였다. 방사선치료후 원발부위에 재발은 드물었으나 전뇌조사에서 불구하고 다른 부위에서 재발하였다. 재발율은 뇌에서 68.7% (11/16)이고 척추에서 25.0%(4/16)이었다. 나이, 성별 발생부위, 병소수, 방사선치료선량등은 각가 생존율과 무관하였다. 이와 같은 결과로 중추신경계 림프종은 방사선 치료의 초기반응은 양호하나 통상적인 방사선치료만으로는 조절이 어려운 질환이다. 따라서 분할치료방법에 의한 방사선량 증가와 항암제의 병용으로 중추신경계 림프종에 대한 치료효과를 향상시키리라 기대된다. From 1982 to 1991, sixteen patients with primary non-Hodgkin's lymphoma of the central nervous system(CNS) were seen Kyung Hee Unviersity Hospital. The most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. Lesions most commonly involved were the parietal lobes and/or deep nuclei. Psitive cerebrospinal fluid cytology was rare at initial presentation. Sixteen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 40 Gy(range=30-50Gy) with variable boost doses. Of 16 patients who underwent surgery and postoperative radiotherapy, fourteen patients died between 2 and 49 months following treatment, and two are alive with no evidence of disease at 8 and 22 months. The 1-and 2-year survival rates were 55.6% and 34.7% respectively with 12 months of median survival. Patterns of failure were analyzed in eleven patients of total 16 patients. Failure at the original site of involvement was uncommon after radiotherapy treatment. In contrast, failure in the brain at sites other than those originally involved was common in spite of the use of whole brain irradiation. Failure occurred in the brain 11/16(68.7%), in spinal axis 4/16(25.0%). The age, sex, location of involvement within CNS, numbers of lesion, or radiation dose did not influence on survival. The authors conclude that primary CNS lymphoma is a locally aggressive disease that is poorly controlled with conventional radiation therapy. The limitation of current therapy for this disease are discussed, and certain promising modality should be made in regarding the management of future patients with this disease.

Accelerated Fractionation In The Treatment of Brain Metastasis From Non-Small Cell Carcinoma of The Lung

홍성언(Seong Eon Hong) 대한방사선종양학회 1994 대한방사선종양학회지 Vol.12 No.2

목적 : 폐암한자에 있어서 뇌전이는 심각한 문제이며 또한 장기간 생존을 기대할 수가 없다. 종양억제효과를 증가시키는 동시에 만발 장애를 감소시켜 전체 치료기간을 가능한 단축시키기 위하여 비소세포성 폐암환자의 뇌전이에 대한 다분할 조사법인 급속분할조사법을 시행하였다. 재료 및 방법 : 1991년부터 1993년까지 비소세포성 폐암으로 확진되어 뇌전이가 발생한 24명의 환자에게 6시간 간격으로 2Gy씩 하루 2회로 총 48Gy를 전뇌에 조사하였다. 단일 병소는 전뇌에 40Gy 조사후 치료범위를 축소하여 8Gy를 추가하였다. 총 26예중 신경증상이 점사 진행되는 양상을 보인 2명은 방사선치료를 중단하였다. 결과 : 방사선치료 도중에 3명은 급성 방사선효과로 오심과 구토를 호소하였으나, 방사선량 증가로 인한 심각한 부작용은 없었다. 통상적인 치료방법인 2주에 30Gy를 조사한 경우(4.5개월)보다 48Gy의 급속분할조사에 의한 방사선치료법이 중간생존기간을 향상시켰으나(7개월)통계학적 의의는 없었다.(p>0.05). 뇌에 국한된 전이 환자와 활동수행 상태가 양호한 군이 다방성 전이나 활동수행상태가 불량한 군보다 중간생존기간과 반년생존율에 있어서 유의한 증가를 나타내었다(p<0.01). 결론 : 뇌전이 단독소견과 양호한 활동수행능력 상태등 양호한 예후인자를 가진 환자는 생존기간 향상이 기대된다. 본 연구결과로 환자의 quality of life를 고려하여 하후 1회 치료법과 2또 3회치료법을 비교하는 다자간의 전형적인 연구가 필요하리라 생각된다. Purpose : Metastatic cancer to the brain is a major problem for the patients with bronchogenic carcinoma, and most of these patients have a limited survival expectancy. To increase tumor control and/or to decrease late morbidity with possible shortening in over-all treatment period multiple adily fraction technique for brain metastasis was performed. The author reperesented the results of accelerated fractionation radiotherapy in patients with brain metastases from non-small cell lung cancer. Materials and Methods : Twenty-six patients with brain metastasesfrom non-small cell lung cancer between 1991 and 1993 received brain radiotherapy with a total dose of 48 Gy at 2 Gy per fraction, twice a day with a interfractional period of 6 hours and delivered 5 days a week. the whole brain was treated to 40Gy and boost dose escalated to 8Gy for single metastatic lesion by reduced field. Twenty-four of the 26 patients completed the radiotherapy. Radiotherapy was interupted in two patients suggesting progressive intracerebral diseases. Results : This radiotherapy regimen appears to be comparable to the conventional scheme in relief from symptoms. Three of the 24 patients experienced nausea and or vomiting during the course of treatment because of acute irradiation toxicity. The author observed no excessive toxicity with escalating dose of irradiation. An increment in median survival, although not statistically significant(p>0.05) was noted with escalating doses(48Gy) of accelerated fractionation(7 months) compared to conventional treatment(4.5 months). Median survival also increased in patients with brain solitary metastasis (9 months) compared to multiple extrathoracic sites(4 months) and in patients with good performance status (9 months versus 3.5 months) they were statistically significant (p<0.01). Conclusion : The increment in survival in patients with good prognostic factors such as controlled primary lesion metastasis in brain only and good performance status appeared encouraging. Based on these results a multi-institutional prospective randomized trial should be initiated to compare the twice-a-day and once-a-day radiotherapy schemes on patients with brain metastasis with careful consideration for the patients quality of life.

Lethal Effects of Radiation and Platinum Analogues on Multicellular Spheroids of HeLa Cells

홍성언(Seong Eon Hong) 대한방사선종양학회 1989 Radiation Oncology Journal Vol.7 No.2

HeLa 세포의 Spheroid를 배양시켜 cis-platinum과 carboplatin으로 처리한 후 그 반응을 세포의 생존분획으로 분석하였다. 체외실험 model인 spheroid를 사용하여 platinum 유사체의 약효와 방사선 감수성을 평가하고 약제에 대한 단층 세포와 spheroid의 감수성 차이를 세포-생존곡선에서 규명하기 위하여 본 실험을 시행하였다. Cis-platinum 농도-곡선에서 spheroid의 Cq=3.4μM이고 Co=1.2μM이었다. 이것은 단충세포에 비하여 Co는 큰 변화가 없으나 Cq가 증가되어 cis-platinum이 저산소층 세포보다 활동적으로 분화하는 표면세포에 주로 작용하였으며, 반대로 carboplatin의 효과는 spheroid에 대한 (Co=15.0μM) 감수성이 단층세포 (Co=32.5μM)에 비하여 크게 증가되어, spheroid의 심층세포에 주로 작용하였다. 방사선과 carboplation의 병용효과를 세표 생존분획이 0.01 수준에서 isobologram으로 분석한 결과 상호작용으로 supra-additive 효과를 나타내었다. 따라서, carboplatin은 cis-platinum에 비하여 신장과 위장에 대한 독성작용이 적고, 방사선과 병용함으로써 더욱 효과적인 종양 치료에 중요한 역할을 할 것으로 기대한다. Multicellular tumor spheroids of HeLa cells have been grown in a stare culture system. Samples of spheroids were exposed for 2 h to graded concentration of cis-platinum and its analogue, carboplatin. and then response assayed by survival of clonogenic cells. The purpose of present experiment is to clarify the effectiveness of these platinum compounds and to evaluate intrinsic radiosensitivity of cells using spheroids of HeLa cells as an experimental in vitro model. Variations of the drug sensitivity of monolayers as well as spheroids were also evaluated in cell-survival curves. In cis-platinum concentration-survival curve, there was a large shoulder extending as far as Cq=3.4 μM, after which there was exponential decrease in survival curve having a Co Value of 1.2 μM in spheroids. While the Co for the spheroids was essentially no significant change, but Cq value was larger than that of monolayers. This suggest that the effect of cis-platinum is greater in the monolayer with actively proliferaing cells than hypoxic one. In the corboplatin concentration-survival curves, the Co value of spheroids was 15.0 μM and the ratio with the Co from monolayer cell (32.5 μM) was 0.46, thus indicating that the spheroids had a greater sensitivity to carboplatin than monolayers. Therefore, 'the effect of carboplatin is mainly on the deeper layers of spheroids acting as hypoxic cell sensitizer. The enhanced effect was obtained for monolayer cells using combined X-ray and carboplatin treatment 2 hours before irradiation. The result shown in isobologram analysis for the level of surviving fraction at 0.01 indicated that the effect of two agents was truely supra-additive. From this experimental data, carboplatin has excited much recent interest as one of the most promising, since it is almost without nephrotoxicity and causes less gastrointestinal toxicity than cis-platinurn. Interaction between carboplatin and radiation might play an important role for more effective local tumor control.