Details of a Researcher - Shigematsu, Naoyuki

Papers - Shigematsu, Naoyuki

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Nuclear disaster after the Earthquake and Tsunami of March 11

Shigematsu Naoyuki, Fukada Junichi, Ohashi Toshio, Kawaguchi Osamu, Kawata Tetsuya

Keio Journal of Medicine 61 ( 1 ) 28 - 34 2012.03

ISSN 0022-9717

We would like to explain the effects of radiation on human health and discuss the actual effects of the contamination with radioactive material present in Tokyo. Currently, external exposure doses are within the allowable range in Tokyo and will have no adverse health effects on adults or children. As for internal exposure doses, there will likely be no problems as regards our ordinary dietary intakes. However, hot spots of Cs-134, Sr-90 and others should be monitored further.

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[Allogeneic hematopoietic stem cell transplantation with fludarabine, melphalan, and total body irradiation as a conditioning for elderly patients with myeloid malignancies].

Nakamura Yukinori, Mori Takehiko, Kato Jun, Aisa Yoshinobu, Nakazato Tomonori, Shigematsu Naoyuki, Okamoto Shinichiro

[Rinshō ketsueki] The Japanese journal of clinical hematology 53 ( 3 ) 318 - 322 2012.03

ISSN 0485-1439

A variety of reduced-intensity conditionings have been used in the reported studies of allogeneic hematopoietic stem cell transplantation (HSCT) for elderly patients with myeloid hematological malignancies. This study retrospectively analyzed the outcome of allogeneic HSCT for 10 patients aged 50 years or older with myeloid hematological malignancies after conditioning with fludarabine (125 mg/m(2)), melphalan (140 mg/m(2)) and total body irradiation (TBI; 8 Gy). Median age of the patients was 56.5 years, and diagnoses included acute myelogenous leukemia, advance myelodysplastic syndrome, and secondary myelofibrosis. Sources of stem cells were bone marrow from sibling (n=4) or unrelated donor (n=6). Both overall and disease-free survival rates were 40.0% (95% CI: 10.6~69.4%). Causes of death were relapse (n=2), fungal infection (n=2), and secondary malignancies (n=2). Because of a high incidence of transplant-related mortality, further refinement of this conditioning is required.

Dose constraint for minimizing grade 2 rectal bleeding following brachytherapy combined with external beam radiotherapy for localized prostate cancer

Shiraishi Yutaka, Yorozu Atsunori, Ohashi Toshio, Toya Kazuhito, Seki Satoshi, Yoshida Kayo, Kaneda Tomoya, Saito Shiro, Nishiyama Toru, Hanada Takashi, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 81 ( 3 ) 2011.11

ISSN 0360-3016

Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 ≤35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 ≤0.5 ml and a V30 ≤35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.

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Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Mizuno Ryuichi, Seki Satoshi, Shiraishi Yutaka, Kouta Ryuichi, Oya Mototsugu, Shigematsu Naoyuki

Radiation Oncology 6 ( 1 ) 2011.10

Background: The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.Methods: We reviewed the records of 267 patients who underwent prostate brachytherapy with loose ¹²⁵I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration.Results: A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty-nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration.Conclusion: We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90.

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Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients receiving high-dose cytarabine and total body irradiation as a conditioning for hematopoietic stem cell transplantation

Mori Takehiko, Kato Jun, Yamane Akiko, Aisa Yoshinobu, Kawata Yusuke, Ichimura Mayu, Tsuneyama Chiaki, Yashima Tomoko, Ogawa Yoko, Tsubota Kazuo, Shigematsu Naoyuki, Shimizu Takayuki, Okamoto Shinichiro

International Journal of Hematology 94 ( 3 ) 261 - 265 2011.09

ISSN 0925-5710

We previously reported a high incidence of kerato-conjunctivitis in patients receiving high-dose cytarabine following total body irradiation (TBI) as a conditioning for hematopoietic stem cell transplantation (HSCT) even on prophylaxis with topical corticosteroid. This study aimed to evaluate whether addition of eye rinse, which was designed to remove cytarabine from ocular surface, further reduces the incidence of kerato-conjunctivitis in the same setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m ² every 12 h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated. All patients received betamethasone sodium phosphate eye drops. Twenty-three patients were further instructed to rinse their eyes with sterile saline every 10-15 min during and for two additional hours after the completion of each cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato-conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively. These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)] observed in 53 patients without eye rinse (P<0.001 and P<0.00001, respectively). These results strongly suggest that eye rinse effectively reduces the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI.

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Phase I study of neoadjuvant chemoradiotherapy consisting of S-1 and cisplatin for patients with resectable advanced gastric cancer (KOGC-01)

Takahashi Tsunehiro, Saikawa Yoshiro, Takaishi Hiromasa, Takeuchi Hiroya, Wada Norihito, Oyama Takashi, Fukuda Kazumasa, Fukada Junichi, Kawaguchi Osamu, Shigematsu Naoyuki, Kitagawa Yuko

Anticancer Research 31 ( 9 ) 3079 - 3083 2011.09

ISSN 0250-7005

Background: The prognosis for advanced gastric cancer is poor, with surgery as the only treatment for resectable advanced gastric cancer. Therefore, treatment options that might improve the prognosis are needed. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. Patients and Methods: The chemotherapy schedule included one cycle repeated after 6 weeks. S-1 was administered orally every day on days 1-21 and CDDP was infused on days 1, 8 and 15. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1-5, 8-12, 15-19, and 22-26. Results: A total of 10 patients were recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m²). The next six patients were entered into level 0 (15 mg/m²), because of dose-limiting toxicity (delaying the second course of chemotherapy in two patients) that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was 20 mg/m². Seven patients underwent surgery and all had an R0 (no residual tumor) resection without surgical complications. Conclusion: Neoadjuvant chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows promise for resectable advanced gastric cancer.

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi Satoshi, Ozawa Soji, Koyanagi Kazuo, Shigematsu Naoyuki, Kubo Atsushi, Ueda Masakazu, Kitajima Yuko Kitagawa, Kitajima Masaki

Experimental and Therapeutic Medicine 2 ( 4 ) 601 - 606 2011.07

ISSN 1792-0981

Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0x10 ¹¹ to 10⁷ M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC₅₀ for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0x10¹⁰ M; TE-2 and TE-3, ≤1.0x10⁹ M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

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Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes

Onishi T., Jinno H., Takahashi M., Hayashida T., Sakata M., Nakahara T., Shigematsu N., Mukai M., Kitagawa Y.

European Surgical Research 45 ( 3-4 ) 344 - 349 2010.12

ISSN 0014-312X

Background: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial. Methods: A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid. Results: Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90). Conclusions: These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.

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CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis

Sanuki-Fujimoto N., Takeda A., Ohashi T., Kunieda Etsuo, Iwabuchi S., Takatsuka K., Koike N., Shigematsu N.

British Journal of Radiology 83 ( 996 ) 1063 - 1071 2010.12

ISSN 0007-1285

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

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A comparison of chromosome repair kinetics in G0 and G1 reveals that enhanced repair fidelity under noncycling conditions accounts for increased potentially lethal damage repair

Liu Cuihua, Kawata Tetsuya, Shigematsu Naoyuki, Cucinotta Francis, George Kerry, Saito Masayoshi, Uno Takashi, Isobe Kouichi, Ito Hisao

Radiation Research 174 ( 5 ) 566 - 573 2010.11

ISSN 0033-7587

Potentially lethal damage (PLD) and its repair were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining and misrejoining in irradiated cells that were either held in noncycling G0 phase or allowed to enter G1 phase of the cell cycle immediately after 6 Gy irradiation. Virally mediated premature chromosome condensation (PCC) methods were combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. Flow cytometry revealed that the vast majority of cells had not yet entered S phase 15 h after release from G0. By this time some 95 of initially produced prematurely condensed chromosome breaks had rejoined, indicating that most repair processes occurred during G1. The rejoining kinetics of prematurely condensed chromosome breaks was similar for each culture condition. However, under noncycling conditions misrepair peaked at 0.55 exchanges per cell, while under cycling conditions (G1) it peaked at 1.1 exchanges per cell. At 12 h postirradiation, complex-type exchanges were sevenfold more abundant for cycling cells (G1) than for noncycling cells (G0). Since most repair in G0/G1 occurs via the non-homologous end-joining (NHEJ) process, increased PLD repair may result from improved cell cycle-specific rejoining fidelity of the NHEJ pathway.

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Preimplant factors affecting postimplant CT-determined prostate volume and the CT/TRUS volume ratio after transperineal interstitial prostate brachytherapy with ¹²⁵I free seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Asakura Hirotaka, Oya Mototsugu, Shigematsu Naoyuki

Radiation Oncology 5 ( 1 ) 2010.09

Background: The aim was to identify preimplant factors affecting postimplant prostate volume and the increase in prostate volume after transperineal interstitial prostate brachytherapy with ¹²⁵I free seeds.Methods: We reviewed the records of 180 patients who underwent prostate brachytherapy with ¹²⁵I free seeds for clinical T1/T2 prostate cancer. Eighty-one (45%) of the 180 patients underwent neoadjuvant hormonal therapy. No patient received supplemental external beam radiotherapy. Postimplant computed tomography was undertaken, and postimplant dosimetric analysis was performed. Univariate and multivariate analyses were performed to identify preimplant factors affecting postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.Results: Preimplant prostate volume by transrectal ultrasound, serum prostate-specific antigen, number of needles, and number of seeds implanted were significantly correlated with postimplant prostate volume by computed tomography. The increase in prostate volume after implantation was significantly higher in patients with neoadjuvant hormonal therapy than in those without. Preimplant prostate volume by transrectal ultrasound, number of needles, and number of seeds implanted were significantly correlated with the increase in prostate volume after implantation. Stepwise multiple linear regression analysis showed that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy were significant independent factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.Conclusions: The results of the present study show that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy are significant preimplant factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.

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Sebaceous carcinoma of the parotid gland

Kumabe Atsuhiro, Kawase Takatsugu, Miura Kouki, Tada Yuichiro, Masubuchi Tatsuo, Kamata Shin Etsu, Tanada Shuji, Kubo Atsushi, Tajima Yasuo, Shigematsu Naoyuki

Clinical Nuclear Medicine 35 ( 4 ) 260 - 262 2010.04

ISSN 0363-9762

Sebaceous carcinoma is a rare malignant tumor typically originating in the skin of the eyelid. We report an unusual case of sebaceous carcinoma originating in the parotid gland of a 23-year-old woman. The patient underwent F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) to determine the initial clinical stage. FDG PET/CT revealed strong uptake in the primary lesion but neither regional lymphatic nor distant metastasis were seen. These findings allowed for an accurate prediction of the nodal status, which contributed to precise determination of the initial stage. FDG PET/CT scans may be useful for the initial staging of cutaneous sebaceous carcinomas as well.

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Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma

Fukada Junichi, Shigematsu Naoyuki, Takeda Atsuya, Ohashi Toshio, Tomita Toshiki, Shiotani Akihiro, Kunieda Etsuo, Kawaguchi Osamu, Fujii Masato, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 76 ( 2 ) 417 - 424 2010.02

ISSN 0360-3016

Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m²]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade ≥3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

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Superiority of radioisotope over blue dye for sentinel lymph node detection in breast cancer

Hayashida T., Jinno H., Sakata M., Takahashi M., Onishi T., Seki H., Sato T., Nakahara T., Shigematsu N., Mukai M., Hibi T., Kitajima M., Kitagawa Y.

European Surgical Research 44 ( 2 ) 111 - 116 2010.02

ISSN 0014-312X

Background: Sentinel lymph node biopsy (SLNB) is commonly performed using radioisotopes and/or blue dye. However, it is still undefined which reagent is more suitable for identifying sentinel lymph nodes (SLN). Patients and Methods: A consecutive series of 640 breast cancer patients who had undergone SLNB at the Keio University Hospital from 2001 to 2006 was analyzed. The SLN was identified by a combination of technetium-99m tin colloid and isosulfan blue dye. The correlation between clinicopathological factors and the distribution of radioisotopes and blue dye was analyzed. The single metastatic lymph node revealed by axillary lymph node dissection (ALND) is the 'true SLN', and the distribution of radioisotopes and blue dye to the 'true SLN' was also analyzed. Results: Blue-dye- and radioisotope-positive SLN were identified in 79.6 and 94.7% of the patients, respectively. Taken together, SLN were identified in 625 patients (97.7%) by radioisotope and/or blue dye. No significant correlation was observed between clinicopathological features and the distribution of the reagents. ALND found 73 patients with single lymph node metastasis, and 73 'true SLN' were identified by blue dye in 65.7% (48/73), and by radioisotope in 95.9% (70/73) of the cases. Conclusion: These data suggest that radioisotopes are superior to blue dye in detecting SLN in breast cancer.

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Factors influencing the long-term survival in patients with esophageal cancer who underwent esophagectomy after chemoradiotherapy

Takeuchi Hiroya, Saikawa Yoshiro, Oyama Takashi, Ozawa Soji, Suda Koichi, Wada Norihito, Takahashi Tsunehiro, Nakamura Rieko, Shigematsu Naoyuki, Ando Nobutoshi, Kitajima Masaki, Kitagawa Yuko

World Journal of Surgery 34 ( 2 ) 277 - 284 2010.02

ISSN 0364-2313

Background: Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT. Methods: For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT. Results: Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis. Conclusions: This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.

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Evaluation of the dosimetric parameters for ¹²⁵ brachytherapy determined in prostate medium using CT images

Hanada Takashi, Yorozu Atsunori, Ohashi Toshio, Shigematsu Naoyuki, Maruyama Koichi

Journal of Radiation Research 51 ( 5 ) 553 - 561 2010

ISSN 0449-3060

In the present study, the prostate medium determined from the CT images of 149 patients was developed. The dosimetric parameters such as Λ, GL(r) and F(r, θ) used in TG-43U1-based calculation for an iodine-125 (¹²⁵I) brachytherapy-source were examined using Monte Carlo code Geant4. Clinical dosimetry parameters such as the D₉₀ were evaluated among a subgroup of 50 randomly selected patients who had been treated with permanent brachytherapy between January 2008 and December 2008 at the Tokyo Medical Center. The results show a slight difference in the dose rate constant Λ (within 1.0%). The radial dose function GL(r) exhibits a prominent difference in the region over 3 cm, and this difference is maintained within 2.9% in the region close to the source. The calculated values of F(r, θ) for the prostate medium were similar to values for water (within 1%), except in the longitudinal axis. A comparison of D₉₀ values shows a systematic dose overestimation of 2.8 ± 0.7 GY in water, where the distribution of the differences can be seen with a spread of 1.8 ± 0.3% compared to that in prostate medium. It was concluded that the introduction of any kind of tissue correction for the TG-43U1-based calculation was not necessary to allow for the differences in elemental compositions and densities between water and prostate medium. PACS number: 87.00.00; 87.55.dk; 87.55.K-; 87.56.B-.

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Chemotherapy for head and neck cancer

Tomita Toshiki, Imanishi Yorihisa, Ozawa Hiroyuki, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Ogawa Kaoru, Fukada Junichi, Shigematsu Naoyuki, Kogashiwa Yasunao, Yamauchi Kohichi, Kohno Naoyuki

Toukeibu Gan 36 ( 3 ) 273 - 277 2010

ISSN 1349-5747

A meta-analysis showed that chemoradiotherapy (CCRT) improved survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). CCRT has become widely used in treating such patients. The purpose of CCRT in the treatment of resectable HNSCC is to improve survival while preserving organs and functions, and so CCRT is a potential alternative to surgery. However, problems regarding CCRT were revealed such as severe dysphasia and difficulty of salvage surgery. Recently, induction chemotherapy has attracted attention again, the purpose of which is to predict the response of subsequent CCRT or to improve outcomes. Moreover, chemotherapy is concurrently used with postoperative radiotherapy or definitively used for recurrent or metastatic HNSCC. In this article, we review the current state of chemotherapy for HNSCC and consider the problems in Japan.

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Early Graphical Appearance of Radiation Pneumonitis Correlates With the Severity of Radiation Pneumonitis After Stereotactic Body Radiotherapy (SBRT) in Patients With Lung Tumors

Takeda Atsuya, Ohashi Toshio, Kunieda Etsuo, Enomoto Tatsuji, Sanuki Naoko, Takeda Toshiaki, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 77 ( 3 ) 685 - 690 2010

ISSN 0360-3016

Purpose: To investigate factors associated with Grade ≥3 radiation pneumonitis (RP) in patients with lung tumors treated with stereotactic body radiotherapy (SBRT). Methods and Materials: We retrospectively analyzed 128 patients with 133 lung tumors treated with SBRT. RP was graded according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate analyses were used to identify predictive factors for RP. Results: The median follow-up period after SBRT was 12 months (range, 5-45 months). Incidences of Grades 0, 1, 2, and 3 RP were 27%, 52%, 16%, and 5%, respectively. No patients suffered Grade 4 or 5 RP. For all patients with Grade 2 or 3, symptoms occurred either simultaneously with or subsequent to graphical appearances. The latent period was the only significant factor associated with Grade ≥3 RP (p < 0.01). A latent period of 1 or 2 months indicated a 40% (6/15) risk for Grade 3. However, the risk for Grade 3 was 1.2% (1/82) 3 months after SBRT. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. However, 4 of 7 patients with Grade 3 RP had severe pulmonary comorbidities. Conclusion: Only the latency period was a significant factor in the development of RP. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. Patients, especially those with severe pulmonary comorbidities, should be carefully observed for the graphical appearance of RP within a few months during the follow-up period after SBRT.

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Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer

Kanai Kunimitsu, Nakashima Jun, Sugawara Akitomo, Shigematsu Naoyuki, Nagata Hirohiko, Kikuchi Eiji, Miyajima Akira, Nakagawa Ken, Kubo Atsushi, Oya Mototsugu

International Journal of Clinical Oncology 14 ( 6 ) 502 - 506 2009.12

ISSN 1341-9625

Background: We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce. Methods: PSA bounce was evaluated in 86 patients with T1-T2 prostate cancer who underwent radioactive seed implantation using iodine-125 (I-125) without hormonal therapy or external-beam radiation therapy (EBRT) from September 2004 to December 2007. A PSA bounce was defined as a rise of at least 0.4 ng/ml greater than a previous PSA level with a subsequent decline equal to, or less than, the initial nadir. Results: Calculated by the Kaplan-Meier method, the incidence of PSA bounce at a 2-year follow-up was 26%. Median time to the PSA bounce was 15 months. Univariate analysis demonstrated that age, dose received by 90% of the prostate gland (D90), volume of gland receiving 100% of the prescribed dose (V100), and V150 were significantly associated with the PSA bounce, while pretreatment PSA level, Gleason score, pretreatment prostate volume, clinical T stage, and V200 were not. In multivariate analysis, age 67 years or less and D90 more than 180 Gy were identified as independent factors for predicting the PSA bounce (P < 0.05). Conclusion: PSA bounce is not a rare phenomenon after prostate brachytherapy. It is more common in younger patients and patients receiving higher doses of radiation.

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Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation

Mori Takehiko, Hasegawa Kaori, Okabe Ai, Tsujimura Natsuki, Kawata Yusuke, Yashima Tomoko, Kobayashi Naoko, Kondo Sakiko, Aisa Yoshinobu, Kato Jun, Tsunoda Kazuyuki, Nagai Tetsuo, Nakagawa Taneaki, Shigematsu Naoyuki, Kubo Atsushi, Ikeda Yasuo, Okamoto Shinichiro

International Journal of Hematology 88 ( 5 ) 583 - 587 2009.12

ISSN 0925-5710

High-dose cytarabine is one of the major components of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), and frequently causes severe oral mucositis. We have recently demonstrated that cytarabine is excreted into the saliva in patients receiving high-dose cytarabine, and proposed that it might locally and directly contribute to the development of oral mucositis. Therefore, this study was performed to assess whether removing the excreted cytarabine in the saliva by intensive mouth rinse during high-dose cytarabine infusion could reduce the incidence of oral mucositis. Fifteen patients with hematologic malignancies undergoing allogeneic HSCT who received total body irradiation (12 Gy) and high-dose cytarabine at a dose of 3 g/m ² every 12 h for 4 days as a conditioning were evaluated. Patients were instructed to rinse their mouths using ice-cold water every 10 min, starting simultaneously with the 2-h cytarabine infusion and continuing up to 1 h after completion of each infusion. Oral mucositis was graded on a daily basis according to the National Cancer Institute, Common Toxicity Criteria. Thirty-five patients who previously underwent the same conditioning without mouth rinse served as controls. The incidence of Grades 2-3 and Grade 3 oral mucositis was significantly reduced in patients who performed mouth rinse as compared with the controls (40 vs. 80%, P = 0.009; 0 vs. 25. 7%, P = 0.02). In conclusion, mouth rinse during and shortly after high-dose cytarabine infusion could be an effective and inexpensive measure in reducing the incidence of moderate to severe oral mucositis caused by high-dose cytarabine. This finding strongly suggests the role of cytarabine excretion in the saliva in the development of cytarabine-associated oral mucositis.

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