Quality of palliative radiotherapy assessed using quality indicators: a multicenter survey†.

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.

Who should receive single-fraction palliative radiotherapy for gastric cancer bleeding?: An exploratory analysis of a multicenter prospective observational study (JROSG 17-3).

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer. Materials and methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival. Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival. Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy.

Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: a multicenter cohort study.

BACKGROUND: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis. METHODS: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group. RESULTS: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group. CONCLUSIONS: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

Diffuse goitre enlargement after immunotherapy for non-small cell lung cancer.

It is well known that a phenomenon called hyperprogressive disease (HPD) often occurs during immunotherapy with immune checkpoint inhibitors. In the present case, we experienced a case of HPD in a potential metastatic thyroid tumour during immunotherapy. HPD can be life-threatening depending on where it appears, so clinicians need to be careful.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab.

INTRODUCTION: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors. MATERIALS AND METHODS: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP. RESULTS: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007). CONCLUSION: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.

Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan.

BACKGROUND: International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. METHODS: Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. RESULTS: Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. CONCLUSIONS: Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Practice patterns for postoperative radiation therapy in patients with metastases to the long bones: a survey of the Japanese Radiation Oncology Study Group.

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens.

Application and limitation of radiomics approach to prognostic prediction for lung stereotactic body radiotherapy using breath-hold CT images with random survival forest: A multi-institutional study.

PURPOSE: To predict local recurrence (LR) and distant metastasis (DM) in early stage non-small cell lung cancer (NSCLC) patients after stereotactic body radiotherapy (SBRT) in multiple institutions using breath-hold computed tomography (CT)-based radiomic features with random survival forest. METHODS: A total of 573 primary early stage NSCLC patients who underwent SBRT between January 2006 and March 2016 and met the eligibility criteria were included in this study. Patients were divided into two datasets: training (464 patients in 10 institutions) and test (109 patients in one institution) datasets. A total of 944 radiomic features were extracted from manually segmented gross tumor volumes (GTVs). Feature selection was performed by analyzing inter-segmentation reproducibility, GTV correlation, and inter-feature redundancy. Nine clinical factors, including histology and GTV size, were also used. Three prognostic models (clinical, radiomic, and combined) for LR and DM were constructed using random survival forest (RSF) to deal with total death as a competing risk in the training dataset. Robust models with optimal hyper-parameters were determined using fivefold cross-validation. The patients were dichotomized into two groups based on the median value of the patient-specific risk scores (high- and low-risk score groups). Gray's test was used to evaluate the statistical significance between the two risk score groups. The prognostic power was evaluated by the concordance index with the 95% confidence intervals (CI) via bootstrapping (2000 iterations). RESULTS: The concordance indices at 3 yr of clinical, radiomic, and combined models for LR were 0.57 [CI: 0.39-0.75], 0.55 [CI: 0.38-0.73], and 0.61 [CI: 0.43-0.78], respectively, whereas those for DM were 0.59 [CI: 0.54-0.79], 0.67 [CI: 0.54-0.79], and 0.68 [CI: 0.55-0.81], respectively, in the test dataset. The combined DM model significantly discriminated its cumulative incidence between high- and low-risk score groups (P < 0.05). The variable importance of RSF in the combined model for DM indicated that two radiomic features were more important than other clinical factors. The feature maps generated on the basis of the most important radiomic feature had visual difference between high- and low-risk score groups. CONCLUSIONS: The radiomics approach with RSF for competing risks using breath-hold CT-based radiomic features might predict DM in early stage NSCLC patients who underwent SBRT although that may not have potential to predict LR.

Acute onset of ulcerative colitis during chemoradiotherapy for anaplastic lymphoma kinase-positive lung adenocarcinoma.

We report a case of acute onset of ulcerative colitis (UC) during chemoradiotherapy in a patient with anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. A 46-year-old male patient with an abnormal chest shadow was referred to our hospital. He was diagnosed with lung adenocarcinoma, clinical stage T1aN3M0 and stage IIIB. Concurrent chemoradiotherapy was selected for his initial therapy. After two cycles of cisplatin and vinorelbine administration, he experienced persistent diarrhoea and anorexia. Findings of the colonoscopy revealed a pancolitis type of UC. After discontinuation of chemotherapy, oral administration of mesalazine was initiated. The development of UC during chemotherapy is very rare and only a few case reports have been published. Although adverse events are rare, it is very important to assess the colitis precisely by performing a colonoscopy when protracted abdominal pain is experienced by the patient, along with diarrhoea or bloody stool during chemotherapy.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method.

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior-posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful.

Solitary oropharyngeal neurofibroma: MR appearance with pathologic correlation and review of the literature.

Although neurofibroma is a common soft tissue tumor of the head and neck, neurofibroma of the oropharynx is extremely rare. Here, we report a case of neurofibroma of the palatine tonsil. Magnetic resonance imaging was useful in demonstrating the location of the tumor as well as its well-defined appearance. The present case showed a target sign; the tumor exhibited peripheral hyperintensity and central hypointensity on T2-weighted images, reflecting its characteristic zonal anatomy.

Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021).

OBJECTIVE: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS: Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS: Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS: Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.

Hypofractionated stereotactic radiotherapy for acoustic neuromas: safety and effectiveness over 8 years of experience.

BACKGROUND: Little information is available about long-term outcomes of hypofractionated stereotactic radiotherapy (hypo-FSRT) for acoustic neuromas. In this study, the safety and effectiveness of hypo-FSRT for unilateral acoustic neuroma were reviewed over 8 years of experience at our institution. METHODS: Between May 1998 and October 2006, 27 patients were consecutively treated by linear accelerator-based hypo-FSRT. Two patients were excluded from this study because they were lost to follow-up within 12 months. The median follow-up period for the rest was 59 (range 24-133) months. Two types of treatment schedules were adopted. Thirteen patients received 30-39 Gy, given in 10-13 fractions (regimen A), whereas after July 2003, 12 patients received 20-24 Gy, given in 5-6 fractions at the tumor periphery (regimen B). These treatments were scheduled to be delivered in three fractions per week (Monday, Wednesday, Friday). The median planning target volume was 2.0, with 1.7 ml (range 0.7-10.6) in regimen A and 5.2 ml (range 0.9-9.3) in regimen B. In the pretreatment audiogram, seven patients (two in regimen A and five in regimen B) had serviceable hearing (Gardner-Robertson Class I-II). RESULTS: Local control rates were 100% with regimen A and 92% with regimen B. Serviceable hearing was preserved in four of five patients in regimen B but no patients in regimen A at the last follow-up. No permanent facial or trigeminal nerve morbidity was observed following treatment, and no salvage surgery was needed. CONCLUSIONS: Hypo-FSRT for acoustic neuromas achieved a high local control rate with minimal facial and trigeminal nerve morbidity.

Preparation of magnetic iron oxide nanoparticles for hyperthermia of cancer in a FeCl2-NaNO3-NaOH aqueous system.

Magnetic iron oxide nanoparticles (MIONPs) were synthesized in a FeCl2-NaNO3-NaOH aqueous system under various initial Fe(2+)/NO⁻3 molar ratios (α) and Fe(2+)/OH- molar ratios (ß) in order to clarify the effects of the initial molar ratio of reactants on the reaction mechanism. The Fe(2+)/NO⁻3 /OH(-) molar ratio of 3 : 1 : 5 led to the formation of magnetic nanoparticles mainly composed of magnetite (Fe3O4) and maghemite (γ-Fe2O3). The 36 nm sized γ-Fe2O3 and 413 nm sized Fe3O4 were obtained by changing the order in which NaNO3 was added to a NaOH solution. The in vitro heat generations of the resulting MIONPs in an agar phantom were measured under an alternating magnetic field (100 kHz, 23.9 kA/m). The temperature rise (ΔT) of the agar phantom for the 36 nm sized γ-Fe2O3 was 55°C in the first 140 s, with a concentration of 58 mg Fe/mL. Our results showed that it is possible to prepare MIONPs with high heating efficiencies under optimal conditions using the present method.

Magnetic SiO2 gel microspheres for arterial embolization hyperthermia.

We have prepared magnetic SiO(2) microspheres with a diameter of 20-30 µm as thermoseeds for hyperthermia of cancer. These were prepared by directly introducing preformed magnetic iron oxide nanoparticles (IONPs) into microspheres of a SiO(2) gel matrix derived from the hydrolysis of tetramethoxysilane (TMOS) in a water-in-oil (W/O) emulsion. Dimethylformamide (DMF) was used as a stabilizer, methanol (CH(3)OH) as a dispersant and ammonia (NH(4)OH) as the catalyst for the formation of the spherical particles in the aqueous phase of the W/O emulsion. The magnetic IONPs were synthesized hydrochemically in an aqueous system composed of ferrous chloride, sodium nitrate and sodium hydroxide. Mono-dispersed magnetic SiO(2) gel microspheres with a diameter of approximately 20 µm were successfully obtained by adding a determined amount of solution with a molar ratio of TMOS/DMF/CH(3)OH/H(2)O/NH(4)OH = 1:1.4:9:20:0.03 to kerosene with a surfactant (sorbitan monooleate/sorbitan monostearate = 3:1 by weight ratio) that was 30 wt% of the total amount of the oil phase. These were estimated to contain up to 60 wt% of IONPs that consisted mainly of Fe(3)O(4) and showed a higher specific absorption rate (SAR = 27.9-43.8 W g(-1)) than that of the starting IONPs (SAR = 25.3 W g(-1)) under an alternating current magnetic field of 300 Oe and 100 kHz.

Primary central nervous system lymphoma in Japan: changes in clinical features, treatment, and prognosis during 1985-2004.

We have conducted nationwide surveys of primary central nervous system lymphoma (PCNSL) treated since 1985. In the present study, we newly collected data between 2000 and 2004 and investigated changes in clinical features and outcome over time. A total of 739 patients with histologically proven PCNSL under going radiotherapy were analyzed. Seventeen institutions were surveyed, and data on 131 patients were collected. These data were compared with updated data that were previously obtained for 466 patients treated during 1985-1994 and 142 patients treated during 1995-1999. Recent trends toward decrease in male/female ratio, increase in aged patients, and increase in patients with multiple lesions were seen. Regarding treatment, decrease in attempts at surgical tumor removal and increases in use of systemic chemotherapy and methotrexate (MTX)-containing regimens were observed. The median survival time was 18, 29, and 24 months for patients seen during 1985-1994, 1995-1999, and 2000-2004, respectively, and the respective 5-year survival rates were 15%, 30%, and 30%. In groups seen during 1995-1999 and during 2000-2004, patients who received systemic or MTX-containing chemotherapy had better prognosis than those who did not. Multivariate analysis of all patients seen during 1985-2004 suggested the usefulness of MTX-containing chemotherapy as well as the importance of age, lactate dehydrogenase level, and tumor multiplicity as prognostic factors. Thus, this study revealed several notable changes in clinical features of PCNSL patients. The prognosis improved during the last 10 years. Advantage of radiation plus chemotherapy, especially MTX-containing chemotherapy, over radiation alone was suggested.

In vitro heat generation by ferrimagnetic maghemite microspheres for hyperthermic treatment of cancer under an alternating magnetic field.

Ferrimagnetic materials can be expected to be useful as thermo seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. Recently, it was reported that ferrimagnetic maghemite (gamma-Fe2O3) microspheres 20-30 microm in diameter prepared in aqueous solution can show excellent heat generating ability. However, these microspheres have many cracks on their surfaces. In this study, the preparation conditions for the microspheres was further optimized in order to obtain crack-free ferrimagnetic microspheres, and the in vitro heat generation of the obtained microspheres was measured in an agar phantom under an alternating magnetic field. Crack-free gamma-Fe2O3 microspheres 20-30 microm in diameter were obtained successfully. Their saturation magnetization and coercive force were 68 emu g(-1) and 198 Oe, respectively. Their heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 42 W g(-1). The microspheres showed in vitro heat generation when they were dispersed in an agar phantom and placed under an alternating magnetic field. It is believed that these microspheres may be useful for the in situ hyperthermic treatment of cancer.