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Shinya Otsuka,
Masaru Inagaki,
Yuuji Kimura,
Kenta Isoda,
Kouji Kitada,
Manabu Nishie,
Ryousuke Hamano,
Naoyuki Tokunaga,
Hideaki Miyasou,
Yousuke Tsunemitsu,
Kazuhide Iwakawa,
Hiromi Iwagaki
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ABSTRACT: Radiofrequency ablation (RFA) therapy combined with hepatectomy was performed in 5 patients with synchronous liver metastases of colorectal cancer. RFA of liver metastases was performed using a Cool-tip electrode (Radionics; Burlington, MA, USA). The ablation time used in each session varied according to the tumor size and intraoperative impedance. In 2 patients, hepatectomy and resection of the colorectal primary lesion were performed synchronously. In patients with multiple liver metastases, relative curative resection was performed using the complementary RFA. In the other 3 patients, synchronous hepatectomy was considered difficult and systematic chemotherapy was performed after resection of the colorectal primary lesion. After systematic chemotherapy, the range of hepatectomy was restricted for liver injury, but relative curative resection was performed using RFA therapy. Computed tomography performed after hepatectomy showed that the region that underwent RFA appeared necrotic with a safety margin. The average observation period was 25 months (maximal survival period, 50 months) and 3 of the patients are alive.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1870-3.
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ABSTRACT: We investigated the applicability of the repairable-conditionally repairable (RCR) model and the multi-target (MT) model to dose conversion in high-dose-per-fraction radiotherapy in comparison with the linear-quadratic (LQ) model. Cell survival data of V79 and EMT6 single cells receiving single doses of 2-12 Gy or 2 or 3 fractions of 4 or 5 Gy each, and that of V79 spheroids receiving single doses of 5-26 Gy or 2-5 fractions of 5-12 Gy, were analyzed. Single and fractionated doses to actually reduce cell survival to the same level were determined by a colony assay. Single doses used in the experiments and surviving fractions at the doses were substituted into equations of the RCR, MT and LQ models in the calculation software Mathematica, and each parameter coefficient was computed. Thereafter, using the coefficients and the three models, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually-determined equivalent single doses for the hypofractionated doses. The equivalent single doses calculated using the RCR, MT and LQ models tended to be lower than the actually determined equivalent single doses. The LQ model seemed to fit relatively well at doses of 5 Gy or less. At 6 Gy or higher doses, the RCR and MT models seemed to be more reliable than the LQ model. In hypofractionated stereotactic radiotherapy, the LQ model should not be used, and conversion models incorporating the concept of the RCR or MT models, such as the generalized linear-quadratic models, appear to be more suitable.
Journal of Radiation Research 10/2012; · 1.68 Impact Factor
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ABSTRACT: Organizing pneumonia (OP), so called bronchiolitis obliterans organizing pneumonia after postoperative irradiation for breast cancer has been often reported. There is little information about OP after other radiation modalities. This cohort study investigated the clinical features and risk factors of OP after stereotactic ablative radiotherapy of the lung (SABR).
Patients undergoing SABR between 2004 and 2010 in two institutions were investigated. Blood test and chest computed tomography were performed at intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1) mixture of patchy and ground-glass opacity, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume receiving < 0.5 Gy, and 4) no evidence of a specific cause.
Among 189 patients (164 with stage I lung cancer and 25 with single lung metastasis) analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These symptoms and pulmonary infiltration rapidly improved after corticosteroid therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP) around the tumor 2 to 7 months before OP. The prior RP history was strongly associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis.
This is the first report on OP after SABR. The incidence appeared to be relatively high. The symptoms were sometimes severe, but corticosteroid therapy was effective. When patients after SABR present with unusual pneumonia, OP should be considered as a differential diagnosis, especially in patients with prior symptomatic RP.
Radiation Oncology 08/2012; 7:123. · 2.32 Impact Factor
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ABSTRACT: Since the dose delivery pattern in high-precision radiotherapy is different from that in conventional radiation, radiobiological assessment of the physical dose used in stereotactic irradiation and intensity-modulated radiotherapy has become necessary. In these treatments, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is almost universarily observed in vitro. In in vivo tumors, however, this decrease in effect can be counterbalanced by rapid reoxygenation, which has been demonstrated in a laboratory study. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to radiosurgery and hypofractionated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear-quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies.
Journal of Radiation Research 02/2012; 53(1):1-9. · 1.68 Impact Factor
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ABSTRACT: To evaluate the compliance of linear-quadratic (LQ) model calculations in the high-dose range as used in stereotactic irradiation in a murine tumor model.
Female 10-week-old Balb/c mice bearing 1-cm-diameter EMT6 tumors in the hind legs were used. Single doses of 10-25 Gy were compared with 2-5 fractions of 4-13 Gy given at 4-hour intervals. Cell survival after irradiation was determined by an in vivo-in vitro assay. Using an α/β ratio determined for in vitro EMT6 cells and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually measured equivalent single doses for the hypofractionated doses. These fractionation schedules were also compared simultaneously to investigate the concordance/divergence of dose-survival curves plotted against actual radiation doses and biologically effective doses (BED).
Equivalent single doses for hypofractionated doses calculated from LQ formalism were lower than actually measured doses by 21%-31% in the 2- or 3-fraction experiments and by 27%-42% in the 4- or 5-fraction experiments. The differences were all significant. When a higher α/β ratio was assumed, the discrepancy became smaller. In direct comparison of the 2- to 5-fraction schedules, respective dose-response curves almost overlapped when cell survival was plotted against actual radiation doses. However, the curves tended to shift downward by increasing the fraction number when cell survival was plotted against BED calculated using an α/β ratio of 3.5 Gy for in vitro EMT6 cells.
Conversion of hypofractionated radiation doses to single doses using the LQ formalism underestimated the in vivo effect of hypofractionated radiation by approximately 20%-40%. The discrepancy appeared to be larger than that seen in the previous in vitro study and tended to increase with the fraction number. BED appeared to be an unreliable measure of tumor response.
International journal of radiation oncology, biology, physics 12/2011; 81(5):1538-43. · 4.59 Impact Factor
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Hiromitsu Iwata,
Yuta Shibamoto,
Fumiya Baba,
Chikao Sugie,
Hiroyuki Ogino,
Rumi Murata,
Takeshi Yanagi, Shinya Otsuka,
Katsura Kosaki,
Taro Murai,
Akifumi Miyakawa
Radiotherapy and Oncology 06/2011; 101(2):267-70. · 5.58 Impact Factor
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Fumiya Baba,
Yuta Shibamoto,
Hiroyuki Ogino,
Rumi Murata,
Chikao Sugie,
Hiromitsu Iwata, Shinya Otsuka,
Katsura Kosaki,
Aiko Nagai,
Taro Murai,
Akifumi Miyakawa
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ABSTRACT: The treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter.
Between February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions.
For all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02).
There was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further.
Radiation Oncology 01/2010; 5:81. · 2.32 Impact Factor
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Shinya Otsuka,
Masaru Inagaki,
Manabu Nishie,
Ryousuke Hamano,
Naoyuki Tokunaga,
Kenji Takahashi,
Yousuke Tsunemitsu,
Kazuya Miyoshi,
Kazuhide Iwakawa,
Masahiko Takahashi,
Hiromi Iwagak
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ABSTRACT: A 25-year-old man with RS rectal cancer received a radical resection of the original tumor and lymph node dissection. Oral tegafur/uracil (UFT)/Leucovorin (LV) therapy has been used for adjuvant chemotherapy, as the pathological Stage was T3N1M0, Stage IIIa. After 10 months from operation, multiple liver metastases were recognized and not resectable. So a systemic chemotherapy by mFOLFOX6+bevacizumab was begun via CV port. After 5 courses of mFOLFOX6+bevacizumab, abdominal CT revealed liver metastases showed remarkable reduction in size. Hepatic resection of S6 segment was enforced, and the patient uneventfully discharged. Pathological findings of S6 segment revealed no residual cancer cells, indicating the histological effect of mFOLFOX6+bevacizumab was Grade 3. And no liver damage was recognized.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2166-8.
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Shinya Otsuka,
Masaru Inagaki,
Manabu Nishie,
Ryousuke Hamano,
Naoyuki Tokunaga,
Kenji Takahashi,
Yousuke Tsunemitsu,
Kazuya Miyoshi,
Masahiko Takahashi,
Toshihide Oosaki,
Hiromi Iwagaki
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ABSTRACT: A 41-year-old man with multiple liver metastases from sigmoid colon cancer received a radical resection of the original tumor and 16 courses of weekly high-dose 5-FU(WHF)chemotherapy via hepatic arterial reservoir. The metastatic lesions showed stable disease(SD), and systemic chemotherapy by mFOLFOX6 was begun via CV port. After 14 courses of mFOLFOX4, abdominal CT revealed liver metastases were remarkably reduced in size. Hepatic resection of lateral segment and radio frequency ablation(RFA)for S6 were enforced, and the patient was uneventfully discharged. Pathological findings of lateral segment revealed no residual cancer cells, indicating that the histological effect of mFOLFOX6 was Grade 3.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2009; 36(3):501-4.
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ABSTRACT: We examined clinicopathological characteristics and prognoses of seventy advanced colorectal cancer cases by measuring pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in tumor and normal tissue. PyNPase activities in cancerous tissue obtained from resected were 82.7 +/- 41.9 U/mg protein, which were significantly higher than 37.2 +/- 24.0 U/mg protein in normal tissue (p < 0.001). On the other hand, DPD activities in cancerous tissue were significantly lower in normal tissue (p < 0.05). In cases with lymphnode metastases, PyNPase activities of cancerous tissue were significantly higher than that of no lymphnode metastases cases (p < 0.05). In cases with grade 2 side-effects or higher by oral adjuvant chemotherapy, DPD activities in normal tissue were significantly lower than that of other cases (p < 0.05). With regard to Dukes' B and C cases that were resected curatively, PyNPase activities of cancerous tissue of higher group's prognosis were worse than that of the lower group. In the group received 5'-DFUR as adjuvant chemotherapy, non-recurrent survival rate of the group exhibiting higher PyNPase activities was better than that of the lower group.
Gan to kagaku ryoho. Cancer & chemotherapy 10/2005; 32(11):1679-81.
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ABSTRACT: We performed radiofrequency ablation (RFA) therapy combined with intrahepatic arterial infusion chemotherapy for 7 patients with liver metastasis from colorectal cancer. Synchronous metastasis accounted for 5 cases and metachronous for 2 cases. Two cases were H1, 2 cases H2, and 3 cases H3. Following the resection of colorectal primary lesion, we performed RFA for liver metastasis, using a Cool-tip electrode purchased from Radionics (Burlington, MA, USA). The mean number of sessions per patient was 5.1 (1-10). Ablation time of each session was changed according to tumor size, as follows: less than 1 cm in diameter: 2 min, 2 cm: 5 min, 2.5 cm: 10 min. By using intra-operative catheterization, weekly intrahepatic arterial infusion chemotherapy was performed for liver metastasis. Excellent ablation was achieved in all cases by CT evaluation and no significant side-effect was observed. Average observation period was 15 months (maximal survival period was 31 months) and 6 patients are alive. RFA therapy combined with intrahepatic arterial infusion chemotherapy achieved excellent therapeutic effect, and maintained good quality of life in patients.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2003; 30(11):1598-601.
