Interobserver variability of 3.0-tesla and 1.5-tesla magnetic resonance imaging/computed tomography fusion image-based post-implant dosimetry of prostate brachytherapy.

This study aimed to compare the interobserver variabilities in magnetic resonance imaging (MRI)/computed tomography (CT) fusion image-based post-implant dosimetry of permanent prostate brachytherapy (PPB) between 1.5-T and 3.0-T MRI. The study included 60 patients. Of these patients, 30 underwent 1.5-T MRI and CT 30 days after seed implantation (1.5-T group), and 30 underwent 3.0-T MRI and CT 30 days after seed implantation (3.0-T group). All patients received PPB alone. Two radiation oncologists performed MRI/CT fusion image-based post-implant dosimetry, and the interobserver variabilities of dose-volume histogram (DVH) parameters [dose (Gy) received by 90% of the prostate volume (prostate D90)], percentage of the prostate volume receiving at least the full prescribed dose (prostate V100), percentage of the prostate volume receiving at least 150% of the prescribed dose (prostate V150), dose (Gy) received by 5% of the urethral volume (urethral D5) and the urethral volume receiving at least 150% of the prescribed dose (urethral V150)] were retrospectively estimated using the paired Student's t test and Pearson's correlation coefficient. The Pearson's correlation coefficients of all DVH parameters were higher in the 3.0-T group than in the 1.5-T group (1.5-T vs 3.0-T: prostate D90, 0.65 vs 0.93; prostate V100, 0.62 vs 0.82; prostate V150, 0.97 vs 0.98; urethral D5, 0.92 vs 0.93; and urethral V150, 0.88 vs 0.93). In the paired Student's t test, no significant differences were observed in any of the DVH parameters between the two radiation oncologists in the 3.0-T group (0.068 ≤ P ≤ 0.842); however, significant differences were observed in prostate D90 (P = 0.004), prostate V100 (P = 0.011) and prostate V150 (P = 0.002) between the oncologists in the 1.5-T group. The interobserver variability of DVH parameters in the MRI/CT fusion image-based post-implant dosimetry analysis of brachytherapy was lower with 3.0-T MRI than with 1.5-T MRI.

Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study.

We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.1- 11.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and non- ADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102.

PURPOSE: The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial. METHODS: In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m(2), days 1-3) and cisplatin (20 mg/m(2), days 1-3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR). RESULTS: The trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47-89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3-4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %). CONCLUSIONS: This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.

Comparison of implant quality between intraoperatively built custom-linked seeds and loose seeds in permanent prostate brachytherapy using sector analysis.

We compared the implant quality of intraoperatively built custom-linked (IBCL) seeds with loose seeds in permanent prostate brachytherapy. Between June 2012 and January 2015, 64 consecutive prostate cancer patients underwent brachytherapy with IBCL seeds (n = 32) or loose seeds (n = 32). All the patients were treated with 144 Gy of brachytherapy alone. Brachytherapy was performed using a dynamic dose calculation technique. Computed tomography/magnetic resonance imaging fusion-based dosimetry was performed 1 month after brachytherapy. Post-implant dose-volume histogram (DVH) parameters, prostate sector dosimetry, operation time, seed migration, and toxicities were compared between the IBCL seed group and the loose seed group. A sector analysis tool was used to divide the prostate into six sectors (anterior and posterior sectors at the base, mid-gland, and apex). V100 (95.3% vs 89.7%; P = 0.014) and D90 (169.7 Gy vs 152.6 Gy; P = 0.013) in the anterior base sector were significantly higher in the IBCL seed group than in the loose seed group. The seed migration rate was significantly lower in the IBCL seed group than in the loose seed group (6% vs 66%; P < 0.001). Operation time per seed was significantly longer in the IBCL seed group than in the loose seed group (1.31 min vs 1.13 min; P = 0.003). Other post-implant DVH parameters and toxicities did not differ significantly between the two groups. Our study showed more dose coverage post-operatively in the anterior base prostate sector and less seed migration in IBCL seed implantation compared with loose seed implantation.

Postoperative External Irradiation of Patients with Primary Biliary Tract Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: The aim of the present study was to assess clinical outcomes of postoperative radiotherapy for biliary tract cancer patients. PATIENTS AND METHODS: Clinical results of 187 patients treated with external irradiation in 31 Japanese Institutions between 2000 and 2011 were retrospectively analyzed. The median radiation dose was 50.4 Gy in fractions of 1.8-2 Gy. RESULTS: Two-year actuarial overall survival and locoregional control (LCs) rates were 56% and 68%, respectively. In multivariate analysis, macroscopic residual tumor (R2) and irradiated doses <54 Gy were significant indicators of poor LC prognosis. For patients with complete resection (R0) or microscopic residual tumor (R1), 2-year LCs were 71% for <54 Gy and 83% for ≥54 Gy; doses ≥54 Gy were associated with high long-term LCs. There was no significant difference in acute adverse event rates between <54 Gy and ≥54 Gy. CONCLUSION: Postoperative irradiation doses of approximately 54 Gy are safe and effective for R0 or R1 resection patients.

Comparison of field-in-field radiotherapy with conformal radiotherapy for unilateral cervical malignant lymphoma.

This study compared field-in-field (FIF) radiotherapy with conformal radiotherapy with physical wedges for the treatment of unilateral cervical malignant lymphoma. Two treatment plans, the FIF technique and conformal RT, were generated for each of 32 patients with unilateral cervical malignant lymphoma. To compare the 2 treatment plans, dose-volume histograms of the planning target volume (PTV), the thyroid, submandibular gland, carotid artery, mucosa, spinal cord, and surrounding normal tissue, and monitor unit (MU) were analyzed. The FIF technique showed significant reduction in the mean dose of thyroid, submandibular gland, carotid artery and mucosa, the maximum dose of the spinal cord and PTV, and the volume receiving＞107% of the prescribed dose of surrounding normal tissue (p＜0.001). In addition, there were gains in the homogeneity index of the PTV for FIF. Furthermore, the total MU was also lower for the FIF technique than for the wedge technique (p＜0.001). Compared with the wedge technique, the FIF technique improved the dose homogeneity of the PTV, reduced the dose to normal structures, and was associated with fewer MUs in the treatment of patients with cervical malignant lymphoma.

High-dose-rate brachytherapy using molds for lip and oral cavity tumors.

BACKGROUND: High-dose-rate (HDR) brachytherapy using the mold technique is a less invasive treatment for early lip and oral cavity cancer. However, limited reports exist regarding the feasibility of this method. In this retrospective study, we evaluated the outcome of this therapy and investigated its feasibility for lip and oral cavity tumors. METHODS: Between May 2002 and December 2010, 17 patients (median age, 80.0 years) with histologically confirmed squamous cell carcinoma of the lip or oral cavity were treated by means of HDR brachytherapy using the mold technique after external beam radiotherapy (EBRT). Tumor sites included the buccal mucosa in eight cases, the gingiva in three cases, the lips in two cases, the floor of the mouth in two cases, and the hard palate in two cases. For all patients, EBRT (30 Gy/15 fractions), was performed before HDR brachytherapy. Two 6-Gy fractions were delivered twice daily for 2 days a week with an interval of 6 hours between the fractions. The total HDR brachytherapy dose was 24 Gy. Prior to EBRT, two patients with neck metastasis underwent neck dissection, and one patient with an exophytic tumor underwent tumor resection. RESULTS: The median follow-up period was 53.4 (range, 4.8-83.4) months. Of the 17 patients, 14 (82.4%) achieved a complete response, and three (17.6%) displayed a partial response. The overall 3- and 5-year survival rates were both 68.8%, the 3- and 5-year disease-specific survival rates were both 86.7%, and the 3- and 5-year local control rates were both 54.1%. Seven patients developed local recurrence at a median time of 3.4 (range, 1.7-29.1) months after treatment. Nodal and lung metastases occurred separately in two patients. By the end of the follow-up period, two patients had died of the primary disease and four patients had died of other causes. CONCLUSIONS: Although there is a need to improve the technical aspects of the treatment protocol, HDR brachytherapy using the mold technique might be a therapeutic option for superficial lip or oral cavity tumors, especially in older patients who have a poor performance status or are in poor physical condition.

A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: the Okayama Lung Cancer Study Group Trial 0501.

BACKGROUND: Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective. METHODS: In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40mg/m(2) on days 1, 8, 29 and 36) and S-1 (80mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary endpoint was the response rate. RESULTS: A partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). At a median follow up of 54 months, the median progression-free survival and median survival time were 9.3 and 31.3 months, respectively. No difference in efficacy was observed when the patients were stratified by histology. Toxicities were generally mild except for grade 3 or worse febrile neutropenia and pneumonitis of 8% and 4%, respectively. No patient developed severe esophagitis. At the time of this analysis, 35 (73%) of the 48 patients recurred; 15 (31%) showed distant metastasis, 17 (35%) had loco-regional disease, and 2 (4%) showed both loco-regional disease and distant metastasis. CONCLUSIONS: This chemoradiotherapy regimen yielded a relatively favorable efficacy with mild toxicities in patients with locally advanced NSCLC.

Impact of intraluminal brachytherapy on survival outcome for radiation therapy for unresectable biliary tract cancer: a propensity-score matched-pair analysis.

PURPOSE: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. METHODS AND MATERIALS: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. RESULTS: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT- group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT- group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT- group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. CONCLUSIONS: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.

Primary CNS lymphoma treated with radiotherapy in Japan: a survey of patients treated in 2005-2009 and a comparison with those treated in 1985-2004.

BACKGROUND: The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995-2004 and those on 466 patients treated during the period 1985-1994. RESULTS: In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995-2004 period, significant changes in the 2005-2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009 periods, respectively, but relapse-free survival did not improve between the 1995-2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. CONCLUSIONS: Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

In vitro assessment of factors affecting the apparent diffusion coefficient of Jurkat cells using bio-phantoms.

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3µm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis.

Patterns of radiotherapy practice for biliary tract cancer in Japan: results of the Japanese radiation oncology study group (JROSG) survey.

BACKGROUND: The patterns of radiotherapy (RT) practice for biliary tract cancer (BTC) in Japan are not clearly established. METHODS: A questionnaire-based national survey of RT used for BTC treatment between 2000 and 2011 was conducted by the Japanese Radiation Oncology Study Group. Detailed information was collected for 555 patients from 31 radiation oncology institutions. RESULTS: The median age of the patients was 69 years old (range, 33-90) and 81% had a good performance status (0-1). Regarding RT treatment, 78% of the patients were treated with external beam RT (EBRT) alone, 17% received intraluminal brachytherapy, and 5% were treated with intraoperative RT. There was no significant difference in the choice of treatment modality among the BTC subsites. Many patients with EBRT were treated with a total dose of 50 or 50.4 Gy (~40%) and only 13% received a total dose ≥60 Gy, even though most institutions (90%) were using CT-based treatment planning. The treatment field consisted of the primary tumor (bed) only in 75% of the patients. Chemotherapy was used for 260 patients (47%) and was most often administered during RT (64%, 167/260), followed by after RT (63%, 163/260). Gemcitabine was the most frequently used drug for chemotherapy. CONCLUSIONS: This study established the general patterns of RT practice for BTC in Japan. Further surveys and comparisons with results from other countries are needed for development and optimization of RT for patients with BTC in Japan.

High-dose-rate intra-cavitary brachytherapy combined with external beam radiation therapy for under 40-year-old patients with invasive uterine cervical carcinoma: clinical outcomes in 118 Patients in a Japanese multi-institutional study, JASTRO.

BACKGROUND: The current study was designed to evaluate the clinical outcomes of curative intent radiation therapy for young patients with invasive uterine cervical carcinoma in Japan. METHODS: One hundred and eighteen patients aged ≤40 were registered in the multi-institutional study of the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) from 26 major institutions in Japan. The age range was 24-39 years and the maximum tumor diameter was 2.0-9.2 cm. The International Federation of Gynecology and Obstetrics clinical stages were Ib, IIa, IIb, IIIa, IIIb and IVa in 17, 6, 40, 2, 50 and 3, respectively. Curative intent radiation therapy consisted of the combination of external beam radiation therapy and high-dose rate intra-cavitary brachytherapy. The total dose of external beam radiation therapy ranged between 44 and 68 Gy. Both the median and mode of total high-dose-rate intra-cavitary brachytherapy dose to point A were 24 Gy in four fractions. Ninety-six patients (58%) received chemotherapy. RESULTS: The 5-year overall survival rate and local control rate of all patients were 61 and 65%, respectively. The 5-year overall survival rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 88, 100, 75, 100, 37 and 0%, respectively. The 5-year local control rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 82, 75, 75, 100, 51 and 0%, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity. CONCLUSIONS: The 5-year overall survival rate of young patients with Stage IIIb was comparatively low at 37%.

Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients.

OBJECTIVES: To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. METHODS: From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On univariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. CONCLUSIONS: Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100.

Endometrial polyps: MR imaging features.

The purpose of this study is to evaluate the diagnostic usefulness of magnetic resonance imaging (MRI) characteristics of endometrial polyps in order to differentiate them from other endometrial lesions. MRI was retrospectively reviewed in 40 patients with pathologically proven endometrial polyps. Special attention was paid to the sizes, shapes, margins, internal structures, signal intensities, and post-contrast enhancement patterns. A central fibrous core, intratumoral cysts, and hemorrhage were seen in 30 (75%), 22 (55%), and 14 (35%) patients, respectively. The predominant signal intensity of the lesions showed iso-to slightly low signal intensity relative to the endometrium on T2-weighted images in 36 (90%), low signal intensity on diffusion-weighted images in 32 (80%), and strong or moderate enhancement on enhanced T1-weighted images in 28 patients (70%), respectively. In 32 (80%) patients, the endometrial polyps showed global or partial early enhancement. On dynamic study, rapid enhancement with a persistent strong enhancement pattern was seen in 17 (42.5%) and a gradually increasing enhancement pattern was seen in 17 patients (42.5%). These MRI features can be helpful to distinguish the endometrial polyps from various other endometrial lesions.

Two-piece customized mold technique for high-dose-rate brachytherapy on cancers of the buccal mucosa and lip.

OBJECTIVE: High-dose-rate (HDR) brachytherapy using a customized mold is a minimally invasive treatment for oral cancer; however, it is difficult to use this technique for buccal and lip cancers involving the commissura labiorum, owing to its anatomic form. The purpose of this study was to introduce an improved customized mold consisting of 2 pieces to allow the fixation of molds to these sites. STUDY DESIGN: Five patients with buccal carcinoma and 1 patient with lip carcinoma were treated with this technique after external beam radiotherapy. One patient with neck metastasis underwent both neck dissection and partial tumor resection before HDR brachytherapy. RESULTS: At the end of the follow-up period, 5 patients had no tumor recurrence, and 1 patient had suffered local recurrence. CONCLUSIONS: Our technique is a viable therapeutic option for patients with buccal and lip carcinomas for whom the therapeutic modalities are limited by age, performance status, and other factors.

Induction chemoradiotherapy followed by surgical resection for clinical T3 or T4 locally advanced non-small cell lung cancer.

PURPOSE: To examine the usefulness of trimodality therapy in patients with clinical T3 or T4 (cT3-4) locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Between 1997 and 2009, a total of 76 LA-NSCLC patients with cT3-4 underwent surgery. Among them, 36 patients underwent induction chemoradiotherapy with docetaxel and cisplatin plus concurrent radiation followed by surgery (IC group). The other 40 patients initially underwent surgery (IS group). The outcomes of the IC and IS groups were then investigated. To minimize possible biases caused by confounding treatment indications, we performed a retrospective cohort analysis by applying a propensity score (PS). Patients were divided into three groups according to PS tertiles, and comparisons between the IC and IS groups were made by PS tertile-stratified Cox proportional hazard models. RESULTS: For the entire cohort, which had a median follow-up duration of 48 months, the 3- and 5-year overall survival rates were 83.8 and 78.9%, respectively, in the IC group, versus 66.8 and 56.5%, respectively, in the IS group (P = 0.0092). After adjustments for potentially confounding variables, the IC group continued to have a significantly longer overall survival than the IS group (P = 0.0045). In addition, when the analysis was limited to 52 patients with cT3-4N0 or N1 disease, the IC group had a significantly longer overall survival than the IS group after adjustments for confounding variables (P = 0.019). CONCLUSIONS: Our study indicates that trimodality therapy is highly effective in patients with cT3-4 LA-NSCLC.

Long-term outcome of induction chemoradiotherapy with docetaxel and cisplatin followed by surgery for non-small-cell lung cancer with mediastinal lymph node metastasis.

The purpose of this study was to show the long-term outcome of induction chemoradiotherapy, using docetaxel and cisplatin with concurrent radiotherapy followed by surgery for non-small-cell lung cancer (NSCLC) with mediastinal nodal metastasis. Between January 2000 and July 2006, 22 consecutive NSCLC patients with pathologically proven mediastinal nodal metastasis were treated with tri-modality therapy. The regimen consisted of docetaxel and cisplatin plus concurrent radiation at a dose of 40-46 Gy. The induction therapy was followed by surgery 4-6 weeks later. The pulmonary resections were composed of a lobectomy in 19 patients, including 3 with a sleeve lobectomy, a bilobectomy in 2 patients and a left pneumonectomy in 1 patient. With a median follow-up duration of 8.7 years, the 3-year and 7-year overall survival (OS) rates for the entire population were 72.7 and 63.6%, respectively. Our results suggest that tri-modality therapy is promising for NSCLC patients with mediastinal nodal metastasis.

T2*-weighted image/T2-weighted image fusion in postimplant dosimetry of prostate brachytherapy.

Computed tomography (CT)/magnetic resonance imaging (MRI) fusion is considered to be the best method for postimplant dosimetry of permanent prostate brachytherapy; however, it is inconvenient and costly. In T2*-weighted image (T2*-WI), seeds can be easily detected without the use of an intravenous contrast material. We present a novel method for postimplant dosimetry using T2*-WI/T2-weighted image (T2-WI) fusion. We compared the outcomes of T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based postimplant dosimetry. Between April 2008 and July 2009, 50 consecutive prostate cancer patients underwent brachytherapy. All the patients were treated with 144 Gy of brachytherapy alone. Dose-volume histogram (DVH) parameters (prostate D90, prostate V100, prostate V150, urethral D10, and rectal D2cc) were prospectively compared between T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based dosimetry. All the DVH parameters estimated by T2*-WI/T2-WI fusion-based dosimetry strongly correlated to those estimated by CT/T2-WI fusion-based dosimetry (0.77 ≤ R ≤ 0.91). No significant difference was observed in these parameters between the two methods, except for prostate V150 (p = 0.04). These results show that T2*-WI/T2-WI fusion-based dosimetry is comparable or superior to MRI-based dosimetry as previously reported, because no intravenous contrast material is required. For some patients, rather large differences were observed in the value between the 2 methods. We thought these large differences were a result of seed miscounts in T2*-WI and shifts in fusion. Improving the image quality of T2*-WI and the image acquisition speed of T2*-WI and T2-WI may decrease seed miscounts and fusion shifts. Therefore, in the future, T2*-WI/T2-WI fusion may be more useful for postimplant dosimetry of prostate brachytherapy.

Ileal perforation induced by acute radiation injury under gefitinib treatment.

Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR.