Masako Hosono

Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy.

BackgroundWe evaluated the efficacy and toxicity of reirradiation for patients with loco-regional relapse of non-small-cell lung cancer after radiation therapy.MethodsBetween 1992 and 2002, 19 patients with loco-regional relapse underwent reirradiation. The median interval between the initial irradiation and reirradiation was 16 months, with a range of 5 to 60 months. The prescribed dose of reirradiation was 50 Gy in 25 fractions over 5 weeks for 18 patients and 60 Gy in 30 fractions over 6 weeks for 1 patient.ResultsFive patients could not receive the prescribed dose of reirradiation. The response rate was 43% among the 14 patients who received the prescribed dose of reirradiation. The overall 1-year and 2-year Kaplan-Meier survival rates were 26% and 11%, respectively, and the median survival time was 7.1 months. The median survival times associated with intervals between the initial irradiation and reirradiation of less than 12 months, 12–18 months, and more than 18 months were 2.1, 7.1, and 11.5 months, respectively. There were significant differences in survival between patients with an interval of less than 12 months and those with an interval of 12–18 months, and between those with an interval of less than 12 months and those with an interval of more than 18 months (generalized Wilcoxon method; P < 0.05 for both). Grade 3 radiation pneumonitis and grade 2 radiation esophagitis occurred in 1 and 3 patients, respectively.ConclusionReirradiation is considered to contribute to salvage in selected patients with relapsed non-small-cell lung cancer. Patients with a long interval after the initial irradiation are good candidates for reirradiation. On the other hand, patients with Eastern Cooperative Oncology Group (ECOG) performance status 3 were not goodcandidates.

Direct impact analysis of multi-leaf collimator leaf position errors on dose distributions in volumetric modulated arc therapy: a pass rate calculation between measured planar doses with and without the position errors*

We propose a new method for analyzing the direct impact of multi-leaf collimator (MLC) leaf position errors on dose distributions in volumetric modulated arc therapy (VMAT). The technique makes use of the following processes. Systematic leaf position errors are generated by directly changing a leaf offset in a linac controller; dose distributions are measured by a two-dimensional diode array; pass rates of the dose difference between measured planar doses with and without the position errors are calculated as a function of the leaf position error. Three different treatment planning systems (TPSs) were employed to create VMAT plans for five prostate cancer cases and the pass rates were compared between the TPSs under various leaf position errors. The impact of the leaf position errors on dose distributions depended upon the final optimization result from each TPS, which was explained by the correlation between the dose error and the average leaf gap width. The presented method determines leaf position tolerances for VMAT delivery for each TPS, which may facilitate establishing a VMAT quality assurance program in a radiotherapy facility.

Use of FDG-microPET for detection of small nodules in a rabbit model of pulmonary metastatic cancer

ObjectiveThe performance of microPET using18F-FDG was evaluated in a rabbit model of hematogenous pulmonary metastatic cancer.MethodsA total of 15 Japanese white rabbits and VX-2 carcinoma were used in this study. In the microPET study, tumor-bearing rabbits were administered intravenously 74 MBq of18F-FDG, and 30 min later, the emission data were acquired for 60 min. The transmission scans were performed with a68Ge/68Ga external point source. To augment the anatomical information, we performed multi-detector row computed tomography (MDCT) in the combination with MDCT and microPET on 10 rabbits. The other 5 rabbits were followed once a week for 5 weeks only by microPET. Tumor/muscle (T/M) ratios were used for quantitative evaluation in this study.ResultsMultiple pulmonary nodules were detected by MDCT and microPET starting 14 days after the tumor injection. The high-uptake lesions in the lung detected by microPET corresponded well to the tumors detected by MDCT. The smallest nodule detected by microPET was ca. 1.5 mm in diameter. Overall, 87 nodules were detected by MDCT and the ratios of lesions detected by microPET to those by MDCT were 35.3%, 77.5%, and 90% for tumors equal to or smaller than 2 mm, 2-4 mm, and 4-6 mm in diameter, respectively. The respective T/M ratios were 2.41 ±0.41, 2.93 ± 0.55, and 3.34 ±0.71. The T/M ratio increased with tumor size, but it was similar in each tumor size category. In the 35-day follow-up protocol, it was possible to follow sequentially the same tumor by the microPET.ConclusionsBy FDG-microPET, it is possible to evaluate tumors larger than 2 mm in diameter and to follow the growth of individual tumors. Our results also suggest that the rabbit model of VX-2 pulmonary metastasis is a stable experimental model for evaluation using FDG. Monitoring of the therapeutic effects of anticancer drugs and radiation therapy could be tried by using this model and microPET.

Non-small cell lung cancer: radiation therapy for locoregional recurrence after complete resection

BackgroundWe investigated patterns of failure after radical radiation therapy in relation to the radiation field in patients with postsurgical locoregional recurrence of non-small cell lung cancer.MethodsBetween 1992 and 2002, 31 patients with locoregional recurrence were treated with radiation therapy. At the time of radiation therapy, the sites of recurrence were the bronchial stump, the regional lymph nodes, the chest wall, and both the regional lymph nodes and the chest wall in 7, 20, 3, and 1 patient, respectively. The prescribed dose was 60 Gy in 30 fractions over 6 weeks in all patients.ResultsThe response rate was 87%. The overall 1-year, 2-year, and 4-year Kaplan-Meier survival rates were 61%, 30%, and 15%, respectively, and the median survival time was 14 months. Locoregional relapse with or without distant metastasis occurred in 15 patients (in-field, 7; marginal, 7; out-field, 1), and distant metastasis alone occurred in 7 patients. The sites of marginal relapse were the upper margin in two patients, the ipsilateral margin in one patient, the contralateral margin in one patient, and the lower margin in three patients, respectively (in one patient, the data for marginal relapse overlapped). In all patients with relapse on the lower margin, the mediastinal lymph nodes were dissected at the initial surgery.ConclusionPostoperative recurrent non-small cell lung cancer showed distinctive features: the response rate was high, and the incidence of marginal relapse was also high, as in small cell lung cancer. The incidence of lower marginal relapse was high, in contrast to that in surgery-naive patients.

Single institutional experience of the treatment of angiosarcoma of the face and scalp

OBJECTIVE Angiosarcoma is a rare malignant neoplasm with a poor prognosis. A retrospective study was performed to accumulate radiotherapy (RT) data. METHODS Data from 17 patients with angiosarcoma of the face and scalp (AFS) who were treated with definitive RT between January 1999 and July 2011 were retrospectively analysed. The total radiation dose was 70 Gy, and the fractional doses were 2.0-2.5 Gy. Combined with RT, chemotherapy using docetaxel alone, recombinant interleukin-2 immunotherapy alone and both of these was performed in 10, 4 and 2 patients, respectively. Three patients underwent limited surgery before RT. RESULTS The response rate was 82%, and the median overall survival (OS) rate was 26 months. Locoregional relapse alone, distant metastasis alone and both of these were confirmed in 4, 5 and 4 patients, respectively. Patients treated with docetaxel showed a better prognosis (p=0.0477), a distant metastasis-free rate (p=0.0063) and a better in-field control rate, although the last was not statistically significant (p=0.1645). CONCLUSION Definitive RT combined with docetaxel chemotherapy provided an effective approach for treating AFS. ADVANCES IN KNOWLEDGE Since patients treated with chemoradiotherpy using docetaxel showed better OS and distant metastasis-free rates than those who did not receive docetaxel, it was warranted to continue use of docetaxel. In chemoradiotherapy at a dose of 70 Gy using docetaxel, 2-year in-field control rate was 67%.

Case report: Uptake of pentavalent technetium-99m dimercaptosuccinic acid by pigmented villonodular synovitis: comparison with computed tomography, magnetic resonance imaging and gallium-67 scintigraphy

The scintigraphic findings of a patient with pigmented villonodular synovitis are described and compared with the computed tomography and magnetic resonance imaging data. Intense uptake of pentavalent technetium-99m dimercaptosuccinic acid without gallium-67 citrate uptake indicates that pigmented villonodular synovitis has the features of a hyperplastic or neoplastic lesion rather than an inflammatory lesion from the point of view of nuclear medicine.

Usefulness of FDG-microPET for early evaluation of therapeutic effects on VX2 rabbit carcinoma

PurposeThe aim of this study was to determine the potential use of high-resolution FDG-microPET for predicting the primary effects of radiotherapy and/or hyperthermia on tumor-bearing rabbits.MethodsTwenty-eight VX2 xenografts in the thighs of rabbits were divided into the following 5 treatment groups: radiotherapy at a single dose of 10, 20 or 30 Gy, hyperthermia (43 degrees Celsius, 1 hour), and the combination of radiotherapy and hyperthermia ( 10 Gy + 43 degrees Celsius, 1 hour). FDG-microPET images were obtained by using a microPET P4 system at pretreatment and at 24 hours and 7 days after treatment. For the evaluation by FDG-microPET, tumor/muscle (T/M) ratios, retention index [RI = (T/M ratio at 120 min - T/M ratio at 60 min) / T/M ratio at 60 min], and time activity curve (TAC) were acquired.ResultsWe divided the xenografts into a responder group (partial response + stable disease, n = 14) and a non-responder group (progressive disease, n = 14). The T/M ratio at 24 hours after the treatment in the responder group was decreased remarkably with that at pre-treatment (p < 0.05), while in the non-responder group it showed no significant change between the time points. The RI and TAC patterns were comparable to T/M ratios in each treatment group. T/M ratios, RI, and TAC indicated marked changes at the time point of 24 hours in the responder group, although the tumors did not show any significant change in volume at that time. Photomicrographs of sections showed that the number of viable tumor cells in the responder group decreased at 24 hours after treatment and that inflammatory cell infiltration was marked and almost all viable tumor cells had disappeared by day 7 after treatment.ConclusionThese results suggest that early evaluation by FDG-microPET, especially 24 hours after treatment, is useful to predict the primary effects of the treatment. Histological analysis showed that inflammatory cell infiltration at 7 days after treatment was considered to be a cause of accumulation of FDG in the tumors that showed a significant decrease in tumor cell number. This false-positive should be noted when predicting tumor response by FDG accumulation.

Rhenium-188-labeled anti-neural cell adhesion molecule antibodies with 2-iminothiolane modification for targeting small-cell lung cancer

We have evaluated the potential of188Re-labeled monoclonal antibodies (MAbs) modified with 2-iminothiolane (2IT) for targeting small-cell lung cancer (SCLC). Radiolabeled MAbs NK1NBL1 and C218 recognizing neural cell adhesion molecule were injected i.v. into athymic mice inoculated with human SCLC tumors, and the biodistribution was examined. NK1NBL1 localized in the tumors better than C218.188Re-labeled MAbs cleared from the blood faster than125I-labeled counterparts, resulting in higher tumor-to-blood ratios. In conclusion, the188Re-labeled MAbs are attractive candidates for imaging and therapy of SCLC.

Localization of Small‐cell Lung Cancer Xenografts with Iodine‐125‐, Indium‐111‐, and Rhenium‐188‐Somatostatin Analogs

We examined the potential of radiolabeled somatostatin analogs, 125I‐Tyr‐3‐octreotide (125I‐octreotide), 111In‐DTPA(diethylenetriaminepentaacetatic acid)‐d‐Phe‐1‐octreotide (111In‐octreotide), and 188Re‐octreotide for targeting small‐cell lung cancer (SCLC) in a mouse model. Tyr‐3‐octreotide was labeled with 125I by the chloramine T method, and 111In‐octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I‐, 111In‐, and 188Re‐octreotides were injected i.v. into athymic mice bearing NCI‐H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5±0.2, 0.3±0.1, 0.3±0.1 %ID/g, and tumor‐to‐blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I‐, 111In‐, and 188Re‐octreotides, respectively. Accumulations of 111In‐octreotide in normal tissues were lower than those of 125I‐ and 188Re‐octreotides. 188Re‐octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In‐octreotide was the most suitable agent to obtain high tumor‐to‐normal tissue contrast for localizing SCLC.

Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia.

The combined effect of granulocyte-colony stimulating factor (GCSF) and hyperthermia in the treatment of experimental tumours was studied to examine the possible involvement of activated granulocytes in the antitumour effect of hyperthermia. Two weeks after transplantation of SCC VII cells (1 x 105) into the instep of the left leg of C3H/HeJ male mice, the mice were given subcutaneous injections of GCSF (0.2mg/kg) for 4 days. On day 4, hyperthermia was applied locally at 43 C for 40min. Hyperthermia inhibited the tumour growth, and this effect was enhanced by pre-treating the animals with GCSF. The numbers of circulating neutrophils in control and GCSF-treated mice were 2728 +/- 517/mul and 3124 +/- 194/mul, respectively ( p = 0.53). Hyperthermia increased the number of neutrophils to 4409 +/- 700/mul ( p < 0.05). Hyperthermia combined with GCSF significantly increased the number of netrophils to 5479 +/- 691/mul ( p < 0.01). Chemiluminescence analysis using L-012 revealed that GCSF enhanced the generation of reactive oxygen species by about 10-fold. Glutathione contents in tumours 24h after hyperthermia decreased by about 50% in both the hyperthermia groups with or without GCSF, as compared to those in the control. The GCSF-enhanced anti-tumour activity of hyperthermia was markedly inhibited by administration of a long-acting superoxide dismutase derivative (SM-SOD). These results suggest that GCSF activates the ability to generate active oxygen species by neutrophils and, thereby, enhances the anti-tumour effect of hyperthermia.