Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study.

OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

Treatment outcome of high-dose-rate interstitial radiation therapy for patients with stage I and II mobile tongue cancer.

OBJECTIVES: The aim of the study was to investigate the outcomes of high-dose-rate interstitial radiation therapy for patients with Stage I and II mobile tongue cancer retrospectively. METHODS: Sixty-seven patients with Stage I and II mobile tongue cancer were treated with high-dose-rate interstitial radiation therapy, with or without external beam radiation therapy, between 1997 and 2007. The median dose of interstitial radiation therapy was 50 Gy in 10 fractions over 6 days. Thirty-five patients received external beam radiation therapy before interstitial radiation therapy. The median dose of external beam radiation therapy was 20 Gy delivered with single-lateral or bilateral fields, including the primary tumor site and upper jugular lymph nodes. Thirty-seven patients received concurrent chemotherapy, including carboplatin, cisplatin, fluorouracil or tegafur, gimeracil and oteracil (TS-1) systemically or with intra-arterial injection. Thirty-three patients received intratumoral injection of bleomycin before catheter insertion. The median follow-up time was 58.6 months (range 15.1-102.4 months). RESULTS: The 5-year overall, cause-specific, progression-free survival rate and local control rate were 88.7, 92.1, 76.0 and 94.0%, respectively. Fourteen patients developed cervical lymph node recurrence, 11 of which were distributed within the external beam radiation therapy field. We found local failures in four cases within 2 years after the treatment and in three cases after >7 years, even though the latter were difficult to distinguish from second primary cancers. CONCLUSIONS: The treatment results of our institutions were equivalent to previous reports. Most cervical lymph node metastases occurred within the external beam radiation therapy field, which implied that the external beam radiation therapy dose of 20-30 Gy was insufficient to prevent late cervical lymph node metastases.

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma.

BACKGROUND: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. PATIENTS AND METHODS: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. RESULTS: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively. CONCLUSION: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.

Retrospective analysis: concurrent chemoradiotherapy and adjuvant chemotherapy for T2N0 glottic squamous cell carcinoma.

This study aimed to evaluate the efficacy and toxicity of concurrent chemoradiotherapy and adjuvant chemotherapy for T2N0 glottic squamous cell carcinoma. Between May 1993 and March 2004, 32 patients with T2N0 glottic squamous cell carcinoma received concurrent chemoradiotherapy as the primary treatment modality for larynx preservation. Radiotherapy was delivered five days a week using a once-daily fractionation of 2.0 Gy (median total dose: 70 Gy). The chemotherapy regimen comprised carboplatin in 4 patients, carboplatin and tegafur and uracil in 7, carboplatin and futraful in 2, and futraful in 19 patients. Twenty-four patients received adjuvant chemotherapy with tegafur and uracil. Initial local tumor control was achieved in 30 patients (94%). The 5-year overall survival and 5-year local control rates were 97% and 70%, respectively. Univariate analysis revealed adjuvant chemotherapy as a significant prognostic factor for the local control rate (P = 0.038). The 5-year local control rate in patients treated or not treated with adjuvant chemotherapy was 82% and 42%, respectively. No significant differences in the local control rate were noted in overall treatment time, total radiation dose, age, and disease extension to the subglottis. With regard to adverse reactions, grade 3 neutropenia and grade 3 hepatotoxicity were observed in 1 and 2 patients, respectively. We observed no severe late complications (RTOG/EORTC criteria Grade 3-4) related to this combination therapy. Concurrent chemoradiotherapy and adjuvant chemotherapy was effective but with mild toxicity, and adjuvant chemotherapy significantly improved local control. We suggest the use of this combination therapy for achieving a local control of T2N0 glottic squamous cell carcinoma.

Preliminary results of radiation therapy for locally advanced or recurrent adenoid cystic carcinomas of the head and neck using combined conventional radiation therapy and hypofractionated inverse planned stereotactic radiation therapy.

PURPOSE: To investigate the clinical outcomes and feasibility of combined conventional radiation therapy (RT) and hypofractionated inverse planned stereotactic radiation therapy (SRT) for locally advanced or recurrent adenoid cystic carcinomas (ACCs) of the head and neck. PATIENTS AND METHODS: Five patients with ACCs of the head and neck were treated with combined conventional RT and inverse planned SRT. Radiation doses of 40 to 50 Gy were delivered with 20 to 25 fractions using conventional RT, and then an additional 20 to 25 Gy was delivered by 4 to 5 fractions of SRT. RESULTS: Median follow-up was 12 months. Local control was obtained in all 5 patients, PR in 2 patients and SD in 3 patients. According to the Radiation Therapy Oncology Group (RTOG) late-radiation morbidity scoring criteria, adverse effects included Grade 2 xerostomia in 1 patient, Grade 2 trismus in 1 patient, and Grade 4 mucosal ulceration in 1 patient. CONCLUSION: Combined treatment with conventional RT and hypofractionated inverse planned SRT may be effective for short-term local control in patients with locally advanced or recurrent ACCs. Further evaluation is needed for long-term follow-up.

Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control.

BACKGROUND: Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1. METHODS: We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated. RESULTS: The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures. CONCLUSIONS: Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.

High-dose-rate brachytherapy for previously irradiated patients with recurrent esophageal cancer.

PURPOSE: Our objective was to assess the feasibility, efficacy, and complications of high-dose-rate (HDR) brachytherapy for patients with recurrent esophageal cancer after external radiotherapy. MATERIALS AND METHODS: Six patients with recurrent esophageal cancer after external radiotherapy were treated with HDR brachytherapy (Ir-192 source) from January 2003 to February 2004. The median age of the patients was 69 years. All patients had received external radiotherapy (median dose 60 Gy) before HDR brachytherapy. All patients underwent HDR brachytherapy once a week with a dose of 4 or 5 Gy per fraction in the esophageal mucosa (median total dose 20 Gy). The Kaplan-Meier method was used to calculate local control rates. RESULTS: The median overall survival period was 30.0 months. Local control was observed in five patients and residual tumor in one patient. Persistent local control was observed in two patients. No patient died of esophageal cancer, and all patients survived. We observed no severe late complications related to HDR brachytherapy. CONCLUSION: These data suggest that HDR brachytherapy is an effective and safe treatment for patients with recurrent esophageal cancer after external radiotherapy.

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study.

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2-135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.

Granular cell tumor presenting as an intradural extramedullary tumor.

Granular cell tumor (GCT) is an uncommon benign tumor, which is thought to originate from a Schwann cell. GCT may involve any part of the body, but in our knowledge, there has been only one previous report of GCT, which arose in the intradural extramedullary space of the spine. We report a case of GCT, which occurred in the intradural extramedullary space.

Acute urinary morbidity after a permanent 125I implantation for localized prostate cancer.

We evaluated the predictive factors of acute urinary morbidity (AUM) after prostate brachytherapy. From November 2005 to January 2007, 62 patients with localized prostate cancer were treated using brachytherapy. The (125)Iodine ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The clinical and treatment parameters were analysed for correlation with AUM. In particular, in this study, Du90 (the minimal dose received by 90% of the urethra), Dup90 (the minimal dose received by 90% of the proximal half of the urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the distal half of the urethra on the penile side) were analysed. We found that 43 patients (69.4%) experienced acute urinary symptoms at 3 months after implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain, and two patients had Grade 2 urinary frequency. None of the patients had ≥Grade 3. Univariate and multivariate analysis revealed that Du90 and Dup90 were significantly correlated with AUM. In this study, Du90 and Dup90 were the most significant predictors of AUM after prostate brachytherapy.

Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer: a single institutional experience.

The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for Stage I small-cell lung cancer (SCLC). From April 2003 to September 2009, a total of eight patients with Stage I SCLC were treated with SBRT in our institution. In all patients, the lung tumors were proven as SCLC pathologically. The patients' ages were 58-84 years (median: 74). The T-stage of the primary tumor was T1a in two, T1b in two and T2a in four patients. Six of the patients were inoperable because of poor cardiac and/or pulmonary function, and two patients refused surgery. SBRT was given using 7-8 non-coplanar beams with 48 Gy in four fractions. Six of the eight patients received 3-4 cycles of chemotherapy using carboplatin (CBDCA) + etoposide (VP-16) or cisplatin (CDDP) + irinotecan (CPT-11). The follow-up period for all patients was 6-60 months (median: 32). Six patients were still alive without any recurrence. One patient died from this disease and one died from another disease. The overall and disease-specific survival rate at three years was 72% and 86%, respectively. There were no patients with local progression of the lesion targeted by SBRT. Only one patient had nodal recurrence in the mediastinum at 12 months after treatment. The progression-free survival rate was 71%. No Grade 2 or higher SBRT-related toxicities were observed. SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer. However, further investigation is needed using a large series of patients.

Association between EGFR-TKI resistance and efficacy of radiotherapy for brain metastases from EGFR-mutant lung adenocarcinoma.

AIM: To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases. PATIENTS AND METHODS: Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24). RESULTS: The response rate for patients with TKI-resistant tumor at three months after RT tended to be lower (11%) than that of those who were TKI-naïve (82%, p=0.006) and for patients with wild-type EGFR (48%, p=0.10). On univariate analysis, central nervous system progression-free and overall survival were significantly shorter for patients with TKI-resistant tumors than for those who were TKI-naïve (p=0.018 and p=0.005, respectively). Multivariate analysis showed that TKI resistance was an independent predictor of poorer overall survival (p=0.011). CONCLUSION: Acquired resistance to TKIs appears to be associated with low efficacy of brain RT.

Stereotactic body radiation therapy for stage I non-small cell lung cancer patients with chronic respiratory insufficiency requiring domiciliary oxygen therapy.

BACKGROUND: The efficacy of stereotactic body radiation therapy (SBRT) for patients treated with domiciliary oxygen therapy is not well-known. PATIENTS AND METHODS: We collected the clinical records of 15 patients with chronic respiratory insufficiency requiring domiciliary oxygen therapy at 1-3 l/min who were treated with SBRT for stage I non-small cell lung cancer. All patients were fixed with a thermoplastic body cast system. SBRT was given in 7-8 fields with an isocenter dose of 40-60 Gy in 4-10 fractions (median, 48 Gy in 4 fractions). RESULTS: The overall 2-year and 5-year survival rates for all patients were 67.4% and 34.7%, while the disease-specific 2-year and 5-year survival rates were 90.0% and 72.0%, respectively. Pulmonary adverse effects were mild in the majority of the patients, although two patients had grade 2 radiation pneumonitis. The oxygen flow required increased slightly at follow-up periods greater than one year, but was still at an acceptable level. CONCLUSION: SBRT was feasible for patients requiring domiciliary oxygen therapy.

Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy: risk factors and dose-volume relationship.

PURPOSE: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. RESULTS: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, ≥42.4 Gy or less), 51.6% vs. 2.0% (V40, ≥0.29 cm(3) or less), 45.8% vs. 2.2% (V30, ≥1.35 cm(3) or less), 42.0% vs. 8.5% (V20, ≥3.62 cm(3) or less), or 25.9% vs. 10.5% (V10, ≥5.03 cm(3) or less). CONCLUSIONS: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.

Acute cardiac impairment associated with concurrent chemoradiotherapy for esophageal cancer: magnetic resonance evaluation.

PURPOSE: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. METHODS AND MATERIALS: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean ± SE. RESULTS: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% ± 2.98% vs. 59.8% ± 2.56% vs. 60.6% ± 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 ± 2.93 vs. 57.0 ± 3.23 mL/m(2)), LV stroke volume index (38.6 ± 1.56 vs. 29.9 ± 1.60 mL/m(2)), and LV ejection fraction (56.9% ± 1.79% vs. 52.8% ± 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 ± 3.05 vs. 72.4 ± 4.04 vs. 85.4 ± 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 ± 0.54 vs. 4.78 ± 0.43 vs. 4.79 ± 0.50 mm), 9 (6.88 ± 0.45 vs. 5.04 ± 0.38 vs. 5.27 ± 0.47 mm), and 10 (9.22 ± 0.48 vs. 8.08 ± 0.34 vs. 8.19 ± 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference (p < 0.05) after CCRT between the groups. CONCLUSIONS: Concurrent chemoradiotherapy for esophageal cancer impairs LVF from an early treatment stage. This impairment is prominent in patients with high LV dose.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PURPOSE: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. METHODS AND MATERIALS: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. RESULTS: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). CONCLUSION: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

Concurrent chemoradiotherapy with S-1 as first-line treatment for patients with oropharyngeal cancer.

PURPOSE: S-1 is an oral fluoropyrimidine. The purpose of this study was to review the clinical outcomes of S-1 with concurrent radiotherapy for patients with oropharyngeal cancer. MATERIALS AND METHODS: Between 2002 and 2007, 38 patients with oropharyngeal cancer treated concurrently with S-1 and definitive radiotherapy were reviewed. The clinical stage was Stage I in 4 patients, Stage II in 7, Stage III in 7, and Stage IV in 20. S-1 was administered orally twice daily for 4 consecutive weeks followed by a 2-week drug withdrawal. The initial dose of S-1 was 65 mg/m(2)/day. All patients were treated using three-dimensional conformal radiotherapy with a median total dose of 65.1 Gy (range, 60.0-71.0 Gy). Clinical outcomes and major acute toxicities were analyzed based on medical records and clinical follow-up. RESULTS: With a median follow-up time of 33 months, the 3-year estimates of local-regional control, distant metastases-free survival, disease-free survival, and overall survival for all patients were 75%, 80%, 65%, and 80%, respectively. The 3-year estimates of local-regional control according to stage were 100% for Stages I and II, 86% for Stage III, and 56% for Stage IV. The rate of ≥ Grade 3 acute mucositis was 32%, and the rate of ≥ Grade 3 hematological toxicities was 8%. No other severe toxicities were observed. CONCLUSIONS: Concurrent chemoradiotherapy with S-1 was found to be effective, especially for early disease. The treatment-related toxicities were acceptable, and the incidence of myelotoxicity was low. Further study must be carried out to compare with other chemotherapy regimens.

Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer.

The purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stage II-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3,50-75%; 4,75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n = 14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p = 0.0006, p = 0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful.

Concurrent chemoradiotherapy with S-1 for T2N0 glottic squamous cell carcinoma.

In this study, we evaluated the feasibility, efficacy and toxicity of concurrent chemoradiotherapy with S-1 (tegafur-gimeracil-oteracil potassium) for T2N0 glottic carcinoma. A total of 23 patients with T2N0 glottic carcinoma received chemoradiotherapy with S-1. Radiotherapy consisted of five daily fractions of 2 Gy per week, to a total median dose of 70 Gy. S-1 was administered 65 mg/m(2) per day for 4 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and twice a day until the end of radiotherapy. Initial local control rate of the primary tumor was achieved in all patients. The median follow-up period for all patients was 38 months. The 3-year local control rate was 95.4%. Regarding adverse reactions, grade 3 mucositis upon clinical examination, mucositis upon functional/symptomatic examination, dysphagia, hepatic toxicity and anemia were observed in 13, 2, 2, 1 and 1 patients, respectively. This chemoradiotherapy did not result in grade 4 acute toxicity or severe late toxicity. Chemoradiotherapy with S-1 was feasible, well tolerated and effective. This therapy is suggested as a possible regimen for improving local control of T2N0 glottic carcinoma.

A Case of Radiation Fibrosis Appearing as Mass-Like Consolidation after SBRT with Elevation of Serum CEA.

We report a case of radiation fibrosis appearing as mass-like consolidation, which was difficult to distinguish from local recurrence. A 72-year-old woman was diagnosed as having primary lung cancer (cT1N0M0 stage IA) in the right upper lobe and was treated with SBRT of 48 Gy in 4 fractions. After 12 months, mass-like consolidation appeared around the irradiated area, and after 13 months, it had increased in size. FDG-PET revealed high uptake (SUV max = 5.61) for the consolidation. CT-guided biopsy was performed, but we could not confirm the diagnosis. Considering her poor respiratory function and her age, short-interval follow-up was performed. After 15 months, the consolidation enlarged at the dorsal side, and carcinoembryonic antigen (CEA) became elevated (14.6 ng/mL). Serum KL-6 (436 U/mL) and SP-D (204 ng/mL) were also elevated. However, after 16 months, serum CEA slightly decreased. The consolidation gradually retracted on follow-up CT images. CEA, KL-6, and SP-D were also decreased by degrees. After 40 months, there is no evidence of local recurrence.