Yoshie Takada

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.

Multi-institutional Analysis of Solitary Extramedullary Plasmacytoma of the Head and Neck Treated with Curative Radiotherapy

PURPOSE The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN). METHODS AND MATERIALS Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12-83). The median dose administered was 50 Gy (range, 30-64 Gy). Survival data were calculated by the Kaplan-Meier method. RESULTS The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity. CONCLUSIONS Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN.

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.

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.

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.

Limited-stage small cell lung cancer: local failure after concurrent chemoradiotherapy with use of accelerated hyperfractionation

PurposeThe aim of this study was to update data of radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer, a retrospective study was conducted.Materials and methodsResults of early concurrent chemoradiotherapy with accelerated hyperfractionation in 30 patients between 1998 and 2005 were retrospectively reviewed. The prescribed dose was 45 Gy in 30 fractions in all patients.ResultsAll patients received a full dose of radiation therapy; however, interruptions for ≥5 days, mainly due to hematologic toxicity, were required in 18 patients (60%). The 5-year Kaplan-Meier survival rate and the median survival time were 26% and 26 months, respectively. The 4-year in-field control rate was 56%. Sites of relapse were local relapse in 9 patients (6 for in-field relapse, 3 for marginal relapse) and distant metastases in 16 patients (11 for distant metastases only, 5 for distant metastases with local relapse). The sites of marginal relapse were the upper margin in two patients and the peripheral margin in one patient. Grade 3 radiation esophagitis was observed in only three patients.ConclusionBecause in-field control was insufficient, a more effective approach should be sought to provide better local control.

Accelerated hyperfractionated irradiation with concomitant boost for stage II laryngeal cancer and locally advanced head and neck cancer.

Objective This study was conducted to evaluate the efficacy and feasibility of our accelerated hyperfractionation with concomitant boost for stage II laryngeal cancer and stages III–IVb locally advanced head and neck cancer. Patients and methods From January 2000 to October 2001, eight patients with AJCC 1998 stage II laryngeal cancer and 11 patients with AJCC 1998 stages III–IVb locally advanced head and neck cancer underwent accelerated hyperfractionated radiation therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8 and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For stages III–IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with 1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients, 16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin. Acute toxicity based on RTOG criteria and tumor response at 1 month post-treatment were estimated as initial effects. Results The overall response rate was 100% in patients with stage II laryngeal cancer and 91% in patients with stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute effects was 47%. Eighteen patients (95%) completed radiation therapy without interruption related to acute side effects, while one had prolongation of the treatment for more than 1 week because of neutropenia. Conclusions Our results demonstrated that accelerated hyperfractionation, mostly combined with concomitant chemotherapy, had a good overall response rate with acceptable toxicity in stage II laryngeal cancers and stages III–IVb head and neck tumors.