Purpose: To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) ($42{\sim}46\;Gy$) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to $54{\sim}66\;Gy$, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, $9{\sim}12\;Gy/3{\sim}4\;fx$). Two cycles of concurrent FP chemotherapy (5-FU $1,000\;mg/m^2$/day, days $2{\sim}6$, $30{\sim}34$, cisplatin $60\;mg/m^2$/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range $1{\sim}149$ months)). The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range $44.4{\sim}66$) and a total radiation dose, including BT, of 60 Gy (range $44.4{\sim}72$), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29.0% at 2 years and 22.7% at 5 years (median 10.4 months). The response to treatment and N-stage were significant factors affecting overall survival. In addition, total radiation dose (${\geq}50\;Gy$ vs. < 50 Gy), BT and fractionation scheme (qd. vs. bid.) were not significant factors for overall survival and disease-free survival. Conclusion: Survival outcome after definitive chemoradiation therapy in unresectable esophageal cancer was comparable to those of other series. The main failure pattern was local recurrence. Survival rate did not improve with increased radiation dose over 50 Gy or the use of brachytherapy or hyperfractionation.
Purpose : It is not a simple task to achieve the ideal isodose curve with a standard vaginal applicator or sing1e plane needle impant in the paravaginal tissue when primary or recurrent gynecological neoplasms(cervical cancers, vaginal cancers and vulvar cancers) are treated as a boost following external beam radiotherapy. The authors introduce the development and construction of a simple, inexpensive, customized applicator for volume implant to maximize the radiation dose to the tumor while minimizing the dose to the rectum and the bladder. Materials and Methods : Nine patients underwent Ir-192 transperineal interstitial implantation for either recurrent(5 cases) or primary(3 cases) cervical cancers or primary vaginal cancer(1 case) between August 1994 and February 1998 at Ajou university hospital. First 3 cases were performed with a sing1e plane implant guided by digital palpation. Because of inadequate isodose coverage in the tumor volume in first 3 cases, we designed and constructed interstitial vaginal applicator for volume implant to improve tumor dose distribution and homogeneity while sparing the surrounding normal tissue. Our applicators consist of vaginal obturator and perineal template that made of the clear acrylamide and dental mold material$(Provil^{(R)})$. The applicators were customized individually according to the tumor size and its location Both HDR and LDR irradiation were given with these applicators accomodating 6 Fr needles(Microselectron Nucletron). The pretreatment planning prior to actual implant was performed whenever possible. Results : Needles can be inserted easily and evenly into the tumor volume through the holes of templates, requiring less efforts and time for the implant procedure. Our applicators made of materials available from commercial vendors. These have an advantage that require easy procedure, and spend relatively short time to construct. Also it was possible to fabricate applicators to individualize according to the tumor size and its location and to achieve the ideal isodose coverage. We found an accurate needle arrangement and ideal dose distribution through the CT scan that was obtained in 3 cases after needle implant. Three patients with primary cervical and vaginal cancers were controlled locally at final follow up. But all recurrent cases failed to do so. Conclusion : The authors introduce inexpensive, simple interstitial vaginal templates which were self-designed and constructed using materials available from commercial vendors such as acrylanide and dental mold material $(Provil^{(R)})$.
The Journal of Korean Society for Radiation Therapy
/
v.16
no.2
/
pp.9-17
/
2004
Purpose : Although Improve of CT, MRI Radio-diagnosis and Radiation Therapy Planing, but we still use ICRU38 Planning system(2D film-based) broadly. 3-Dimensional ICR plan(CT image based) is not only offer tumor and normal tissue dose but also support DVH information. On this study, we plan irradiation-goal dose on CTV(CTV plan) and irradiation-goal dose on ICRU 38 point(ICRU38 plan) by use CT image. And compare with tumor-dose, rectal-dose, bladder-dose on both planning, and analysis DVH Method and Material : Sample 11 patients who treated by Ir-192 HDR. After 40Gy external radiation therapy, ICR plan established. All the patients carry out CT-image scanned by CT-simulator. And we use PLATO(Nucletron) v.14.2 planing system. We draw CTV, rectum, bladder on the CT image. And establish plan irradiation-$100\%$ dose on CTV(CTV plan) and irradiation-$100\%$ dose on A-point(ICRU38 plan) Result : CTV volume($average{\pm}SD$) is $21.8{\pm}26.6cm^3$, rectum volume($average{\pm}SD$) is $60.9{\pm}25.0cm^3$, bladder volume($average{\pm}SD$) is $116.1{\pm}40.1cm^3$ sampled 11 patients. The volume including $100\%$ dose is $126.7{\pm}18.9cm^3$ on ICRU plan and $98.2{\pm}74.5cm^3$ on CTV plan. On ICRU planning, the other one's $22.0cm^3$ CTV volume who residual tumor size excess 4cm is not including $100\%$ isodose. 8 patient's $12.9{\pm}5.9cm^3$ tumor volume who residual tumor size belows 4cm irradiated $100\%$ dose. Bladder dose(recommended by ICRU 38) is $90.1{\pm}21.3\%$ on ICRU plan, $68.7{\pm}26.6\%$ on CTV plan, and rectal dose is $86.4{\pm}18.3\%,\;76.9{\pm}15.6\%$. Bladder and Rectum maximum dose is $137.2{\pm}50.1\%,\;101.1{\pm}41.8\%$ on ICRU plan, $107.6{\pm}47.9\%,\;86.9{\pm}30.8\%$ on CTV plan. Therefore CTV plan more less normal issue-irradiated dose than ICRU plan. But one patient case who residual tumor size excess 4cm, Normal tissue dose more higher than critical dose remarkably on CTV plan. $80\%$over-Irradiated rectal dose(V80rec) is $1.8{\pm}2.4cm^3$ on ICRU plan, $0.7{\pm}1.0cm^3$ on CTV plan. $80\%$over-Irradiated bladder dose(V80bla) is $12.2{\pm}8.9cm^3$ on ICRU plan, $3.5{\pm}4.1cm^3$ on CTV plan. Likewise, CTV plan more less irradiated normal tissue than ICRU38 plan. Conclusion : Although, prove effect and stability about previous ICRU plan, if we use CTV plan by CT image, we will reduce normal tissue dose and irradiated goal-dose at residual tumor on small residual tumor case. But bigger residual tumor case, we need more research about effective 3D-planning.
Park Won;Choi Yoon-La;Huh Seung-Jae;Yoon Sang-Min;Park Young-Je;Nam Hee-Rim;Ahn Yong-Chan;Lim Do-Hoon;Park Hee-Chul
Radiation Oncology Journal
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v.24
no.1
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pp.37-43
/
2006
Purpose: We wanted to determine the clinical characteristics and prognosis according to the VEGF expression in stage II cervical carcinoma patients treated with definitive radiotherapy. Materials and Methods: We enrolled 31 patients who were diagnosed with cervical cancer from 1995 to 2003 at Samsung Medical Center and their paraffin block tissue samples were available for study. The median age of the patients was 65 years. The mean tumor size was 4.1 cm $(range:\;1.2{\sim}8.2cm)$. Seven patients (22.6%) were suspected of having pelvic lymph node metastasis. An external beam irradiation dose of 45-56.4 Gy was administered to the whole pelvis with a 15 MV linear accelerator, and an additional 24 Gy was given to point A by HDR intracavitary brachytherapy. VEGF staining was defined as positive when more than 10% of the tumor cells were stained. The median follow-up duration was 58 months. Results: A positive VEGF expression was observed in 21 patients (67.7%), There was no significant correlation between the VEGF expression and pelvic lymph node metastasis, tumor size and the response of radiotherapy. During follow-up, 7 patients had recurrence. The complete response rate was not significant between the VEGF(-) and VEGF(+) tumors. However, the VEGF(+) tumors showed a significantly higher recurrence rate in comparison with the VEGF(-) tumors (p=0.040), The three year disease-free survival rates were 100% and 66.7%, respectively, for patients with VEGF(-) or VEGF(+) tumor (p=0.047), Conclusion: The VEGF expression was a significant factor for recurrence and disease-free survival. However, the significance of the VEGF expression is still controversial because of the various definitions of VEGF expression and the mismatches of the clinical data in the previous studies.
Purpose : In spite of recent remarkable improvement of diagnostic imaging modalities such as CT, MRI, and PET and radiation therapy planing systems, ICR plan of uterine cervix cancer, based on recommendation of ICRU38(2D film-based) such as Point A, is still used widely. A 3-dimensional ICR plan based on CT image provides dose-volume histogram(DVH) information of the tumor and normal tissue. In this study, we compared tumor-dose, rectal-dose and bladder-dose through an analysis of DVH between CTV plan and ICRU38 plan based on CT image. Method and Material : We analyzed 11 patients with a cervix cancer who received the ICR of Ir-192 HDR. After 40Gy of external beam radiation therapy, ICR plan was established using PLATO(Nucletron) v.14.2 planing system. CT scan was done to all the patients using CT-simulator(Ultra Z, Philips). We contoured CTV, rectum and bladder on the CT image and established CTV plan which delivers the 100% dose to CTV and ICRU plan which delivers the 100% dose to the point A. Result : The volume$(average{\pm}SD)$ of CTV, rectum and bladder in all of 11 patients is $21.8{\pm}6.6cm^3,\;60.9{\pm}25.0cm^3,\;111.6{\pm}40.1cm^3$ respectively. The volume covered by 100% isodose curve is $126.7{\pm}18.9cm^3$ in ICRU plan and $98.2{\pm}74.5cm^3$ in CTV plan(p=0.0001), respectively. In (On) ICRU planning, $22.0cm^3$ of CTV volume was not covered by 100% isodose curve in one patient whose residual tumor size is greater than 4cm, while more than 100% dose was irradiated unnecessarily to the normal organ of $62.2{\pm}4.8cm^3$ other than the tumor in the remaining 10 patients with a residual tumor less than 4cm in size. Bladder dose recommended by ICRU 38 was $90.1{\pm}21.3%$ and $68.7{\pm}26.6%$ in ICRU plan and in CTV plan respectively(p=0.001) while rectal dose recommended by ICRU 38 was $86.4{\pm}18.3%$ and $76.9{\pm}15.6%$ in ICRU plan and in CTV plan, respectively(p=0.08). Bladder and rectum maximum dose was $137.2{\pm}50.1%,\;101.1{\pm}41.8%$ in ICRU plan and $107.6{\pm}47.9%,\;86.9{\pm}30.8%$ in CTV plan, respectively. Therefore, the radiation dose to normal organ was lower in CTV plan than in ICRU plan. But the normal tissue dose was remarkably higher than a recommended dose in CTV plan in one patient whose residual tumor size was greater than 4cm. The volume of rectum receiving more than 80% isodose (V80rec) was $1.8{\pm}2.4cm^3$ in ICRU plan and $0.7{\pm}1.0cm^3$ in CTV plan(p=0.02). The volume of bladder receiving more than 80% isodose(V80bla) was $12.2{\pm}8.9cm^3$ in ICRU plan and $3.5{\pm}4.1cm^3$ in CTV plan(p=0.005). According to these parameters, CTV plan could also save more normal tissue compared to ICRU38 plan. Conclusion : An unnecessary excessive radiation dose is irradiated to normal tissues within 100% isodose area in the traditional ICRU plan in case of a small size of cervix cancer, but if we use CTV plan based on CT image, the normal tissue dose could be reduced remarkably without a compromise of tumor dose. However, in a large tumor case, we need more research on an effective 3D-planing to reduce the normal tissue dose.
Kim Hunjung;Cho Young Kap;Kim Chulsu;Kim Woo Chul;Lee Sukho;Loh J K
Radiation Oncology Journal
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v.17
no.2
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pp.113-119
/
1999
Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.
Chun Mison;Kang Seunghee;Kil Hoon-Jong;Oh Young-Taek;Sohn Jeong-Hye;Jung Hye-Young;Ryu Hee Suk;Lee Kwang-Jae
Radiation Oncology Journal
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v.20
no.4
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pp.343-352
/
2002
Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.
Kim Hun Jung;Kim Woo Chul;Lee Mee Jo;Kim Chul Su;Song Eun Seop;Loh John J K.
Radiation Oncology Journal
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v.22
no.3
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pp.200-207
/
2004
Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.
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