• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4285-4289
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• 2015

Purpose: Blood hemoglobin levels are known to influence response to radiotherapy. This retrospective analysis compared the effect of hemoglobin levels upon response to radiation among patients treated with radiation alone (by accelerated hyperfractionated radiotherapy) versus those treated with concurrent cisplatin chemoradiotherapy. Materials and Methods: Among patients treated for locally advanced carcinoma of the cervix (LACC) during 2009-10, a total of 60 fulfilled the eligibility criteria. In this time frame, external beam radiotherapy was delivered with either concurrent chemoradiotherapy (CRT, n=31) (45Gy over 25 fractions, with weekly cisplatin at 40mg/m2), or with accelerated hyperfractionated radiotherapy (AHRT, n=29) (20Gy over 10 daily fractions over the first two weeks, followed by 30Gy over 20 fractions over the next two weeks, with two fractions of 1.5Gy per day, without the use of chemotherapy). Mean weekly hemoglobin (MWH) levels of all patients were calculated as the arithmetic means of weekly recorded blood hemoglobin levels. As per MWH, patients in both of the AHRT or the CRT groups were classified into two subgroups-those with MWH between 10-10.9g/dL, or with MWH>11g/dL. Complete response (CR) to external beam RT phase (prior to brachytherapy) was declared after clinical examinations and computed tomography. The CR rate was noted for both MWH sub-groups within each of the AHRT and CRT groups. Results: Within the AHRT group, patients with MWH>11g/dL had a much better CR rate in comparison to those with MWH:10-10.9g/dL (80% vs. 21.1%) which was statistically significant (p 0.0045). Within the CRT group, there was no significant difference in the outcomes within the MWH>11g/dL and MWH:10-10.9g/dL sub-groups (CR rates of 80% vs. 61.9%, p=0.4285). Conclusions: The importance of maintaining a minimum hemoglobin level of 11g/dL during RT is much greater for patients treated with RT alone, than for patients treated with concurrent chemoradiotherapy. Enhanced haemoglobin levels during RT may to an extent negate the ill-effects that may otherwise arise due to non-use of concurrent chemotherapy.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.215-219
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• 1991

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991, Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGy following 3 cycles of induction MVP (Mitomycin C 6 mg/$m^2$, Vinblastine 6 mg/$m^2$, Cisplatin 60 mg/$m^2$) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 46 were analyzed for this preliminary report. The response rate of induction chemotherapy was $62.5\%$ : partial response, $50\%$ and minimal response, $12.5\%$. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6595-6597
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• 2015

Objective: To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophageal cancer. Methods: Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectively analyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu ($500mg/m^2$) injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time, late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patients were firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4Gy). Results: All patients completed treatment, including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and 3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months. The adverse reactions included myelosuppression, which was mainly degree I and II. The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Conclusion: Lobaplatin plus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advanced stage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.221-225
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• 1991

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than $10\%$ of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4 Gy with twice a day fractinations up to 49.4 Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2 Gy for 12 patients and 65.4 Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were $88\%,\;62\%,\;and\;38\%$, respectively. Corresponding disease free suwival rates were $88\%,\;41\%,\;and\;21\%$, respectively. Actuarial cumulative local failure rates at 9, 12 and 15 month were $36\%,\;43\%,\;and\;59\%$, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.345-352
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• 2001

Purpose : To evaluate the treatment results and prognostic factors after radiotherapy in stage IIB uterine cervix cancer. Materials and methods : We retrospectively analyzed the records of 90 patients with stage IIB uterine cervix cancer who received radiotherapy between 9/94 and 12/99. Age was ranged from 28 to 79 years (median 57). Tumor size was $\geq4\;cm$ in 64 patients. Preteatment SCC level was measured in 75 patients. Twenty nine patients received conventional radiotherapy (QD) and the others received modified hyper-fractionated radiotherapy (BID). Only 7 patients in BID had tumor size <4 cm. All patients received high dose rate brachytherapy $(4\;Gy\times7\;or\;5\;Gy\times6)$. No Patient received concurrent chemotherapy during radiotherapy. Follow up period was ranging from 9 to 76 months (median 38). Results : The 5-year overall and disease free survival rates were $73.4\%\;and\;71.6\%$, respectively. Local recurrences occurred in $10\%$ of patients, and distant metastasis in $18.9\%$. There was a significant correlation between OS/DFS and tumor size $(<4cm;\;OS\;95.2\%,\;DFS\;91.4\%,\;\geq4cm;\;OS\;63.4\%,\;DFS\;63.4\%)$. Pretreatment SCC level was one of prognostic factors only in univariate analysis. Conclusion : With modified hyperfractionated radiotherapy, there was very low local recurrence rate $(6.6\%)$ and high 5-year overall and disease free survival rate $(75.4\%\;and\;70.5\%)$, which is comparable to results after concurrent chemoradiotherapy in bulky, locally advanced stage IIB uterine cervix cancer.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.154-164
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• 2007

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.24-34
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• 2008

Purpose: To assess the efficacy of the use of accelerated hyperfractionated radiotherapy(AHRT) for locally advanced uterine cervix cancers. Materials and Methods: Between May 2000 and September 2002, 179 patients were identified with FIGO stage IIB, IIIB, and IVA cancers. Of the 179 patients, 45 patients were treated with AHRT(AHRT group) and 134 patients were treated with conventional radiotherapy(CRT group), respectively. Patients undergoing the AHRT regimen received a dose of 30 Gy in 20 fractions(1.5 $Gy{\times}2$ fractions/day) to the whole pelvis. Subsequently, with a midline block, we administered a parametrial boost with a dose of 20 Gy using 2 Gy fractions. Patients also received two courses of low-dose-rate brachytherapy, up to a total dose of 85{\sim}90 Gy to point A. In the CRT group of patients, the total dose to point A was $85{\sim}90$ Gy. The overall treatment duration was a median of 37 and 66 days for patients that received AHRT and CRT, respectively. Statistical analysis was calculated by use of the Kaplan-Meier method, the log-rank test, and Chi-squared test. Results: For patients that received cisplatin-based concurrent chemotherapy and radiotherapy, the local control rate at 5 years was 100% and 79.2% for the AHRT and CRT group of patients, respectively(p=0.028). The 5-year survival rate for patients with a stage IIB bulky tumor was 82.6% and 62.1% for the AHRT group and CRT group, respectively(p=0.040). There was no statistically significant difference for severe late toxicity between the two groups(p=0.561). Conclusion: In this study, we observed that treatment with AHRT with concurrent chemotherapy allows a significant advantage of local control and survival for locally advanced uterine cervix cancers.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.349-356
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• 1997

Purpose : To evaluate the efficacy of hyperfractionated radiation therapy in carcinoma of the cervix, especially on huge exophytic and endophytic stage Ib, IIa and IIb Materials and Materials : Fourty one patients with carcinoma of the cervix treated with hyperfractionated radiation therapy at the Department of Therapeutic Radiology, Dongsan Hospital, Keimyung University. School of Medicine from Jul, 1991 to Apr, 1994. According to FIGO s1aging system, therewere stage Ib (3 patients) IIa (6 patients) with exophytic ($\geq$5cm in dinmeter) and huge endophytic mass. and IIb (32 patients) with median age of 55 yeavs old. Radiation therapy consisted of hyperfractionated external irradition to the whole pelvis (120cGy/fraction, 2 fraction/day (minimum interval of 6 hours), 3600-5520cGy) and boost parametrial doses (for a total of 4480-6480cGy) with midline shield $(4\times10cm)$, and combined with intracavitary irradiation (up to 7480-8520cGy in Ib, IIa and 8480-9980cGy in IIb to point A). The maximum and mean follow up durations were 70 and 47 months respectively . Results : Five year local control rate was $78\%$ and the actuarial overall five year survival rate was $66.1\%$ for all patients, $44.4\%$ for stage Ib, IIa and $71.4\%$ for stage IIb. In bulky IIb (above 5cm in tumor size, 11 patients) five year local control rate and five rear survival rate was $88.9\%,\;73\%$ respectively Pelvic lymph node status (negative : $74\%,\;positive:25\%$, p=0.0015) was significant Prognostic factor affecting to five rear survival rate. There was marginally significant survival difference by total dose to A point ($>84Gy\;:\;70\%,\;>84Gy\;:\;42.8\%$, p=0.1). We consider that the difference of total dose to A point by stage (mean Ib,IIa : 79Gy. IIb 89Gy P=0.001) is one of the causes in worse local control and survival of Ib,IIa than IIb The overall recurrence rate was $39\%$ (16/41). The rates of local failure alone. distant failure alone. and combined local and distant failure were $9.7\%,\;19.5\%,\;and\;9.7\%$, respectively. Two Patients developed leukopenia ($\geq$ grade 3) and Three patients develoued grade 3 gastrointestinal complication. Above grade 3 complication was not noted. There was no treatment related death noted. Conclusion : We thought that it may be necessary to increase A point dose to more than 85Gy in hyperfractionated radiotherapy of huge exophytic and endophvtic stage Ib,IIa. We considered that hyperfractionated radiation therapy may be tolerable in huge exophytic and endophytic stage IIb cervical carcinoma with acceptable morbidity and possible survival gain but this was results in small patient group and will be confirmed by long term follow up in many patients.