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.

Factors influencing survival outcome for radiotherapy for biliary tract cancer: a multicenter retrospective study.

PURPOSE: To seek for the possible factors influencing overall survival (OS) with radiotherapy (RT) for biliary tract cancer. MATERIALS AND METHODS: Data were collected retrospectively from RT database of 31 institutions in Japan. All patients underwent at least external beam RT. The factors influencing OS were investigated. RESULTS: Data of 498 patients were analyzed. Median OS of the 212 patients who underwent surgery was significantly better than that of the 286 patients without surgery (31 vs. 15 months, p<0.001). The OS for the R0 or R1 resection group was significantly longer than that for the R2 or non-surgery group, as well as for n0 compared to n1 (all p<0.001). Chemoradiotherapy (CRT), both sequential and concurrent, resulted in a better OS than RT alone for the n1 group (31 vs. 13 months, p<0.001), and marginally better for the R0/R1 group (p=0.065; p=0.054 for concurrent CRT). However, no such benefit was observed for the R2/non-surgical patients. Multivariate analysis identified performance status, clinical stage, and surgery as significant factors. CONCLUSION: Surgery, especially R0/R1 resection, seemed as the gold standard for treatment of biliary tract cancer including RT, even in the highly heterogeneous population obtained from the multicenter retrospective study. The possibility was shown that CRT yielded better survival benefit especially for n1 patients. We recommend that future prospective trials include an arm of adjuvant CRT at least for n1 and possibly R0/R1 patients.

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.

Tumor response after low-dose preoperative radiotherapy combined with chemotherapy for squamous cell esophageal carcinoma.

AIM: Patients with T3 or more squamous cell esophageal cancer underwent low-dose preoperative radiotherapy with chemotherapy, to reduce local recurrence, followed by surgery. The aim was to ascertain tumor response and assess prognostic factors. PATIENTS AND METHODS: Between May 2002 and June 2011, 37 consecutive patients with esophageal cancer underwent chemoradiotherapy followed by surgery. The numbers of patients in clinical stages IIA/IIIA/IIIB/IIIC were 2/24/7/4, respectively. All were given a dose of 30 Gy in 15 fractions, with concurrent chemotherapy using cisplatin and fluorouracil. Curative surgery was performed a median of 1.2 months after completion of chemoradiotherapy. RESULTS: Based on the findings from surgery, 26 patients (70%) achieved a stage reduction and six patients (16%) had a complete pathological response. The numbers of patients undergoing resections microscopically complete, with microscopically positive margins, and macroscopically positive margins were 33, 3, and 1, respectively. During a median follow-up period of 22.5 months, the two-year progression-free survival and overall survival were 62.1% [95% confidence interval (CI)=45.8 to 78.4%] and 71.9% [95% CI=55.1 to 88.7%], respectively. Statistically significant prognostic factors for overall survival were age [hazard ratio=6.6; 95% CI=1.1 to 38; p=0.04] and pathological T factor [hazard ratio=10.2; 95% CI=1.4 to 77; p=0.02]. No patients died as a result of surgery. CONCLUSION: Seventy percent of patients with esophageal cancer who received radiotherapy dose of 30 Gy in 15 fractions combined with chemotherapy achieved a stage reduction with low toxicity.

Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma.

This study aimed to retrospectively evaluate the efficacy of radiotherapy for primary intraocular non-Hodgkin lymphoma (PIOL). Between May 1998 and October 2010, 22 immunocompetent patients (four men, 18 women; median age 70 years, range 53-79 years) were diagnosed with PIOL. Magnetic resonance imaging showed no intracranial involvement in any patient. Patients received radiotherapy at a median total dose of 30 Gy (range 30-40 Gy). Three-year overall survival, progression-free survival and local control rates were 89% (95% confidence interval [CI]: 75, 103), 49% (95% CI: 24, 73) and 95% (95% CI: 86, 105) over a median of 36 months of observation, respectively. Twelve patients (55%) had intracranial relapse at a median of 28 months after initiation of radiotherapy. Visual acuity improved or was stable in 81% of treated eyes. The only grade ≥ 3 toxicity was cataract formation (five patients). Radiotherapy without chemotherapy for PIOL achieved high local control rates with acceptable toxicities.

Significance of the number of brain metastases for identifying patients who don't need whole brain radiotherapy: implication as oligometastases of the brain.

BACKGROUND AND PURPOSE: To investigate the significance of the number of brain metastases in the treatment with stereotactic radiotherapy (SRT) with or without whole brain radiotherapy (WBRT). MATERIAL AND METHODS: Between February 2003 and October 2010, 218 consecutive patients with brain metastases who underwent SRT alone or WBRT plus SRT were investigated. The prognostic factors affecting overall survival and brain progression-free survival were analyzed by multivariate and univariate analysis. By logistic regression analysis, factors associated with the number recurrences of brain metastasis after SRT were also investigated. RESULTS: The median overall and brain progression-free survivals were 7.2 months and 4.3 months, respectively. Significant prognostic factors for overall survival in multivariate analyses were performance status (hazard ratio [HR] = 1.71, 95% confidence interval [CI] 1.13-2.57, p = 0.01) and the number of brain metastases (HR = 1.75, 95% CI 1.08-2.83, p = 0.02). Cut-off line of the number of brain metastases was between 3 and 4, and 3 or fewer brain metastases were significantly better than 4 or more in prognosis by univariate and multivariate analysis (p < 0.01, p = 0.02). CONCLUSIONS: The patients with 3 or fewer brain metastases were associated with brain progression free survival and 3 or fewer brain relapse. Repeated SRT without WBRT may be effective for patients with 3 or fewer brain metastases.

Preliminary results of fractionated stereotactic radiotherapy after cyst drainage for craniopharyngioma in adults.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for craniopharyngioma. METHODS AND MATERIALS: Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo Medical University Hospital. They received FSRT alone after histologic confirmation by needle biopsy and underwent cyst drainage via endoscopy. The median prescription dose fraction was 30 Gy in six fractions. All patients except 1 were followed up until December 2009 or death. RESULTS: The median follow-up period was 52 months (range, 4-117 months). Of the 17 patients, 3 experienced recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%. One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight patients had improved visual fields at a median of 2.5 months after FSRT, but hormonal functions did not improve in any patient. CONCLUSIONS: FSRT after cyst drainage seems to be safe and effective for patients with craniopharyngiomas, and it may be a safe alternative to surgery.

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin.

PURPOSE: Cisplatin has shown a high tumor response rate among head and neck carcinomas, and the tumor response is related to the cisplatin dosage. The purpose of this study was to evaluate the efficacy and toxicity of selective intraarterial chemoradiation therapy for oropharyngeal carcinomas with high-dose cisplatin. MATERIALS AND METHODS: This retrospective study consisted of 21 patients with oropharyngeal carcinoma, stages II-IVB, in whom intraarterial chemoradiation therapy was performed between 2000 and 2008. All patients were given two courses of selective intraarterial infusions of cisplatin (300 mg/m(2)), systemic chemotherapy with 5-fluorouracil, and simultaneous radiation therapy (58-61 Gy/30 fractions), with a 1-week rest period. RESULTS: The 2-year overall survival rate of the 15 patients who completed the therapeutic regimen was 71.3%. The 2-year locoregional control rate and disease-free survival rate were 95.0% and 67.7%, respectively. CONCLUSION: Selective intraarterial high-dose cisplatin chemotherapy with concomitant radiation therapy shows results similar to those of original methods in terms of survival and locoregional control with a reduction in the number of procedure times.

Diagnosis of uveal malignant melanoma by a new semiquantitative assessment of N-isopropyl-p-[123I]-iodoamphetamine.

PURPOSE: To semiquantify the uptake of N-isopropyl-p-[(123)I]-iodoamphetamine (I-123 IMP) in patients with uveal malignant melanoma reproducibly and objectively. METHODS: Fifty-two patients were examined. Twenty-nine patients had malignant melanoma (group A), three were clinically diagnosed with metastatic choroidal tumor, and 20 patients were given either histological or clinical diagnoses of either benign pigmented lesion or tumor (group B). Early and delayed I-123 IMP images were obtained and standardized by Neurostat software. Using fusion software, we applied a three-dimensional region of interest (3D-ROI) template to the standardized I-123 IMP, and calculated the retention index and tumor-to-nontumor (T/N) ratio of the delayed phase using the maximum count for each ROI. RESULTS: Sensitivity at the retention index cutoff of 30 was 82.4%, specificity was 85.2%, and accuracy was 83.6%. Sensitivity at the T/N ratio of the delayed phase cutoff of 1.3 was 91.2%, specificity was 77.8%, and accuracy was 85.2%. The positive predictive value of the T/N ratio was better than that of the retention index. The negative predictive value of the retention index was better than that of the T/N ratio. CONCLUSION: This new semiquantitative estimation method is reproducible and objective, especially when the examinations are performed repeatedly for evaluation of both therapy and follow-up.

Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival.

AIM: To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma. PATIENTS AND METHODS: The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months). RESULTS: At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater. CONCLUSION: Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.

Results of radiation therapy for superficial esophageal cancer using the standard radiotherapy method recommended by the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

BACKGROUND: Superficial esophageal cancer (SEC) is defined as esophageal cancer limited to the submucosal layers, including mucosal cancer and submucosal cancer, and is squamous cell carcinoma in most patients. In 2000, the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group for SEC published a consensus guideline of standard radiotherapy methods. In this study, the interim treatment outcomes of SEC patients, who had received radiation therapy following the standard radiotherapy methods, were investigated. PATIENTS AND METHODS: From 2000 to 2003, a total of 141 SEC patients were treated in 24 institutions in Japan. RESULTS: The 1-, 2- and 3-year survival rates were 95%, 90% and 90%, respectively, for patients with mucosal cancer and 90%, 81% and 70%, respectively, for patients with submucosal cancer. The overall survival was better in patients who had undergone chemotherapy than in patients who had received radiation therapy alone, though the difference was not statistically significant. The clinical target volume (CTV) did not influence overall survival and intracavitary irradiation did not influence the local control rate in either patients with mucosal or submucosal cancer. Radiation-induced esophageal ulcer was not observed in this series. CONCLUSION: The standard radiotherapy methods are safe and effective for treating SEC. However, the usefulness of chemotherapy and intracavitary irradiation and the optimal setting of the CTV should be clarified by future randomized trials.

Two cases of stereotactic radiosurgical boost as an initial treatment for young nasopharyngeal cancer patients.

Case 1: A 14-year-old boy with nasopharyngeal cancer (T4N0M0) was treated with stereotactic radiosurgery (SRS) as a boost therapy after conventional radiotherapy. Persistent residual tumor visible with MR remained after conventional radiotherapy comprising 59.6 Gy in total. We therefore performed SRS to add a further irradiation dose while causing minimal damage to adjacent normal tissue. SRS was performed using multiple non-coplanar arcs delivered to the residual tumor, which was defined to add 2 mm margins to the residual tumor. This was 30 cc as defined by CT and MR images. Twenty Gy were administered to the periphery of the planning target volume (PTV), corresponding to the 80% isodose line. No recurrences or late complications have been observed 4 years and 6 months after the SRS. Case 2: A 27-year-old man with nasopharyngeal cancer (T1N0M0) was treated with SRS as a boost therapy following conventional radiotherapy with 55 Gy. The SRS was performed using multiple non-coplanar arcs delivered to the PTV, which was 10 cc as defined by CT and MR images as in case 1. Sixteen Gy were administered to the periphery of the residual tumor, corresponding to the 80% isodose line. The tumor was not visible on follow-up MR images and no complications have been observed 4 years and 2 months after the SRS.

[Second malignancies following radiotherapy: an analysis of 54 cases accumulated by mail survey in Japan].

The increasing incidence of second malignant neoplasms after radiotherapy, while due in part to increasing numbers of survivors, is also thought to be related to new modalities of radiotherapy and/or increasingly more intensive combined modality treatment. From a mail survey conducted in 2000 concerning secondary neoplasms following radiotherapy, 62 patients were collected from 22 hospitals in Japan. The following patients were excluded: benign (4 cases) or unknown (2) first primary diseases, unknown histology of a second malignancy (1), and short latent period (from initial radiotherapy to diagnosis of second neoplasm) (1). Fifty-four patients with second malignancies were analyzed. The most common histology of second malignancies was squamous cell carcinoma (24 cases), followed by sarcoma (16), glioma (5), adenocarcinoma (3), leukemia (3), and others (3). The mean latent period was 17.7 (2-38) years. We investigated the correlation of the latent period with patient's characteristics or initial therapeutic factors. Multivariate analysis revealed that the latent period was significantly shortened in patients with combined chemotherapy and radiotherapy.