Author Correction: Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer.

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Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer.

To compare the outcome of low-dose rate brachytherapy (LDR-BT) and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer, we examined 488 LDR-BT and 269 IG-IMRT patients. IG-IMRT treated older and advanced disease with more hormonal therapy than LDR-BT, which excluded T3b-T4 tumor and initial PSA > 50 ng/ml. The actuarial five-year biochemical failure-free survival rate was 88.7% and 96.7% (p = 0.0003) in IG-IMRT and LDR-BT, respectively; it was 88.2% (85.1% for IG-IMRT and 94.9% for LDR-BT, p = 0.0578) for the high-risk group, 95.2% (91.6% and 97.0%, p = 0.3361) for the intermediate IG-IMRT and 96.8% (95.7% and 97%, p = 0.8625) for the low-risk group. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. IPTW showed a statistically significant difference between LDR-BT and IG-IMRT in high risk (p = 0.0009) and high risk excluding T3-4/initial PSA > 50 ng/ml group (p = 0.0073). IG-IMRT showed more gastrointestinal toxicity (p = 0.0023) and less genitourinary toxicity (p < 0.0001) than LDR-BT. LDR-BT and IG-IMRT showed equivocal outcome in low- and intermediate-risk groups. For selected high-risk patients, LDR-BT showed more potential to improve PSA control rate than IG-IMRT.

Outcome and toxicity of stereotactic body radiotherapy with helical tomotherapy for inoperable lung tumor: analysis of Grade 5 radiation pneumonitis.

To analyze outcomes and toxicities of stereotactic body radiotherapy with helical tomotherapy (HT-SBRT) for inoperable lung tumors, the medical records of 30 patients with 31 lung tumors treated with HT-SBRT were reviewed. The 3-year local control, cause-specific survival and overall survival rates (LC, CCS and OS, respectively) were analyzed using the Kaplan-Meier method. Toxicities were graded using Common Terminology Criteria for Adverse Events ver. 4. To investigate the factors associated with Grade 5 radiation pneumonitis (G5 RP), several parameters were analyzed: (i) patient-specific factors (age, gross tumor volume and PTV, and the interstitial pulmonary shadow on pretreatment CT); and (ii) dosimetry-specific factors (conformity index, homogeneity index, mean lung dose, and V5, V10, V15, V20 and V25 of the total lungs). The median duration of observation for all patients was 36.5 months (range, 4-67 months). The 3-year LC, CCS and OS were 82, 84 and 77%, respectively. Regarding Grade 3 or higher toxicities, two patients (6.7%) developed G5 RP. GTV was significantly associated with G5 RP (P = 0.025), and there were non-significant but slight associations with developing G5 RP for V5 (P = 0.067) and PTV (P = 0.096). HT-SBRT led to standard values of LC, CCS and OS, but also caused a markedly higher incidence of G5 RP. It is essential to optimize patient selection so as to avoid severe radiation pneumonitis in HT-SBRT.

Hypofractionated stereotactic radiotherapy with the hypoxic sensitizer AK-2123 (sanazole) for reirradiation of brain metastases: a preliminary feasibility report.

Reirradiation is a challenging field in the treatment of recurrent brain metastases. Because of the elevated risk of radiation toxicity due to previous irradiation, only a limited dose is prescribed. To enhance radiosensitivity, in the present analysis six patients received hypofractionated stereotactic radiotherapy (hSRT) with daily oral administration of the hypoxic sensitizer AK-2123 (sanazole) for progressive brain metastases after previous radiotherapy. The patients received daily oral administration of 1.0 g/day sanazole up to 2 h before radiotherapy. Three partial and three stable responses were observed, with no sanazole-related toxicity, except for a case of mild nausea. Brain failure with subsequent death occurred in one patient. The other patients maintained good performance status until disease progression in other lesions. hSRT with a hypoxic radiation sensitizer appears to have the potential to enhance the efficacy of radiotherapy.

Feasibility trial for daily oral administration of the hypoxic sensitizer AK-2123 (Sanazole) in radiotherapy.

BACKGROUND: To examine the feasibility of daily oral administration of the hypoxic tumor radiation sensitizer, sanazole (AK-2123). PATIENTS AND METHODS: We analyzed the toxicity associated with 44 treatments of 42 patients, who received daily oral administration of 1 g/day sanazole (level A, 1-9g, 12 treatments; Level B, 10 g, 33 treatments) 2 h before radiotherapy. Eligibility criteria were as follows: Patients who were unable to receive standard treatment because of older age and/or fragile status and/or refractory disease. Five patients with advanced tumors treated with pre- or postoperative adjuvant radiotherapy were also included. RESULTS: Toxicity was assessed during 44 treatment sessions. Eight patients (18%) showed sanazole-related paresthesia in the extremities, similar to the rate (15%) reported in a preceding multi-institutional international phase III study, which used intravenous administration. No sanazole-related toxicity rated grade 3 or higher was observed. Forty out of the 44 treatment sessions (91%) were completed. CONCLUSION: This study validates the feasibility of daily oral administration of sanazole. Further studies to establish suitable applications are warranted.

Evaluation of dosimetry and excess seeds in permanent brachytherapy using a modified hybrid method: a single-institution experience.

Permanent prostate brachytherapy is frequently performed worldwide, and many studies have demonstrated its favorable outcomes. Implant seeds used in this procedure contain a precise amount of radionuclide and are completely sealed. Because these seeds are not manufactured in Japan, they are expensive (6300 yen per seed) and therefore need careful management as a radioisotope. The proper implantation technique requires considerable procedure time, good dosimetric outcomes and simple radioactive isotope management. To evaluate the modified hybrid interactive technique based on these considerations, we assessed 313 patients who underwent hybrid interactive brachytherapy without additional external beam radiotherapy. We evaluated the duration of the procedure, dosimetric factors and the total number of excess seeds. The dosimetric results from computed tomography on Day 30 of follow-up were: 172 Gy (range 130-194 Gy) for pD90, 97.8% (83.5-100%) for pV100, 54.6% (27.5-82.4%) for pV150, 164 Gy (120-220 Gy) for uD90, 194 Gy (126-245 Gy) for uD30, 210 Gy (156-290 Gy) for uD5, 0.02 ml (0-1.2 ml) for rV100 and 0 ml (0-0.2 ml) for rV150. The number of excess seeds was determined by subtracting the number of implanted seeds from the expected number of seeds calculated from previously proposed nomograms. As per our method, nine excess seeds were used for two patients, whereas using the nomograms, the number of excess seeds was approximately eight per patient. Our modified hybrid interactive technique reduced the number of excess seeds while maintaining treatment quality.

Assessment of radiation dermatitis using objective analysis for patients with breast cancer treated with breast-conserving therapy: influence of body weight.

PURPOSE: To evaluate the effect of patient factors on radiation dermatitis for patients with breast cancer who underwent postoperative radiotherapy after breast-conserving surgery. MATERIALS AND METHODS: The study population comprised 87 patients who underwent breast-conserving surgery followed by 50 Gy/25 fractions (median) of radiotherapy with or without boost radiation (10 Gy/5 fractions). We examined their treated and contralateral breast skin color by use of an objective analyzer, and expressed findings as L, a, b ratios by dividing by pre-RT values. Next, we examined correlation between patient factors (age, height, body weight, and body mass index, BMI) and change of L and a values by use of correlation coefficients. RESULTS: Radiation therapy caused changes in a and L ratios (p < 0.0001) but not in b ratio. The a ratio (reddish) increased 1.4-fold and peaked after radiotherapy. The L ratio (darkening) decreased by 10 % and reached a minimum value between completion of radiotherapy and 1 month after treatment. Although, age and height did not affect Δ value, body weight and BMI correlated significantly with Δa value (p = 0.0012 and 0.0017) not with ΔL value. CONCLUSION: Body weight and BMI predict degree of radiation dermatitis, and more reddish dermatitis was observed for heavier patients than for their lighter counterparts.

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract.

BACKGROUND: To assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise. METHODS: We quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan. RESULTS: The median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm3 (range, 7.17-14.3 cm3) and 1.99 for pituitary adenoma, and 6.86 cm3 (range 6.05-14.6 cm3) and 2.41 for meningioma. PTV volume was 10.1±1.74 cm3 for group 1 with a margin of 1-2 mm around the CTV (n=3) and 9.28±1.8 cm3 (p=0.51) for group 2 with no margin (n=7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1±3.26 cm3) than group 2 (6.91±0.7 cm3, p=0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring. CONCLUSION: Quality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.

Stereotactic body radiation therapy for head and neck tumor: disease control and morbidity outcomes.

We evaluated the efficacy and safety of stereotactic body radiation therapy (SBRT) for patients with head and neck tumors. From April 2005 through April 2008, 34 patients with head and neck tumors were treated with CyberKnife SBRT. Twenty-one of them had prior radiotherapy. Treatment sites were orbit (n = 7), cervical lymph nodes (n = 6), nasopharynx (n = 5), oropharynx (n = 4) and others (n = 12). The prescribed dose ranged from 19.5 to 42 Gy (median, 30 Gy) in 3-8 fractions for consecutive days. The target volume ranged from 0.7 to 78.1 cm(3) (median, 11.6 cm(3)). The median follow-up was 16 months. Treatment was well tolerated without significant acute complications in any cases. Complete response rate and partial response rate were 32.4% and 38.6%, respectively. The overall survival rates were 70.6% and 58.3% at 12 and 24 months, respectively. The overall survival was better in patients without prior radiotherapy within the previous 24 months or in case of smaller target volume. Six patients suffered severe late complications. All these patients had prior radiotherapy, and 2 of them developed massive hemorrhage in the pharynx and both died of this complication 5 and 28 months, respectively, after SBRT. Our preliminary results suggest that SBRT is an effective treatment modality for head and neck tumors. However, re-irradiation has significant risk of severe and even fatal late complications in the form of necrosis and hemorrhage in re-irradiated areas.

Longitudinal practical measurement of skin color and moisture during and after breast-conserving therapy: influence of neoadjuvant systemic therapy.

PURPOSE: The aim of this study was to assess radiation dermatitis, especially exploring the influence of neoadjuvant systemic therapy (NST). MATERIALS AND METHODS: We examined maximum toxicity using the Common Toxicity Criteria version 3 score (CTC v3) following radiotherapy between 40 patients treated with NST and 59 patients without NST. In addition, objective skin color (L*, a*, b* values) and moisture analyses were applied in 13 NST and 25 control patients, and the ratio of the values for the irradiated side to the nonirradiated side was calculated. RESULTS: For the CTC v3 assessment, 27 grade 1 (68%) and 13 grade 2 (32%) reactions occurred in the NST group and 44 grade 1 (75%) and 15 grade 2 (25%) reactions in the control group. All ratios except the b* ratio showed significant alterations when radiotherapy was added. The ratio of the a* value peaked at the completion of radiotherapy, whereas the L* ratio bottomed out 1 month later. Furthermore, moisture change remained even 1 year after treatment. Boost irradiation doses caused enhanced alterations in the L* and a* ratios. Furthermore, the L* and a* ratios had good agreement with the CTC v3 assessment. NST did not enhance alterations. CONCLUSION: Objective analysis is useful for detailed assessment of radiation dermatitis. NST did not worsen skin reactions.

Prognostic and clinical evaluation of axillary lymph node metastasis in esophageal cancer.

Axillary lymph node metastasis (ALNM) from esophageal cancer is rare. Its prognosis and effective treatments remain unknown. Between 1997 and 2005, esophagectomy was performed in 361 patients with esophageal cancer in our hospital. ALNM was identified in four patients (1.1%). All patients had left ALNM with ipsilateral left supraclavicular lymph node metastasis. In two patients ALNM developed after radical esophagectomy with regional lymphadenectomy and in the other two patients after chemoradiotherapy of primary lesions. Axillary lymphadenectomy with chemoradiotherapy was given to all patients. Median survival time and disease-free survival (DFS) after initial treatment for primary esophageal cancer were 30.5 months and 11.5 months, respectively. One patient, who had a small number of regional lymph node metastases (two lymph nodes) at esophagectomy and prolonged DFS (22 months) until axillary node recurrence, is still alive, 67 months after axillary lymphadenectomy. The other three patients, who had larger numbers of regional lymph node metastases (average, 8.3) and shorter DFS (average, 9.7 months), died of recurrence an average of 13.3 months after axillary lymphadenectomy. In conclusion, although ALNM is considered a type of distant organ metastasis, if it is a solitary recurrence, good survival may be obtained after appropriate loco-regional therapy. The number of metastatic regional lymph nodes at initial esophagectomy and the duration of DFS until axillary node recurrence can help to guide the decision whether aggressive treatments are warranted.

Phase I/II trial of biweekly docetaxel and cisplatin with concurrent thoracic radiation for stage III non-small-cell lung cancer.

OBJECTIVES: We conducted phase I and II studies of biweekly docetaxel and cisplatin with concurrent radiotherapy, followed by consolidation chemotherapy with the same drugs in patients with locally advanced, unresectable non-small-cell lung cancer (NSCLC). Our objectives were to define the maximum-tolerated dose and dose-limiting toxicity (DLT) in the phase I study, and to determine the response rate, toxicity, and survival rate at the recommended dose (RD) in the phase II study. METHODS: Patients with unresectable stage IIIA and IIIB NSCLC were studied. Six to eight cycles of docetaxel and cisplatin were administered at 2-week intervals. In the phase I study, patients received four dose levels: level 1, docetaxel/cisplatin=30/40 mg/m2; level 2, 35/40; level 3, 40/40; and level 4, 45/40. Radiotherapy was delivered at a rate of 2 Gy per fraction/day up to a total dose of 60 Gy over the course of 6 weeks, during the first three cycles of chemotherapy. RESULTS: DLT comprised neutropenia at level 4 in the phase I study (n=15), and level 3 was considered the RD. In the phase II study (n=46), two patients had a complete response (4.3%) and 34 had a partial response (73.9%), for an overall response rate of 78.2% [95% CI (66.3-90.2%)]. The survival rate was 69.1% at 1 year and 39.6% at 2 years, with a median survival time of 19.1 months. Leukopenia, neutropenia, anemia, and radiation esophagitis were the most common toxic reactions, with Grade > or = 3 reactions occurring at rates of 77, 70, 17, and 8%, respectively. CONCLUSION: Biweekly docetaxel and cisplatin with concurrent RT was active and well tolerated in patients with unresectable stage III NSCLC.

Pattern of 111In-chloride bone marrow scintigraphy in myelodysplastic syndrome; comparison with clinical characteristics.

111In-chloride bone marrow scintigraphy (bone marrow scintigraphy) was performed in patients with myelodysplastic syndrome (MDS), tracer accumulation was classified into patterns, and the relationship between the accumulation patterns and prognostic factors was investigated to assess the usefulness of bone marrow scintigraphy. The subjects were 14 patients diagnosed with MDS. Accumulation of the bone marrow scintigraphy tracer was classified according to the degree of accumulation in the axial bone marrow and peripheral expansion. International Prognostic Scoring System (IPSS), which are frequently used for prognostic evaluation of MDS, and conversion to leukemia were investigated in prognostic factors. We also investigated the relationship between enlargement of the liver and spleen and the prognostic factors. The accumulation patterns were as follows: pattern I, The normal accumulation pattern (2 cases); pattern II, the expanded accumulation pattern (6 cases); pattern III, low accumulation pattern (5 cases); and pattern IV, heterogeneous accumulation pattern (1 case). The relationships between the two prognostic factors and accumulation patterns were investigated, and the prognosis was found to be significantly poorer in the patients with the low accumulation pattern than the expanded accumulation pattern. Enlargement of the liver and spleen was not significantly correlated with the prognostic factors.