[Show abstract][Hide abstract] ABSTRACT: Radiation-induced organizing pneumonia (RIOP) is an important complication of postoperative radiotherapy for breast cancer. Unfortunately, conventional corticosteroid therapy is frequently associated with relapses. The aim of this retrospective study was to evaluate the outcomes of steroid treatment in patients with RIOP. In total, 26 patients diagnosed with RIOP from among 2404 women who received radiotherapy after breast-conserving surgery for breast cancer were included and classified into steroid (n = 7) and nonsteroid (n = 19) groups. Serum, sputum, and bronchoalveolar lavage composition; subjective symptoms (cough, fever, and dyspnea); migratory progression; and RIOP relapse were compared between the groups. Treatment type did not affect the duration of the subjective symptoms, which was 1.6 and 1.7 months for the steroid and nonsteroid groups, respectively. In contrast, RIOP relapse and new pulmonary lesions developed in five patients in the steroid group and only three patients in the nonsteroid group (P = 0.014). By assessing RIOP duration as the time to resolution of symptoms and discontinuation of therapy, the median duration of RIOP was significantly longer in the steroid (17.1 months) than that in the nonsteroid group (2.3 months, P = 0.005), primarily because of frequent relapses. After remission, persistent pulmonary dysfunction did not occur in the nonsteroid group. This single-center retrospective study demonstrates that steroid therapy results in frequent relapses and significantly prolongs RIOP duration. Corticosteroid treatment is considered a critical factor in RIOP recurrence.
[Show abstract][Hide abstract] ABSTRACT: Lung cancer is a leading cause of cancer death in the world. The results from concurrent chemoradiotherapy (CRT) are still disappointing, although long-term survival can be observed in certain populations of patients. Local control is a critical problem in CRT; dose escalation of thoracic radiation (TRT) in CRT has not been effective.
The authors developed a novel TRT scheme of accelerated hyperfractionation using concomitant boost TRT (ccbRT). Total doses of 64 Gy and 40 Gy were given to the gross tumor volume and elective clinical target volume, respectively, for 20 working days, combined with systemic chemotherapy with cisplatin (day 1) and vinorelbine (days 1, 8) with a 3-week interval (NP regimen). The purpose of this phase II study was to evaluate the efficacy and toxicity of this novel treatment.
From July 2002 to July 2010, 56 patients were enrolled in this study. One patient was excluded from the analysis. All 55 patients completed ccbRT, and 52 patients (94.5%) underwent at least 2 cycles of NP. Grade 3 esophagitis and grade 3 radiation pneumonitis were observed in 18.2% and 3.6% of the patients. Complete response and partial response were achieved in 24.5% and 69.1% of the patients, resulting in a response rate of 93.6%. The median progression-free survival (PFS) and overall survival (OS) times were 16.7 months and 58.2 months.
CRT using ccbRT with concurrent NP is safe and effective for locally advanced non-small-cell lung cancer, with good PFS and excellent OS.
Clinical Lung Cancer 02/2014; · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Lung cancer is a leading cause of cancer death in the world. The results from concurrent chemoradiation therapy (CRT) are still disappointing, although long term survival can be observed in certain population of the patients While local control is a critical problem in CRT, dose escalation of thoracic radiation (TRT) in CRT has not been effective.
Patients and Methods
We developed a novel TRT scheme of accelerated hyperfractionation using concomitant boost TRT (ccbRT). A total of 64 Gy and 40 Gy were given to the gross tumor volume and elective clinical target volume, respectively, for 20 working days, combined with systemic chemotherapy with cisplatin (day 1) and vinorelbine (days 1, 8) with a 3 week interval (NP). The purpose of this phase II study was to evaluate the efficacy and toxicity of this novel treatment.
From July 2002 to July 2010, 56 patients were enrolled in this study. One patient was excluded from the analysis. All 55 patients completed ccbRT, and 52 patients (94.5%) underwent at least 2 cycles of NP. Grade 3 esophagitis and grade3 radiation pneumonitis were observed in 18.2% and 3.6% of the patients. Complete response and partial response were achieved in 24.5% and 69.1% of the patients, resulting in a response rate of 93.6%. The median progression-free survival (PFS) and overall survival (OS) time were 16.7 months and 58.2 months.
CRT using ccbRT with concurrent NP is safe and effective for locally advanced NSCLC, with good PFS and excellent OS.
Clinical Lung Cancer 01/2014; · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer.
A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared.
No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured.
Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.
Annals of Surgical Oncology 02/2012; 19(7):2135-41. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have developed a treatment protocol for esophageal cancer involving a single course of induction chemotherapy followed by chemoradiotherapy. This study aimed to determine if it was possible to predict the effects of chemoradiotherapy on the basis of the response to induction chemotherapy, assessed by positron emission tomography (PET).
Sixteen patients with Stage II-IVA esophageal cancer were treated using this protocol from April 2007 to July 2010. Chemotherapy involved a fluorouracil and platinum-based combination regimen. All patients received PET scans before and 12-24 days after the beginning of induction chemotherapy. Associations between the response to induction chemotherapy assessed by PET and the effects of chemoradiotherapy were evaluated.
Induction chemotherapy followed by chemoradiotherapy resulted in complete response (CR) in 10 of the 16 patients. The reduction in maximum standardized uptake value (SUV(max)) was 58 ± 12% in patients with CR (n = 10), compared with 14 ± 16% in patients without CR (n = 6) (P < 0.0001). Using a cut-off value of 55% for SUV(max) reduction rate, eight of 10 cancers with CR and six of six cancers without CR were correctly identified, providing a sensitivity and specificity of 80 and 100%, respectively. The overall 1-year survival rates for patients with an SUV(max) reduction rate >55% (responders) were 100%, compared with 60% for patients with an SUV(max) reduction rate ≤55% (non-responders), respectively.
The response to a single course of induction therapy assessed by PET was significantly associated with the effects of chemoradiotherapy.
International Journal of Clinical Oncology 07/2011; 17(3):225-32. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze the patterns of the first sites of failure in patients with clinical stage I thoracic esophageal cancer after involved field radiotherapy and to determine whether elective nodal irradiation is necessary for these patients. Materials and
Between 2000 and 2007, 68 patients aged 43-84 years with clinical stage I thoracic esophageal cancer received definitive radiotherapy. The radiation field included the primary tumor with a 3-cm margin in the cranio-caudal direction. Patterns of lymph node failure were classified according to the first sites of failure. In-field, regional and distant lymph node failures were defined as lymph node failures within the irradiated area, within the mediastinum or perigastric area beyond the irradiated area, and outside the regional lymph nodes, respectively.
The 3 year overall and disease-free survival rates were 76 and 66%, respectively (median follow-up: 42 months). Twenty-two of the 68 patients exhibited treatment failure. Local failure with or without recurrence in other sites was observed in 11 patients, lymph node failure in 10 patients, and distant metastasis in 1. Of the 10 patients with lymph node failure, sites of failure were in-field in 1 patient, in-field and distant in 1, regional in 3, distant in 2 and distant and regional in 3.
Involved field radiotherapy did not result in significant incidence of regional lymph node failure in clinical stage I thoracic esophageal cancer patients. However, further investigation is needed to establish the optimal radiotherapy field for clinical stage I thoracic esophageal cancer.
Japanese Journal of Clinical Oncology 06/2011; 41(8):1007-12. · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze the outcome in T1-2 hypopharyngeal cancer (HPC) patients treated with definitive radiotherapy (RT).
A total of 103 patients with T1-2 hypopharyngeal squamous cell carcinoma treated with radical RT between March 2000 and June 2008 at our institution were analyzed. Pre-RT neck dissection (ND) was performed in 26 patients with advanced neck disease. Chemotherapy was used concurrently with RT in 14 patients. Sixty patients were associated with synchronous or metachronous malignancies. The median follow-up for surviving patients was 41 months.
The 3-year overall and cause-specific survival rates were 70% and 79%, respectively. The 3-year local control rates were 87% for T1 and 83% for T2 disease. The ultimate local control rate was 89%, including 7 patients in whom salvage was successful. The ultimate local control rate with laryngeal preservation was 82%. Tumors of the medial wall of the pyriform sinus tended to have lower control rates compared with tumors of the lateral or posterior pharyngeal wall. Among patients with N2b-3 disease, the 3-year regional control rates were 74% for patients with pre-RT ND and 40% for patients without ND. The 3-year locoregional control rates were as follows: Stage I, 100%; Stage II, 84%; Stage III, 67%; Stage IVA, 43%; Stage IVB, 67%. Forty-two patients developed disease recurrence, with 29 (70%) patients developing recurrence within the first year. Of the 103 patients, 6 developed late complications higher than or equal to Grade 3.
Definitive RT accomplished a satisfactory local control rate and contributed to organ preservation.
International journal of radiation oncology, biology, physics 06/2011; 82(2):e129-35. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chemoradiotherapy (CRT) has been proposed as an alternative therapy to esophagectomy for esophageal cancer, because of its favorable survival rate and mild toxicity. However, no comparative studies of esophagectomy and CRT have been reported in patients with clinical stage I esophageal squamous cell carcinoma.
A total of 54 patients with clinical stage I esophageal squamous cell carcinoma were treated with definitive CRT and 116 patients with esophagectomy at Osaka Medical Center for Cancer and Cardiovascular Diseases between 1995 and 2008, and were included in the analysis. Overall survival and recurrence rates were evaluated.
Complete follow-up data were available for 169 of the 170 patients (99%). The median (range) observation period was 67 (10-171) months in the esophagectomy group and 30 (4-77) months in the CRT group (P<0.0001). The 1- and 3-year overall survival rates were 97.4% and 85.5%, respectively, in the esophagectomy group and 98.1% and 88.7%, respectively, in the CRT group (P=0.78). Cox proportional hazards modeling showed that the overall survival was comparable between the two groups after adjusting for age, sex, and tumor size. The hazard ratio of CRT for overall survival was 0.95 (95% confidence interval 0.37-2.47). The incidence of local recurrence, including metachronous esophageal cancer, was significantly higher in the CRT group than in the esophagectomy group (P<0.0001). Most local recurrences in the CRT group were intramucosal carcinomas, and were cured after salvage treatment, mainly using endoscopy.
The overall survival rate of patients with clinical stage I esophageal cancer treated with CRT was comparable to that in those treated with esophagectomy, despite a high local recurrence rate. Locally recurrent carcinoma was endoscopically treatable in most patients, with no effect on overall survival. CRT seems to be a viable alternative to esophagectomy in patients with clinical stage I esophageal cancer.
The American Journal of Gastroenterology 02/2011; 106(6):1048-54. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of endoscopic screening for esophageal cancer in patients with hypopharyngeal cancer remains controversial and its impact on prognosis has not been adequately discussed. We studied the use of endoscopic screening to detect esophageal cancer in hypopharyngeal cancer patients by analyzing the incidence, stage and prognosis.
We included 64 patients with hypopharyngeal cancer who received radical radiotherapy at our institute. Chromoendoscopic esophageal examinations with Lugol dye solution were routinely performed at and after treatment for hypopharyngeal cancer.
Twenty-eight esophageal cancers were detected in 28 (41%) patients (18 synchronous and 10 metachronous cancers). Of the 28 cancers, 23 were stage 0 or I cancer and 15 of these were treated with endoscopic resection. Local control was achieved in all of these 23 stage 0 or I cancers. The 5-year overall survival rates with esophageal cancer were 83% in stage 0, 47% in stage I and 0% in stage IIA-IVB.
This study showed a strikingly high incidence of esophageal cancer in hypopharyngeal cancer patients. We suppose that the combination of early detection by chromoendoscopic examination and endoscopic resection for associated esophageal cancer in hypopharyngeal cancer patients improve prognosis and maintain quality of life.
Japanese Journal of Clinical Oncology 05/2010; 40(10):938-43. · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer.
The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined.
The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >or= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >or= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity.
Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.
International journal of radiation oncology, biology, physics 04/2009; 75(4):1003-7. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution.
Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30Gy/15 fractions was followed by HDR-ISBT of 30Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20Gy/10 fractions was delivered with a midline block. The median followup period was 55 months.
The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3.
A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT.
[Show abstract][Hide abstract] ABSTRACT: Hormone-refractory prostate cancer is one of the intractable human cancers in the world. Here, we examined the direct tumor-killing activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] through induction of Type I interferon (IFN) in the hormone-resistant human prostate cancer cell lines PC3 and DU145. Preferential binding of HVJ-E to PC3 and DU145 over hormone-sensitive prostate cancer cell and normal prostate epithelium was observed, resulting in a number of fused cells. After HVJ-E treatment, a number of IFN-related genes were up-regulated, resulting in Type I IFN production in PC3 cells. Then, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type I IFN expression after Sendai virus infection was up-regulated in cancer cells after HVJ-E treatment. Produced IFN-alpha and -beta enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. When HVJ-E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed and 85% of the mice became tumor-free. Although co-injection of an anti-asialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ-E, significant suppression of tumor growth was observed even in the presence of anti-asialo GM1 antibody. This suggests that natural killer cell activation made small contribution to tumor regression following HVJ-E treatment in hormone-resistant prostate cancer model in vivo. Thus, HVJ-E effectively targets hormone-resistant prostate cancer by inducing apoptosis in tumor cells, as well as activating anti-tumor immunity.
International Journal of Cancer 01/2009; 124(10):2478-87. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective study analyzed the effect of the activity of high-dose-rate (HDR) (192)Ir source on late rectal bleeding after HDR intracavitary radiotherapy (ICRT) in patients with uterine cervix cancer.
One hundred thirty-two patients who underwent HDR-ICRT and external beam radiotherapy (EBRT) were analyzed. The rectal point dose in ICRT was calculated by inserting a lead wire into the rectal lumen and summed with the whole-pelvic EBRT dose. The rectal biologic effective dose (BED) was calculated. The relationship between averaged source activity or the BED and late rectal bleeding were analyzed.
Three-year actuarial rectal bleeding probabilities were 46% (> or =100 Gy(3)) and 18% (< or = 100 Gy(3)), respectively (p < 0.005). When patients were divided into four groups according to rectal BED (> or = or < or =100 Gy(3)) and source activity (> or = or < or =2.4 cGy.m(2).h(-1)), the group with both a high BED and high activity showed significantly greater probability (58% at 3 years; p < 0.005). It was noted that the probability of the group with BED of 100 Gy(3) or greater was high, but that was not the case with 2.4 cGy.m(2).h(-1) or less.
This is the first clinical report concerning the source activity effect of HDR (192)Ir on late rectal bleeding in patients undergoing HDR-ICRT. This suggests that when source activity is higher than 2.4 cGy.m(2).h(-1), ICRT should be performed with more caution not to exceed 100 Gy(3) in total.
International Journal of Radiation OncologyBiologyPhysics 08/2008; 71(5):1329-34. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively.
Between May 1995 and April 2002, 35 patients with prostate cancer [Stage > or = T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level > or = 20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23-117 months).
The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated.
HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.